Welcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.

I'm Pradip Kamat coming to you from Children’s Healthcare of Atlanta/Emory University School of Medicine and I'm Rahul Damania, from Cleveland Clinic Children’s Hospital. We are two Pediatric ICU physicians passionate about all things MED-ED in the PICU. PICU Doc on Call focuses on interesting PICU cases & management in the acute care pediatric setting so let’s get into our episode.

Welcome to our Episode today of a 7 yo M who presents to the PICU after a severe Motor Vehicle Accident.

Here is the case presented by Rahul

A 7-year-old male child is admitted to the PICU after sustaining severe trauma. The patient was brought to the emergency department after a motor vehicle accident that involved an 18-wheeler truck & the family’s car; in this severe accident the 7 yo was noted to be restrained however upon impact was ejected from the vehicle. He was unconscious and had multiple injuries, including a laceration on the head and bruising on the chest. The EMS was activated and the patient presented to the ED for acute stabilization. Upon examination, the patient was found to have a Glasgow Coma Scale score of 8, indicating a serious head injury. He had multiple bruises and abrasions on the chest and arms, and his pulse was rapid and weak. The patient was resuscitated with colloid and blood products, intubated, and transferred to the pediatric intensive care unit for further management.

Notably, a CT scan of the head showed a skull fracture and a subdural hematoma. A chest X-ray showed multiple rib fractures and bilateral pulmonary opacities with no evidence of pneumothorax. The patient was also found to have a grade 2 liver laceration and a splenic injury. Pelvic x-ray and cardiac FAST exam were unrevealing.

To summarize key elements from this case, this patient has:

• A traumatic brain injury
• Pulmonary contusions and is at risk for PARDS
• Liver and spleen injury
• Anemia
• Pertinent negative includes: No pelvic injuries or injuries to great vessels in the chest

Rahul, let's approach the PICU medical management of this case based on a culmination of various guidelines published in the Pediatric Critical Care literature. Namely, let's use this case to dive deep into guidelines for:

Traumatic brain injury (TBI)

****Transfusion and Anemia Expertise Initiative (****TAXI)

pediatric blunt liver and spleen injury management, are also known as the ATOMAC protocol, as well as general PICU management of acute trauma.

As we take the management of this pediatric trauma patient in a systems-based fashion let's first go into the Management of Pediatric Traumatic Brain Injuries, can you start us off with some key management considerations?

• Based on the March 2019 TBI guidelines published in Pediatric Critical Care Medicine in 2019 (PCCM20(3S):p S1-S82, March 2019)
• This patient should have an ICP monitor or even an EVD placed for CSF diversion in consultation with the NS and trauma team. A CPP of at least >50 in our 7 yo patient and ICP < 20 mm Hg has been shown to improve outcomes and reduce mortality.

Just as a quick review, CPP stands for cerebral perfusion pressure, which is the pressure that maintains blood flow to the brain. The formula for CPP is:

CPP = MAP (mean arterial pressure) - ICP (intracranial pressure)

Monitoring does not affect outcomes directly; rather the information from monitoring can be used to direct treatment decisions. Treatment informed by data from monitoring may result in better outcomes than treatment informed solely by data from clinical assessment. In short, it is important to have qualitative and quantitative data to optimize your decision-making.

As we talked about ICP control is so crucial for this patient, Pradip, can you talk to us about some practical points in controlling ICP?

• Appropriate patient position (head midline and elevated 15-30, make certain that cervical collar is not too tight but allows for venous drainage from the skull) is recommended. Control fever, treat hypoxia, and hypercarbia, and avoid hypotension.
• Sedation and analgesia are at the discretion of the treating physician but routine boluses must be avoided to prevent cerebral hypoperfusion. Also, continuous use of propofol for sedation or ICP management is not recommended.

That's a great initial set of practical management tips, head position, temperature control to avoid hyperthermia, and avoidance of hypotension to ensure optimal CPPs. Propofol may have a deleterious effect in some patients as it can reduce the SVR and predispose patients to hypotension, especially when employed in a bolus fashion.

Rahul, what about NMB?

• Neuromuscular blockade may be required if ICP remains elevated despite adequate sedation. Muscle relaxation can also prevent shivering, fighting against the ventilator, and permit hyperventilation if it is required. Intermittent dosing of short-acting agents (eg, vecuronium or rocuronium) is preferred.
• Seizure prophylaxis with levetiracetam or phenytoin to prevent post-traumatic seizures is recommended for the first 7 days. Uncontrolled seizures can increase ICP.
• For ICP management: Any ICP > 20 mmHg for > 5 minutes requires intervention:
• First-tier therapies include: CSF drainage, bolus/infusion of hypertonic saline, sedation-analgesia/NMB
• Second-tier therapies used for refractory intracranial hypertension (20-40% of severe TBI cases) include Hyperventilation, surgery for decompressive craniectomy or to remove mass lesion (a repeat CT scan may be required), hyperventilation, moderate hypothermia (32-34), barbiturate coma, higher levels of osmolar therapy.

I think this is a great time to incorporate an essential physiologic concept, of cerebral metabolic rate of oxygen consumption.

CMRO2 refers to the cerebral metabolic rate of oxygen consumption, which is a measure of the amount of oxygen used by the brain. CMRO2 can be increased during periods of Increased neural activity, Hypercapnia, Hypoxia, increased temperature and increased ICP

It is important to note that these factors can impact the brain's oxygen consumption, and in some cases, an increase in CMRO2 can lead to a decline in brain function if the brain is not able to adequately meet its increased oxygen demand.

• Let's pivot to the next organ system in this patient — our patient had bilateral pulmonary contusions, about this patient meet at-risk PARDS criteria? and what would be your mechanical ventilation strategy?
• The patient has bilateral contusions. One study (Intensive Care Med Nov 2019, 36(7):) reported that Pediatric ARDS in children with pulmonary contusion is independently associated with lower GCS scores. This patient is at risk for PARDS based on the presence of bilateral contusions and initial GCS < 8. The incidence of PARDS in TBI is ~ 9%, and its presence is associated with significantly increased morbidity and mortality. (Nair AB, Cohen MJ, Flori HR. Pediatr Crit Care Med 2020; 21:122–128). There are no clear oxygenation/Ventilation guidelines in TBI-associated PARDS. We should avoid high positive pressures (PIP) and high positive end-expiratory pressures (PEEP) as long as oxygenation remains adequate; otherwise high PIP and PEEP may increase intrathoracic pressure and impede venous drainage. We target a PCO2 35-45 mmHg and avoid hyperventilation to prevent cerebral ischemia due to decreased cerebral blood flow.

To summarize, PARDS in trauma is a heterogenous disease — it is important to pay attention to the cardiopulmonary interactions of increased positive intrathoracic pressure as this can have effects on preload to the heart as well as venous drainage of the cerebral vasculature.

Pradip, What about fluid status?

• Additionally, we should pay close attention to fluid status: Treat hypovolemia with isotonic fluids (eg, normal saline) to achieve normal, rather than excess, volume status. We should avoid the administration of hypotonic fluids (eg, D5W). Although recent evidence from basic science research, observational research, and clinical trials suggests that using balanced crystalloids rather than saline may have beneficial effects on acid–base balance, renal physiology, and patient outcomes, we need to be careful about using balanced fluids in TBI so as to not cause iatrogenic hyponatremia. Although adult studies have reported poor outcomes with fluid overload in pediatric patients, the role of FO in pediatric TBI outcomes is not clear. Drawing from adult studies it is best to be vigilant about fluid balance and avoid fluid overload.

Intensivists should pay close attention to serum electrolytes and glucose while managing Trauma patients: Serum Na should be monitored at least twice daily in TBI patients. If hyponatremia develops despite the use of NS, we should think of SIADH or CSW.

Our patient in our case was noted in the PICU to become progressively hypothermic, Rahul can you highlight the effect of hypothermia in the setting of pediatric trauma?

• Yes, I think it is important for us to review the terrible triad of trauma. The "triad of death" in trauma refers to a combination of three physiological conditions that often occur together and significantly increase the risk of death in trauma patients. The triad of death is a dangerous state, as each component can contribute to the others, exacerbating the risk of death. The triad includes acidosis, hypothermia, and coagulopathy. Early recognition and aggressive management of these conditions are crucial in improving outcomes in trauma...]]>Approach to Pediatric Trauma 

  Welcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.

  I'm Pradip Kamat coming to you from Children’s Healthcare of Atlanta/Emory University School of Medicine and I'm Rahul Damania, from Cleveland Clinic Children’s Hospital. We are two Pediatric ICU physicians passionate about all things MED-ED in the PICU. PICU Doc on Call focuses on interesting PICU cases & management in the acute care pediatric setting so let’s get into our episode.

  Welcome to our Episode today of a 7 yo M who presents to the PICU after a severe Motor Vehicle Accident.

  Here is the case presented by Rahul

  A 7-year-old male child is admitted to the PICU after sustaining severe trauma. The patient was brought to the emergency department after a motor vehicle accident that involved an 18-wheeler truck & the family’s car; in this severe accident the 7 yo was noted to be restrained however upon impact was ejected from the vehicle. He was unconscious and had multiple injuries, including a laceration on the head and bruising on the chest. The EMS was activated and the patient presented to the ED for acute stabilization. Upon examination, the patient was found to have a Glasgow Coma Scale score of 8, indicating a serious head injury. He had multiple bruises and abrasions on the chest and arms, and his pulse was rapid and weak. The patient was resuscitated with colloid and blood products, intubated, and transferred to the pediatric intensive care unit for further management.

  Notably, a CT scan of the head showed a skull fracture and a subdural hematoma. A chest X-ray showed multiple rib fractures and bilateral pulmonary opacities with no evidence of pneumothorax. The patient was also found to have a grade 2 liver laceration and a splenic injury. Pelvic x-ray and cardiac FAST exam were unrevealing.

  To summarize key elements from this case, this patient has:

  • A traumatic brain injury
  • Pulmonary contusions and is at risk for PARDS
  • Liver and spleen injury
  • Anemia
  • Pertinent negative includes: No pelvic injuries or injuries to great vessels in the chest
  
  

  Rahul, let's approach the PICU medical management of this case based on a culmination of various guidelines published in the Pediatric Critical Care literature. Namely, let's use this case to dive deep into guidelines for:

  Traumatic brain injury (TBI)

  ****Transfusion and Anemia Expertise Initiative (****TAXI)

  pediatric blunt liver and spleen injury management, are also known as the ATOMAC protocol, as well as general PICU management of acute trauma.

  As we take the management of this pediatric trauma patient in a systems-based fashion let's first go into the Management of Pediatric Traumatic Brain Injuries, can you start us off with some key management considerations?

  • Based on the March 2019 TBI guidelines published in Pediatric Critical Care Medicine in 2019 (PCCM20(3S):p S1-S82, March 2019)
  • This patient should have an ICP monitor or even an EVD placed for CSF diversion in consultation with the NS and trauma team. A CPP of at least >50 in our 7 yo patient and ICP < 20 mm Hg has been shown to improve outcomes and reduce mortality.
  
  

  Just as a quick review, CPP stands for cerebral perfusion pressure, which is the pressure that maintains blood flow to the brain. The formula for CPP is:

  CPP = MAP (mean arterial pressure) - ICP (intracranial pressure)

  Monitoring does not affect outcomes directly; rather the information from monitoring can be used to direct treatment decisions. Treatment informed by data from monitoring may result in better outcomes than treatment informed solely by data from clinical assessment. In short, it is important to have qualitative and quantitative data to optimize your decision-making.

  As we talked about ICP control is so crucial for this patient, Pradip, can you talk to us about some practical points in controlling ICP?

  • Appropriate patient position (head midline and elevated 15-30, make certain that cervical collar is not too tight but allows for venous drainage from the skull) is recommended. Control fever, treat hypoxia, and hypercarbia, and avoid hypotension.
  • Sedation and analgesia are at the discretion of the treating physician but routine boluses must be avoided to prevent cerebral hypoperfusion. Also, continuous use of propofol for sedation or ICP management is not recommended.
  
  

  That's a great initial set of practical management tips, head position, temperature control to avoid hyperthermia, and avoidance of hypotension to ensure optimal CPPs. Propofol may have a deleterious effect in some patients as it can reduce the SVR and predispose patients to hypotension, especially when employed in a bolus fashion.

  Rahul, what about NMB?

  • Neuromuscular blockade may be required if ICP remains elevated despite adequate sedation. Muscle relaxation can also prevent shivering, fighting against the ventilator, and permit hyperventilation if it is required. Intermittent dosing of short-acting agents (eg, vecuronium or rocuronium) is preferred.
  • Seizure prophylaxis with levetiracetam or phenytoin to prevent post-traumatic seizures is recommended for the first 7 days. Uncontrolled seizures can increase ICP.
  • For ICP management: Any ICP > 20 mmHg for > 5 minutes requires intervention:
  • First-tier therapies include: CSF drainage, bolus/infusion of hypertonic saline, sedation-analgesia/NMB
  • Second-tier therapies used for refractory intracranial hypertension (20-40% of severe TBI cases) include Hyperventilation, surgery for decompressive craniectomy or to remove mass lesion (a repeat CT scan may be required), hyperventilation, moderate hypothermia (32-34), barbiturate coma, higher levels of osmolar therapy.
  
  

  I think this is a great time to incorporate an essential physiologic concept, of cerebral metabolic rate of oxygen consumption.

  CMRO2 refers to the cerebral metabolic rate of oxygen consumption, which is a measure of the amount of oxygen used by the brain. CMRO2 can be increased during periods of Increased neural activity, Hypercapnia, Hypoxia, increased temperature and increased ICP

  It is important to note that these factors can impact the brain's oxygen consumption, and in some cases, an increase in CMRO2 can lead to a decline in brain function if the brain is not able to adequately meet its increased oxygen demand.

  • Let's pivot to the next organ system in this patient — our patient had bilateral pulmonary contusions, about this patient meet at-risk PARDS criteria? and what would be your mechanical ventilation strategy?
  • The patient has bilateral contusions. One study (Intensive Care Med Nov 2019, 36(7):) reported that Pediatric ARDS in children with pulmonary contusion is independently associated with lower GCS scores. This patient is at risk for PARDS based on the presence of bilateral contusions and initial GCS < 8. The incidence of PARDS in TBI is ~ 9%, and its presence is associated with significantly increased morbidity and mortality. (Nair AB, Cohen MJ, Flori HR. Pediatr Crit Care Med 2020; 21:122–128). There are no clear oxygenation/Ventilation guidelines in TBI-associated PARDS. We should avoid high positive pressures (PIP) and high positive end-expiratory pressures (PEEP) as long as oxygenation remains adequate; otherwise high PIP and PEEP may increase intrathoracic pressure and impede venous drainage. We target a PCO2 35-45 mmHg and avoid hyperventilation to prevent cerebral ischemia due to decreased cerebral blood flow.
  
  

  To summarize, PARDS in trauma is a heterogenous disease — it is important to pay attention to the cardiopulmonary interactions of increased positive intrathoracic pressure as this can have effects on preload to the heart as well as venous drainage of the cerebral vasculature.

  Pradip, What about fluid status?

  • Additionally, we should pay close attention to fluid status: Treat hypovolemia with isotonic fluids (eg, normal saline) to achieve normal, rather than excess, volume status. We should avoid the administration of hypotonic fluids (eg, D5W). Although recent evidence from basic science research, observational research, and clinical trials suggests that using balanced crystalloids rather than saline may have beneficial effects on acid–base balance, renal physiology, and patient outcomes, we need to be careful about using balanced fluids in TBI so as to not cause iatrogenic hyponatremia. Although adult studies have reported poor outcomes with fluid overload in pediatric patients, the role of FO in pediatric TBI outcomes is not clear. Drawing from adult studies it is best to be vigilant about fluid balance and avoid fluid overload.
  
  

  Intensivists should pay close attention to serum electrolytes and glucose while managing Trauma patients: Serum Na should be monitored at least twice daily in TBI patients. If hyponatremia develops despite the use of NS, we should think of SIADH or CSW.

  Our patient in our case was noted in the PICU to become progressively hypothermic, Rahul can you highlight the effect of hypothermia in the setting of pediatric trauma?

  • Yes, I think it is important for us to review the terrible triad of trauma. The "triad of death" in trauma refers to a combination of three physiological conditions that often occur together and significantly increase the risk of death in trauma patients. The triad of death is a dangerous state, as each component can contribute to the others, exacerbating the risk of death. The triad includes acidosis, hypothermia, and coagulopathy. Early recognition and aggressive management of these conditions are crucial in improving outcomes in trauma patients.
  
  

  Rahul, let’s wrap this section up by talking about hyperglycemia, our patient was noted to have a few blood sugars around 200 mg/dl during the first four hours of his PICU admission, can you shed some light on this?

  • Hyperglycemia is also commonly seen in TBI patients. The optimal strategy for glucose administration or control remains controversial although it's reasonable to withhold glucose in the IVF in the first 48hrs with close monitoring to prevent hypoglycemia.
  
  

  The last part of this episode will cover a bit on transfusion in the critical care setting as well as the management of blunt abdominal trauma.

  • Our patient was noted to have a Hgb of 6.8 mg/dL and an INR of 1.8. How should we tackle anemia and also balance the elevated INR?
  • Per the Pediatric Transfusion and Anemia Expertise Initiative–Control/Avoidance of Bleeding (TAXI-CAB)guidelines published as a supplement in the January 2022 Vol 23, supplement 15 of PCCM journal, the guideline concluded that there is insufficient pediatric evidence to support specific thresholds for coagulation tests, including INR, and platelet count, and the transfusion of plasma and platelets in critically ill pediatric patients with severe trauma, moderate-to-severe TBI, or nontraumatic ICH.
  • It is unclear if an INR of 1.8 would change much with an FFP transfusion. Some studies have reported a significant change in INR with FFP only when INR > 2.5 (Arch Surg 2010; 145:899–906). If a procedure such as an ICP monitor or EVD was being placed, the NS team would suggest FFP administration for an INR > 1.5. Similarly it's reasonable to target a platelet count > 100K during the neurosurgical procedure. Although it is not necessary to continue to maintain a platelet count of > 100K once hemostasis is achieved.
  
  

  What about blood transfusion?

  • Even though there is a lack of evidence in pediatric patients, the TAXI-CAB experts concluded that a balanced resuscitation strategy/ratio for RBC/plasma/ platelet of 1:1:1 or 2:1:1 in injured children with hemorrhagic shock or with life-threatening hemorrhage might be considered. This transfusion strategy can be stopped once the hemorrhage is controlled. In our case, the patient currently has no ongoing bleeding or shock. The Hgb is 6.8. Per the September 2018 TAXI_CAB guidelines published in the PCCM supplement (Vol 19, supplement 3): In Critically ill children with acute brain injury (e.g., severe traumatic brain injury, or cerebrovascular stroke), an RBC transfusion could be considered if the Hb falls between 7 – 10 g/dL. They also recommended against the use of invasive brain oxygenation monitoring to guide RBC transfusion. Based on these guidelines, I would transfuse blood to this patient.
  
  

  Once hemostasis is achieved it is reasonable to watch the trend in CBC, coagulation profile every 12 hours. It is not necessary to maintain a platelet count of > 100K once hemostasis is achieved. Similarly, the routine correction of an INR below 2 with FFP is not recommended as studies show a significant change in INR with FFP only when INR > 2.5. In patients with acute brain injury, RBC transfusion must be considered if hgb falls between 7-10g/dL

  Finally, in our case, the patient sustained a liver and splenic injury, can you use this case to tell us more about the ATOMAC guidelines?

  Absolutely, so the Arizona-Texas-Oklahoma-Memphis-Arkansas Consortium (ATOMAC) consists of a group of Level I pediatric trauma centers from across the United States dedicated to performing clinical and preclinical studies aimed at optimizing management and functional outcomes for injured children. The strongly recommended guidelines include:

  1. Management of pediatric BLSI may be based on hemodynamic status, rather than injury grade.
  2. A shortened period of bed rest of 1 day or less for stable children with unchanged hemoglobin levels.
  3. A transfusion threshold of 7.0 g/dl is reasonable for children undergoing non-operative management.
  4. Unstable patients should be considered for surgery, urgent embolization, or continued non-operative management, depending on other injuries and the center's resources
  
  

  A recent study (Stewart et al Trauma Acute Care Surg. 2023 Jan 16.) reported that the ATOMAC guideline fostered high rates of non-operative management with low ICU utilization and LOS, while demonstrating safety in implementation, irrespective of injury grade.

  In this patient, I would recommend serial CBC monitoring every 4 to 6 hours!

  To summarize, the most commonly injured abdominal organ in blunt trauma is the spleen followed by the liver. Intra-abdominal solid organ injuries are graded by the appearance on the computed tomography scans. Higher the grade, the more injury. Most intra-abdominal blunt trauma injuries are managed non-operatively provided the patient is hemodynamically stable. Pay close attention to, localized tenderness, ecchymosis, abrasion, flank tenderness, and flank or abdominal mass along with elevation of liver enzymes or drops in hgb.

  For any trainees out there, we would highly recommend familiarizing yourself with TBI guidelines TAXI guidelines and the ATOMAC protocols as these will provide a framework for the management of Pediatric Trauma.

  Pediatric trauma like many diagnoses in the PICU involves a multidisciplinary approach with close communication. The approach sense outside of the pediatric ICU as many of these patients undergo long-term rehab in inpatient and outpatient facilities.

  This concludes our episode on the PICU management of the patient with trauma. We hope you found value in our short, case-based podcast. We welcome you to share your feedback, subscribe & place a review on our podcast! Please visit our website picudoconcall.org which showcases our episodes as well as our Doc on Call management cards. PICU Doc on Call is co-hosted by myself Dr. Pradip Kamat and Dr. Rahul Damania. Stay tuned for our next episode! Thank you!

  • References
  • Fuhrman & Zimmerman - Textbook of Pediatric Critical Care Chapter 117 Evaluation, Stabilization, and initial management after trauma (Naiditch JA et al) pages 1363-1374. Also Chapter 118 Traumatic Brain Injury(Kochanek PM et al.) page 1375-1399. Also Chapter 119 Pediatric Thoracic Trauma (Fitzgerald et al) pages 1401-1407. Also Chapter 120. Pediatric Abdominal trauma (Vogel AM et al) pages 1408-1416
  • Kochanek, Patrick M.; Tasker, Robert C.; Carney, Nancy; Totten, Annette M.; Adelson, P. David; Selden, Nathan R.; Davis-O’Reilly, Cynthia; Hart, Erica L.; Bell, Michael J.; Bratton, Susan L.; Grant, Gerald A.; Kissoon, Niranjan; Reuter-Rice, Karin E.; Vavilala, Monica S.; Wainwright, Mark S. Guidelines for the Management of Pediatric Severe Traumatic Brain Injury, Third Edition: Update of the Brain Trauma Foundation Guidelines. Pediatric Critical Care Medicine. 20(3S):S1-S82, March 2019
  • Emeriaud, Guillaume, Khemani R et al. on behalf of the Second Pediatric Acute Lung Injury Consensus Conference (PALICC-2) Group on behalf of the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network Executive Summary of the Second International Guidelines for the Diagnosis and Management of Pediatric Acute Respiratory Distress Syndrome (PALICC-2). Pediatric Critical Care Medicine. 24(2):143-168, February 2023
  • Nellis ME, Karam O, Valentine SL, Bateman ST, Remy KE, Lacroix J, Cholette JM, Bembea MM, Russell RT, Steiner ME, Goobie SM, Tucci M, Stricker PA, Stanworth SJ, Delaney M, Lieberman L, Muszynski JA, Bauer DF, Steffen K, Nishijima D, Ibla J, Emani S, Vogel AM, Haas T, Goel R, Crighton G, Delgado D, Demetres M, Parker RI; Pediatric Critical Care Transfusion and Anemia EXpertise Initiative—Control/Avoidance of Bleeding (TAXI-CAB), in collaboration with the Pediatric Critical Care Blood Research Network (BloodNet), and the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network. Executive Summary of Recommendations and Expert Consensus for Plasma and Platelet Transfusion Practice in Critically Ill Children: From the Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding (TAXI-CAB). Pediatr Crit Care Med. 2022 Jan 1;23(1):34-51. doi: 10.1097/PCC.0000000000002851. PMID: 34989711; PMCID: PMC8820267.
  • Tasker, Robert C. MA, MBBS, MD, FRCP1,2, Turgeon, Alexis F. MD, MSc, FRCPC3; Spinella, Philip C. MD, FCCM4; for the Pediatric Critical Care Transfusion and Anemia Expertise Initiative (TAXI), in collaboration with Pediatric Critical Care Blood Research Network (BloodNet), and the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network. Recommendations on RBC Transfusion in Critically Ill Children With Acute Brain Injury From the Pediatric Critical Care Transfusion and Anemia Expertise Initiative. Pediatric Critical Care Medicine 19(9S):p S133-S136, September 2018. | DOI: 10.1097/PCC.0000000000001589
  • Stewart S, Fraser JA, Shah N, Rentea RM, Aguayo P, Juang D, Fraser JD, Snyder CL, Hendrickson RJ, St Peter SD, Oyetunji TA. INSTITUTIONAL OUTCOMES OF BLUNT LIVER & SPLENIC INJURY IN THE ATOMAC ERA. J Trauma Acute Care Surg. 2023 Jan 16. doi: 10.1097/TA.0000000000003870. Epub ahead of print. PMID: 36649594.
  
  ]]>7a207dca-b36c-4d3b-be9e-1060301261f5Sun, 19 Feb 2023 03:00:00 -040022:03falsefull6666How to Learn & Retain Knowledge from a Medical PodcastDear Listeners & Peds ICU community, WE are back on air!

  Welcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.

  I'm Pradip Kamat coming BACK to you from Children’s Healthcare of Atlanta/Emory University School of Medicine

  and I'm Rahul Damania from Cleveland Clinic Children’s Hospital and we are two Pediatric ICU physicians passionate about all things MED-ED in the PICU.

  PICU Doc on Call focuses on interesting PICU cases & management in the acute care pediatric setting.

  As we turn into a new year, we would like to introduce Season 2 of PICU Doc on Call. 

  Yes Pradip, I am super excited for this year & I want to take this moment to thank YOU all, our listener community for making PICU Doc on Call such a success as we share our passion for medical education thru this forum!

  This episode will give you a quick layout of how we will be organizing each episode of PICU doc on call this year. We will also highlight some tips and tricks on how to best learn from a medical podcast. Our goal in this episode is to provide you a framework on some best practices in medical podcasting and how to retain information from a podcast. Especially for our past & future episodes, we hope you can use this audio learning platform to assist you in applying the knowledge at the bedside when you are working in the acute care setting.

  Let’s get into our first learning objective,

  Rahul, did you know that learning via podcasts can actually benefit your brain & change the neural chemistry.

  In fact, a 2016 med ed study published  out of UC Berkeley concluded that listening to narrative stories from podcasts can stimulate multiple parts of your brain such as the limbic system and can enhance mood as it modulates dopamine and serotonin driven neural pathways. Think about listening to your favorite true-crime podcast  — the suspense actually allows for you to stimulate centers in your medulla that increase the amount of endorphines, dopamine and serotonin that keep you on the edge of your seat.

  That is so unique, so based on this, I do want to highlight some of the key elements which will make our podcast or any medical podcast you listen to beneficial. These pearls will also help you if you are developing a medical podcast of your own!

  The first concept here is that many podcasts provide narratives.

  When it comes to medical podcasts, narratives are in the form of medical cases which allow for you to retain content knowledge as a patient case invokes emotion and this can help you remember information more robustly.

  When listening to a podcast, you have to use your imagination to picture what’s going on. For example, if I painted a 2 yo M with a history of rhinorrhea at home for about a week who now presents to the ED with subcostal & intercostal retractions that then progresses to intubation in the PICU, you not only are envisioning a patient in front of you, but also are shifting your mind across settings. Our brain has to work at the pace of the audio, so hopefully your mind doesn’t wander off like it does when reading a textbook page. And because you have to actively think, you can retain much more.

  The second advantage of audio learning is that it provides flexibility and accessibility

  When it comes to incorporating a podcast into your daily learning, it is easy, at any time of the day, you can open up your smart phone and access your Apple podcast or Spotify app and listen to a short episode on a certain topic. I would really encourage you to have a portion of the day, whether it is your commute, during chores, or even during a workout to incorporate listening to a podcast in your daily learning. Especially for PICU DOC ON CALL, our episodes are on average around 20 minutes to really capture your attention span.

  In fact, a very interesting study published in 2022 by Wolpaw et al. looking at knowledge retention from a podcast showed that

  trainees preferred podcast learning over reading for many topics.

  When compared to textbook reading, podcast learning (seated or on a treadmill) produced significantly better learning gain, and equivalent retention for two of the three topics which they piloted in the study. This study even hooked the resident & med student participants to an EEG to highlight increased attention when using an audiobased tool.

  Finally, a good medical podcast follows a consistent outline or organization & is rooted in principles of multi-media learning.

  Multi-media learning theory specifically comes from Dr. Richard Mayer from UC Santa Barbara. His lab focuses on learning science and use of ed technologies.

  Some of the key multi-media principles which make podcasts such a unique form of learning involve:

  Dual channel processing — the fact that we can utilize both visual and audio representations.

  WE are really passionate about this theory on PICU Doc on Call, so make sure you check out our chalk talk infographic & show notes which are paried with each episode; they will help you garner a visual representation of the content we cover!

  That’s great, I think another unique multi-media principle is to have a minimization of extraneous load, i.e. the fact is that effective podcasts cut out redudancy, have optimal length of segments, & have user controls like double speed, etc.

  The key summary which we would like to impart on you:

  Utilize medical podcasts to actively learn — try to identify relevant material which is new to you and create a schema so that you are able to connect the information to your prior knolwedge. This idea of knowledge construction where you can integrate new information with prior experience is crucial in creating long-term memory with podcasts. Podcasts are unique to Adult Learning theory because they are a great self directed way to enhance your learning. Imagine this, you see a patient with ARDS in the PICU or on transport, you can easily direct your learning to a podcast to help solidify what you see & optimize your management decisions.

  This is great, Pradip, do you have other tips on how we can effectively learn from a medical podcast?

  Yes, I like to hit the pause button often during an in-depth podcast. It helps me stop for a moment and digest the information so I can link it to my clinical experience or knowledge which I have read in the past.

  I also try to keep a small notebook in my pocket which I can write out anything that resonates with me — writing it down helps me remember & I can have an area which acts as my second brain as I develop lectures or even teach on rounds.

  Such great advice, I also think listening to a podcast and discussing the contents with a colleague or your learner group is so essential. This principle comes from a highly recommended book on learning science called Make it Stick by Peter Brown and colleagues out of their research lab in St Louis and one of the quotes which really resonate with me is:

  “Learning is deeper and more durable when it’s effortful. Learning that’s easy is like writing in sand, here today and gone tomorrow.”

  Taking that extra effort to construct a mini-chalk talk for your learner group after you listen to the podcast or incorporate it into your next fellow didactics may be helpful for you to retain the new information!

  To wrap up this episode, Rahul do you mind sharing with our listeners on how each of our upcoming podcasts in Season 2 will be organized?

  Start with a case to highlight the PICU topic at hand

  We will provide you a case summary highlighting the pertinent positives and negatives

  Go into a board style multiple choice question to help assess your knowledge

  Provide diagnostic and management frameworks highlighting...]]>Dear Listeners & Peds ICU community, WE are back on air!

  Welcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.

  I'm Pradip Kamat coming BACK to you from Children’s Healthcare of Atlanta/Emory University School of Medicine

  and I'm Rahul Damania from Cleveland Clinic Children’s Hospital and we are two Pediatric ICU physicians passionate about all things MED-ED in the PICU.

  PICU Doc on Call focuses on interesting PICU cases & management in the acute care pediatric setting.

  As we turn into a new year, we would like to introduce Season 2 of PICU Doc on Call. 

  Yes Pradip, I am super excited for this year & I want to take this moment to thank YOU all, our listener community for making PICU Doc on Call such a success as we share our passion for medical education thru this forum!

  This episode will give you a quick layout of how we will be organizing each episode of PICU doc on call this year. We will also highlight some tips and tricks on how to best learn from a medical podcast. Our goal in this episode is to provide you a framework on some best practices in medical podcasting and how to retain information from a podcast. Especially for our past & future episodes, we hope you can use this audio learning platform to assist you in applying the knowledge at the bedside when you are working in the acute care setting.

  Let’s get into our first learning objective,

  Rahul, did you know that learning via podcasts can actually benefit your brain & change the neural chemistry.

  In fact, a 2016 med ed study published  out of UC Berkeley concluded that listening to narrative stories from podcasts can stimulate multiple parts of your brain such as the limbic system and can enhance mood as it modulates dopamine and serotonin driven neural pathways. Think about listening to your favorite true-crime podcast  — the suspense actually allows for you to stimulate centers in your medulla that increase the amount of endorphines, dopamine and serotonin that keep you on the edge of your seat.

  That is so unique, so based on this, I do want to highlight some of the key elements which will make our podcast or any medical podcast you listen to beneficial. These pearls will also help you if you are developing a medical podcast of your own!

  The first concept here is that many podcasts provide narratives.

  When it comes to medical podcasts, narratives are in the form of medical cases which allow for you to retain content knowledge as a patient case invokes emotion and this can help you remember information more robustly.

  When listening to a podcast, you have to use your imagination to picture what’s going on. For example, if I painted a 2 yo M with a history of rhinorrhea at home for about a week who now presents to the ED with subcostal & intercostal retractions that then progresses to intubation in the PICU, you not only are envisioning a patient in front of you, but also are shifting your mind across settings. Our brain has to work at the pace of the audio, so hopefully your mind doesn’t wander off like it does when reading a textbook page. And because you have to actively think, you can retain much more.

  The second advantage of audio learning is that it provides flexibility and accessibility

  When it comes to incorporating a podcast into your daily learning, it is easy, at any time of the day, you can open up your smart phone and access your Apple podcast or Spotify app and listen to a short episode on a certain topic. I would really encourage you to have a portion of the day, whether it is your commute, during chores, or even during a workout to incorporate listening to a podcast in your daily learning. Especially for PICU DOC ON CALL, our episodes are on average around 20 minutes to really capture your attention span.

  In fact, a very interesting study published in 2022 by Wolpaw et al. looking at knowledge retention from a podcast showed that

  trainees preferred podcast learning over reading for many topics.

  When compared to textbook reading, podcast learning (seated or on a treadmill) produced significantly better learning gain, and equivalent retention for two of the three topics which they piloted in the study. This study even hooked the resident & med student participants to an EEG to highlight increased attention when using an audiobased tool.

  Finally, a good medical podcast follows a consistent outline or organization & is rooted in principles of multi-media learning.

  Multi-media learning theory specifically comes from Dr. Richard Mayer from UC Santa Barbara. His lab focuses on learning science and use of ed technologies.

  Some of the key multi-media principles which make podcasts such a unique form of learning involve:

  Dual channel processing — the fact that we can utilize both visual and audio representations.

  WE are really passionate about this theory on PICU Doc on Call, so make sure you check out our chalk talk infographic & show notes which are paried with each episode; they will help you garner a visual representation of the content we cover!

  That’s great, I think another unique multi-media principle is to have a minimization of extraneous load, i.e. the fact is that effective podcasts cut out redudancy, have optimal length of segments, & have user controls like double speed, etc.

  The key summary which we would like to impart on you:

  Utilize medical podcasts to actively learn — try to identify relevant material which is new to you and create a schema so that you are able to connect the information to your prior knolwedge. This idea of knowledge construction where you can integrate new information with prior experience is crucial in creating long-term memory with podcasts. Podcasts are unique to Adult Learning theory because they are a great self directed way to enhance your learning. Imagine this, you see a patient with ARDS in the PICU or on transport, you can easily direct your learning to a podcast to help solidify what you see & optimize your management decisions.

  This is great, Pradip, do you have other tips on how we can effectively learn from a medical podcast?

  Yes, I like to hit the pause button often during an in-depth podcast. It helps me stop for a moment and digest the information so I can link it to my clinical experience or knowledge which I have read in the past.

  I also try to keep a small notebook in my pocket which I can write out anything that resonates with me — writing it down helps me remember & I can have an area which acts as my second brain as I develop lectures or even teach on rounds.

  Such great advice, I also think listening to a podcast and discussing the contents with a colleague or your learner group is so essential. This principle comes from a highly recommended book on learning science called Make it Stick by Peter Brown and colleagues out of their research lab in St Louis and one of the quotes which really resonate with me is:

  “Learning is deeper and more durable when it’s effortful. Learning that’s easy is like writing in sand, here today and gone tomorrow.”

  Taking that extra effort to construct a mini-chalk talk for your learner group after you listen to the podcast or incorporate it into your next fellow didactics may be helpful for you to retain the new information!

  To wrap up this episode, Rahul do you mind sharing with our listeners on how each of our upcoming podcasts in Season 2 will be organized?

  Start with a case to highlight the PICU topic at hand

  We will provide you a case summary highlighting the pertinent positives and negatives

  Go into a board style multiple choice question to help assess your knowledge

  Provide diagnostic and management frameworks highlighting relevant literature which surround the topic.

  We aim to make this season’s podcasts very dynamic, engaging, & practical. We hope to have you listen to our podcast and actually garner some content that you can incorporate in your practice as well as even utilize to teach your learners/colleagues

  Just a quick anecdote, I recently gave a lecture to the EM residency at Cleveland Clinic & before the didactic session, I did assign a podcast to listen to! I see this flipping the class room idea in the undergraduate medical school realm & I really think leveraging this model in the graduate med ed realm is on the horizon.

  This concludes our first Season 2 episode on How to Learn & Retain Knowledge from a Medical Podcast. We hope you found value in our short podcast. We really would like to welcome you to share your feedback, subscribe & place a review on our podcast! Please visit our website picudoconcall.org which showcases our episodes as well as our Doc on Call infographics. PICU Doc on Call is co-hosted by myself Dr. Pradip Kamat and Dr. Rahul Damania. Stay tuned for our next episode! Thank you!

  References:

  Wolpaw J, Ozsoy S, Berenholtz S, Wright S, Bowen K, Gogula S, Lee S, Toy S. A Multimodal Evaluation of Podcast Learning, Retention, and Electroencephalographically Measured Attention in Medical Trainees. Cureus. 2022 Nov 9;14(11):e31289. doi: 10.7759/cureus.31289. PMID: 36514626; PMCID: PMC9733582.

  Brown, Peter C. Make It Stick : the Science of Successful Learning. Cambridge, Massachusetts :The Belknap Press of Harvard University Press, 2014.

  
  

  
  

  
  

  ]]>750dfec4-12be-4466-9bb0-bca210ab40dfSun, 12 Feb 2023 03:00:00 -040011:08falsefull6565Hypnotic Gummies: An Approach to Cannabis ToxicityWelcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.

  I'm Pradip Kamat coming to you from Children’s Healthcare of Atlanta/Emory University School of Medicine

  and I'm Rahul Damania from Cleveland Clinic Children’s Hospital. We are two Pediatric ICU physicians passionate about all things MED-ED in the PICU. PICU Doc on Call focuses on interesting PICU cases & management in the acute care pediatric setting so let’s get into our episode:

  Welcome to our Episode a three-year-old girl with altered mental status and acute respiratory failure

  Here's the case presented by Rahul—

  A three-year-old presents to the PICU with altered mental status and difficulty breathing.

  Per the mother, the patient was in the usual state of health on the day prior to admission when the mother left her in the care of her maternal grandmother. When mom arrived home later in the afternoon, mom was unable to wake her and reported that she seemed "stiff". She did not have any abnormal movements or shaking episodes. Mom called 911 and the patient was brought to our ED. No known head trauma, though the patient is in the care of MGM throughout the day. No emesis. No recent sick symptoms. No witnessed ingestion, however, the patient's mother reports that MGM is on multiple medications (Xarelto, zolpidem, Buspar, gabapentin, and acetaminophen) and uses THC-containing products specifically THC gummies. In the ED: The patient had waxing and waning mentation with decreased respiratory effort. GCS was recorded at 7. Arterial blood gas was performed showing an initial pH of 7.26/61/31/0. The patient was intubated for airway protection in the setting of likely ingestion. The patient has no allergies, immunizations are UTD.

  BP 112/52 (67) | Pulse 106 | Temp 36.2 °C (Tympanic) | Resp (!) 14 | Ht 68.5 cm | Wt 14.2 kg | SpO2 100% | BMI 30.26 kg/m²

  Physical exam was unremarkable-pupils were 4-5mm and sluggish. There was no rash, no e/o of trauma

  Initial CMP was normal with AG of 12, CBC was unremarkable, and Respiratory viral panel was negative. Serum toxicology was negative for acetaminophen, salicylates, and alcohol.

  Basic Urine drug screen was positive for THC

  To summarize key elements from this case, this patient has:

  • Altered mental status: - waxing and waning with GCS less than 8 suggestive of decreased ventilatory effort pre-intubation
  • impending acute respiratory failure
  • Dilated but reactive pupils
  • All of which brings up a concern for possible ingestion such as THC (but cannot rule out other ingestion)
  • This episode will be organized…
  • Pharmacology of Cannabis
  • Clinical presentation of Cannabis toxicity
  • Workup & management of Cannabis toxicity
  
  

  
  

  The Cannabis sativa plant contains over 500 chemical components called cannabinoids, which exert their psychoactive effect on specific receptors in the central nervous system and immune system. The 2 best-described cannabinoids are THC and cannabidiol (CBD)—and are the most commonly used for medical purposes. Patients with intractable epilepsy or chronic cancer pain may be using these drugs. THC is the active ingredient of the cannabis plant that is responsible for most symptoms of central nervous system intoxication. The term cannabis and the common name, marijuana, are often used interchangeably).

  
  

  Rahul, can you shed some light on the pharmacokinetics/pharmacodynamics of cannabis?

  Cannabis exists in various forms: marijuana (dried, crushed flower heads, and leaves), hashish (resin), and hash oil (concentrated resin extract), which can be smoked, inhaled, or ingested. THC is the active ingredient of the cannabis plant that is responsible for most symptoms of central nervous system intoxication, in contrast to CBD, the main non-psychoactive component of cannabis. The potency of cannabis is usually based on the THC content of the preparation. The THC is lipid soluble and highly protein bound and has a volume of distribution of 2.5 to 3.5 L/kg. The THC binds to brain cannabinoid receptors, producing dose- and time-dependent stimulant, hallucinogenic, or sedative effects. Cannabis can be consumed through inhalation (smoking or vaporization) and oral ingestion, as well as via transcutaneous, rectal, and vaginal routes. On inhalation of cannabis, due to rapid delivery to the brain, the THC serum concentrations peak within 15 to 30 minutes and have a duration of up to 4 hours. Approximately 2 to 3 mg of inhaled THC is sufficient to produce drug effects in a naive user.

  In contrast to oral consumption, due to poor bioavailability, cannabis has a delayed onset of psychoactive effects that ranges from 30 minutes to 3 hours, lasting up to 12 hours. Because of enterohepatic circulation and slow release from lipid storage compartments, the elimination half-life of THC after oral intake ranges from 25 to 36 hours. In naive users, psychotropic effects occur with 5 to 20 mg of ingested THC.

  Pradip, what's the mechanism of action of THC?**

  There are 2 known cannabinoid receptors: CB-1 and CB-2. The CB-1 is a G-protein coupled receptor that provides inhibitory modulation of neurotransmitters, including norepinephrine, dopamine, serotonin, γ-aminobutyric acid, and acetylcholine. The CB-1 receptors are found in high densities in the cerebellum, basal ganglia, cerebral cortex, and hippocampus. The action of cannabinoids at these locations is thought to contribute to cannabis' ability to produce the cognitive and motor impairment of cannabinoid toxidrome

  THC can produce wide-ranging symptoms and signs involving the neurological (euphoria, disorientation, impaired memory, ataxia, stupor or coma), ophthalmological (dilated and sluggish pupils with injected conjunctiva), cardiovascular (tachycardia), and gastrointestinal (nausea, vomiting, increased appetite, or thirst) systems.

  Rahul, what are the manifestations of Cannabis toxicity in children?

  Unintentional Cannabis poisoning in children may be a consequence of legalizing cannabis for adult use. Edible gummies, chocolates, and baked goods with THCannabinol are now available in most parts of the US & Canada. A recent NEJM study (Myran et al NEJM Aug 2022) reported that the legalization of cannabis products was associated with an increased incidence in hospitalizations for children with cannabis poisoning in certain provinces of Canada. The potency of cannabis in a single product can be variable and potentially high. A single food item can contain 400 mg or more of THC (10–20 times the typical oral dose of THC). In some instances, a single chocolate bar or brownie can contain 10 to 50 adult doses of THC, a toxic dose for a young child. Among children under 10 years presenting to a children's hospital with THC exposure, 50% are related to an edible cannabis product, with cases attributed to poor child supervision or lack of adequate storage or child-resistant packaging

  More recently, Canna-vaping or the use of the vaporized form of THC is common amongst teenagers. The THC can also be extracted by lipophilic volatile organic solvents (eg, butane or propane) into a highly concentrated waxy resin (commonly referred to as “dab,” “shatter,” or “butane hash oil”) with a THC content often exceeding 70% by weight.

  The manifestations of cannabis intoxication among infants are primarily related to changes in the sensorium, from encephalopathy to frank coma. Older children and adults with marijuana intoxication typically present with diverse symptoms, ranging from cardiovascular (tachycardia, hypertension), ophthalmological (conjunctival injection, nystagmus), respiratory (tachypnea, bradypnea), and gastrointestinal (dry mouth, increased appetite) to neurological (sleepiness, somnolence, ataxia, slurred speech) abnormalities

  The term “edibles” is commonly used to refer to food products containing cannabis. Edibles are available in numerous forms including baked goods, candies, gummies, lozenges, butter, oils, and beverages. Typically, edibles are sought out for recreational use due to their greater concentration of THC. Also newer synthetic versions of THC are constantly being developed and may remain undetected on drug testing.

  
  

  • If you had to work up this patient with cannabis toxicity, what would be your diagnostic approach?
  • Acute cannabis intoxication is a clinical diagnosis especially with a clear h/o of an adult using THC gummies with unintentional ingestion by the toddler is highly suggestive of acute cannabis intoxication. Cannabis intoxication should be suspected when an afebrile child with no prior medical history presents with neurological impairment, such as drowsiness, lethargy, or coma with no focal neurological signs.
  • Labs include: Blood gas, basic metabolic panel (to check serum glucose and electrolytes), serum toxicology panel, urine drug screen, etc. may be sent.
  • EKG, and chest radiograph is warranted based on clinical manifestation such as chest pain.
  • cEEG may be required if a comatose patient is intubated.
  • We need to be aware of co-investments such as cocaine, opioids, acetaminophen, etc, and expand the workup accordingly.
  • If our history, physical, and diagnostic investigation led us to acute cannabis toxicity as our diagnosis what would be your general management of framework?
  • PICU care of the infant or older child with acute cannabis intoxication is largely supportive with a focus on airway, breathing, and hemodynamics. Naloxone will not reverse coma, apnea, or hypoventilation associated with cannabis and intubation may be needed.
  • Provide IV fluids to correct hypovolemia, and correct any electrolyte abnormalities, especially...]]>Welcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.

    I'm Pradip Kamat coming to you from Children’s Healthcare of Atlanta/Emory University School of Medicine

    and I'm Rahul Damania from Cleveland Clinic Children’s Hospital. We are two Pediatric ICU physicians passionate about all things MED-ED in the PICU. PICU Doc on Call focuses on interesting PICU cases & management in the acute care pediatric setting so let’s get into our episode:

    Welcome to our Episode a three-year-old girl with altered mental status and acute respiratory failure

    Here's the case presented by Rahul—

    A three-year-old presents to the PICU with altered mental status and difficulty breathing.

    Per the mother, the patient was in the usual state of health on the day prior to admission when the mother left her in the care of her maternal grandmother. When mom arrived home later in the afternoon, mom was unable to wake her and reported that she seemed "stiff". She did not have any abnormal movements or shaking episodes. Mom called 911 and the patient was brought to our ED. No known head trauma, though the patient is in the care of MGM throughout the day. No emesis. No recent sick symptoms. No witnessed ingestion, however, the patient's mother reports that MGM is on multiple medications (Xarelto, zolpidem, Buspar, gabapentin, and acetaminophen) and uses THC-containing products specifically THC gummies. In the ED: The patient had waxing and waning mentation with decreased respiratory effort. GCS was recorded at 7. Arterial blood gas was performed showing an initial pH of 7.26/61/31/0. The patient was intubated for airway protection in the setting of likely ingestion. The patient has no allergies, immunizations are UTD.

    BP 112/52 (67) | Pulse 106 | Temp 36.2 °C (Tympanic) | Resp (!) 14 | Ht 68.5 cm | Wt 14.2 kg | SpO2 100% | BMI 30.26 kg/m²

    Physical exam was unremarkable-pupils were 4-5mm and sluggish. There was no rash, no e/o of trauma

    Initial CMP was normal with AG of 12, CBC was unremarkable, and Respiratory viral panel was negative. Serum toxicology was negative for acetaminophen, salicylates, and alcohol.

    Basic Urine drug screen was positive for THC

    To summarize key elements from this case, this patient has:

    • Altered mental status: - waxing and waning with GCS less than 8 suggestive of decreased ventilatory effort pre-intubation
    • impending acute respiratory failure
    • Dilated but reactive pupils
    • All of which brings up a concern for possible ingestion such as THC (but cannot rule out other ingestion)
    • This episode will be organized…
    • Pharmacology of Cannabis
    • Clinical presentation of Cannabis toxicity
    • Workup & management of Cannabis toxicity
    
    

    
    

    The Cannabis sativa plant contains over 500 chemical components called cannabinoids, which exert their psychoactive effect on specific receptors in the central nervous system and immune system. The 2 best-described cannabinoids are THC and cannabidiol (CBD)—and are the most commonly used for medical purposes. Patients with intractable epilepsy or chronic cancer pain may be using these drugs. THC is the active ingredient of the cannabis plant that is responsible for most symptoms of central nervous system intoxication. The term cannabis and the common name, marijuana, are often used interchangeably).

    
    

    Rahul, can you shed some light on the pharmacokinetics/pharmacodynamics of cannabis?

    Cannabis exists in various forms: marijuana (dried, crushed flower heads, and leaves), hashish (resin), and hash oil (concentrated resin extract), which can be smoked, inhaled, or ingested. THC is the active ingredient of the cannabis plant that is responsible for most symptoms of central nervous system intoxication, in contrast to CBD, the main non-psychoactive component of cannabis. The potency of cannabis is usually based on the THC content of the preparation. The THC is lipid soluble and highly protein bound and has a volume of distribution of 2.5 to 3.5 L/kg. The THC binds to brain cannabinoid receptors, producing dose- and time-dependent stimulant, hallucinogenic, or sedative effects. Cannabis can be consumed through inhalation (smoking or vaporization) and oral ingestion, as well as via transcutaneous, rectal, and vaginal routes. On inhalation of cannabis, due to rapid delivery to the brain, the THC serum concentrations peak within 15 to 30 minutes and have a duration of up to 4 hours. Approximately 2 to 3 mg of inhaled THC is sufficient to produce drug effects in a naive user.

    In contrast to oral consumption, due to poor bioavailability, cannabis has a delayed onset of psychoactive effects that ranges from 30 minutes to 3 hours, lasting up to 12 hours. Because of enterohepatic circulation and slow release from lipid storage compartments, the elimination half-life of THC after oral intake ranges from 25 to 36 hours. In naive users, psychotropic effects occur with 5 to 20 mg of ingested THC.

    Pradip, what's the mechanism of action of THC?**

    There are 2 known cannabinoid receptors: CB-1 and CB-2. The CB-1 is a G-protein coupled receptor that provides inhibitory modulation of neurotransmitters, including norepinephrine, dopamine, serotonin, γ-aminobutyric acid, and acetylcholine. The CB-1 receptors are found in high densities in the cerebellum, basal ganglia, cerebral cortex, and hippocampus. The action of cannabinoids at these locations is thought to contribute to cannabis' ability to produce the cognitive and motor impairment of cannabinoid toxidrome

    THC can produce wide-ranging symptoms and signs involving the neurological (euphoria, disorientation, impaired memory, ataxia, stupor or coma), ophthalmological (dilated and sluggish pupils with injected conjunctiva), cardiovascular (tachycardia), and gastrointestinal (nausea, vomiting, increased appetite, or thirst) systems.

    Rahul, what are the manifestations of Cannabis toxicity in children?

    Unintentional Cannabis poisoning in children may be a consequence of legalizing cannabis for adult use. Edible gummies, chocolates, and baked goods with THCannabinol are now available in most parts of the US & Canada. A recent NEJM study (Myran et al NEJM Aug 2022) reported that the legalization of cannabis products was associated with an increased incidence in hospitalizations for children with cannabis poisoning in certain provinces of Canada. The potency of cannabis in a single product can be variable and potentially high. A single food item can contain 400 mg or more of THC (10–20 times the typical oral dose of THC). In some instances, a single chocolate bar or brownie can contain 10 to 50 adult doses of THC, a toxic dose for a young child. Among children under 10 years presenting to a children's hospital with THC exposure, 50% are related to an edible cannabis product, with cases attributed to poor child supervision or lack of adequate storage or child-resistant packaging

    More recently, Canna-vaping or the use of the vaporized form of THC is common amongst teenagers. The THC can also be extracted by lipophilic volatile organic solvents (eg, butane or propane) into a highly concentrated waxy resin (commonly referred to as “dab,” “shatter,” or “butane hash oil”) with a THC content often exceeding 70% by weight.

    The manifestations of cannabis intoxication among infants are primarily related to changes in the sensorium, from encephalopathy to frank coma. Older children and adults with marijuana intoxication typically present with diverse symptoms, ranging from cardiovascular (tachycardia, hypertension), ophthalmological (conjunctival injection, nystagmus), respiratory (tachypnea, bradypnea), and gastrointestinal (dry mouth, increased appetite) to neurological (sleepiness, somnolence, ataxia, slurred speech) abnormalities

    The term “edibles” is commonly used to refer to food products containing cannabis. Edibles are available in numerous forms including baked goods, candies, gummies, lozenges, butter, oils, and beverages. Typically, edibles are sought out for recreational use due to their greater concentration of THC. Also newer synthetic versions of THC are constantly being developed and may remain undetected on drug testing.

    
    

    • If you had to work up this patient with cannabis toxicity, what would be your diagnostic approach?
    • Acute cannabis intoxication is a clinical diagnosis especially with a clear h/o of an adult using THC gummies with unintentional ingestion by the toddler is highly suggestive of acute cannabis intoxication. Cannabis intoxication should be suspected when an afebrile child with no prior medical history presents with neurological impairment, such as drowsiness, lethargy, or coma with no focal neurological signs.
    • Labs include: Blood gas, basic metabolic panel (to check serum glucose and electrolytes), serum toxicology panel, urine drug screen, etc. may be sent.
    • EKG, and chest radiograph is warranted based on clinical manifestation such as chest pain.
    • cEEG may be required if a comatose patient is intubated.
    • We need to be aware of co-investments such as cocaine, opioids, acetaminophen, etc, and expand the workup accordingly.
    • If our history, physical, and diagnostic investigation led us to acute cannabis toxicity as our diagnosis what would be your general management of framework?
    • PICU care of the infant or older child with acute cannabis intoxication is largely supportive with a focus on airway, breathing, and hemodynamics. Naloxone will not reverse coma, apnea, or hypoventilation associated with cannabis and intubation may be needed.
    • Provide IV fluids to correct hypovolemia, and correct any electrolyte abnormalities, especially hypoglycemia.
    • Most adolescents and adults presenting with acute cannabis toxicity have mild intoxication, with dysphoria that can be managed supportively in a dimly lit room, decreased stimulation, and, for patients with marked anxiety or agitation, benzodiazepines. Chest pain in adolescents and adults may arise from a pneumothorax (prolonged breath holding during cannabis use), exacerbation of underlying pulmonary disease (eg, asthma), or, rarely, myocardial ischemia or infarction.
    • Patient may complain of cannabis hyperemesis syndrome, which consists of abdominal pain, vomiting, or nausea relieved by hot showers. Although cannabis hyperemesis syndrome is seen with chronic ingestion, it may be seen with acute on chronic use. Acute treatment consists of symptomatic care, including intravenous fluid hydration, antiemetics (eg, ondansetron), benzodiazepines, and cessation of cannabis use.
    • Pradip, what are some clinical pearls regarding Cannabis for pediatric critical care medicine folks?
    • Pearl # 1: Acute cannabis intoxication can result in altered mental status & acute respiratory failure in infants and children.
    • Pearl # 2: Cannabis intoxication should be suspected when an afebrile child with no prior medical history presents with neurological impairment, such as drowsiness, lethargy, or coma with no focal neurological signs.
    • Pearl # 3: Studies have reported that daily cannabis : Studies have reported exposure was associated with a significantly higher propofol dose to achieve adequate sedation compared to those without cannabis exposure. However, there was not an increased incidence of adverse events in these patients. Similarly, studies report an increased need for fentanyl and midazolam in patients with daily cannabis exposure. It is hypothesized that propofol may impart a portion of its sedative effect via the endocannabinoid system. In patients with daily cannabis exposure, down-regulation of the cannabinoid (CB)-1 receptor in chronic cannabis users versus partial agonism/antagonism at the CB-1 receptor by other phytocannabinoids in marijuana products that may compete with propofol, increasing the required dose.
    
    

    This concludes our episode on acute cannabis ingestion We hope you found value in our short, case-based podcast. We welcome you to share your feedback, subscribe & place a review on our podcast! Please visit our website picudoconcall.org which showcases our episodes as well as our Doc on Call management cards. PICU Doc on Call is co-hosted by myself Dr. Pradip Kamat and Dr. Rahul Damania. Stay tuned for our next episode! Thank you!

    
    

    References

    • Fuhrman & Zimmerman - Textbook of Pediatric Critical Care Chapter 132- Sedation and Analgesia Heard C. et al. page1599-1600
    • Reference 1: Barrus DG, Capogrossi KL, Cates SC, et al. Tasty THC: promises and challenges of cannabis edibles. Methods Rep RTI Press. 2016;2016. doi:10.3768/rtipress.2016.op.0035.1611.
    • Reference 2: Wong K, Baum C. Acute Cannabis toxicity. Pediatric Emergency Care. November 2019, Volume 35 (11), p 799–804.
    • Reference 3: Boadu O, Gombolay GY, Caviness VS, et al. Intoxication from accidental marijuana ingestion in pediatric patients: what may lie ahead. Pediatr Emerg Care. 2018
    • Blohm E, Sell P, Neavyn M. Cannabinoid toxicity in pediatrics. Curr Opin Pediatr. 2019;31:256–261.
    • Imasogie N, Rose RV, Wilson A. High quantities: Evaluating the association between cannabis use and propofol anesthesia during endoscopy. PLoS One. 2021 Mar 4;16(3):e0248062.
    
    

    
    

    ]]>618c8a54-c67b-4f3e-b3a9-39de81f4b97aSun, 02 Oct 2022 03:00:00 -040017:00falsefull6464A Somnolent ToddlerWelcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.

    I'm Pradip Kamat coming to you from Children’s Healthcare of Atlanta/Emory University School of Medicine and I'm Rahul Damania from Cleveland Clinic Children’s Hospital. We are two Pediatric ICU physicians passionate about all things MED-ED in the PICU. PICU Doc on Call focuses on interesting PICU cases & management in the acute care pediatric setting so let’s get into our episode:

    Welcome to our Episode: A Somnolent Toddler.

    Here's the case:

    A 2 yo M presents to the PICU after being found increasingly sleepy throughout the day. The toddler is otherwise previously healthy and was noted to be in his normal state of health prior to today. The mother dropped the toddler off at his Grandmother’s home early this morning. Grandmother states that he was playing throughout the day, and she noticed around lunchtime the toddler stumbles around and acts more sleepy. She states that this was around his nap time so she did not feel it was too out of the ordinary. The toddler 1 hr later was still very sleepy, and the grandmother noticed that the toddler had some shallow breathing. She called mother very concerned as she also found her purse open where she typically keeps her pills. The grandmother has a history of MI and afib as well as hypertension. She is prescribed a multitude of medications. Given the child’s increased lethargy, the grandmother presents the patient to the ED. In the ED, the child is noted to be afebrile with HR 55 & RR of 18. His blood pressure is 78/40. On exam he has minimal reactivity to his pupils, he has shallow breathing and laying still on the bed. A POC glucose is 68 mg/dL. Acute resuscitation is begun and the patient presents to the PICU.

    To summarize key elements from this case, this patient has:

    • Drowsiness
    • Bradycardia
    • Normotension
    • This is in the setting of being at grandma’s home and having access to many medications
    • Given the hemodynamic findings and CNS obtundation, this patient’s presentation brings up concern for a clonidine or beta-blocker ingestion.
    • This episode will be organized:
    • Beta-Blocker poisoning
    • We will also examine other medications that potentially can be toxic to a toddler (one pill can kill) present in Grandma's purse which include: TCA, CCB, Opioids, oral anti-diabetic agents, digoxin, etc.
    
    

    The presence of a grandparent is a risk factor for unintentional pediatric exposure to pharmaceuticals commonly referred to as the Granny Syndrome. Grandparents’ medications account for 10% to 20% of unintentional pediatric intoxications in the United States. To kids, all pills look like candy.

    • Let’s start with a multiple choice.
    • An overdose of which of the following medications may mimic the presentation of Metoprolol overdose?
    • A. Verapamil toxicity
    • B. Ketamine toxicity
    • C. Valium toxicity
    • D. Lithium toxicity
    
    

    The correct answer is A, verapamil toxicity.

    • Verapamil is a non DHP CCB.
    • It acts at the level of the SA and AV node similar to Metoprolol, a beta-1-specific antagonist.
    • Both cause bradycardia and AV node block.
    • Valium though a CNS depressant, can cause CV depression as well, however, would have fewer changes on the conduction system compared to a non-DHP CCB.
    
    

     What is the mechanism of toxicity with beta-blockers?

    
    

    Beta-blockers are competitive inhibitors at beta-adrenergic binding sites, which results in decreased production of intracellular cyclic adenosine monophosphate (cAMP) with a resultant blunting of multiple metabolic and cardiovascular effects of circulating catecholamines.

    
    

    • They attenuate the effect of adrenergic catecholamines on the heart
    • Decrease inotropic and chronotropic response. Some drugs like Propranolol can act as Na channel blockers (myocyte membrane stabilizing activity) at high doses resulting in arrhythmias and seizures. Toxic doses of drugs like Sotalol can result in K channel blockade giving rise to prolonged QT and risk for torsades.
    • The anti-alpha-adrenergic activity of agents like carvedilol, and labetalol can result in peripheral vasodilation and hypotension.
    • In addition, beta-adrenergic receptor antagonism inhibits both glycogenolysis and gluconeogenesis, which may result in hypoglycemia.
    
    

    Rahul can you tell us about the pharmacokinetics of beta-blockers:

    
    

    Beta-blockers exhibit intraclass pharmacokinetic variability with regards to absorption, bioavailability, hepatic first-pass metabolism, and lipid solubility, protein binding. Drugs like propranolol are lipid soluble with a high volume of distribution and can cross the blood-brain barrier, whereas drugs like atenolol and nadolol are water-soluble and have a low volume of distribution. The onset of action for most immediate release agents is typically 2-6hours.

    
    

    All beta-blockers, regardless of their designed selectivity, can lose selectivity in overdose.

    
    

    Bradycardia, hypotension & conduction delays are the hallmarks of acute beta-blocker overdose. Hypoglycemia and seizures are also seen in some cases. Risk factors for toxicity include young age (unintentional -primarily seen in children < 6 years or suicidal seen in teenagers ), co-ingestion of other medications such as TCA, Ca channel blockers, and neuroleptic agents, extended-release preparations, and known cardiac disease. In many studies looking at BB overdose, Approximately 80% of exposures were unintentional.

    Pradip, what would be the typical clinical presentation of a beta-blocker overdose:

    Rahul, of most the patients we see are toddlers who have had unintentional exposure to the drug such as our case presentation. There is an adult who uses the prescribed medication and the child gets access to the medication. A child can present with depressed mental status, seizures, bradycardia, hypotension, and shock. Very rarely a child with underlying airway hyper-responsiveness can present with bronchospasm. Toxicity with beta-blockers is less severe (compared to channel blocker ingestion) and can be asymptomatic or present with bradycardia and drowsiness. Hypothermia, hypoglycemia, and seizures have been reported in children. Beta-blockers that are not sustained-release formulations are all rapidly absorbed from the gastrointestinal tract. The first critical signs of overdose can appear 20 minutes post-ingestion but are more commonly observed within 1-2 hours. In all clinically significant beta-blocker overdoses, symptoms develop within 6 hours.

    If you had to work up this patient with a beta-blocker, what would be your diagnostic approach?

    • A good history from caregivers. Exposure to beta-blockers prescribed to a parent or grandparent can lead to the diagnosis.
    • Typical labs sent include: Blood gas (to asses metabolic acidosis), serum lactate, CMP (hypokalemia or hypocalcemia can worsen arrhythmias as well as to evaluate for hypoglycemia)
    • EKG, cEEG in a comatose patient
    • Look for co-ingestions using serum or urine comprehensive toxicological screening.
    • beta-HCG in teenagers
    
    

    What is the approach to managing a patient with beta-blocker overdose?

    • The patient needs to be admitted to the PICU for close observation. Contact State Poison control centers for reporting and their management recommendations.
    
    

    
    

    • Besides the maintenance of patient’s airway and breathing, the goal of therapy is to restore perfusion to critical organ systems by increasing cardiac output. This may be accomplished by improving myocardial contractility, increasing heart rate, or both.
    
    

    
    

    • Prehospital: Activated charcoal is indicated in the first few hours especially if the patient is not altered.
    
    

    
    

    • The asymptomatic patient needs observation for at least six hours for immediate release of medications whereas sotalol may require 12 hours.
    
    

    
    

    • Treatment beyond monitoring is not necessary if the only manifestation is asymptomatic bradycardia.
    
    

    
    

    • So Rahul, let's say the patient is bradycardic, how would you pivot your management framework?
    
    

    
    

    • For patient who is bradycardia+hypotension: The first line is the judicious use of crystalloid boluses (patient can develop pulmonary edema with excessive fluids). Atropine may be considered.
    
    

    
    

    • Glucagon: stimulates adenyl cyclase via the glucagon receptor instead of the blocked beta-adrenergic receptor. The effect is seen within minutes. If no improvement in ten minutes additional dose of glucagon is less likely to be effective. The typical pediatric dose is 50-150 mcg/kg IV bolus.
    
    

    
    

    • Hyperinsulinemia-euglycemia (HIE) therapy: Insulin increases both inotropy and chronotropy. Regular insulin (range 1-10U/Kg/hr is used.) Start at 1U/Kg/hr and titrate upwards every 30-40 minutes till HD improvement is seen. Add dextrose to counter hypoglycemia: 0.25 g/kg of 25% dextrose IV bolus, and an infusion of 10% dextrose. Need to watch K closely. The clinical effect is typically seen in 15-30minutes.
    
    

    
    

    • Vasopressors: Use high dose NE or epinephrine. One case series of 20 patients (Musselman M. et al, Ann Emerg Med. 2011) reported no significant difference in mean arterial pressure (from baseline) in patients receiving high-dose insulin euglycaemic therapy in addition to vasopressors compared to vasopressors alone.
    
    

    
    

    • Lipid Emulsion Therapy: reserved for severe cases refractory to all...]]>Welcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.

      I'm Pradip Kamat coming to you from Children’s Healthcare of Atlanta/Emory University School of Medicine and I'm Rahul Damania from Cleveland Clinic Children’s Hospital. We are two Pediatric ICU physicians passionate about all things MED-ED in the PICU. PICU Doc on Call focuses on interesting PICU cases & management in the acute care pediatric setting so let’s get into our episode:

      Welcome to our Episode: A Somnolent Toddler.

      Here's the case:

      A 2 yo M presents to the PICU after being found increasingly sleepy throughout the day. The toddler is otherwise previously healthy and was noted to be in his normal state of health prior to today. The mother dropped the toddler off at his Grandmother’s home early this morning. Grandmother states that he was playing throughout the day, and she noticed around lunchtime the toddler stumbles around and acts more sleepy. She states that this was around his nap time so she did not feel it was too out of the ordinary. The toddler 1 hr later was still very sleepy, and the grandmother noticed that the toddler had some shallow breathing. She called mother very concerned as she also found her purse open where she typically keeps her pills. The grandmother has a history of MI and afib as well as hypertension. She is prescribed a multitude of medications. Given the child’s increased lethargy, the grandmother presents the patient to the ED. In the ED, the child is noted to be afebrile with HR 55 & RR of 18. His blood pressure is 78/40. On exam he has minimal reactivity to his pupils, he has shallow breathing and laying still on the bed. A POC glucose is 68 mg/dL. Acute resuscitation is begun and the patient presents to the PICU.

      To summarize key elements from this case, this patient has:

      • Drowsiness
      • Bradycardia
      • Normotension
      • This is in the setting of being at grandma’s home and having access to many medications
      • Given the hemodynamic findings and CNS obtundation, this patient’s presentation brings up concern for a clonidine or beta-blocker ingestion.
      • This episode will be organized:
      • Beta-Blocker poisoning
      • We will also examine other medications that potentially can be toxic to a toddler (one pill can kill) present in Grandma's purse which include: TCA, CCB, Opioids, oral anti-diabetic agents, digoxin, etc.
      
      

      The presence of a grandparent is a risk factor for unintentional pediatric exposure to pharmaceuticals commonly referred to as the Granny Syndrome. Grandparents’ medications account for 10% to 20% of unintentional pediatric intoxications in the United States. To kids, all pills look like candy.

      • Let’s start with a multiple choice.
      • An overdose of which of the following medications may mimic the presentation of Metoprolol overdose?
      • A. Verapamil toxicity
      • B. Ketamine toxicity
      • C. Valium toxicity
      • D. Lithium toxicity
      
      

      The correct answer is A, verapamil toxicity.

      • Verapamil is a non DHP CCB.
      • It acts at the level of the SA and AV node similar to Metoprolol, a beta-1-specific antagonist.
      • Both cause bradycardia and AV node block.
      • Valium though a CNS depressant, can cause CV depression as well, however, would have fewer changes on the conduction system compared to a non-DHP CCB.
      
      

       What is the mechanism of toxicity with beta-blockers?

      
      

      Beta-blockers are competitive inhibitors at beta-adrenergic binding sites, which results in decreased production of intracellular cyclic adenosine monophosphate (cAMP) with a resultant blunting of multiple metabolic and cardiovascular effects of circulating catecholamines.

      
      

      • They attenuate the effect of adrenergic catecholamines on the heart
      • Decrease inotropic and chronotropic response. Some drugs like Propranolol can act as Na channel blockers (myocyte membrane stabilizing activity) at high doses resulting in arrhythmias and seizures. Toxic doses of drugs like Sotalol can result in K channel blockade giving rise to prolonged QT and risk for torsades.
      • The anti-alpha-adrenergic activity of agents like carvedilol, and labetalol can result in peripheral vasodilation and hypotension.
      • In addition, beta-adrenergic receptor antagonism inhibits both glycogenolysis and gluconeogenesis, which may result in hypoglycemia.
      
      

      Rahul can you tell us about the pharmacokinetics of beta-blockers:

      
      

      Beta-blockers exhibit intraclass pharmacokinetic variability with regards to absorption, bioavailability, hepatic first-pass metabolism, and lipid solubility, protein binding. Drugs like propranolol are lipid soluble with a high volume of distribution and can cross the blood-brain barrier, whereas drugs like atenolol and nadolol are water-soluble and have a low volume of distribution. The onset of action for most immediate release agents is typically 2-6hours.

      
      

      All beta-blockers, regardless of their designed selectivity, can lose selectivity in overdose.

      
      

      Bradycardia, hypotension & conduction delays are the hallmarks of acute beta-blocker overdose. Hypoglycemia and seizures are also seen in some cases. Risk factors for toxicity include young age (unintentional -primarily seen in children < 6 years or suicidal seen in teenagers ), co-ingestion of other medications such as TCA, Ca channel blockers, and neuroleptic agents, extended-release preparations, and known cardiac disease. In many studies looking at BB overdose, Approximately 80% of exposures were unintentional.

      Pradip, what would be the typical clinical presentation of a beta-blocker overdose:

      Rahul, of most the patients we see are toddlers who have had unintentional exposure to the drug such as our case presentation. There is an adult who uses the prescribed medication and the child gets access to the medication. A child can present with depressed mental status, seizures, bradycardia, hypotension, and shock. Very rarely a child with underlying airway hyper-responsiveness can present with bronchospasm. Toxicity with beta-blockers is less severe (compared to channel blocker ingestion) and can be asymptomatic or present with bradycardia and drowsiness. Hypothermia, hypoglycemia, and seizures have been reported in children. Beta-blockers that are not sustained-release formulations are all rapidly absorbed from the gastrointestinal tract. The first critical signs of overdose can appear 20 minutes post-ingestion but are more commonly observed within 1-2 hours. In all clinically significant beta-blocker overdoses, symptoms develop within 6 hours.

      If you had to work up this patient with a beta-blocker, what would be your diagnostic approach?

      • A good history from caregivers. Exposure to beta-blockers prescribed to a parent or grandparent can lead to the diagnosis.
      • Typical labs sent include: Blood gas (to asses metabolic acidosis), serum lactate, CMP (hypokalemia or hypocalcemia can worsen arrhythmias as well as to evaluate for hypoglycemia)
      • EKG, cEEG in a comatose patient
      • Look for co-ingestions using serum or urine comprehensive toxicological screening.
      • beta-HCG in teenagers
      
      

      What is the approach to managing a patient with beta-blocker overdose?

      • The patient needs to be admitted to the PICU for close observation. Contact State Poison control centers for reporting and their management recommendations.
      
      

      
      

      • Besides the maintenance of patient’s airway and breathing, the goal of therapy is to restore perfusion to critical organ systems by increasing cardiac output. This may be accomplished by improving myocardial contractility, increasing heart rate, or both.
      
      

      
      

      • Prehospital: Activated charcoal is indicated in the first few hours especially if the patient is not altered.
      
      

      
      

      • The asymptomatic patient needs observation for at least six hours for immediate release of medications whereas sotalol may require 12 hours.
      
      

      
      

      • Treatment beyond monitoring is not necessary if the only manifestation is asymptomatic bradycardia.
      
      

      
      

      • So Rahul, let's say the patient is bradycardic, how would you pivot your management framework?
      
      

      
      

      • For patient who is bradycardia+hypotension: The first line is the judicious use of crystalloid boluses (patient can develop pulmonary edema with excessive fluids). Atropine may be considered.
      
      

      
      

      • Glucagon: stimulates adenyl cyclase via the glucagon receptor instead of the blocked beta-adrenergic receptor. The effect is seen within minutes. If no improvement in ten minutes additional dose of glucagon is less likely to be effective. The typical pediatric dose is 50-150 mcg/kg IV bolus.
      
      

      
      

      • Hyperinsulinemia-euglycemia (HIE) therapy: Insulin increases both inotropy and chronotropy. Regular insulin (range 1-10U/Kg/hr is used.) Start at 1U/Kg/hr and titrate upwards every 30-40 minutes till HD improvement is seen. Add dextrose to counter hypoglycemia: 0.25 g/kg of 25% dextrose IV bolus, and an infusion of 10% dextrose. Need to watch K closely. The clinical effect is typically seen in 15-30minutes.
      
      

      
      

      • Vasopressors: Use high dose NE or epinephrine. One case series of 20 patients (Musselman M. et al, Ann Emerg Med. 2011) reported no significant difference in mean arterial pressure (from baseline) in patients receiving high-dose insulin euglycaemic therapy in addition to vasopressors compared to vasopressors alone.
      
      

      
      

      • Lipid Emulsion Therapy: reserved for severe cases refractory to all other therapies. Mechanism: may create a “lipid sink” to pull lipid-soluble toxins out of tissues and trap them in the vascular compartment; delivers free fatty acids to the heart for improved metabolic functioning. For children, a 20% lipid emulsion is used. Typically a 1.5 mL/kg bolus is administered. if the patient shows improvement, then can consider an infusion at 0.25-0.5 mL/kg/minute until hemodynamic recovery.
      
      

      Please visit our episode # 4 titled PICU Applications of Lipid Emulsion Therapy

      
      

      • If all else fails- The patient may require Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) cannulation. Cardiac pacing may be effective in increasing the rate of myocardial contraction if pharmacological therapy fails.
      
      

      
      

      Pradip, this was a great case. Let’s go into other medications which may be found in Grandmother’s purse and the antidotes which are commonly employed in cases of ingestion:

      • Clonidine: Grandma's purse may have clonidine patches or tabs (used for sleep, hypertension, etc.). Most patients present with somnolence, along with bradycardia or hypotension.
      • First things first: maintain airway, breathing, and hemodynamics. Especially in this patient with marked central nervous system depression, we should consider trialing intravenous naloxone(0.1 mg/kg, maximum single dose: 2 mg). This may be repeated every one to two minutes up to 10 mg total dose. Please note, Naloxone has been utilized to treat seriously poisoned clonidine overdose patients with inconsistent results. Finally, in symptomatic patients with enteral clonidine overdose, it is important to note that HD or CRRT has a limited role. Another important point to remember in a child who may have an overdose with clonidine is to have the child fully exposed and have any adherent transdermal patches be removed.
      • We advocate the early use of activated charcoal + supportive care with attention to airway, breathing, and circulation. The antidote Flumazenil can be used to reverse severe benzodiazepine toxicity.
      
      
      1. ACE inhibitors → Include drugs like captopril, and enalapril, which block the conversion of angiotensin I to angiotensin II, thereby lowering arteriolar resistance to decrease BP. Mild toxicity may be produced with a single, supra-therapeutic dose; however, severe toxic effects and deaths are rare and are often attributed to co-ingestants. There are reports of children 6 years of age and younger who have ingested up to 8mg/kg captopril or up to 2mg/kg enalapril or lisinopril and remained asymptomatic. The primary toxic effect of ACE inhibitor ingestion is hypotension. Asymptomatic patients should be observed for at least four hours post-ingestion with frequent monitoring of vital signs. Hyperkalemia and hyponatremia may be seen due to the aldosterone blocking effect of ACE inhibitors.
      
      

      
      

      Symptomatic or hypotensive patients should be admitted for at least 24 hours post-ingestion or until symptoms have completely resolved. Patients should be given adequate IV fluids to maintain a satisfactory blood pressure and a good urine output. Oral-activated charcoal may be given to patients who have ingested a large overdose, given they present within 1-2 hours. Although the role of naloxone in the setting of ACE inhibitor overdose remains unclear, it may be considered, especially in cases of severe hypotension where fluid overload is a concern. (Mechanism) ACE inhibitors inhibit the metabolism of enkephalins and potentiate their opioid effect, which includes lowering BP.

      1. Calcium Channel Blockers
      2. Watch for hypotension and bradycardia, conduction defects, and ultimately cardiovascular collapse. The patient may be asymptomatic initially. Hyperglycemia from the blockade of insulin release from the pancreas and metabolic acidosis from hypo-perfusion may be seen.
      3. administration of intravenous (IV) calcium, glucagon, catecholamines, and high-dose insulin therapy. Intravenous lipid emulsion therapy lacks clear evidence for efficacy but is a consideration if all else fails. Methylene blue has been tried especially in amlodipine toxicity. In severe refractory cases, cannulation to VA ECMO has been used.
      4. Oral anti-diabetic medications or sulfonyl ureas: • Binding of sulfonylurea to the sulfonylurea receptor 1(SUR1) subunit closes the ATP-dependent K channel, thus leading to insulin secretion. Can lower blood sugar to a dangerous level resulting in confusion, irritability, lethargy, tachypnea, tachycardia, sweating, hypothermia, seizures, altered mental status, coma, and even death. The patient requires observation X 24hrs or longer if an extended-release preparation is ingested. Use activated charcoal for 1-2 hours if not altered. Correct hypoglycemia with IV dextrose. Octreotide IV has been used to inhibit release of insulin.
      5. Tricyclic antidepressants are now rarely used due to the wide availability of SSRIs. Overdose can cause cardiac arrhythmia (Na Channel blockade), hypotension (due to peripheral alpha-adrenergic blockade), cardiac arrest, seizures, and coma. Among patients who are asymptomatic more than 6 hours after ingestion, symptoms are unlikely to develop; however, delayed toxic effects may occur, particularly if there are co-ingestants that delay gastrointestinal motility.
      6. Management includes: close monitoring of vital signs and serial examinations for evidence of anti-muscarinic toxicity and for cardiac and neurologic manifestations that can be used to guide treatment strategies. Supportive care includes maintenance of airway, breathing, and hemodynamics. Activated charcoal can be used within 1-2 hrs of ingestion. If the QRS is prolonged (>100m secs) or there is HD instability NaHCO3 bolus followed by a continuous infusion is required. Use fluids for hypotension. For fluid refractory hypotension consider vasopressors such as epinephrine or norepinephrine. Use benzodiazepine for seizures. If hemodynamic instability persists despite all the above, consider intravenous lipid emulsion therapy. For prolonged QT-MagSO4 is frequently used.
      7. Opioids and other pain meds (acetaminophen, NSAIDs, aspirin, or even topical products containing methyl-salicylate, camphor): Treatment is supportive with close attention to airway, breathing, and hemodynamics. Naloxone can be used for opioid ingestion (listeners can get more details about opioid poisoning from our episode # 61). Methyl salicylate can cause nausea, vomiting, hyperthermia, blood sugar abnormalities, weakness, ringing in the ears, fast breathing rate, seizures, and coma, 1/2 teaspoon can be fatal in a toddler. NAC can be used for acetaminophen toxicity. Salicylate toxicity requires alkalization of urine as well as hemodialysis depending on the level or the presence of neurological symptoms.
      8. Digoxin: Fortunately digoxin use has declined since 1990 and so has the incidence of toxicity associated with it. Digoxin increases intracellular calcium in myocardial cells indirectly, by inhibiting the sodium-potassium pump in the cell membrane. A child can present with non-specific GI symptoms (vomiting, diarrhea, abdominal pain), lethargy, and confusion followed by sinus bradycardia, AV block, and ventricular ectopy. Ventricular tachycardia and atrial fibrillation can occur with severe toxicity. Hyperkalemia may be seen with digoxin toxicity. Besides supportive care, digoxin-specific antibody fragments are used to form complexes with digoxin, which are then excreted in the urine.
      9. Alcohols: Perfumes, hand sanitizers (used extensively during the pandemic) and mouthwashes contain concentrated alcohol. Acute alcohol poisoning can result in vomiting, seizures, hypoglycemia, hypothermia, respiratory insufficiency, and unconsciousness. Treatment is mainly supportive.
      10. Nicotine: Exposure to liquid nicotine used to refill e-cigarettes or nicotine gum in a small child can be deadly. With an estimated median lethal dose between 1 and 13 mg per kilogram of body weight, 1 teaspoon (5 ml) of a 1.8% nicotine solution could be lethal to a 90-kg person. Low dose exposure can result in tachycardia, vomiting well as truncal ataxia, and even seizures. With a higher dose, we see signs of muscarinic cholinergic toxicity, including extreme secretions and gastrointestinal disturbance. The highest level of poisoning can result in NM blockade, respiratory failure, and even death. Treatment is supportive although atropine can be used to combat cholinergic activity.
      11. Before we get into our summary for this episode, we want to stress the importance of having a collaborative approach in the management of these ingestions, notifying poison control, toxicology, coordinating care with PICU team members including pharmacists, as well as having proactive communication with ECMO primers are tenants of high-quality care.
      
      

      
      

      Rahul, let’s go ahead and summarize today’s episode:

      1. Most patients who develop toxicity from beta-blocker overdose do so within two hours of ingestion, and virtually all do so within six hours. Bradycardia and hypotension are the most common effects. Cardiogenic shock and ventricular dysrhythmias can occur with severe overdose. Hypoglycemia is seen more often in children.
      2. Grandma’s purse can be a potpourri of medications that can be very toxic to a toddler resulting in the “one pill can kill” phenomenon. In this episode, we have described a few of the medications individually but many times this may not be the case and the toddler may have ingested more than one type of medication thus further complicating the diagnosis as well as the management. Sticking to good supportive care, consultation with state poison control as well as a toxicologist is helpful in such cases.
      
      

      As pediatric intensivists, we are pediatricians at heart and our job is to educate parents/grandparents to keep children safe: Keep all purses out of reach of small children, Keep...]]>5f97f84c-6e8b-4e18-b5f2-9b2131397bcaSun, 25 Sep 2022 03:00:00 -040028:57falsefull6363An Approach to GalactosemiaWelcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.

      I'm Pradip Kamat coming to you from Children’s Healthcare of Atlanta/Emory University School of Medicine

      and I'm Rahul Damania from Cleveland Clinic Children’s Hospital and we are two Pediatric ICU physicians passionate about all things MED-ED in the PICU. PICU Doc on Call focuses on interesting PICU cases & management in the acute care pediatric setting so let’s get into our episode:

      Welcome to our Episode of a 4-day-old with jaundice and vomiting.

      Here's the case presented by Rahul:

      A full-term 4-day-old boy presents to the ED after recently being discharged from the newborn nursery. Per mom, the patient "look yellow" and was having difficulty with feeding. The mother states that the patient would be increasingly sleepy, and will only latch to the breast for five minutes. The patient has been having decreased wet diapers, and the stool is loose and non-bloody. Mother was concerned today as the child continue to look yellow, especially in the eyes, had four episodes of vomiting, and overall was acting lethargic. The patient presented to the emergency room afebrile, tachypneic, and tachycardic. The patient was noted to have initial serum glucose of 70. As the patient was increasingly dehydrated, laboratory testing was difficult to obtain. The infant was fussy for the caregivers. The patient was resuscitated with 2 x 10 per kilo boluses and responded well. Point of care ultrasound noted normal four-chamber cardiac anatomy and squeeze. Given the instability of the patient, a RAM cannula was initiated, and the patient presented to the PICU.

      To summarize key elements from this case, this 4-day-old infant has:

      • an acute presentation of jaundice and poor feeding
      • Prominent GI symptoms and dehydration
      • A sepsis-like presentation with hemodynamic instability responsive to fluids
      • All of which brings up a concern for inborn error of metabolism, likely galactosemia.
      • This episode will be organized…
      • Clinical Presentation
      • Laboratory Findings & Biochemistry
      • Management of Galactosemia
      
      

      Rahul, let's start with a short multiple choice question:

      • Of the following biochemical enzymes, which of the following is deficient in classic galactosemia?
      • A. UDP Glucoronyl Transferase
      • B. Aldolase B
      • C. Galactose 1 Uridyl Transferase
      • D. Galactokinase
      
      

      The correct answer is C. Galactose 1 Uridyl Transferase aka GALT. Classic galactosemia is caused by a complete deficiency of galactose-1-phosphate uridyl transferase (GALT). We should contrast this with galactokinase deficiency. These two present quite differently — GALT deficiency presents like our patient with jaundice, vomiting, hepatomegaly, renal dysfunction, and sepsis. Galactokinase deficiency has less of systemic symptoms and these patients similar to GALT deficiency have cataracts that are usually bilateral and resolved with dietary therapy. To go through our other answer choices, remember that Aldolase B is the rate-limiting enzyme in fructose metabolism, thus a deficiency in this enzyme would cause hereditary fructose intolerance.

      With this lead in question, let’s pivot into the biochemistry of galactose and review key lab findings in our patient with galactosemia. Rahul, can you give us a quick summary of how galactose is metabolized in our body?

      Galactose is a sugar found primarily in human milk and milk products as part of the disaccharide lactose.

      Lactose is hydrolyzed to glucose and galactose by the intestinal enzyme lactase.

      The galactose then is converted to glucose for use as an energy source, however it needs a series of reactions:

      1. Galactokinase → which catalyzes the rxn galactose to galactose 1 PO4
      2. Our rate limiting enzyme Galactose-1-phosphate uridyl transferase (GALT). GALT helps place a sugar moiety on galactose 1 PO4 to turn it into glucose 1 Phos which can then be utilized in glycolysis or glycogenesis.
      
      

      A complete deficiency in GALT is known as classic galactosemia. If unrecognized, these patients typically develop typically have failure to thrive, liver and kidney dysfunction, and sepsis. If detected later in life or even if treated with dietary modification, these children can have cataracts, abnormal neurodevelopment, and even premature ovarian failure.

      So these children can get cataracts, why is that?

      Yes, this is interesting and seen in many abnormalities of sugar metabolism. Cataracts may be present at birth but generally appear after two weeks as a result of increased accumulation of a sugar alcohol, galactitol, that is derived from the abnormally metabolized galactose, which ends up depositing in the lens. Cataracts usually are bilateral and can resolve with dietary therapy.

      This is a great basic science review, let’s get back to our case now and go into the lab findings which were found in our patient. Remember thus far, the patient came to the PICU on RAM cannula after resuscitation due to hemodynamic instability…

      Yes, so this patient’s labs were notable for transaminitis, an elevated PT to 51.3, and an INR of 5.5. He was treated empirically with intravenous (IV) antibiotics and fresh frozen plasma with little change in status, and liver transplantation was discussed with the parents early in his course. On DOL 4, 6, his NBS was reported as having low GALT activity, concerning for galactosemia, and he was placed on a galactose-restricted diet. An RBC enzyme testing for GALT and DNA testing were sent. Notably, his blood culture resulted, and was noted to have gram-negative rods, which ended up being pan sensitive E Coli.

      This is a classic presentation of Galactosemia, can you go break down his labs & presentation a bit?

      Yes, among infants with galactosemia who present with sepsis, the most common organism is Escherichia coli  - this is seen in about 76 percent of cases. Less frequent findings are coagulopathy, ascites, and seizures. Please note, the principal cause of early mortality in classic galactosemia is sepsis, most often caused by Escherichia coli.

      To summarize, classic galactosemia should be considered in any newborn who presents with the findings noted in our case which include — jaundice, vomiting, hepatomegaly, poor feeding, failure to thrive, lethargy, diarrhea, or sepsis; it should also be suspected in any infant with a positive newborn screening (NBS) test. It is important to note, that affected infants may become symptomatic before NBS results are available.

      Great point, say you have an NBS which notes an abnormal GALT enzyme or a high clinical suspicion. What is the gold standard for diagnosis?

      The demonstration of nearly complete absence of galactose-1-phosphate uridyl transferase (GALT) activity in red blood cells (RBCs) is the gold standard for diagnosis. A quantitative assay of RBC GALT activity (using a fluoroimmunoassay or radioimmunoassay) is necessary to confirm the diagnosis.

      It is important to note that quantitative assay of RBC GALT activity may be affected for as long as three months by any RBC transfusion, so holding an extra red top during the initial presentation is important when you have a broad differential.

      Once we have confirmed the diagnosis or even have a very high index of suspicion, what is our management framework in these children?

      Supportive care & hallmarks of critical care are very important. The main goal of long-term treatment of classic galactosemia is to minimize dietary galactose intake. Galactose should be excluded from the diet as soon as galactosemia is suspected. Other initial care should be provided as needed to treat jaundice, sepsis, and abnormalities of the liver, kidneys, and central nervous system. Supportive therapy typically includes hydration, antibiotics, and treatment of coagulopathy, although problems usually resolve quickly after the dietary treatment is begun.

      It is important to have close communication with the metabolic team as well as your dietitians in the PICU. These children are typically placed on soy-based infant formulas appropriate for galactosemia which include Alsoy, Isomil, Nursoy, and ProSobee.

      Lactose-free infant formulas should not be used, because they have not been proven to be safe for patients with galactosemia.

      The dietary component is very important as long-term you will be monitoring these children’s neurodevelopment, growth, ovarian function, and vision.

      In a survey of 177 patients with galactosemia who were at least six years old and had no other cause for poor outcome, 45 percent had developmental delay and many affected children had speech and language problems. Moreover, premature ovarian failure occurred in most females with classic galactosemia, affecting 81 percent of females in this study.

      Great discussion today! If you’re interested in more inborn errors of metabolism feel free to check out our episodes on this podcast topic would integrate with our past episode, Acute Metabolic Emergencies in the PICU.

      Let’s summarize today’s podcast:

      1. Classic galactosemia is caused by complete deficiency of galactose-1-phosphate uridyl transferase (GALT). It is an autosomal-recessive disorder and detected on NBS in all states in the US.
      2. Newborns with a positive screening test for galactosemia should be changed immediately to a soy-based infant formula pending confirmation of the diagnosis.
      3. Infants with classic galactosemia usually present in the first few days after initiation of galactose-containing human breast milk or cow's milk-based feedings. Signs and symptoms include jaundice, vomiting, hepatomegaly, failure to thrive, poor feeding,...]]>Welcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.

         I'm Pradip Kamat coming to you from Children’s Healthcare of Atlanta/Emory University School of Medicine

         and I'm Rahul Damania from Cleveland Clinic Children’s Hospital and we are two Pediatric ICU physicians passionate about all things MED-ED in the PICU. PICU Doc on Call focuses on interesting PICU cases & management in the acute care pediatric setting so let’s get into our episode:

         Welcome to our Episode of a 4-day-old with jaundice and vomiting.

         Here's the case presented by Rahul:

         A full-term 4-day-old boy presents to the ED after recently being discharged from the newborn nursery. Per mom, the patient "look yellow" and was having difficulty with feeding. The mother states that the patient would be increasingly sleepy, and will only latch to the breast for five minutes. The patient has been having decreased wet diapers, and the stool is loose and non-bloody. Mother was concerned today as the child continue to look yellow, especially in the eyes, had four episodes of vomiting, and overall was acting lethargic. The patient presented to the emergency room afebrile, tachypneic, and tachycardic. The patient was noted to have initial serum glucose of 70. As the patient was increasingly dehydrated, laboratory testing was difficult to obtain. The infant was fussy for the caregivers. The patient was resuscitated with 2 x 10 per kilo boluses and responded well. Point of care ultrasound noted normal four-chamber cardiac anatomy and squeeze. Given the instability of the patient, a RAM cannula was initiated, and the patient presented to the PICU.

         To summarize key elements from this case, this 4-day-old infant has:

         • an acute presentation of jaundice and poor feeding
         • Prominent GI symptoms and dehydration
         • A sepsis-like presentation with hemodynamic instability responsive to fluids
         • All of which brings up a concern for inborn error of metabolism, likely galactosemia.
         • This episode will be organized…
         • Clinical Presentation
         • Laboratory Findings & Biochemistry
         • Management of Galactosemia
         
         

         Rahul, let's start with a short multiple choice question:

         • Of the following biochemical enzymes, which of the following is deficient in classic galactosemia?
         • A. UDP Glucoronyl Transferase
         • B. Aldolase B
         • C. Galactose 1 Uridyl Transferase
         • D. Galactokinase
         
         

         The correct answer is C. Galactose 1 Uridyl Transferase aka GALT. Classic galactosemia is caused by a complete deficiency of galactose-1-phosphate uridyl transferase (GALT). We should contrast this with galactokinase deficiency. These two present quite differently — GALT deficiency presents like our patient with jaundice, vomiting, hepatomegaly, renal dysfunction, and sepsis. Galactokinase deficiency has less of systemic symptoms and these patients similar to GALT deficiency have cataracts that are usually bilateral and resolved with dietary therapy. To go through our other answer choices, remember that Aldolase B is the rate-limiting enzyme in fructose metabolism, thus a deficiency in this enzyme would cause hereditary fructose intolerance.

         With this lead in question, let’s pivot into the biochemistry of galactose and review key lab findings in our patient with galactosemia. Rahul, can you give us a quick summary of how galactose is metabolized in our body?

         Galactose is a sugar found primarily in human milk and milk products as part of the disaccharide lactose.

         Lactose is hydrolyzed to glucose and galactose by the intestinal enzyme lactase.

         The galactose then is converted to glucose for use as an energy source, however it needs a series of reactions:

         1. Galactokinase → which catalyzes the rxn galactose to galactose 1 PO4
         2. Our rate limiting enzyme Galactose-1-phosphate uridyl transferase (GALT). GALT helps place a sugar moiety on galactose 1 PO4 to turn it into glucose 1 Phos which can then be utilized in glycolysis or glycogenesis.
         
         

         A complete deficiency in GALT is known as classic galactosemia. If unrecognized, these patients typically develop typically have failure to thrive, liver and kidney dysfunction, and sepsis. If detected later in life or even if treated with dietary modification, these children can have cataracts, abnormal neurodevelopment, and even premature ovarian failure.

         So these children can get cataracts, why is that?

         Yes, this is interesting and seen in many abnormalities of sugar metabolism. Cataracts may be present at birth but generally appear after two weeks as a result of increased accumulation of a sugar alcohol, galactitol, that is derived from the abnormally metabolized galactose, which ends up depositing in the lens. Cataracts usually are bilateral and can resolve with dietary therapy.

         This is a great basic science review, let’s get back to our case now and go into the lab findings which were found in our patient. Remember thus far, the patient came to the PICU on RAM cannula after resuscitation due to hemodynamic instability…

         Yes, so this patient’s labs were notable for transaminitis, an elevated PT to 51.3, and an INR of 5.5. He was treated empirically with intravenous (IV) antibiotics and fresh frozen plasma with little change in status, and liver transplantation was discussed with the parents early in his course. On DOL 4, 6, his NBS was reported as having low GALT activity, concerning for galactosemia, and he was placed on a galactose-restricted diet. An RBC enzyme testing for GALT and DNA testing were sent. Notably, his blood culture resulted, and was noted to have gram-negative rods, which ended up being pan sensitive E Coli.

         This is a classic presentation of Galactosemia, can you go break down his labs & presentation a bit?

         Yes, among infants with galactosemia who present with sepsis, the most common organism is Escherichia coli  - this is seen in about 76 percent of cases. Less frequent findings are coagulopathy, ascites, and seizures. Please note, the principal cause of early mortality in classic galactosemia is sepsis, most often caused by Escherichia coli.

         To summarize, classic galactosemia should be considered in any newborn who presents with the findings noted in our case which include — jaundice, vomiting, hepatomegaly, poor feeding, failure to thrive, lethargy, diarrhea, or sepsis; it should also be suspected in any infant with a positive newborn screening (NBS) test. It is important to note, that affected infants may become symptomatic before NBS results are available.

         Great point, say you have an NBS which notes an abnormal GALT enzyme or a high clinical suspicion. What is the gold standard for diagnosis?

         The demonstration of nearly complete absence of galactose-1-phosphate uridyl transferase (GALT) activity in red blood cells (RBCs) is the gold standard for diagnosis. A quantitative assay of RBC GALT activity (using a fluoroimmunoassay or radioimmunoassay) is necessary to confirm the diagnosis.

         It is important to note that quantitative assay of RBC GALT activity may be affected for as long as three months by any RBC transfusion, so holding an extra red top during the initial presentation is important when you have a broad differential.

         Once we have confirmed the diagnosis or even have a very high index of suspicion, what is our management framework in these children?

         Supportive care & hallmarks of critical care are very important. The main goal of long-term treatment of classic galactosemia is to minimize dietary galactose intake. Galactose should be excluded from the diet as soon as galactosemia is suspected. Other initial care should be provided as needed to treat jaundice, sepsis, and abnormalities of the liver, kidneys, and central nervous system. Supportive therapy typically includes hydration, antibiotics, and treatment of coagulopathy, although problems usually resolve quickly after the dietary treatment is begun.

         It is important to have close communication with the metabolic team as well as your dietitians in the PICU. These children are typically placed on soy-based infant formulas appropriate for galactosemia which include Alsoy, Isomil, Nursoy, and ProSobee.

         Lactose-free infant formulas should not be used, because they have not been proven to be safe for patients with galactosemia.

         The dietary component is very important as long-term you will be monitoring these children’s neurodevelopment, growth, ovarian function, and vision.

         In a survey of 177 patients with galactosemia who were at least six years old and had no other cause for poor outcome, 45 percent had developmental delay and many affected children had speech and language problems. Moreover, premature ovarian failure occurred in most females with classic galactosemia, affecting 81 percent of females in this study.

         Great discussion today! If you’re interested in more inborn errors of metabolism feel free to check out our episodes on this podcast topic would integrate with our past episode, Acute Metabolic Emergencies in the PICU.

         Let’s summarize today’s podcast:

         1. Classic galactosemia is caused by complete deficiency of galactose-1-phosphate uridyl transferase (GALT). It is an autosomal-recessive disorder and detected on NBS in all states in the US.
         2. Newborns with a positive screening test for galactosemia should be changed immediately to a soy-based infant formula pending confirmation of the diagnosis.
         3. Infants with classic galactosemia usually present in the first few days after initiation of galactose-containing human breast milk or cow's milk-based feedings. Signs and symptoms include jaundice, vomiting, hepatomegaly, failure to thrive, poor feeding, lethargy, diarrhea, and sepsis (particularly due to Escherichia coli).
         
         

         This concludes our episode on the approach to Galactosemia. We hope you found value in our short, case-based podcast. We welcome you to share your feedback, subscribe & place a review on our podcast! Please visit our website picudoconcall.org which showcases our episodes as well as our Doc on Call management cards. PICU Doc on Call is co-hosted by myself Dr. Pradip Kamat and Dr. Rahul Damania. Stay tuned for our next episode! Thank you!

         
         

         References

         • National Newborn Screening and Genetics Resource Center; 2002 Newborn Screening and Genetic Testing Symposium.
         • Lak R, Yazdizadeh B, Davari M, et al. Newborn screening for galactosaemia. Cochrane Database Syst Rev 2017; 12:CD012272.
         • 
           
         • Welling L, Bernstein LE, Berry GT, et al. International clinical guideline for the management of classical galactosemia: diagnosis, treatment, and follow-up. J Inherit Metab Dis 2017; 40:171.
         
         

         
         

         ]]>72d6c752-223e-44cb-a818-aa0a215d71c4Sun, 28 Aug 2022 03:00:00 -040014:04falsefull6262Approach to the Toddler with Somnolence and Difficulty BreathingWelcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.

         I'm Pradip Kamat coming to you from Children’s Healthcare of Atlanta/Emory University School of Medicine. I'm Rahul Damania from Cleveland Clinic Children’s Hospital and we are two Pediatric ICU physicians passionate about all things MED-ED in the PICU. PICU Doc on Call focuses on interesting PICU cases & management in the acute care pediatric setting so let’s get into our episode:

         Here's the case presented by Rahul:

         A 21-month-old girl was brought to an OSH ED for somnolence and difficulty breathing, which developed after she accidentally ingested an unknown amount of liquid medicine that was used by her grandfather. Per the mother, the patient’s grandfather was given the liquid medication for the treatment of his opioid addiction. The patient took some unknown amount from the open bottle that was left on the counter by the grandfather. Immediately after ingestion of the medicine, the patient initially became irritable and had some generalized pruritus. The patient subsequently became sleepy followed by difficulty breathing and her lips turned grey. The patient was rushed to an outside hospital ED for evaluation.

         OSH ED: The patient arrived unresponsive and blue, she was noted to be sleepy and difficult to arouse on arrival, with pinpoint pupils and hypoxic to 88%. , but After receiving Naloxone, however, she became awake and interactive. Her glucose on presentation was 58 mg/dL and Her initial VBG resulted 7.3/49.6/+2. She continued to have intermittent episodes of somnolence without apnea. Poison control called and recommend starting a naloxone infusion; she was also given dextrose bolus. The patient was admitted to the PICU.

         To summarize key elements from this case, this patient has:

         Accidental ingestion of an unknown medication

         Altered mental status

         Difficulty breathing—with grey lips suggestive of hypoventilation/hypoxia

         All of which brings up a concern for a toxidrome which is our topic of discussion for today

         The typical symptoms seen in our patient of pinpoint pupils, respiratory depression, and a decreased level of consciousness is known as the “opioid overdose triad” Given the history of opioid addiction in the grandfather, the liquid medicine given to him is most likely methadone.In fact, in this case, the mother brought the bottle of medicine, which was subsequently confirmed to be prescription methadone given to prevent opioid withdrawal in the grandfather.

          

         To dive deeper into this episode, let’s start with a multiple choice question:

         Which of the following opioids carries the greatest risk of QTc prolongation?

         A. Methadone

         B. Morphine

         C. Fentanyl

         D. Dilaudid

         
         

         The correct answer is methadone. Methadone prolongs QT interval due to its interactions with the cardiac potassium channel (KCNH2) and increases the risk for Torsades in a dose-dependent manner. Besides the effect on cardiac repolarization, methadone is also associated with the development of bradycardia mediated via its anticholinesterase properties and through its action as a calcium channel antagonist. Hypokalemia, hypocalcemia, hypomagnesemia, and concomitant use of other drugs belonging to the family of CYP3A4 system inhibitors such as erythromycin can prolong Qtc. Even in absence of these risk factors, methadone alone can prolong QTc.

          

         Thanks for that, I think it is very important to involve your Pediatric Pharmacy team to also help with management as children may be concurrent qt prolonging meds.

         
         

         Rahul, what are some of the pharmacological and clinical features of methadone poisoning?

         
         

         Methadone is a synthetic opioid analgesic made of a racemic mixture of two enantiomers d-methadone and l-methadone. besides its action on mu and kappa receptors, it is also an NMDA receptor antagonist. Due to its long action, methadone is useful as an analgesic and to suppress opioid withdrawal symptoms (hence used for opioid detoxification). Methadone causes constipation, nausea, and vomiting (due to its effect on the chemoreceptor trigger zone).

         Methadone is well absorbed in the GI tract and can be detected in the plasma within 30 minutes. Although its half-life is 10-18 hours, it can be as high as 25 hours or longer in acute overdoses. In infants and children, a single dose of methadone clinical manifestations can last X 72 hours. The action of methadone is similar to morphine and is primarily on mu, delta, and kappa receptors. It causes drowsiness, respiratory depression, hypotension, and miosis. Cerebral edema has been associated with severe toxicity.

         Pradip, If you had to work up this patient with methadone ingestion, what would be your diagnostic approach?

         
         

         The classic triad of miosis + respiratory depression and altered mental status with a quick response to Naloxone is diagnostic of opioid poisoning. History of methadone exposure such as in our case above will help clinch the diagnosis.

         Blood gas, CMP, CBC, Routine and comprehensive drug screens (may help with co-existing toxins).

         
         

         Methadone is usually not tested on a standard drug screen unless specifically requested. Standard urine immunoassays are not able to detect synthetic opioids such as methadone.

         Methadone ingestion is confirmed when both methadone and methadone metabolite (EDDP) are detected in the urine using high-performance liquid chromatography. However such testing is costly and may take time. The window of methadone detection can range from 3-4 days (rarely up to 14 days).

         
         

         EKG

         beta-HCG in a female teenager.

         Always follow your state's poison control recommendations.

         
         

         If our history, physical, and diagnostic investigation led us to methadone ingestion as our diagnosis, what would be your general management of framework?

         
         

         Symptomatic and good supportive PICU care with continuous monitoring of airway patency is the mainstay of treatment in patients who present with mild to moderate methadone toxicity. Charcoal lavage may be tried in mild intoxication in a patient who is not altered.

         Administer oxygen and assist ventilation for respiratory depression.

         Naloxone is an opioid antagonist and the antidote of choice, especially in severe toxicity. For children under 5years of age (or < 20Kg): Use 0.1mg/kg. For children > 5 years or over 20Kg 2mg IV every 2-3hours. Naloxone can be administered SC, IM, IV, via the endotracheal tube or even intranasally. Continuous infusion is likely to be necessary for patients who have ingested methadone, as the duration of action of Naloxone is 1 to 2 hours, compared with a duration of action of 24 hours for methadone. The infusion should be started at a rate such that two-thirds of the dose effective for initial reversal is administered each hour, and titrated as needed. Naloxone can potentiate withdrawal in opioid-dependent patients. A side effect of naloxone use can be transient hypertension or pulmonary edema (both rare) and such risks should not preclude its use.

         
         

         Early intubation and ventilation assistance should be performed if respiratory depression does not respond to naloxone. Adequate circulatory support with IV fluids and vasopressors (if needed) should be assured if a patient presents with a circulatory collapse that does not reverse with naloxone. Treat seizures with benzodiazepines, propofol, and/or barbiturates.

         Monitor for QT prolongation and dysrhythmias. Torsades de pointes

         Correct electrolyte abnormalities. Intravenous magnesium and overdrive pacing as indicated

         Very rarely ECMO may be required if life-threatening pulmonary edema refractory to standard measures.

         
         

         Pradip, it was found in our case that the patient had significant hypoglycemia. Can you shed some light on this in relation to the methadone overdose?

         
         

         Blood glucose needs to be carefully monitored. Most studies report hypoketotic, hyperinsulinemic, and hypoglycemia after an acute, unintentional methadone exposure, especially with high doses. Possible etiologies of hypoglycemia may include promotion of pancreatic insulin release, suppression of counter-regulatory mechanisms such as glucagon, epinephrine, and sympathoadrenal responses to hypoglycemia as well as impairment of glycogenolysis and gluconeogenesis.

         
         

         As we wrap up today, let’s also go through the criteria for observation, admission, and ICU-level care. All patients who develop CNS or respiratory depression should be admitted for observation (for at least 24 hours) even after adequate response to naloxone therapy. Patients who require intubation or a naloxone infusion will obviously require an intensive care unit admission. Patients should not be discharged until they have remained awake and alert for 4 to 6 hours after the Naloxone infusion has been discontinued.

         Patients with mild toxicity who do not require Naloxone should be observed for at least 8 hours.

         Please also work closely with toxicologists and local poison control as well!

         
         

         Pradip, what are some clinical pearls or pitfalls to avoid?

         Remember the triad of pinpoint pupils+respiratory depression+altered mental status is highly suggestive of opioid poisoning

         Naloxone is the drug of choice in opioid overdose, an infusion may be needed for longer-acting agents such as methadone.

         
         

         In addition to Naloxone, close attention to airway patency and maintenance of respiration is required in the PICU

         So today we learned about the management of methadone ingestion in a toddler. Liquid methadone...]]>Welcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.

         I'm Pradip Kamat coming to you from Children’s Healthcare of Atlanta/Emory University School of Medicine. I'm Rahul Damania from Cleveland Clinic Children’s Hospital and we are two Pediatric ICU physicians passionate about all things MED-ED in the PICU. PICU Doc on Call focuses on interesting PICU cases & management in the acute care pediatric setting so let’s get into our episode:

         Here's the case presented by Rahul:

         A 21-month-old girl was brought to an OSH ED for somnolence and difficulty breathing, which developed after she accidentally ingested an unknown amount of liquid medicine that was used by her grandfather. Per the mother, the patient’s grandfather was given the liquid medication for the treatment of his opioid addiction. The patient took some unknown amount from the open bottle that was left on the counter by the grandfather. Immediately after ingestion of the medicine, the patient initially became irritable and had some generalized pruritus. The patient subsequently became sleepy followed by difficulty breathing and her lips turned grey. The patient was rushed to an outside hospital ED for evaluation.

         OSH ED: The patient arrived unresponsive and blue, she was noted to be sleepy and difficult to arouse on arrival, with pinpoint pupils and hypoxic to 88%. , but After receiving Naloxone, however, she became awake and interactive. Her glucose on presentation was 58 mg/dL and Her initial VBG resulted 7.3/49.6/+2. She continued to have intermittent episodes of somnolence without apnea. Poison control called and recommend starting a naloxone infusion; she was also given dextrose bolus. The patient was admitted to the PICU.

         To summarize key elements from this case, this patient has:

         Accidental ingestion of an unknown medication

         Altered mental status

         Difficulty breathing—with grey lips suggestive of hypoventilation/hypoxia

         All of which brings up a concern for a toxidrome which is our topic of discussion for today

         The typical symptoms seen in our patient of pinpoint pupils, respiratory depression, and a decreased level of consciousness is known as the “opioid overdose triad” Given the history of opioid addiction in the grandfather, the liquid medicine given to him is most likely methadone.In fact, in this case, the mother brought the bottle of medicine, which was subsequently confirmed to be prescription methadone given to prevent opioid withdrawal in the grandfather.

          

         To dive deeper into this episode, let’s start with a multiple choice question:

         Which of the following opioids carries the greatest risk of QTc prolongation?

         A. Methadone

         B. Morphine

         C. Fentanyl

         D. Dilaudid

         
         

         The correct answer is methadone. Methadone prolongs QT interval due to its interactions with the cardiac potassium channel (KCNH2) and increases the risk for Torsades in a dose-dependent manner. Besides the effect on cardiac repolarization, methadone is also associated with the development of bradycardia mediated via its anticholinesterase properties and through its action as a calcium channel antagonist. Hypokalemia, hypocalcemia, hypomagnesemia, and concomitant use of other drugs belonging to the family of CYP3A4 system inhibitors such as erythromycin can prolong Qtc. Even in absence of these risk factors, methadone alone can prolong QTc.

          

         Thanks for that, I think it is very important to involve your Pediatric Pharmacy team to also help with management as children may be concurrent qt prolonging meds.

         
         

         Rahul, what are some of the pharmacological and clinical features of methadone poisoning?

         
         

         Methadone is a synthetic opioid analgesic made of a racemic mixture of two enantiomers d-methadone and l-methadone. besides its action on mu and kappa receptors, it is also an NMDA receptor antagonist. Due to its long action, methadone is useful as an analgesic and to suppress opioid withdrawal symptoms (hence used for opioid detoxification). Methadone causes constipation, nausea, and vomiting (due to its effect on the chemoreceptor trigger zone).

         Methadone is well absorbed in the GI tract and can be detected in the plasma within 30 minutes. Although its half-life is 10-18 hours, it can be as high as 25 hours or longer in acute overdoses. In infants and children, a single dose of methadone clinical manifestations can last X 72 hours. The action of methadone is similar to morphine and is primarily on mu, delta, and kappa receptors. It causes drowsiness, respiratory depression, hypotension, and miosis. Cerebral edema has been associated with severe toxicity.

         Pradip, If you had to work up this patient with methadone ingestion, what would be your diagnostic approach?

         
         

         The classic triad of miosis + respiratory depression and altered mental status with a quick response to Naloxone is diagnostic of opioid poisoning. History of methadone exposure such as in our case above will help clinch the diagnosis.

         Blood gas, CMP, CBC, Routine and comprehensive drug screens (may help with co-existing toxins).

         
         

         Methadone is usually not tested on a standard drug screen unless specifically requested. Standard urine immunoassays are not able to detect synthetic opioids such as methadone.

         Methadone ingestion is confirmed when both methadone and methadone metabolite (EDDP) are detected in the urine using high-performance liquid chromatography. However such testing is costly and may take time. The window of methadone detection can range from 3-4 days (rarely up to 14 days).

         
         

         EKG

         beta-HCG in a female teenager.

         Always follow your state's poison control recommendations.

         
         

         If our history, physical, and diagnostic investigation led us to methadone ingestion as our diagnosis, what would be your general management of framework?

         
         

         Symptomatic and good supportive PICU care with continuous monitoring of airway patency is the mainstay of treatment in patients who present with mild to moderate methadone toxicity. Charcoal lavage may be tried in mild intoxication in a patient who is not altered.

         Administer oxygen and assist ventilation for respiratory depression.

         Naloxone is an opioid antagonist and the antidote of choice, especially in severe toxicity. For children under 5years of age (or < 20Kg): Use 0.1mg/kg. For children > 5 years or over 20Kg 2mg IV every 2-3hours. Naloxone can be administered SC, IM, IV, via the endotracheal tube or even intranasally. Continuous infusion is likely to be necessary for patients who have ingested methadone, as the duration of action of Naloxone is 1 to 2 hours, compared with a duration of action of 24 hours for methadone. The infusion should be started at a rate such that two-thirds of the dose effective for initial reversal is administered each hour, and titrated as needed. Naloxone can potentiate withdrawal in opioid-dependent patients. A side effect of naloxone use can be transient hypertension or pulmonary edema (both rare) and such risks should not preclude its use.

         
         

         Early intubation and ventilation assistance should be performed if respiratory depression does not respond to naloxone. Adequate circulatory support with IV fluids and vasopressors (if needed) should be assured if a patient presents with a circulatory collapse that does not reverse with naloxone. Treat seizures with benzodiazepines, propofol, and/or barbiturates.

         Monitor for QT prolongation and dysrhythmias. Torsades de pointes

         Correct electrolyte abnormalities. Intravenous magnesium and overdrive pacing as indicated

         Very rarely ECMO may be required if life-threatening pulmonary edema refractory to standard measures.

         
         

         Pradip, it was found in our case that the patient had significant hypoglycemia. Can you shed some light on this in relation to the methadone overdose?

         
         

         Blood glucose needs to be carefully monitored. Most studies report hypoketotic, hyperinsulinemic, and hypoglycemia after an acute, unintentional methadone exposure, especially with high doses. Possible etiologies of hypoglycemia may include promotion of pancreatic insulin release, suppression of counter-regulatory mechanisms such as glucagon, epinephrine, and sympathoadrenal responses to hypoglycemia as well as impairment of glycogenolysis and gluconeogenesis.

         
         

         As we wrap up today, let’s also go through the criteria for observation, admission, and ICU-level care. All patients who develop CNS or respiratory depression should be admitted for observation (for at least 24 hours) even after adequate response to naloxone therapy. Patients who require intubation or a naloxone infusion will obviously require an intensive care unit admission. Patients should not be discharged until they have remained awake and alert for 4 to 6 hours after the Naloxone infusion has been discontinued.

         Patients with mild toxicity who do not require Naloxone should be observed for at least 8 hours.

         Please also work closely with toxicologists and local poison control as well!

         
         

         Pradip, what are some clinical pearls or pitfalls to avoid?

         Remember the triad of pinpoint pupils+respiratory depression+altered mental status is highly suggestive of opioid poisoning

         Naloxone is the drug of choice in opioid overdose, an infusion may be needed for longer-acting agents such as methadone.

         
         

         In addition to Naloxone, close attention to airway patency and maintenance of respiration is required in the PICU

         So today we learned about the management of methadone ingestion in a toddler. Liquid methadone is highly toxic and even as one little teaspoon can lead to fatality in a toddler. Besides appropriate storage of methadone to prevent accidental ingestion by toddlers, early recognition of the classic opioid triad (AMS+Pinpoint pupils+respiratory depression) and prompt medical intervention can be life-saving.

         This concludes our episode on Methadone ingestion. We hope you found value in our short, case-based podcast. We welcome you to share your feedback, subscribe & place a review on our podcast! Please visit our website picudoconcall.org which showcases our episodes as well as our Doc on Call management cards. PICU Doc on Call is co-hosted by myself Dr. Pradip Kamat and Dr. Rahul Damania. Stay tuned for our next episode! Thank you!

         
         

         References:

         Fuhrman & Zimmerman - Textbook of Pediatric Critical Care Chapter 126 Toxidromes and Their treatment by Prashant Joshi. Page 1497.

         Reference 1: Sachdeva DK, Stadnyk JM. Are one or two dangerous? Opioid exposure in toddlers. J Emerg Med. 2005 Jul;29(1):77-84. doi: 10.1016/j.jemermed.2004.12.015. PMID: 15961014.

         Reference 2: Boyer EW, McCance-Katz EF, Marcus S. Methadone and buprenorphine toxicity in children. Am J Addict. 2010 Jan-Feb;19(1):89-95. doi: 10.1111/j.1521-0391.2009.00002.x. PMID: 20132125.

         Reference 3: Glatstein M, Finkelstein Y, Scolnik D. Accidental methadone ingestion in an infant: case report and review of the literature. Pediatr Emerg Care. 2009 Feb;25(2):109-11. doi: 10.1097/PEC.0b013e318196faff. PMID: 19225381.

         ]]>bd237783-9d92-4ca0-9228-6031c562eeddSun, 14 Aug 2022 03:00:00 -040017:04falsefull6161Approach to Antifungals in the PICUWelcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.

         I'm Pradip Kamat coming to you from Children’s Healthcare of Atlanta/Emory University School of Medicine. Today we are joined by two wonderful clinical pharmacists — Whitney Moore & Stephanie Yasechko.

         Whitney is a Clinical Pharmacy Specialist at Children’s Healthcare of Atlanta. She is on Twitter at @MoorephinRx.

         Stephanie is a Pediatric Lung Transplant Clinical Pharmacy Specialist at Cincinnati Children’s Hospital Medical Center.

         We are so excited to have you both on today. My name is Rahul Damania and I am a Pediatric Intensivist at Cleveland Clinic Children’s Hospital; Welcome to PICU Doc On Call where we focus on all things MED-ED in the PICU. Our podcast focuses on interesting PICU cases & management in the acute care pediatric setting so let’s get into our episode:

         Welcome to our Episode an 18 yo immunocompromised patient with headache & sore throat

         Here's the case presented by Rahul:

         An 18-year-old female (40 kg) with PMH significant for fibrolamellar carcinoma of the liver, presents to the ED with headache and sore throat. She is febrile to 38.3, tachycardic, tachypneic, and has a WBC of 27K on her CBC. She is markedly hypotensive with BP on the arrival of 99/65. Cultures were drawn, the patient was given x1 doses of vancomycin and meropenem, and she was transported to the PICU for further workup and management. Due to her progressive hemodynamic instability, increased inflammatory markers, and marked immunocompromised state, the team is considering broadening her anti-microbial coverage.

         To summarize key elements from this case, this patient has:

         • Fibrolamellar carcinoma of the liver
         • A presentation of headache, sore throat, and hemodynamic instability with concern for sepsis
         • A current regimen of just antibacterials, which brings up the consideration of adding anti-fungal coverage in her clinically ill state.
         
         

         Our episode today will be covering anti-fungal agents in the PICU.

         We will review general mycology, understand different classes of antifungals, and highlight practical clinical pearls in the acute care setting.

         As mentioned, this patient has risk factors for an immunocompromised state due to her underlying liver condition. As we dive deeper into antifungals, Whitney, can you please give us an overview of common fungal pathogens in the PICU?

         Before we discuss the major drugs, it’s important that we take some time to briefly review the most common fungi we encounter clinically since it’s hard to choose the right agent when you don’t know exactly what you are treating.

         Clinically, Candida is probably the most common fungal pathogen encountered, especially in warm, moist environments. It is important to determine what type of species is growing. The three major species known to cause infection are C. albicans, C. glabrata, and C. krusei, but it is important to differentiate these species when identified since they have different resistance patterns.

         Cryptococcus is another type of fungus that is known to cause meningitis or fungemia, especially in immunocompromised or cirrhotic patients. Both Candida and Cryptococcus are classified as yeast on Gram stain. Treating cryptococcus will require the use of an agent that has good penetration to the CNS.

         Endemic fungi known as Coccidia, Histoplasma, and Blastomyces are known to cause disseminated infections in immunocompromised hosts; however, each fungus is associated with a different geographic region in the United States. With any type of infection, it is always very important to consider your patients’ exposures and recent travel history.

         And finally, there are two major molds that have the potential to be pathogenic. The first is Aspergillus which is identified via hyphae (tall filaments) on Gram stain well known to cause invasive pulmonary infections in the immunocompromised, specifically those who are neutropenic and/or received a lung transplant. Cystic fibrosis patients are also well-known hosts to aspergillus. The next mold is Mucorates, otherwise known as Mucor. Mucor has the propensity to cause an aggressive infection that necessitates surgical debridement. While rare, you can see this pathogen affect patients who are diabetic, neutropenic, taking chronic steroids or other immunosuppressants, or who have just sustained a trauma.

         So now that we have some background on fungal pathogens and who they most commonly affect, let’s now dive into the medications we have available to treat them, but first, let’s circle back to our case.

         While cultures remained negative for bacteria, the patient’s headache and sore throat worsened, congestion developed, and ENT was consulted to evaluate nasal cavities which appeared concerning for necrosis. The patient was then taken to the OR for investigation and debridement, and fungal cultures were taken.

         After a close consult with ID, the recommendation was made to empirically treat with liposomal amphotericin B at 10 mg/kg IV once daily due to CNS concern and immunocompromised host status.

         As mentioned in the case, the patient was started on amphotericin B, let’s take a step back and review some key classes of anti-fungal medications commonly used in the PICU.

         As a big picture, we will be covering Poleyenes, Azoles, and Echinocandins

         Whitney, do you mind highlighting our first class, the polyenes?

         The first class of antifungal agents we will discuss is polyenes. Within this class, there are two agents that we encounter clinically: Amphotericin B and Nystatin. These two agents bind to ergosterol in the fungal cell membrane to disrupt fungal cell permeability and cause rapid cell death.

         For the purposes of this podcast, we will focus our attention on amphotericin B, as this agent is a broad spectrum IV antifungal agent used clinically to treat most all fungal infections including cryptococcus, aspergillus, fusarium, and mucor.

         However, this medication is known for its many toxicities including electrolyte derangements, headaches, fevers, and renal impairment. There is a liposomal formulation of this medication in which most hospitals now have on formulary exclusively to help mitigate some of these adverse effects, but this formulation is also known to cause them to a lesser extent, and electrolytes should be closely monitored and aggressively replaced during therapy.

         Nephrotoxicity also means the use of concomitant nephrotoxic medications should be minimized as much as possible. So in our patient case, since blood cultures remained no growth to date, vancomycin, as well as meropenem, were discontinued.

         Returning to our case, Histopathology and debridement ended up showing evidence for mucormycosis susceptible to posaconazole and isavuconazole. Let's talk a little bit now about the Azole class.

         The azoles are our second group of antifungals; this class of antifungals works by preventing the formation of ergosterol, and there are five common azoles that every clinician should be familiar with, and taking into consideration our case, we will start by discussing posaconazole and isavuconazole.

         Posaconazole is a broad spectrum azole that covers all of your Candida as well as both Aspergillus and Mucor. It is available both IV and orally, in the form of tablets and a suspension. The oral formulations are not interchangeable since the oral suspension has erratic pharmacokinetics given that it is highly lipophilic and difficult to absorb. Therefore, it is recommended to use the tablets when able, especially given their convenience of once daily dosing.

         Otherwise, the drug will require therapeutic drug monitoring to ensure the patient is achieving adequate levels. The target trough concentration for adequate posaconazole prophylaxis is > 700 ng/mL and > 1,250 ng/mL for treatment drawn 5-7 days following medication initiation.

         Like most all of the other drugs in this class, posaconazole is a strong CYP3A4 and p-glycoprotein inhibitor; therefore, many drug interactions exist. These types of azoles are also known to prolong QTc and cause hepatotoxicity.

         It is important to highlight that children in the PICU may frequently be frequently on concurrent medications which also prolong the QT interval. Having close collaboration with your clinical pharmacy team and a daily discussion of the medications the patient may be on is essential in optimizing electrocardiographic monitoring for these patients.

         Now that we have talked about posaconazole, let’s contrast this with isavuconazole (cresemba). Whitney, do you mind highlighting some similarities & differences?

         Isavuconazole is the newest azole and is also available in an IV and PO formulation. Coverage is pretty similar to posaconazole; however, the additional benefits of this agent are that it does not require therapeutic drug monitoring, has QTc prolonging effects, or have as significant of drug interactions when compared to the other azoles, given that it is a moderate CYP3A4 inhibitor versus a strong one.

         Major side effects to be mindful of include hypersensitivity and skin reactions, hypokalemia, hepatotoxicity, peripheral edema, and cough.

         To summarize, Given that our patient here is an oncology patient with chemotherapy and anti-emetics on board, isavuconazole is the drug of choice for her due to the lack of QTc prolonging and minimal drug interactions. Therefore, we can then narrow her from the liposomal  amphotericin B to isavuconazole, where we would first load her with 372 mg IV Q8H x6 doses, and then continue her on a maintenance dose of 372 mg IV or PO when able for as long as she is receiving chemotherapy and is immunosuppressed.

         Ok,]]>Welcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.

         I'm Pradip Kamat coming to you from Children’s Healthcare of Atlanta/Emory University School of Medicine. Today we are joined by two wonderful clinical pharmacists — Whitney Moore & Stephanie Yasechko.

         Whitney is a Clinical Pharmacy Specialist at Children’s Healthcare of Atlanta. She is on Twitter at @MoorephinRx.

         Stephanie is a Pediatric Lung Transplant Clinical Pharmacy Specialist at Cincinnati Children’s Hospital Medical Center.

         We are so excited to have you both on today. My name is Rahul Damania and I am a Pediatric Intensivist at Cleveland Clinic Children’s Hospital; Welcome to PICU Doc On Call where we focus on all things MED-ED in the PICU. Our podcast focuses on interesting PICU cases & management in the acute care pediatric setting so let’s get into our episode:

         Welcome to our Episode an 18 yo immunocompromised patient with headache & sore throat

         Here's the case presented by Rahul:

         An 18-year-old female (40 kg) with PMH significant for fibrolamellar carcinoma of the liver, presents to the ED with headache and sore throat. She is febrile to 38.3, tachycardic, tachypneic, and has a WBC of 27K on her CBC. She is markedly hypotensive with BP on the arrival of 99/65. Cultures were drawn, the patient was given x1 doses of vancomycin and meropenem, and she was transported to the PICU for further workup and management. Due to her progressive hemodynamic instability, increased inflammatory markers, and marked immunocompromised state, the team is considering broadening her anti-microbial coverage.

         To summarize key elements from this case, this patient has:

         • Fibrolamellar carcinoma of the liver
         • A presentation of headache, sore throat, and hemodynamic instability with concern for sepsis
         • A current regimen of just antibacterials, which brings up the consideration of adding anti-fungal coverage in her clinically ill state.
         
         

         Our episode today will be covering anti-fungal agents in the PICU.

         We will review general mycology, understand different classes of antifungals, and highlight practical clinical pearls in the acute care setting.

         As mentioned, this patient has risk factors for an immunocompromised state due to her underlying liver condition. As we dive deeper into antifungals, Whitney, can you please give us an overview of common fungal pathogens in the PICU?

         Before we discuss the major drugs, it’s important that we take some time to briefly review the most common fungi we encounter clinically since it’s hard to choose the right agent when you don’t know exactly what you are treating.

         Clinically, Candida is probably the most common fungal pathogen encountered, especially in warm, moist environments. It is important to determine what type of species is growing. The three major species known to cause infection are C. albicans, C. glabrata, and C. krusei, but it is important to differentiate these species when identified since they have different resistance patterns.

         Cryptococcus is another type of fungus that is known to cause meningitis or fungemia, especially in immunocompromised or cirrhotic patients. Both Candida and Cryptococcus are classified as yeast on Gram stain. Treating cryptococcus will require the use of an agent that has good penetration to the CNS.

         Endemic fungi known as Coccidia, Histoplasma, and Blastomyces are known to cause disseminated infections in immunocompromised hosts; however, each fungus is associated with a different geographic region in the United States. With any type of infection, it is always very important to consider your patients’ exposures and recent travel history.

         And finally, there are two major molds that have the potential to be pathogenic. The first is Aspergillus which is identified via hyphae (tall filaments) on Gram stain well known to cause invasive pulmonary infections in the immunocompromised, specifically those who are neutropenic and/or received a lung transplant. Cystic fibrosis patients are also well-known hosts to aspergillus. The next mold is Mucorates, otherwise known as Mucor. Mucor has the propensity to cause an aggressive infection that necessitates surgical debridement. While rare, you can see this pathogen affect patients who are diabetic, neutropenic, taking chronic steroids or other immunosuppressants, or who have just sustained a trauma.

         So now that we have some background on fungal pathogens and who they most commonly affect, let’s now dive into the medications we have available to treat them, but first, let’s circle back to our case.

         While cultures remained negative for bacteria, the patient’s headache and sore throat worsened, congestion developed, and ENT was consulted to evaluate nasal cavities which appeared concerning for necrosis. The patient was then taken to the OR for investigation and debridement, and fungal cultures were taken.

         After a close consult with ID, the recommendation was made to empirically treat with liposomal amphotericin B at 10 mg/kg IV once daily due to CNS concern and immunocompromised host status.

         As mentioned in the case, the patient was started on amphotericin B, let’s take a step back and review some key classes of anti-fungal medications commonly used in the PICU.

         As a big picture, we will be covering Poleyenes, Azoles, and Echinocandins

         Whitney, do you mind highlighting our first class, the polyenes?

         The first class of antifungal agents we will discuss is polyenes. Within this class, there are two agents that we encounter clinically: Amphotericin B and Nystatin. These two agents bind to ergosterol in the fungal cell membrane to disrupt fungal cell permeability and cause rapid cell death.

         For the purposes of this podcast, we will focus our attention on amphotericin B, as this agent is a broad spectrum IV antifungal agent used clinically to treat most all fungal infections including cryptococcus, aspergillus, fusarium, and mucor.

         However, this medication is known for its many toxicities including electrolyte derangements, headaches, fevers, and renal impairment. There is a liposomal formulation of this medication in which most hospitals now have on formulary exclusively to help mitigate some of these adverse effects, but this formulation is also known to cause them to a lesser extent, and electrolytes should be closely monitored and aggressively replaced during therapy.

         Nephrotoxicity also means the use of concomitant nephrotoxic medications should be minimized as much as possible. So in our patient case, since blood cultures remained no growth to date, vancomycin, as well as meropenem, were discontinued.

         Returning to our case, Histopathology and debridement ended up showing evidence for mucormycosis susceptible to posaconazole and isavuconazole. Let's talk a little bit now about the Azole class.

         The azoles are our second group of antifungals; this class of antifungals works by preventing the formation of ergosterol, and there are five common azoles that every clinician should be familiar with, and taking into consideration our case, we will start by discussing posaconazole and isavuconazole.

         Posaconazole is a broad spectrum azole that covers all of your Candida as well as both Aspergillus and Mucor. It is available both IV and orally, in the form of tablets and a suspension. The oral formulations are not interchangeable since the oral suspension has erratic pharmacokinetics given that it is highly lipophilic and difficult to absorb. Therefore, it is recommended to use the tablets when able, especially given their convenience of once daily dosing.

         Otherwise, the drug will require therapeutic drug monitoring to ensure the patient is achieving adequate levels. The target trough concentration for adequate posaconazole prophylaxis is > 700 ng/mL and > 1,250 ng/mL for treatment drawn 5-7 days following medication initiation.

         Like most all of the other drugs in this class, posaconazole is a strong CYP3A4 and p-glycoprotein inhibitor; therefore, many drug interactions exist. These types of azoles are also known to prolong QTc and cause hepatotoxicity.

         It is important to highlight that children in the PICU may frequently be frequently on concurrent medications which also prolong the QT interval. Having close collaboration with your clinical pharmacy team and a daily discussion of the medications the patient may be on is essential in optimizing electrocardiographic monitoring for these patients.

         Now that we have talked about posaconazole, let’s contrast this with isavuconazole (cresemba). Whitney, do you mind highlighting some similarities & differences?

         Isavuconazole is the newest azole and is also available in an IV and PO formulation. Coverage is pretty similar to posaconazole; however, the additional benefits of this agent are that it does not require therapeutic drug monitoring, has QTc prolonging effects, or have as significant of drug interactions when compared to the other azoles, given that it is a moderate CYP3A4 inhibitor versus a strong one.

         Major side effects to be mindful of include hypersensitivity and skin reactions, hypokalemia, hepatotoxicity, peripheral edema, and cough.

         To summarize, Given that our patient here is an oncology patient with chemotherapy and anti-emetics on board, isavuconazole is the drug of choice for her due to the lack of QTc prolonging and minimal drug interactions. Therefore, we can then narrow her from the liposomal  amphotericin B to isavuconazole, where we would first load her with 372 mg IV Q8H x6 doses, and then continue her on a maintenance dose of 372 mg IV or PO when able for as long as she is receiving chemotherapy and is immunosuppressed.

         Ok, so far we have covered posaconazole, isavuconazle, let’s close out this class by highlighting voriconazole, itraconazole and fluconazole?

         So while our patient was growing Mucor which was susceptible to both posaconazole and isavuconazole, another agent to highlight voriconazole. While it does not cover Mucor, it is the drug of choice in the treatment of Aspergillus and has good Fusarium coverage as well.

         It is also available in both IV and PO which can be converted 1:1. However, it does have the most toxicities compared to any of the other azoles which can include hallucinations, visual disturbances, and phototoxicity. Therefore, therapeutic drug monitoring is essential with a goal trough level of about 2-6 mcg/mL.

         Absolutely, Stephanie, I want to also highlight Itraconazole. This is the azole most commonly used to treat Histoplasma and Blastomyces. It can also be used as a prophylactic agent for Aspergillus. It is only available orally as a solution and as a capsule, but they are not interchangeable. The capsules must be taken on an acidic stomach and with a full meal while the solution needs to be administered in a fasting state. This drug is also monitored via a serum trough concentration with a goal level > 0.5 mcg/mL.

         It is important to keep in mind, however, that this agent has two black box warnings. The first is that it may cause negative inotropic properties which may lead to heart failure, and the other is that it has the potential to lead to torsades de pointes. Therefore, it should not be used in patients with a history of heart failure and/or ventricular dysfunction.

         And finally, the last azole and most narrow azole we are going to discuss is fluconazole. Fluconazole is the drug of choice for Candida albicans, Cryptococcus, and Coccidia. This drug is available both IV and orally with a 1:1 conversion, and distributes everywhere in the body, including the CNS.

         Our final discussion today will be on echinocandins, Stephanie, how do these agents work?

         These agents work mechanistically by inhibiting 1,3-beta-D glucan synthase which is also involved in the synthesis of the fungal cell wall.

         There are three agents in this class (caspofungin, micafungin, and anidulafungin). All three are available IV only, have a similar spectrum of activity which is essentially all Candida as well as Aspergillus, and are dosed once daily.

         The great thing about these agents is that they have very few drug reactions and do not require therapeutic drug monitoring.

         To summarize our discussion today, we spoke about major classes of antifungals, polyenes, azoles, and echinocandins. While each of them has its own specific coverage, it is important to also monitor for side effects and toxicities. Working closely with your clinical pharmacist and infectious disease physicians is a high-fidelity strategy to optimize therapeutic treatment.

         Also, in the spirit of anti-microbials, I would like to add that if you have not checked out our prior episode number 23: PICU Bugs and Drugs, I would highly recommend you listening as it covers the: Rational Use of Antibiotics In The PICU!

         
         

         This concludes our episode on Approach to Anti-fungals in the PICU. We hope you found value in our short, case-based podcast. We welcome you to share your feedback, subscribe & place a review on our podcast! Please visit our website picudoconcall.org which showcases our episodes as well as our Doc on Call management cards. PICU Doc on Call is co-hosted by myself Dr. Pradip Kamat and Dr. Rahul Damania. A special thank you to Dr. Whitney Moore & Stephanie Yasechko for joining us today and sharing their expertise. Stay tuned for our next episode! Thank you!

         
         

         • References:
         • Antifungal Therapeutic Drug Monitoring Recommendations for Adult and Pediatric Patients. The Michigan Medicine University of Michigan. January 31, 2017.
         • Curran, M. There’s a Fungus Among Us: A Beginner’s Guide to Antifungals. TLDRPharmcy.com. February 14, 2018.
         • Lexi-Drugs. Hudson, OH: Lexicomp. Accessed June 5, 2022.
         
         

         
         

         
         

         ]]>124f89b4-1970-4ab8-bed6-32dbdd688cb2Sun, 07 Aug 2022 03:00:00 -040014:51falsefull6060Approach to a Brain AbscessWelcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.

         I'm Pradip Kamat coming to you from Children’s Healthcare of Atlanta/Emory University School of Medicine and I'm Rahul Damania from Cleveland Clinic Children’s Hospital. We are two Pediatric ICU physicians passionate about all things MED-ED in the PICU. PICU Doc on Call focuses on interesting PICU cases & management in the acute care pediatric setting so let’s get into our episode:

         Welcome to our Episode about a 4-year-old girl with a chief complaint of headache and vomiting

         Here's the case:

         A 4-year-old presents to the PICU with headaches + vomiting and abnormal CT scan findings. The patient presented to the ED with h/o abdominal pain X 5 days with nonbilious, non-bloody emesis. Initial CBC, UA was normal. The patient was given some pain meds and IV fluids. Further history revealed that the patient has been having severe headaches for the last 5 days and had emesis secondary to the headaches resulting in generalized, non-specific abdominal pain. No h/o of trauma or seizures, no h/o of fever or diarrhea, no h/o toxic ingestions h/o recent travel, exposure to sick contacts, COVID test negative. No family h/o migraines, her immunizations are UTD. Besides the normal UA and CBC, her CMP was also normal.

         A CT scan of the head revealed right frontoparietal mass with moderate surrounding edema, 6 mm leftward midline shift, diffuse sulcal narrowing, and right cisternal narrowing. Imaging of the abdomen (US and CT w/ contrast) was unremarkable. An MRI done revealed: Right parietal diffusion restricting lesion, most compatible with abscess. Moderate surrounding vasogenic edema. Given her abdominal pain- Abdominal KUB as well as contrast CT scan of abdomen and pelvis were performed and revealed no abdominopelvic pathology.

         In the ED her vitals were normal and the patient was afebrile. On her PE: the patient appeared sleepy but woke up and answered questions appropriately. No focal deficits, PERRL, normal tone and strength. The rest of her physical exam was completely normal. She now is transferred to the PICU for serial neurological exams.

         To summarize key elements from this case, this patient has:

         • Headache with altered mental status
         • No focal deficits
         • Vomiting
         • surprisingly no fever
         • Imaging showing right frontoparietal mass.
         • All of which brings up a concern for brain abscess
         • This episode will be organized…
         • Epidemiology and pathogenesis
         • Diagnosis
         • Management
         
         

         Rahul, can you inform our listeners about the epidemiology of brain abscesses?

         Only about 25% of brain abscesses occur in children. Incidence in developed countries is about 1-2% while in developing countries it's about 8%. Peak incidence in children is seen between the ages of 4-7 years and is more common in males. Brain abscess in the neonatal age group is rare but are associated with a higher risk of complications and mortality.

         Risk factors for brain abscess include Otologic infections (ear, sinus, and dental infections), Congenital heart disease (30% of patients with BA have an underlying heart defect) with intra-cardiac or intrapulmonary shunting (pulmonary AV malformations in hemorrhagic telangiectasis), immunodeficiencies (solid organ transplantation, HIV, etc), prolonged steroid use, diabetes, alcoholism neurosurgical procedures, trauma. Other rare causes can be airway foreign bodies, congenital dermal sinuses, and esophageal procedures (such as dilatations).

         Brain abscess typically begins with a localized area of cerebritis which evolves through various stages (typically 10-14 days) to develop into an encapsulated collection of purulent material with peripheral gliosis or fibrosis.

         40-50% of the spread of infection is via a contiguous site of infection such as otitis, sinusitis or mastoiditis or from head trauma or neurosurgical procedure. 30-40% is spread through the hematogenous route from endocarditis, pulmonary infections, or dental abscess.

         90% of brain abscesses in children are supratentorial. Mastoiditis, sphenoidal sinusitis, otitis media results in BA in the temporal lobe or cerebellum. Frontal lobe BA are due to frontal or ethmoid sinusitis or dental infections. BA from hematogenous spread results in multiple abscesses and typically follows the distribution of the middle cerebral artery including parietal and occipital lobes.

         Rahul, what are some of the common pathogens seen in brain abscesses?

         A meta-analysis reported the most common organisms in children with BA. These include streptococcus species seen in 36% (seen mostly with otologic infections, and strep viridans with endocarditis) followed by staphylococcal sp seen in 18% (head trauma, surgery, or skin infections) and gram-negative enteric bacteria seen in 16% (Proteus, Klebsiella, E. coli and Enterobacteriae. Citrobacter, E Coli, or proteus species are seen in neonates.

         BAs from opportunistic microorganisms are usually multiple. They can occur in HIV-positive children with a low CD4 count; the most common pathogens are Toxoplasma, Nocardia, and Mycobacterium spp. Fungal abscesses (mainly Aspergillus or Candida) typically affect solid organ transplants recipients or children treated for leukemia

         To summarize, altered mental status in a patient who is immunocompromised, think of opportunistic infections. Remember these patients can present even without a fever!

         
         

         Rahul, what are some of the typical clinical features seen in patients with a brain abscess?

         
         

         Clinical features would depend on site, size, involvement of surrounding area, patient’s immune status, and organisms involved. Fever with headache is typical. Vomiting is usually associated with headaches. Neurological manifestations include-Seizures, hemiplegia, cranial nerve palsies, and altered level of consciousness ranging from drowsiness to coma. Neonates can have bulging fontanelle and even increased head circumference.

         The classic triad of fever +headache +neurological deficits is clinically seen in a small percentage (~33%) of patients. Frontal abscesses may remain asymptomatic especially if they are small. Pott's Puffy tumor also called Pott's edematous tumor (PET), is a sub-periosteal abscess of the frontal bone, associated with osteomyelitis of the frontal bone. which can give rise to BA. Meningeal signs are seen in 25% of patients with BA.

         To summarize, Pott puffy tumor is osteomyelitis of the frontal bone with associated subperiosteal abscess causing swelling and edema over the forehead and scalp. It is a complication of frontal sinusitis or trauma.

         
         

         If you had to work up this patient with a brain abscess what would be your diagnostic approach?

         
         

         • I would start with a CBC with diff, Blood Cx, ESR, CRP, and CMP. Such tests are abnormal in only 20% of pediatric patients with BA.
         • After CT or MRI, an LP can be attempted. LP would be contraindicated if there is a non-communicating obstructive hydrocephalous and brain shift. CSF fluid analysis, gm stain, and cultures could be helpful to find an organism and tailor therapy. Although CSF studies can be normal in 30% of patients with a BA. The sudden worsening of a preexisting headache can indicate a rupture of the brain abscess into the ventricular space or impending herniation from the lesion’s mass effect. Significant alteration in mental status is an ominous clinical finding. Abscesses located within their brainstem typically present with fever, headaches, hemiparesis, and focal cranial nerve findings involving CN III, CN VI, and CN VII.
         
         

         
         

         • MRI is considered as the gold standard (low radiation risk, better resolution, and lower toxicity of contrast compared to CT). MR imaging may require sedation and take a longer time compared to CT (which is readily available and may not require sedation due to the speed of image acquisition and can be performed quickly prior to an LP). MR has higher sensitivity and specificity in the differential diagnosis with cystic or neoplastic lesions. An MR study for bacterial BA will show a necrotic center with the low signal at the DW-MR (diffusion-weighted magnetic resonance) and a T2-hypointensity with enhancement for the peripheral capsule. Fungal abscesses show a hypointense center in the T2-weighed image with variable expression in DW-MR.
         • CT may reveal a mass lesion but MRI will help confirm the diagnosis and characterize the abscess better. Pus obtained from the aspiration or biopsy during the operating room can be used for culture.
         • Cultures (for aerobic and anaerobic bacteria, Mycobacterium, fungi, protozoa), Gram, and special stains (for fungi, Mycobacterium, Nocardia) and polymerase chain reaction should be performed on blood, CSF, and pus of the cerebral abscess. It is best to involve our ID colleagues in a patient with BA to guide diagnostic studies as well as therapies. The culture positivity of blood and CSF samples is low (22-28% of cases). The rate of micro-organism isolation from abscess samples is about 60–80%, with polymicrobial involvement in about 20–30% of cases.
         • Other studies can be obtained on a case-by-case basis depending on the primary focus would include an echocardiogram, CXR, abdominal US or CT, and bone imaging.
         • Besides infectious disease and NS experts, consults with cardiology, hematology, OMFS, and ENT experts may be required.
         
         

         To summarize, your approach to brain abscesses involves imaging, isolation of the lesion, and fluid/tissue diagnosis. Diagnostics such as an echo may reveal a primary source. This is definitely a...]]>Welcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.

         I'm Pradip Kamat coming to you from Children’s Healthcare of Atlanta/Emory University School of Medicine and I'm Rahul Damania from Cleveland Clinic Children’s Hospital. We are two Pediatric ICU physicians passionate about all things MED-ED in the PICU. PICU Doc on Call focuses on interesting PICU cases & management in the acute care pediatric setting so let’s get into our episode:

         Welcome to our Episode about a 4-year-old girl with a chief complaint of headache and vomiting

         Here's the case:

         A 4-year-old presents to the PICU with headaches + vomiting and abnormal CT scan findings. The patient presented to the ED with h/o abdominal pain X 5 days with nonbilious, non-bloody emesis. Initial CBC, UA was normal. The patient was given some pain meds and IV fluids. Further history revealed that the patient has been having severe headaches for the last 5 days and had emesis secondary to the headaches resulting in generalized, non-specific abdominal pain. No h/o of trauma or seizures, no h/o of fever or diarrhea, no h/o toxic ingestions h/o recent travel, exposure to sick contacts, COVID test negative. No family h/o migraines, her immunizations are UTD. Besides the normal UA and CBC, her CMP was also normal.

         A CT scan of the head revealed right frontoparietal mass with moderate surrounding edema, 6 mm leftward midline shift, diffuse sulcal narrowing, and right cisternal narrowing. Imaging of the abdomen (US and CT w/ contrast) was unremarkable. An MRI done revealed: Right parietal diffusion restricting lesion, most compatible with abscess. Moderate surrounding vasogenic edema. Given her abdominal pain- Abdominal KUB as well as contrast CT scan of abdomen and pelvis were performed and revealed no abdominopelvic pathology.

         In the ED her vitals were normal and the patient was afebrile. On her PE: the patient appeared sleepy but woke up and answered questions appropriately. No focal deficits, PERRL, normal tone and strength. The rest of her physical exam was completely normal. She now is transferred to the PICU for serial neurological exams.

         To summarize key elements from this case, this patient has:

         • Headache with altered mental status
         • No focal deficits
         • Vomiting
         • surprisingly no fever
         • Imaging showing right frontoparietal mass.
         • All of which brings up a concern for brain abscess
         • This episode will be organized…
         • Epidemiology and pathogenesis
         • Diagnosis
         • Management
         
         

         Rahul, can you inform our listeners about the epidemiology of brain abscesses?

         Only about 25% of brain abscesses occur in children. Incidence in developed countries is about 1-2% while in developing countries it's about 8%. Peak incidence in children is seen between the ages of 4-7 years and is more common in males. Brain abscess in the neonatal age group is rare but are associated with a higher risk of complications and mortality.

         Risk factors for brain abscess include Otologic infections (ear, sinus, and dental infections), Congenital heart disease (30% of patients with BA have an underlying heart defect) with intra-cardiac or intrapulmonary shunting (pulmonary AV malformations in hemorrhagic telangiectasis), immunodeficiencies (solid organ transplantation, HIV, etc), prolonged steroid use, diabetes, alcoholism neurosurgical procedures, trauma. Other rare causes can be airway foreign bodies, congenital dermal sinuses, and esophageal procedures (such as dilatations).

         Brain abscess typically begins with a localized area of cerebritis which evolves through various stages (typically 10-14 days) to develop into an encapsulated collection of purulent material with peripheral gliosis or fibrosis.

         40-50% of the spread of infection is via a contiguous site of infection such as otitis, sinusitis or mastoiditis or from head trauma or neurosurgical procedure. 30-40% is spread through the hematogenous route from endocarditis, pulmonary infections, or dental abscess.

         90% of brain abscesses in children are supratentorial. Mastoiditis, sphenoidal sinusitis, otitis media results in BA in the temporal lobe or cerebellum. Frontal lobe BA are due to frontal or ethmoid sinusitis or dental infections. BA from hematogenous spread results in multiple abscesses and typically follows the distribution of the middle cerebral artery including parietal and occipital lobes.

         Rahul, what are some of the common pathogens seen in brain abscesses?

         A meta-analysis reported the most common organisms in children with BA. These include streptococcus species seen in 36% (seen mostly with otologic infections, and strep viridans with endocarditis) followed by staphylococcal sp seen in 18% (head trauma, surgery, or skin infections) and gram-negative enteric bacteria seen in 16% (Proteus, Klebsiella, E. coli and Enterobacteriae. Citrobacter, E Coli, or proteus species are seen in neonates.

         BAs from opportunistic microorganisms are usually multiple. They can occur in HIV-positive children with a low CD4 count; the most common pathogens are Toxoplasma, Nocardia, and Mycobacterium spp. Fungal abscesses (mainly Aspergillus or Candida) typically affect solid organ transplants recipients or children treated for leukemia

         To summarize, altered mental status in a patient who is immunocompromised, think of opportunistic infections. Remember these patients can present even without a fever!

         
         

         Rahul, what are some of the typical clinical features seen in patients with a brain abscess?

         
         

         Clinical features would depend on site, size, involvement of surrounding area, patient’s immune status, and organisms involved. Fever with headache is typical. Vomiting is usually associated with headaches. Neurological manifestations include-Seizures, hemiplegia, cranial nerve palsies, and altered level of consciousness ranging from drowsiness to coma. Neonates can have bulging fontanelle and even increased head circumference.

         The classic triad of fever +headache +neurological deficits is clinically seen in a small percentage (~33%) of patients. Frontal abscesses may remain asymptomatic especially if they are small. Pott's Puffy tumor also called Pott's edematous tumor (PET), is a sub-periosteal abscess of the frontal bone, associated with osteomyelitis of the frontal bone. which can give rise to BA. Meningeal signs are seen in 25% of patients with BA.

         To summarize, Pott puffy tumor is osteomyelitis of the frontal bone with associated subperiosteal abscess causing swelling and edema over the forehead and scalp. It is a complication of frontal sinusitis or trauma.

         
         

         If you had to work up this patient with a brain abscess what would be your diagnostic approach?

         
         

         • I would start with a CBC with diff, Blood Cx, ESR, CRP, and CMP. Such tests are abnormal in only 20% of pediatric patients with BA.
         • After CT or MRI, an LP can be attempted. LP would be contraindicated if there is a non-communicating obstructive hydrocephalous and brain shift. CSF fluid analysis, gm stain, and cultures could be helpful to find an organism and tailor therapy. Although CSF studies can be normal in 30% of patients with a BA. The sudden worsening of a preexisting headache can indicate a rupture of the brain abscess into the ventricular space or impending herniation from the lesion’s mass effect. Significant alteration in mental status is an ominous clinical finding. Abscesses located within their brainstem typically present with fever, headaches, hemiparesis, and focal cranial nerve findings involving CN III, CN VI, and CN VII.
         
         

         
         

         • MRI is considered as the gold standard (low radiation risk, better resolution, and lower toxicity of contrast compared to CT). MR imaging may require sedation and take a longer time compared to CT (which is readily available and may not require sedation due to the speed of image acquisition and can be performed quickly prior to an LP). MR has higher sensitivity and specificity in the differential diagnosis with cystic or neoplastic lesions. An MR study for bacterial BA will show a necrotic center with the low signal at the DW-MR (diffusion-weighted magnetic resonance) and a T2-hypointensity with enhancement for the peripheral capsule. Fungal abscesses show a hypointense center in the T2-weighed image with variable expression in DW-MR.
         • CT may reveal a mass lesion but MRI will help confirm the diagnosis and characterize the abscess better. Pus obtained from the aspiration or biopsy during the operating room can be used for culture.
         • Cultures (for aerobic and anaerobic bacteria, Mycobacterium, fungi, protozoa), Gram, and special stains (for fungi, Mycobacterium, Nocardia) and polymerase chain reaction should be performed on blood, CSF, and pus of the cerebral abscess. It is best to involve our ID colleagues in a patient with BA to guide diagnostic studies as well as therapies. The culture positivity of blood and CSF samples is low (22-28% of cases). The rate of micro-organism isolation from abscess samples is about 60–80%, with polymicrobial involvement in about 20–30% of cases.
         • Other studies can be obtained on a case-by-case basis depending on the primary focus would include an echocardiogram, CXR, abdominal US or CT, and bone imaging.
         • Besides infectious disease and NS experts, consults with cardiology, hematology, OMFS, and ENT experts may be required.
         
         

         To summarize, your approach to brain abscesses involves imaging, isolation of the lesion, and fluid/tissue diagnosis. Diagnostics such as an echo may reveal a primary source. This is definitely a coordinated effort with ID, neurosurgery, as well as neurology. These patients may also require prophylactic anti-epileptics peri-biopsy.

         
         

         
         

         If our history, physical, and diagnostic investigation led us to brain abscess as our diagnosis what would be your general management of framework?

         
         

         As we have mentioned before, A multidisciplinary team approach involving the PCCM, NS, ID, radiologists, and pharmacists are required for the successful management of patients with BA in the PICU.

         Again, good basic PICU care with close attention to airway patency, adequacy of oxygenation/ventilation as well as stability of hemodynamics should be the first line approach in such patients admitted to the PICU. Good access for medication administration may include the need for a PICC line. Attention to neuro-status by frequent physical exams including attention to the patient's handling of oral secretions should be a priority. Continuous EEG may be required depending on the site, size, and involvement of the surrounding area.

         Long-term antibiotics are the mainstay of therapy: A combination of vancomycin+ceftriaxone and metronidazole for 4-6 weeks if surgically drained vs 8 weeks for those without surgical drainage. Along the same lines, it is important to anticipate PICC lines or stable central lines for the long-term abx therapy.

         
         

         Non-operative approach can be considered in patient with multiple small abscess or a single abscess which is < 2.5cm. Non surgical approach is also considered in patients with surgically inaccessible lesions, early cerebritis, or medical comorbidities that puts patient at high surgical risk.

         What about operative approach?

         Operative approach involves aspiration (typically CT guided), or excision. Aspiration results in removal of infected nidus (source control) as well as provision of material for gm stain/Cx. Excision of the abscess cavity may be useful when it is located in a periventricular or posterior fossa distribution, is loculated, or contains a foreign body. Excision should also be considered for abscesses that enlarge after 2 weeks of antibiotic therapy or that fail to shrink after 3 to 4 weeks of antibiotics. Primary excision may be the procedure of choice for lesions located in the cerebellum. Compared to aspiration, excision of BA in nonvital areas of brain had a lower rate of re-operation, a higher rate of postoperative abscess clearance, and better neurologic improvement after 1 month with no difference in long-term neurological outcomes or mortality.

         Rahul, what are some of the prognostic features of BA?

         
         

         BA from a contiguous focus of infection and those developing after a traumatic injury tend to have a better prognosis. Poorer prognosis is associated with delayed diagnosis, immunocompromised status, rupture of the abscess into the ventricular space, fungal etiology, and pretreatment neurologic compromise.

         
         

         Let’s summarize

         
         

         1. The classic triad of diagnosis of BA- headache +fever+ neurological deficit is seen in only 1/3rd of the patients with BA. Therefore a high index of suspicion is required based on patients risk factors such as immunosuppression, cyanotic heart disease etc.
         2. Early imaging with CT/MRI is necessary to diagnosis
         3. Antibiotic therapy should not be delayed. Triple therapy with vancomycin +ceftriaxone and metronidazole is typically initiated at diagnosis.
         
         

         This concludes our episode on brain abscesses. We hope you found value in our short, case-based podcast. We welcome you to share your feedback, subscribe & place a review on our podcast! Please visit our website picudoconcall.org which showcases our episodes as well as our Doc on Call management cards. PICU Doc on Call is co-hosted by myself Dr. Pradip Kamat and Dr. Rahul Damania. Stay tuned for our next episode! Thank you!

         
         

         References

         • Fuhrman & Zimmerman - Textbook of Pediatric Critical Care Chapter 67 Central nervous system infections and related conditions (Havlin KM et al.)
         • Reference 1: Mameli, C., Genoni, T., Madia, C. et al. Brain abscess in pediatric age: a review. Childs Nerv Syst 35, 1117–1128 (2019).
         • Reference 2: Panda PK, Natarajan V, Vigneshwar NKV, Sharawat IK. Clinical Presentation and Outcome of Children with Brain Abscess. Ann Indian Acad Neurol. 2021 Nov-Dec;24(6):951-952. doi: 10.4103/aian.AIAN_794_20. Epub 2021 Jan 19. PMID: 35359509; PMCID: PMC8965945.
         
         

         
         

         
         

         
         

         ]]>0ea597a9-2530-4f87-b510-331807a4b525Sun, 31 Jul 2022 03:00:00 -040018:23falsefull5959Lemierre’s SyndromeWelcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.

         I'm Pradip Kamat coming to you from Children’s Healthcare of Atlanta/Emory University School of Medicine

         and I'm Rahul Damania from Cleveland Clinic Children’s Hospital and we are two Pediatric ICU physicians passionate about all things MED-ED in the PICU. PICU Doc on Call focuses on interesting PICU cases & management in the acute care pediatric setting so let’s get into our episode:

         Welcome to our Episode an 18 -year old with sore throat, and unilateral L-sided neck pain for ~2 weeks.

         Here's the case presented by Rahul:

         An 18-year-old female presents to the ED with cough, fever, fatigue, sore throat, and unilateral L-sided neck pain for ~2 weeks. The patient also has been having non-specific chest pain, weight loss, and decreased appetite for ~ 1 month.

         Patient has no recent travel h/o, no h/o of vaping or illicit drug use, and there were no sick contacts at home. Vitals revealed an HR 105, BP 116/66, Temp 38.3, and respiratory rate 35, She was 65 Kg and SPO2 on 2L NC was 100%. Physical exam was negative except (L) neck tender to palpation. There was no goiter, lymphadenopathy or hepatosplenomegaly.

         An initial chest x-ray was significant for possible multi-lobar pneumonia versus metastases. A Chest CT revealed multifocal septic emboli in the lungs. Echo did not show any gross vegetation. She has no rash or any trauma to the neck or difficulty swallowing, no oral ulcers, joint pain, or diarrhea. She had no recent dental work or drinking of unpasteurized milk or eating raw fish or meat. She was admitted to the PICU as she had hypotension requiring fluid boluses, and lab works significant for hyponatremia, rhabdomyolysis, worsening AKI, elevated ferritin, and elevated D-dimer. Her serum uric acid was 9.9, LDH = 230 (normal) ,ESR 78 (normal = 20 or less). Her serum lactate and serum troponin and BNP were all normal. Pertinently, US neck revealed an occlusive thrombus in the (L) IJ vein (done so as to avoid contrast in face of AKI), and blood cultures sent.

         To summarize key elements from this case, this 18-year-old female presents with

         • fever +cough+sore throat
         • Fatigue + Weight loss
         • (L) neck pain
         • Hypotension with abnormal labs including a concerning WBC with (L) shift, anemia, AKI, elevated uric acid, and ESR
         • Chest CT with possible pulmonary emboli
         • US showing occlusion.
         • All of which brings up a concern for possible malignancy or pulmonary emboli from a septic focus in the neck and a possible diagnosis of Lemierre syndrome
         • This episode will be organized…
         • Definition
         • Diagnosis (physical, laboratory)
         • Management
         • Rahul: What is the definition of Lemierre’s syndrome?
         • Lemierre’s syndrome, also known as post-anginal septicemia or necrobacillosis, is characterized by bacteremia, internal jugular vein thrombophlebitis, and metastatic septic emboli secondary to acute pharyngeal infections. All of which are seen in our above case presentation. Previously called as the forgotten disease as its incidence was decreasing due to the increasing use of antibiotics especially penicillin for URI. However, recently there is an increase in Lemierre’s disease cases with decreased use of antibiotics due to antibiotic stewardship. The recent increase in Lemierre disease due to decreased antibiotic use has not been proven and remain controversial.
         • Rahul what are some of the causative organisms of Lemierre syndrome?
         • The most common causative agent of Lemierre’s syndrome is Fusobacterium necrophorum, followed by Fusobacterium nucleatum and anaerobic bacteria such as streptococci, staphylococci, and Klebsiella pneumoniae.
         • Rahul: Can you tell our listeners about the pathophysiology of Lemierre’s syndrome?
         • Lemierre syndrome can occur in health adults (more common in males in the age group of 14-24 years). Risk factors include immunocompromised patients, organisms, and environmental conditions. Lipopolysaccharides in F. necrophorum have endotoxic properties and are important virulence factors. The causative bacteria invade the pharyngeal mucosa previously weakened by preceding viral or bacterial pharyngitis, and lateral pharyngeal space, resulting in subsequent internal jugular vein septic thrombophlebitis and metastatic infections.
         • Pneumonia or pleural empyema is the most common metastatic infection in Lemierre’s syndrome. Septic syndrome co-occurring with ear, neck and pulmonary empyema is a rare emerging medical condition. Proposed routes of infection are direct invasion and lymphatic or hematogenous spread to the connective tissue and associated clinical abscess formation or distant septic embolic metastasis.
         • Once infection has reached the IJV, hematogenous spread to other sites can occur, causing various complications and ultimately death due to septic shock if antibiotics are delayed.
         • The lungs are most commonly affected in up to 85% of cases. Lung lesions commonly appear as necrotic cavitary lesions but can also present as infiltrates, pleural effusions, empyema, lung abscesses, and necrotizing mediastinitis. Epidural and brain abscesses have been as complications of Lemierre’s syndrome and presumably result from the retrograde intracranial extension of IJV thrombosis. Less common infections include: soft tissue abscesses, pyomyositis, splenic and liver abscesses, osteomyelitis, endocarditis, pericarditis, renal abscess, and brain abscess.
         • Atypical Lemierre’s syndrome involves thrombophlebitis of vessels other than the IJ. It may also involve bacteria other than Fusobacterium necrophorum or F. nucleatum.
         • To summarize, In Lemierre syndrome the disease course is usually rapid and irreversible; therefore, timely diagnosis and prompt antibiotic therapy is important. Lemierre syndrome must be suspected in any patient with acute tonsillo-pharyngitis with persistent neck pain and septic syndrome. Septic pelvic thrombophlebitis complicated by multiple septic emboli after intrauterine device insertion has been reported in adults.
         
         

         Pradip: What are some of the clinical manifestations of Lemierre Syndrome?

         In any patient deep neck infections, subsequent septicemia, thrombophlebitis of the IJV, and metastatic infections (ascending or descending septic emboli) should arouse suspicion for Lemierre's syndrome. In any ill-appearing patient with acute tonsillopharyngitis (throat pain, dysphagia, productive cough) with high fevers, malaise, and neck pain with tenderness should lead to the suspicion of Lemierres syndrome. Patients can also develop trismus. Most young people present with pharyngitis initially, but the old-aged group present with distant complications, such as empyema or brain abscess. Persistent headache with focal neurological signs should alert the clinician of Sagittal sinus venous thrombosis, brain abscess or meningitis.

         If you had to work up this patient with Lemierre syndrome what would be your diagnostic approach?

         • A good history and physical exam is very important. Any ill-appearing patient with sore throat, high fever, neck pain +tenderness should prompt further evaluation of Lemierre syndrome.
         • CBC with differential, blood cultures (aerobic and anaerobic), CRP, CMP, DIC panel should be sent.
         • Contrast-enhanced computed tomography (CT) of the neck is the imaging of choice as it detects vascular thrombosis of the IJV and other complications such as pulmonary emboli, empyema, osteomyelitis, and brain or epidural abscess. CT shows intra-luminal filling defects, thrombosis, and enhancement of the IJV along with soft tissue swelling.
         • Doppler ultrasonography although less sensitive than CT can be used especially if contrast cannot be used due to AKI (as in our case above). US will show an echogenic region within a dilated IJV or a complex mass of cystic and solid components. US can also detect clots in blood vessels. Magnetic resonance imaging has been used in specific cases to detect IJV thrombosis especially when CNS complication such as brain abscess is suspected.
         • An echocardiogram would be helpful to evaluate for intra-cardiac vegetations given septic emboli in the lungs were seen in our patient.
         
         

         If our history, physical, and diagnostic investigation led us to Lemierre syndrome as our diagnosis what would be your general management of framework?

         • The ill-appearing patient should be admitted to the PICU as the patient will require prompt attention to airway, breathing, and hemodynamics. Adequate IV access should be obtained as these patients can become hemodynamically unstable from sepsis.
         • A multidisciplinary team approach involving the PCCM, infectious disease, hematologists, and ENT physicians is warranted. After appropriate cultures are obtained - Metronidazole and beta-lactamase inhibiting agents like piperacillin-tazobactam....]]>Welcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.

           I'm Pradip Kamat coming to you from Children’s Healthcare of Atlanta/Emory University School of Medicine

           and I'm Rahul Damania from Cleveland Clinic Children’s Hospital and we are two Pediatric ICU physicians passionate about all things MED-ED in the PICU. PICU Doc on Call focuses on interesting PICU cases & management in the acute care pediatric setting so let’s get into our episode:

           Welcome to our Episode an 18 -year old with sore throat, and unilateral L-sided neck pain for ~2 weeks.

           Here's the case presented by Rahul:

           An 18-year-old female presents to the ED with cough, fever, fatigue, sore throat, and unilateral L-sided neck pain for ~2 weeks. The patient also has been having non-specific chest pain, weight loss, and decreased appetite for ~ 1 month.

           Patient has no recent travel h/o, no h/o of vaping or illicit drug use, and there were no sick contacts at home. Vitals revealed an HR 105, BP 116/66, Temp 38.3, and respiratory rate 35, She was 65 Kg and SPO2 on 2L NC was 100%. Physical exam was negative except (L) neck tender to palpation. There was no goiter, lymphadenopathy or hepatosplenomegaly.

           An initial chest x-ray was significant for possible multi-lobar pneumonia versus metastases. A Chest CT revealed multifocal septic emboli in the lungs. Echo did not show any gross vegetation. She has no rash or any trauma to the neck or difficulty swallowing, no oral ulcers, joint pain, or diarrhea. She had no recent dental work or drinking of unpasteurized milk or eating raw fish or meat. She was admitted to the PICU as she had hypotension requiring fluid boluses, and lab works significant for hyponatremia, rhabdomyolysis, worsening AKI, elevated ferritin, and elevated D-dimer. Her serum uric acid was 9.9, LDH = 230 (normal) ,ESR 78 (normal = 20 or less). Her serum lactate and serum troponin and BNP were all normal. Pertinently, US neck revealed an occlusive thrombus in the (L) IJ vein (done so as to avoid contrast in face of AKI), and blood cultures sent.

           To summarize key elements from this case, this 18-year-old female presents with

           • fever +cough+sore throat
           • Fatigue + Weight loss
           • (L) neck pain
           • Hypotension with abnormal labs including a concerning WBC with (L) shift, anemia, AKI, elevated uric acid, and ESR
           • Chest CT with possible pulmonary emboli
           • US showing occlusion.
           • All of which brings up a concern for possible malignancy or pulmonary emboli from a septic focus in the neck and a possible diagnosis of Lemierre syndrome
           • This episode will be organized…
           • Definition
           • Diagnosis (physical, laboratory)
           • Management
           • Rahul: What is the definition of Lemierre’s syndrome?
           • Lemierre’s syndrome, also known as post-anginal septicemia or necrobacillosis, is characterized by bacteremia, internal jugular vein thrombophlebitis, and metastatic septic emboli secondary to acute pharyngeal infections. All of which are seen in our above case presentation. Previously called as the forgotten disease as its incidence was decreasing due to the increasing use of antibiotics especially penicillin for URI. However, recently there is an increase in Lemierre’s disease cases with decreased use of antibiotics due to antibiotic stewardship. The recent increase in Lemierre disease due to decreased antibiotic use has not been proven and remain controversial.
           • Rahul what are some of the causative organisms of Lemierre syndrome?
           • The most common causative agent of Lemierre’s syndrome is Fusobacterium necrophorum, followed by Fusobacterium nucleatum and anaerobic bacteria such as streptococci, staphylococci, and Klebsiella pneumoniae.
           • Rahul: Can you tell our listeners about the pathophysiology of Lemierre’s syndrome?
           • Lemierre syndrome can occur in health adults (more common in males in the age group of 14-24 years). Risk factors include immunocompromised patients, organisms, and environmental conditions. Lipopolysaccharides in F. necrophorum have endotoxic properties and are important virulence factors. The causative bacteria invade the pharyngeal mucosa previously weakened by preceding viral or bacterial pharyngitis, and lateral pharyngeal space, resulting in subsequent internal jugular vein septic thrombophlebitis and metastatic infections.
           • Pneumonia or pleural empyema is the most common metastatic infection in Lemierre’s syndrome. Septic syndrome co-occurring with ear, neck and pulmonary empyema is a rare emerging medical condition. Proposed routes of infection are direct invasion and lymphatic or hematogenous spread to the connective tissue and associated clinical abscess formation or distant septic embolic metastasis.
           • Once infection has reached the IJV, hematogenous spread to other sites can occur, causing various complications and ultimately death due to septic shock if antibiotics are delayed.
           • The lungs are most commonly affected in up to 85% of cases. Lung lesions commonly appear as necrotic cavitary lesions but can also present as infiltrates, pleural effusions, empyema, lung abscesses, and necrotizing mediastinitis. Epidural and brain abscesses have been as complications of Lemierre’s syndrome and presumably result from the retrograde intracranial extension of IJV thrombosis. Less common infections include: soft tissue abscesses, pyomyositis, splenic and liver abscesses, osteomyelitis, endocarditis, pericarditis, renal abscess, and brain abscess.
           • Atypical Lemierre’s syndrome involves thrombophlebitis of vessels other than the IJ. It may also involve bacteria other than Fusobacterium necrophorum or F. nucleatum.
           • To summarize, In Lemierre syndrome the disease course is usually rapid and irreversible; therefore, timely diagnosis and prompt antibiotic therapy is important. Lemierre syndrome must be suspected in any patient with acute tonsillo-pharyngitis with persistent neck pain and septic syndrome. Septic pelvic thrombophlebitis complicated by multiple septic emboli after intrauterine device insertion has been reported in adults.
           
           

           Pradip: What are some of the clinical manifestations of Lemierre Syndrome?

           In any patient deep neck infections, subsequent septicemia, thrombophlebitis of the IJV, and metastatic infections (ascending or descending septic emboli) should arouse suspicion for Lemierre's syndrome. In any ill-appearing patient with acute tonsillopharyngitis (throat pain, dysphagia, productive cough) with high fevers, malaise, and neck pain with tenderness should lead to the suspicion of Lemierres syndrome. Patients can also develop trismus. Most young people present with pharyngitis initially, but the old-aged group present with distant complications, such as empyema or brain abscess. Persistent headache with focal neurological signs should alert the clinician of Sagittal sinus venous thrombosis, brain abscess or meningitis.

           If you had to work up this patient with Lemierre syndrome what would be your diagnostic approach?

           • A good history and physical exam is very important. Any ill-appearing patient with sore throat, high fever, neck pain +tenderness should prompt further evaluation of Lemierre syndrome.
           • CBC with differential, blood cultures (aerobic and anaerobic), CRP, CMP, DIC panel should be sent.
           • Contrast-enhanced computed tomography (CT) of the neck is the imaging of choice as it detects vascular thrombosis of the IJV and other complications such as pulmonary emboli, empyema, osteomyelitis, and brain or epidural abscess. CT shows intra-luminal filling defects, thrombosis, and enhancement of the IJV along with soft tissue swelling.
           • Doppler ultrasonography although less sensitive than CT can be used especially if contrast cannot be used due to AKI (as in our case above). US will show an echogenic region within a dilated IJV or a complex mass of cystic and solid components. US can also detect clots in blood vessels. Magnetic resonance imaging has been used in specific cases to detect IJV thrombosis especially when CNS complication such as brain abscess is suspected.
           • An echocardiogram would be helpful to evaluate for intra-cardiac vegetations given septic emboli in the lungs were seen in our patient.
           
           

           If our history, physical, and diagnostic investigation led us to Lemierre syndrome as our diagnosis what would be your general management of framework?

           • The ill-appearing patient should be admitted to the PICU as the patient will require prompt attention to airway, breathing, and hemodynamics. Adequate IV access should be obtained as these patients can become hemodynamically unstable from sepsis.
           • A multidisciplinary team approach involving the PCCM, infectious disease, hematologists, and ENT physicians is warranted. After appropriate cultures are obtained - Metronidazole and beta-lactamase inhibiting agents like piperacillin-tazobactam. Ceftriaxone or a carbapenem. Metronidazole is bactericidal; it shows excellent penetration into most tissues including the cerebrospinal fluid.
           • If IJV suppuration is due to an infected CVL and not a complication of pharyngitis- consideration should be given to the initiation of vancomycin.
           • Antibiotic therapy should be continued for at least 3-6 weeks. Once the infection is controlled, therapy can be completed orally. The initial clinical response may be slow as Lemierre syndrome is an endovascular infection and antibiotics may have difficulty penetrating the fibrin clot. Pleural effusion or abscess drainage may be required in selected cases.
           • Another important aspect of therapy is the use of anticoagulant therapy with heparin. Anticoagulation plays a part in preventing septic embolic events originating from IJV thrombosis. We typically start low molecular weight heparin such as Lovenox 1mg/kg sc BID with a goal heparin assay of 0.5-1 (done 4 hours after 2nd or 3rd dose). Lovenox dose needs adjustment in AKI.
           • Fusobacterium necrophorum is intrinsically resistant to macrolides, fluoroquinolones, tetracyclines, and aminoglycosides. Fusobacterium necrophorum is resistant to Pn G due to the production of penicillinase.
           
           

           
           

           Rahul, what are some clinical pearls or pitfalls to avoid?

           • Suspect Lemierre syndrome in any ill-appearing patient presenting with high fevers, sore throat, and neck pain with tenderness.
           • Once septic thrombophlebitis has occurred, complications should be evaluated including descending or ascending infections, such as pneumonia, empyema, or brain abscess.
           • CT scan of the neck with IV contrast is the study of choice
           • Initiate antibiotics early after a blood culture with metronidazole and a beta-lactamase inhibiting antibiotics such as ceftriaxone, piperacillin-tazobactam, or carbapenem such as meropenem
           • anticoagulation therapy with low molecular weight heparin should be considered in consultation with hematology.
           
           

           This concludes our episode on Lemierre syndrome. We hope you found value in our short, case-based podcast. We welcome you to share your feedback, subscribe & place a review on our podcast! Please visit our website picudoconcall.org which showcases our episodes as well as our Doc on Call management cards. PICU Doc on Call is co-hosted by myself Dr. Pradip Kamat and Dr. Rahul Damania. Stay tuned for our next episode! Thank you!

           References

           • Fuhrman & Zimmerman - Textbook of Pediatric Critical Care Chapter 107: Franzon D et al. Bacterial and Fungal Infections. page 1265
           • Reference 1: Lee WS, Jean SS, Chen FL, Hsieh SM, Hsueh PR. Lemierre's syndrome: A forgotten and re-emerging infection. J Microbiol Immunol Infect. 2020 Aug;53(4):513-517. doi: 10.1016/j.jmii.2020.03.027. Epub 2020 Apr 4. PMID: 32303484.
           • Reference 2: Walkty A, Embil J. Lemierre's Syndrome. N Engl J Med. 2019 Mar 21;380(12):e16. doi: 10.1056/NEJMicm1808378. PMID: 30893539.
           
           

           
           

           
           

           ]]>9e79cb8b-992a-4597-8e89-9b8b87cd6cd9Sun, 17 Jul 2022 03:00:00 -040016:05falsefull5858Pulmonary HemorrhageWelcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.

           Welcome to our Episode a 16-year-old who is coughing up blood.

           Here's the case:

           A 16-year-old female with h/o SLE was transferred to the PICU due to hypoxia requiring increasing FIO2. A few hours prior to admission to the PICU patient also started coughing up blood and had difficulty breathing. The patient was admitted to the general pediatric floor 2 days earlier for pneumonia requiring an IV antibiotic and O2 via NC. Once transferred to the PICU, she had a rapid deterioration with progressive hematemesis, worsening respiratory distress, and saturations in the low 70s requiring escalating FIO2. The patient was emergently intubated using ketamine + fentanyl and rocuronium. Chest radiograph showed: Worsening bibasilar alveolar and interstitial airspace disease concerning pulmonary hemorrhage. The patient was initially placed on HFOV Paw 26, FIO2 70%, Hz 8, Dp 70, and later transitioned to airway pressure release ventilation or APRV. The patient was also started on inhaled tranexamic acid or TXA and high-dose pulse steroids. The patient initially continued to have some blood coming out from the ETT with suctioning but secretions became clear in ~24 hours.

           The mother reported that the patient has never had hematemesis/hemoptysis before, or bleeding from any site in the past. Denied history of frequent respiratory infections or recent URI symptoms. The patient has been vaccinated/boosted x3 vs covid. Her COVID PCR is negative. The mother states that she does not engage in tobacco products or alcohol.

           A physical exam revealed a well-developed teenage girl laying supine in bed deeply sedated and mechanically ventilated. There was decreased AE at lung bases and coarse breath sounds throughout. There was no hepatosplenomegaly and exams of the heart, abdomen and other systems were normal. There was no skin rash and extremities were well perfused with no clubbing in the fingers. The pulmonary team was consulted and a workup was started for pulmonary hemorrhage.

           To summarize key elements from this case, this patient has:

           • Autoimmune disease: Systemic lupus erythematosus
           • Respiratory Failure warranting MV 2/2 Pulmonary hemorrhage
           • Her presentation and deterioration bring up a concern for diffuse alveolar hemorrhage our topic of discussion for today.
           • This episode will be organized…
           • Definition
           • Etiology
           • Pathophysiology
           • Diagnosis
           • Management
           • Rahul: How do we define pulmonary hemorrhage (PH):
           • PH is defined as the extravasation of blood into airways and/or lung parenchyma. Blood in the airways produces a diffusion barrier resulting in hypoxemia. Due to the reduction of airway diameter from accumulated blood, there is increased airway resistance and even airway obstruction. Subsequently, ventilation can be impaired leading to increased WOB as well as myocardial work required for O2 delivery. Repeated episodes of PH can result in interstitial fibrosis thus changing lung compliance. Hemoptysis by definition is any bleeding from below the vocal cords. PH can be classified as focal or diffuse. Diffuse is further classified as diffuse immune or diffuse nonimmune.
           
           

           Loss of 10% of a patient’s circulating blood volume into the lungs, regardless of age, causes a significant alteration in cardiorespiratory function and should be considered massive. In adults, massive pulmonary hemorrhage is defined as blood loss of 600mL or more in 24 hours. In infants, the involvement of at least two pulmonary lobes by confluent foci of extravasated RBCs constitutes as massive PH. “Enough bleeding to make one nervous is probably massive.”

           Let's pivot and talk about etiologies.

           • Pradip, What are some of the causes of pulmonary hemorrhage in the PICU?
           • Non-immune diffuse PH is usually seen in patients with congenital heart disease (TAPVR, pulmonary atresia, mitral stenosis, hypoplastic left heart syndrome to name a few) neonates (secondary to sepsis, HIE, BW < 1500 gms, persistent pulmonary hypertension) and due to coagulopathy. bronchiectasis, infections such as TB, mycetomas are also important causes of PH. Cocaineas and vaping (typically adulterated with other substances) are also important toxic causes of DAH.
           • Diffuse PH due to immune causes includes pulmonary-renal syndromes (good pastures, Wegener granulomatosis, SLE, anti-phospholipid syndrome PAN, HSP), drug-induced vasculitis (PTU, methimazole, hydralazine, and minocycline) and infections such as hantavirus, CMV, legionella, etc. Lupus and PAN account for the majority of the vasculitis resulting in PH.
           • Focal PH: FB aspiration with chronic retention, pulmonary sequestration, AV fistula, thrombus or embolus, and neoplasms.
           • Idiopathic pulmonary hemosiderosis a diagnosis of exclusion presents with the triad of hemoptysis, microcytic hypochromic anemia, and diffuse alveolar-filling opacities. Nonspecific lung injury not attributed to vasculitis or immune deposits is noted on microscopic examination.
           
           

           Alright to summarize diffuse pulmonary hemorrhage — think about non-immune causes secondary to heart disease and immune causes secondary to rheumatologic conditions. Our patient in our case likely had immune-mediated PH.

           Let's conclude our episode by going through diagnostics and management.

           • If you had to work up this patient with PH, what would be your diagnostic approach?
           • We can start with a chest radiograph. Typically in PH, you can see ground-glass diffuse opacities or consolidations; sometimes a mosaic-type perfusion pattern can indicate a true arteriolar vasculitis. In some patients, the chest radiograph can be normal. High Resolution Computed tomography(HRCT) has higher sensitivity and the classic features include ground-glass opacities in a random distribution.
           • Bronchoscopy and bronchoalveolar lavage (BAL) are other diagnostic tools. In bronchoalveolar lavage, the pathologist must search for hemosiderin-laden macrophages, which usually appear 24–48 h after the DAH has started. The presence of >5% of hemosiderin-laden macrophages highly suggests the presence of blood from DAH.
           • Echocardiogram
           • Labs: Blood gas, CMP, CBC, Coagulation panel, ESR, CRP, specific auto-antibodies (consult with renal or rheumatology colleagues). Urine analysis, In some rare cases a biopsy (skin, lung, or kidney) may be needed in pulmonary-renal syndromes.
           
           

           I would also highly recommend a collaborative approach with pulmonary specialists, rheumatologists, intensivists, and hematology.

           • If our history, physical, and diagnostic investigation led us to PH as our diagnosis what would be your general management framework?
           • Initially, we must focus on basic PICU care with maintenance of airway and oxygenation/ventilation as well as hemodynamic stability. O2 supplementation EVEN mechanical ventilation may be required; Prior to intubation placement of the patient in Trendelenburg position (which helps clots exit the airway) may be helpful. PEEP should be increased on conventional ventilation for tamponade effect as well as help with hypoxemia. We typically use HFOV with deep sedation +/- chemical paralysis or APRV mode on a conventional ventilator. It is important to correct any coagulation factor deficiency as well as transfuse platelets or pRBCs as needed.
           • Increased PEEP, HFOV, and APRV all create increased mean airway pressure which not only has a local tamponade but increases intrathoracic pressure to decrease preload and downstream pulmonary hydrostatic pressure.
           
           

           
           

           What are some other modalities used in DAH?

           
           

           • Endobronchial tamponade (Fogarty catheter, cuffed endotracheal tube) can be tried if bleeding is restricted to a segment of a particular lung. Right upper lobe bleeding is best managed by intubating the left main stem bronchus with a cuffed endotracheal tube and inflating the cuff of the tube. Utilization of a double-lumen or Carlens-type endotracheal tube may also be helpful in isolating the bleeding segment. Consult with anesthesia colleagues may be helpful in the management of such patients.
           • There may be a role for rigid bronchoscopy to identify the source and type of bleeding. Rigid Bronchoscopy can also be used for large volume lavage as well as suctioning of blood and even control the source of bleeding. The help of general or cardiothoracic surgery colleagues is invaluable in such patients. For focal PH- surgical resection of the involved segment or selective embolization of bronchial vessels may be needed.
           • What about medical management?
           • Specific pulmonary-renal syndromes can be treated using corticosteroids and other immunosuppressive agents. Plasmapheresis is an option for Good Pastures syndrome. High-dose methylprednisolone (30mg/kg or 1gm daily X 3 days followed by slow taper) is typically used in diffuse immune-mediated PH. Cyclophosphamide is the drug of choice for the treatment of patients with Wegener granulomatosis
           • Are there any therapeutics on the horizon?
           • One study by O’Neil et al in Crit Care Explor 2020 reported the use of Inhaled Tranexamic Acid As a Novel Treatment for Pulmonary Hemorrhage in Critically Ill Pediatric Patients-Cessation of pulmonary hemorrhage was achieved in 18 of 19 patients (95%) with inhaled tranexamic acid with no major adverse events recorded. The study also reported that other variables such as oxygenation and coagulation were not affected by the use of inhaled TXA in our study. Additionally, they reported that the patients received significantly less blood product after receiving inhaled...]]>Welcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.

             Welcome to our Episode a 16-year-old who is coughing up blood.

             Here's the case:

             A 16-year-old female with h/o SLE was transferred to the PICU due to hypoxia requiring increasing FIO2. A few hours prior to admission to the PICU patient also started coughing up blood and had difficulty breathing. The patient was admitted to the general pediatric floor 2 days earlier for pneumonia requiring an IV antibiotic and O2 via NC. Once transferred to the PICU, she had a rapid deterioration with progressive hematemesis, worsening respiratory distress, and saturations in the low 70s requiring escalating FIO2. The patient was emergently intubated using ketamine + fentanyl and rocuronium. Chest radiograph showed: Worsening bibasilar alveolar and interstitial airspace disease concerning pulmonary hemorrhage. The patient was initially placed on HFOV Paw 26, FIO2 70%, Hz 8, Dp 70, and later transitioned to airway pressure release ventilation or APRV. The patient was also started on inhaled tranexamic acid or TXA and high-dose pulse steroids. The patient initially continued to have some blood coming out from the ETT with suctioning but secretions became clear in ~24 hours.

             The mother reported that the patient has never had hematemesis/hemoptysis before, or bleeding from any site in the past. Denied history of frequent respiratory infections or recent URI symptoms. The patient has been vaccinated/boosted x3 vs covid. Her COVID PCR is negative. The mother states that she does not engage in tobacco products or alcohol.

             A physical exam revealed a well-developed teenage girl laying supine in bed deeply sedated and mechanically ventilated. There was decreased AE at lung bases and coarse breath sounds throughout. There was no hepatosplenomegaly and exams of the heart, abdomen and other systems were normal. There was no skin rash and extremities were well perfused with no clubbing in the fingers. The pulmonary team was consulted and a workup was started for pulmonary hemorrhage.

             To summarize key elements from this case, this patient has:

             • Autoimmune disease: Systemic lupus erythematosus
             • Respiratory Failure warranting MV 2/2 Pulmonary hemorrhage
             • Her presentation and deterioration bring up a concern for diffuse alveolar hemorrhage our topic of discussion for today.
             • This episode will be organized…
             • Definition
             • Etiology
             • Pathophysiology
             • Diagnosis
             • Management
             • Rahul: How do we define pulmonary hemorrhage (PH):
             • PH is defined as the extravasation of blood into airways and/or lung parenchyma. Blood in the airways produces a diffusion barrier resulting in hypoxemia. Due to the reduction of airway diameter from accumulated blood, there is increased airway resistance and even airway obstruction. Subsequently, ventilation can be impaired leading to increased WOB as well as myocardial work required for O2 delivery. Repeated episodes of PH can result in interstitial fibrosis thus changing lung compliance. Hemoptysis by definition is any bleeding from below the vocal cords. PH can be classified as focal or diffuse. Diffuse is further classified as diffuse immune or diffuse nonimmune.
             
             

             Loss of 10% of a patient’s circulating blood volume into the lungs, regardless of age, causes a significant alteration in cardiorespiratory function and should be considered massive. In adults, massive pulmonary hemorrhage is defined as blood loss of 600mL or more in 24 hours. In infants, the involvement of at least two pulmonary lobes by confluent foci of extravasated RBCs constitutes as massive PH. “Enough bleeding to make one nervous is probably massive.”

             Let's pivot and talk about etiologies.

             • Pradip, What are some of the causes of pulmonary hemorrhage in the PICU?
             • Non-immune diffuse PH is usually seen in patients with congenital heart disease (TAPVR, pulmonary atresia, mitral stenosis, hypoplastic left heart syndrome to name a few) neonates (secondary to sepsis, HIE, BW < 1500 gms, persistent pulmonary hypertension) and due to coagulopathy. bronchiectasis, infections such as TB, mycetomas are also important causes of PH. Cocaineas and vaping (typically adulterated with other substances) are also important toxic causes of DAH.
             • Diffuse PH due to immune causes includes pulmonary-renal syndromes (good pastures, Wegener granulomatosis, SLE, anti-phospholipid syndrome PAN, HSP), drug-induced vasculitis (PTU, methimazole, hydralazine, and minocycline) and infections such as hantavirus, CMV, legionella, etc. Lupus and PAN account for the majority of the vasculitis resulting in PH.
             • Focal PH: FB aspiration with chronic retention, pulmonary sequestration, AV fistula, thrombus or embolus, and neoplasms.
             • Idiopathic pulmonary hemosiderosis a diagnosis of exclusion presents with the triad of hemoptysis, microcytic hypochromic anemia, and diffuse alveolar-filling opacities. Nonspecific lung injury not attributed to vasculitis or immune deposits is noted on microscopic examination.
             
             

             Alright to summarize diffuse pulmonary hemorrhage — think about non-immune causes secondary to heart disease and immune causes secondary to rheumatologic conditions. Our patient in our case likely had immune-mediated PH.

             Let's conclude our episode by going through diagnostics and management.

             • If you had to work up this patient with PH, what would be your diagnostic approach?
             • We can start with a chest radiograph. Typically in PH, you can see ground-glass diffuse opacities or consolidations; sometimes a mosaic-type perfusion pattern can indicate a true arteriolar vasculitis. In some patients, the chest radiograph can be normal. High Resolution Computed tomography(HRCT) has higher sensitivity and the classic features include ground-glass opacities in a random distribution.
             • Bronchoscopy and bronchoalveolar lavage (BAL) are other diagnostic tools. In bronchoalveolar lavage, the pathologist must search for hemosiderin-laden macrophages, which usually appear 24–48 h after the DAH has started. The presence of >5% of hemosiderin-laden macrophages highly suggests the presence of blood from DAH.
             • Echocardiogram
             • Labs: Blood gas, CMP, CBC, Coagulation panel, ESR, CRP, specific auto-antibodies (consult with renal or rheumatology colleagues). Urine analysis, In some rare cases a biopsy (skin, lung, or kidney) may be needed in pulmonary-renal syndromes.
             
             

             I would also highly recommend a collaborative approach with pulmonary specialists, rheumatologists, intensivists, and hematology.

             • If our history, physical, and diagnostic investigation led us to PH as our diagnosis what would be your general management framework?
             • Initially, we must focus on basic PICU care with maintenance of airway and oxygenation/ventilation as well as hemodynamic stability. O2 supplementation EVEN mechanical ventilation may be required; Prior to intubation placement of the patient in Trendelenburg position (which helps clots exit the airway) may be helpful. PEEP should be increased on conventional ventilation for tamponade effect as well as help with hypoxemia. We typically use HFOV with deep sedation +/- chemical paralysis or APRV mode on a conventional ventilator. It is important to correct any coagulation factor deficiency as well as transfuse platelets or pRBCs as needed.
             • Increased PEEP, HFOV, and APRV all create increased mean airway pressure which not only has a local tamponade but increases intrathoracic pressure to decrease preload and downstream pulmonary hydrostatic pressure.
             
             

             
             

             What are some other modalities used in DAH?

             
             

             • Endobronchial tamponade (Fogarty catheter, cuffed endotracheal tube) can be tried if bleeding is restricted to a segment of a particular lung. Right upper lobe bleeding is best managed by intubating the left main stem bronchus with a cuffed endotracheal tube and inflating the cuff of the tube. Utilization of a double-lumen or Carlens-type endotracheal tube may also be helpful in isolating the bleeding segment. Consult with anesthesia colleagues may be helpful in the management of such patients.
             • There may be a role for rigid bronchoscopy to identify the source and type of bleeding. Rigid Bronchoscopy can also be used for large volume lavage as well as suctioning of blood and even control the source of bleeding. The help of general or cardiothoracic surgery colleagues is invaluable in such patients. For focal PH- surgical resection of the involved segment or selective embolization of bronchial vessels may be needed.
             • What about medical management?
             • Specific pulmonary-renal syndromes can be treated using corticosteroids and other immunosuppressive agents. Plasmapheresis is an option for Good Pastures syndrome. High-dose methylprednisolone (30mg/kg or 1gm daily X 3 days followed by slow taper) is typically used in diffuse immune-mediated PH. Cyclophosphamide is the drug of choice for the treatment of patients with Wegener granulomatosis
             • Are there any therapeutics on the horizon?
             • One study by O’Neil et al in Crit Care Explor 2020 reported the use of Inhaled Tranexamic Acid As a Novel Treatment for Pulmonary Hemorrhage in Critically Ill Pediatric Patients-Cessation of pulmonary hemorrhage was achieved in 18 of 19 patients (95%) with inhaled tranexamic acid with no major adverse events recorded. The study also reported that other variables such as oxygenation and coagulation were not affected by the use of inhaled TXA in our study. Additionally, they reported that the patients received significantly less blood product after receiving inhaled TXA.
             • How does TXA work and what are the applications clinically?
             • Tranexamic acid (TXA) is a lysine analog that blocks the conversion of plasminogen to plasmin and inhibits binding of plasmin to fibrin which stabilizes the fibrin matrix, thereby reducing bleeding. Systemic TXA, however, may be associated with serious complications including venous thromboembolism, neurotoxicity, and seizures. In our patients, we use inhaled or endotracheally instilled TXA (250-500mg of 100mg/ml solution) every 6 hours. Nebulization is done over 15-20minutes and can be delivered in line during mechanical ventilation. Dosing frequency was subsequently decreased based on patients’ responses.
             
             

             Rahul, can you summarize today's episode on DAH:

             Diffuse alveolar hemorrhage is a medical emergency. 33% can present without hemoptysis. Along with clinical findings of cough, hemoptysis, and dyspnea the presence of hemosiderin-laden macrophages confirms the diagnosis of pulmonary hemorrhage. Protecting the airway and optimizing oxygenation/ventilation is the most important part of management. Then identify and stop the offending agent if possible and administer treatments accordingly.

             This concludes our episode on a pulmonary hemorrhage. We hope you found value in our short, case-based podcast. We welcome you to share your feedback, subscribe & place a review on our podcast! Please visit our website picudoconcall.org which showcases our episodes as well as our Doc on Call management cards. PICU Doc on Call is co-hosted by myself Dr. Pradip Kamat and Dr. Rahul Damania. Stay tuned for our next episode! Thank you!

             
             

             References

             • Fuhrman & Zimmerman - Textbook of Pediatric Critical Care 6th edition. Chapter 52: Pneumonitis and interstitial Disease. Parakininkas D. Pages 603-607
             • Reference 1: Martínez-Martínez MU, Oostdam DAH, Abud-Mendoza C. Diffuse Alveolar Hemorrhage in Autoimmune Diseases. Curr Rheumatol Rep. 2017 May;19(5):27. doi: 10.1007/s11926-017-0651-y. PMID: 28397125.
             • Reference 2: States LJ, Fields JM. Pulmonary hemorrhage in children. Semin Roentgenol. 1998 Apr;33(2):174-86. doi: 10.1016/s0037-198x(98)80021-7. PMID: 9583112.
             
             ]]>f3c2fd4b-4e96-4502-b35e-dc9c42194d7fSun, 10 Jul 2022 03:00:00 -040017:21falsefull5757Approach to Acid Base DisordersWelcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.

             I'm Pradip Kamat coming to you from Children’s Healthcare of Atlanta/Emory University School of Medicine

             and I'm Rahul Damania from Cleveland Clinic Children’s Hospital. We are two Pediatric ICU physicians passionate about all things MED-ED in the PICU. PICU Doc on Call focuses on interesting PICU cases & management in the acute care pediatric setting so let’s get into our episode:

             In today's episode, we discuss about a 12-year-old male with lethargy after ingestion.

             Here's the case presented by Rahul:

             A 12-year-old male is found unresponsive at home. He was previously well and has no relevant past medical history. The mother states that he was recently in an argument with his sister and thought he was going into his room to “have some space.” The mother noticed the patient was in his room for about 1 hour. After coming into the room she noticed him drooling, minimally responsive, and cold to the touch. The patient was noted to be moaning in pain pointing to his abdomen and breathing fast. Dark red vomitus was surrounding the patient. The mother called 911 as she was concerned about his neurological state. With 911 on the way, the mother noticed a set of empty vitamins next to the patient. She noted that these were the iron pills the patient’s sister was on for anemia. EMS arrives for acute stabilization, and the patient is brought to the ED. En route, serum glucose was normal. The patient presents to the ED with hypothermia, tachycardia, tachypnea, and hypertension. His GCS is 8, he has poor peripheral perfusion and a diffusely tender abdomen. He continues to have hematemesis and is intubated for airway protection along with declining neurological status. After resuscitation, he presents to the Pediatric ICU. Upon intubation, an arterial blood gas is drawn. His pH is 7.22/34/110/-6 — serum HCO3 is 16, and his AG is elevated.

             To summarize key elements from this case, this patient has:

             • Lethargy and unresponsiveness after acute ingestion.
             • His hematemesis is most likely related to his acute ingestion.
             • And finally, he has an anion gap metabolic acidosis, as evidenced by his low pH and low HCO3.
             • All of these salient factors bring up the concern for acute iron ingestion! In today’s episode, we will not only go through acute management pearls for iron poisoning, but also go back to the fundamentals, and cover ACID BASE disorders.
             • We will break this episode down into giving a broad overview of acid base, build a stepwise approach, and apply our knowledge with integrated cases.
             
             

             We will use a physiologic approach to cover this topic!

             • Pradip, can you give us a quick overview of some general principles when it comes to tackling this high-yield critical care topic?
             • Absolutely, internal acid base homeostasis is paramount for maintaining life. Moreover, we know that accurate and timely interpretation of an acid–base disorder can be lifesaving.
             • When we conceptualize acid base today, we will focus on pH, HCO3, and CO2.
             • As we go into each disorder keep in mind to always correlate your interpretation of blood gasses to the clinical status of the patient.
             • Going back to basic chemistry, can you comment on the relationship between CO2 and HCO3?
             • Yes, now this is a throwback. However, we have to review the Henderson–Hasselbalch equation. The equation has constants & logs involved, however in general this equation shows that the pH is determined by the ratio of the serum bicarbonate (HCO3) concentration and the PCO2, not by the value of either one alone. In general, an acid–base disorder is called “respiratory” when it is caused by a primary abnormality in respiratory function (i.e., a change in the PaCO2) and “metabolic” when the primary change is attributed to a variation in the bicarbonate concentration.
             • Now that we have some fundamentals down, let’s move into definitions. Can you define acidemia and alkalemia and comment on how the sampling sites may vary these definitions?
             • Acidemia is defined as an arterial pH below 7.35.
             • Alkalemia is defined as an arterial pH above 7.45.
             • Thus, normal pH range for an arterial blood gas is 7.35 to 7.45.
             • Bicarbonate (HCO3) concentration, 21 to 27 mEq/L; and for PCO2, 35 to 45 mmHg.
             • What about the venous side?
             • Normal values for peripheral venous blood gases differ from those of arterial blood due to the uptake and buffering of metabolically produced CO2 in the capillary circulation and the addition of organic acids produced by the tissue bed drained by the vein.
             • The range for peripheral venous pH is approximately 0.03 to 0.04 pH units lower than in arterial blood, the HCO3 concentration is approximately 2 to 3 mEq/L higher, and the PCO2 is approximately 3 to 8 mmHg (0.4 to 1.1 kPa) higher.
             
             

             These subtleties are important physiological considerations as you trend blood gasses. For example, if you have a venous blood gas of 7.32, on the arterial side, it may be correlated to 7.35. Similarly on the venous side if you have a CO2 of 48, on the arterial side, this value may be about 5 mmHg lower, so around 43.

             Rahul, we mentioned that prior to chasing gasses, it is important to assess the patient’s clinical state. Can you comment on this a bit further?

             Yes, so the key here is that various signs and symptoms often provide clues regarding the underlying acid–base disorder; these include the patient’s vital signs (which may indicate shock or sepsis), neurologic state, pulmonary status (respiratory rate and presence or absence of Kussmaul respiration), and gastrointestinal symptoms (vomiting and diarrhea). We saw some of these in our case. We should also take into account any medications that affect acid–base balance in our assessment of acute acid-base changes. Relevant medications include laxatives, diuretics, topiramate, etc. Also, watch for specific ingestions such as methanol for example which can cause blindness.

             As we dive into the various disorders, can you frame an approach to acid base blood gas interpretation?

             Here are 3 steps:

             Establish the primary acid base abnormality — are we dealing with an acidemia or alkalemia.Establish what value correlates with the primary acid base disorder:

             CO2 HCO3

             For example, when you diagnose an acidemia, a metabolic acidosis is characterized by a low serum HCO3. Also, it is important to note for each 10 mmHg pCO2, pH falls by 0.08 units.

             Assess for compensation:

             • For example, in a metabolic alkalosis, your lungs will compensate by increasing your CO2 via hypoventilation.
             • Please note that renal compensation may take 24-48 hours after your initial respiratory acidosis/alkalosis.
             
             

             Yes, I think this point of compensation is important to note especially when assessing for mixed disorders. If we take for example an acute respiratory acidosis, the normal compensatory response to acute respiratory acidosis is an increase in the serum HCO3 concentration by approximately 1 mEq/L for every 10 mmHg elevation in the PCO2. When the respiratory acidosis persists for more than three to five days, the HCO3 increases by approximately 3.5 to 5 mEq/L for every 10 mmHg elevation in the PCO2.

             Important to note, with the exception of chronic respiratory alkalosis and mild to moderate respiratory acidosis compensatory responses do not usually return the arterial pH to normal.

             Yes, in fact, in contrast with older data, data from more recent studies indicate that the pH in chronic respiratory acidosis may be normal and, in individual cases, higher than generally recognized (pH >7.40).

             Let’s revisit our index case to review the acid base disturbance. Do you mind refreshing our memory on his initial ABG?

             • pH 7.22/34/110/-6 — serum HCO3 was 16 meQ/L.
             
             

             
             

             Rahul, take us through the step-wise approach:

             1. Acidemia as evidenced by a low pH of 7.22
             2. What supports an acidemia is a low bicarbonate so we can say it is metabolic
             3. And in the case of a metabolic acidosis it is important for us to assess the degree of compensation using winter’s formula.
             
             

             What is Winter’s formula?

             • PaCO2 = 1.5 × [HCO3−] + 8±2 mm Hg
             • In this case, our expected CO2 given our Bicarb is 16 would be 30-34, and our patient’s was 34, so this is a true metabolic acidosis.
             
             

             The patient had an anion gap metabolic acidosis, can you tell us a bit more about what is the anion gap?

             • Disorders that produce metabolic acidosis by increasing organic acid generation like in the case of ingestion or cases with increased accumulation of phosphoric and sulfuric acid such as severe chronic kidney disease can usually result in an increased serum anion gap.
             • The anion gap can conceptually be understood as Na + All unmeasured cations  =  Cl + HCO3 + All unmeasured anions. In general it the is positives minus negatives, and clinically we simplify this as. Na - (Cl + HCO3), normal is 8-12. If the anion gap is elevated, we recognize that this is some organic acid that is creating a gap between positives and negatives.
             
             

             Now Rahul, let's say we have a patient with hypoalbuminemia, would this affect the anion gap?

             • Yes, it definitely can in healthy individuals, the major unmeasured anion responsible for the existence of a serum anion gap is albumin.
             • This circulating protein has a significant net negative charge in the physiologic pH range. As a result, the expected baseline value for the anion gap must be adjusted downward in patients with...]]>Welcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.

               I'm Pradip Kamat coming to you from Children’s Healthcare of Atlanta/Emory University School of Medicine

               and I'm Rahul Damania from Cleveland Clinic Children’s Hospital. We are two Pediatric ICU physicians passionate about all things MED-ED in the PICU. PICU Doc on Call focuses on interesting PICU cases & management in the acute care pediatric setting so let’s get into our episode:

               In today's episode, we discuss about a 12-year-old male with lethargy after ingestion.

               Here's the case presented by Rahul:

               A 12-year-old male is found unresponsive at home. He was previously well and has no relevant past medical history. The mother states that he was recently in an argument with his sister and thought he was going into his room to “have some space.” The mother noticed the patient was in his room for about 1 hour. After coming into the room she noticed him drooling, minimally responsive, and cold to the touch. The patient was noted to be moaning in pain pointing to his abdomen and breathing fast. Dark red vomitus was surrounding the patient. The mother called 911 as she was concerned about his neurological state. With 911 on the way, the mother noticed a set of empty vitamins next to the patient. She noted that these were the iron pills the patient’s sister was on for anemia. EMS arrives for acute stabilization, and the patient is brought to the ED. En route, serum glucose was normal. The patient presents to the ED with hypothermia, tachycardia, tachypnea, and hypertension. His GCS is 8, he has poor peripheral perfusion and a diffusely tender abdomen. He continues to have hematemesis and is intubated for airway protection along with declining neurological status. After resuscitation, he presents to the Pediatric ICU. Upon intubation, an arterial blood gas is drawn. His pH is 7.22/34/110/-6 — serum HCO3 is 16, and his AG is elevated.

               To summarize key elements from this case, this patient has:

               • Lethargy and unresponsiveness after acute ingestion.
               • His hematemesis is most likely related to his acute ingestion.
               • And finally, he has an anion gap metabolic acidosis, as evidenced by his low pH and low HCO3.
               • All of these salient factors bring up the concern for acute iron ingestion! In today’s episode, we will not only go through acute management pearls for iron poisoning, but also go back to the fundamentals, and cover ACID BASE disorders.
               • We will break this episode down into giving a broad overview of acid base, build a stepwise approach, and apply our knowledge with integrated cases.
               
               

               We will use a physiologic approach to cover this topic!

               • Pradip, can you give us a quick overview of some general principles when it comes to tackling this high-yield critical care topic?
               • Absolutely, internal acid base homeostasis is paramount for maintaining life. Moreover, we know that accurate and timely interpretation of an acid–base disorder can be lifesaving.
               • When we conceptualize acid base today, we will focus on pH, HCO3, and CO2.
               • As we go into each disorder keep in mind to always correlate your interpretation of blood gasses to the clinical status of the patient.
               • Going back to basic chemistry, can you comment on the relationship between CO2 and HCO3?
               • Yes, now this is a throwback. However, we have to review the Henderson–Hasselbalch equation. The equation has constants & logs involved, however in general this equation shows that the pH is determined by the ratio of the serum bicarbonate (HCO3) concentration and the PCO2, not by the value of either one alone. In general, an acid–base disorder is called “respiratory” when it is caused by a primary abnormality in respiratory function (i.e., a change in the PaCO2) and “metabolic” when the primary change is attributed to a variation in the bicarbonate concentration.
               • Now that we have some fundamentals down, let’s move into definitions. Can you define acidemia and alkalemia and comment on how the sampling sites may vary these definitions?
               • Acidemia is defined as an arterial pH below 7.35.
               • Alkalemia is defined as an arterial pH above 7.45.
               • Thus, normal pH range for an arterial blood gas is 7.35 to 7.45.
               • Bicarbonate (HCO3) concentration, 21 to 27 mEq/L; and for PCO2, 35 to 45 mmHg.
               • What about the venous side?
               • Normal values for peripheral venous blood gases differ from those of arterial blood due to the uptake and buffering of metabolically produced CO2 in the capillary circulation and the addition of organic acids produced by the tissue bed drained by the vein.
               • The range for peripheral venous pH is approximately 0.03 to 0.04 pH units lower than in arterial blood, the HCO3 concentration is approximately 2 to 3 mEq/L higher, and the PCO2 is approximately 3 to 8 mmHg (0.4 to 1.1 kPa) higher.
               
               

               These subtleties are important physiological considerations as you trend blood gasses. For example, if you have a venous blood gas of 7.32, on the arterial side, it may be correlated to 7.35. Similarly on the venous side if you have a CO2 of 48, on the arterial side, this value may be about 5 mmHg lower, so around 43.

               Rahul, we mentioned that prior to chasing gasses, it is important to assess the patient’s clinical state. Can you comment on this a bit further?

               Yes, so the key here is that various signs and symptoms often provide clues regarding the underlying acid–base disorder; these include the patient’s vital signs (which may indicate shock or sepsis), neurologic state, pulmonary status (respiratory rate and presence or absence of Kussmaul respiration), and gastrointestinal symptoms (vomiting and diarrhea). We saw some of these in our case. We should also take into account any medications that affect acid–base balance in our assessment of acute acid-base changes. Relevant medications include laxatives, diuretics, topiramate, etc. Also, watch for specific ingestions such as methanol for example which can cause blindness.

               As we dive into the various disorders, can you frame an approach to acid base blood gas interpretation?

               Here are 3 steps:

               Establish the primary acid base abnormality — are we dealing with an acidemia or alkalemia.Establish what value correlates with the primary acid base disorder:

               CO2 HCO3

               For example, when you diagnose an acidemia, a metabolic acidosis is characterized by a low serum HCO3. Also, it is important to note for each 10 mmHg pCO2, pH falls by 0.08 units.

               Assess for compensation:

               • For example, in a metabolic alkalosis, your lungs will compensate by increasing your CO2 via hypoventilation.
               • Please note that renal compensation may take 24-48 hours after your initial respiratory acidosis/alkalosis.
               
               

               Yes, I think this point of compensation is important to note especially when assessing for mixed disorders. If we take for example an acute respiratory acidosis, the normal compensatory response to acute respiratory acidosis is an increase in the serum HCO3 concentration by approximately 1 mEq/L for every 10 mmHg elevation in the PCO2. When the respiratory acidosis persists for more than three to five days, the HCO3 increases by approximately 3.5 to 5 mEq/L for every 10 mmHg elevation in the PCO2.

               Important to note, with the exception of chronic respiratory alkalosis and mild to moderate respiratory acidosis compensatory responses do not usually return the arterial pH to normal.

               Yes, in fact, in contrast with older data, data from more recent studies indicate that the pH in chronic respiratory acidosis may be normal and, in individual cases, higher than generally recognized (pH >7.40).

               Let’s revisit our index case to review the acid base disturbance. Do you mind refreshing our memory on his initial ABG?

               • pH 7.22/34/110/-6 — serum HCO3 was 16 meQ/L.
               
               

               
               

               Rahul, take us through the step-wise approach:

               1. Acidemia as evidenced by a low pH of 7.22
               2. What supports an acidemia is a low bicarbonate so we can say it is metabolic
               3. And in the case of a metabolic acidosis it is important for us to assess the degree of compensation using winter’s formula.
               
               

               What is Winter’s formula?

               • PaCO2 = 1.5 × [HCO3−] + 8±2 mm Hg
               • In this case, our expected CO2 given our Bicarb is 16 would be 30-34, and our patient’s was 34, so this is a true metabolic acidosis.
               
               

               The patient had an anion gap metabolic acidosis, can you tell us a bit more about what is the anion gap?

               • Disorders that produce metabolic acidosis by increasing organic acid generation like in the case of ingestion or cases with increased accumulation of phosphoric and sulfuric acid such as severe chronic kidney disease can usually result in an increased serum anion gap.
               • The anion gap can conceptually be understood as Na + All unmeasured cations  =  Cl + HCO3 + All unmeasured anions. In general it the is positives minus negatives, and clinically we simplify this as. Na - (Cl + HCO3), normal is 8-12. If the anion gap is elevated, we recognize that this is some organic acid that is creating a gap between positives and negatives.
               
               

               Now Rahul, let's say we have a patient with hypoalbuminemia, would this affect the anion gap?

               • Yes, it definitely can in healthy individuals, the major unmeasured anion responsible for the existence of a serum anion gap is albumin.
               • This circulating protein has a significant net negative charge in the physiologic pH range. As a result, the expected baseline value for the anion gap must be adjusted downward in patients with hypoalbuminemia.
               • Thus, Corrected serum anion gap  =  (Serum anion gap measured) + (2.5  x  [4.5 - Observed serum albumin])
               • It is also important to note: In addition to hypoalbuminemia, marked hyperkalemia may affect the interpretation of the anion gap.
               
               

               With a metabolic acidosis, think about two things, calculate anion gap & the Winter’s formula for compensation.

               Clinically, what would be a good differential to keep in mind for an elevated anion gap metabolic acidosis?

               • Traditionally the Mnemonic was taught as mud piles, however, I wanted to add a little bit of a flare, and that is considering "CAT MUDPILES":
               • Carbon monoxide and Cyanide
               • Aminoglycosides
               • Theophylline
               • Methanol
               • Uremia
               • Diabetic ketoacidosis
               • Paracetamol/Acetaminophen, Paraldhyde
               • Iron, Isoniazid, Inborn errors of metabolism
               • Lactic acidosis
               • Ethanol (due to lactic acidosis), Ethylene glycol
               • Salicylates
               
               

               Lactic acidosis is frequently encountered in the pediatric intensive care setting. It is one of our most common causes of an elevated anion gap metabolic acidosis and in general indicates poor oxygen delivery, mitochondrial paralysis, or increased oxygen consumption. Please review our podcast entitled oxygen delivery to review this foundational PICU concept.

               • As an advanced integration, can you comment on the delta anion gap/delta HCO3 ratio in patients with elevated anion gap metabolic acidosis?
               • The most common causes of acute, high AG acidosis in the PICU are are lactic acidosis and ketoacidosis. The degree to which the AG rises in relation to the fall in bicarbonate (HCO3) varies with the cause of the metabolic acidosis. When the AG increases in magnitude as a result of metabolic acidosis, that increase should be compared with the magnitude of the fall in HCO3.
               • This represents the delta AG/delta HCO3 ratio, where delta AG is the patient's value of the AG minus the normal AG, and delta HCO3 is the normal serum HCO3 (ie, 24 mEq/L) minus the patient's serum HCO3
               • In our patient, he had a delta AG of 9 divided by a delta HCO3 of 8. The normal value is between 1 & 1.6.
               • What if you have a low delta AG/delta bicarbonate ratio?
               • A lower value (in which the delta AG is less than expected from the delta HCO3) can be seen in a number of settings:
               • In ketoacidosis, D-lactic acidosis, or toluene intoxication, the accumulating organic acid anions can be excreted by the kidney as sodium and/or potassium salts. As a result, in these disorders, the delta AG/delta HCO3 ratio is often below 1, and the serum AG may be normal.
               • A higher value of the ratio above 1.6, usually reflects a mixed acid-base disorder in which a high AG acidosis coexists with a process that elevates the serum HCO3.
               • As we pivot back to our case, he had an elevated anion gap metabolic acidosis 2/2 to acute iron poisoning, after the A B C tenants, what are our next steps in management?
               • Severe symptoms and an anion gap MA are indications for iron chelation using (IV) deferoxamine. You would definitely want to consult with a medical toxicologist and/or regional poison control center.
               • At times in acute iron overdose, you may note radio-opaque pills visible on a plain radiograph of the abdomen. This may also be a sign of severe poisoning.
               
               

               Important to note, because iron does not bind to activated charcoal, GI decontamination for acute iron poisoning consists of whole-bowel irrigation (WBI) and, rarely, orogastric lavage via upper endoscopy. The severity of disease can be guided based on plain abdominal radiographs. In most patients, the risk of gastric lavage following iron overdose outweighs the limited benefit.

               • To wrap up our discussion on metabolic acidosis, what are some common causes of non-anion gap metabolic acidosis?
               • In the big picture, NAGMA usually results from a loss of bicarbonate or an isolated reduction in renal acid excretion.
               • The most common NAGMA we see in the PICU:
               • Diarrhea or NG losses
               • Proximal (type 2) RTA or even Type 1 & Type 4 RTA where there is impaired renal acid excretion.
               • We also frequently encounter hyperchloremia and a NAGMA with resuscitation of 0.9% normal saline as it provides a chloride load; adult studies show that infusing more than 3-4L can cause acidosis.
               • Frequently as a fellow when we see a metabolic acidosis, we reflexively think about administering bicarbonate. Can you shed some clinical pearls on this management decision?
               • I think in a pinch it is appropriate to consider, especially if blood pH is <7.1 or, in some patients, <7.2 & clinically the patient is deteriorating.
               • Although intravenous bicarbonate may be helpful if administered to children with severe acute metabolic acidosis, the therapeutic focus should be on slowing the rate of acid generation (ie correcting the cause of acidosis).
               • In general, shooting for a goal of pH >7.2 and/or serum bicarbonate concentration >16 mEq/L should be considered. We frequently dose Bicarbonate as 1-4 meQ/kg keeping in mind that your typical vial has 50 meQ of bicarbonate.
               • As mixed disorders are important to also recognize let's conclude this episode by revisiting some compensation formulas.
               • To review:
               • Acute respiratory acidosis (less than a day) the serum HCO3 concentration increases by approximately 1 mEq/L for every 10 mmHg elevation in the PCO2 from normal.
               • Chronic respiratory acidosis (usually three to five days) serum HCO3 increases by about 4 mEq/L for every 10 mmHg elevation in PCO2 in patients with chronic respiratory acidosis.
               • Acute respiratory alkalosis, the serum HCO3 concentration reduces by 2 mEq/L for every 10 mmHg decline in the PCO2 from normal. In chronic, HCO3 will fall by 4 mEq/L.
               • What about for a metabolic alkalosis?
               • The respiratory compensation to metabolic alkalosis should raise the PCO2 by approximately 0.7 mmHg for every 1 mEq/L elevation in the serum HCO3 concentration.
               • A very-easy-to-use relationship: PCO2  =  HCO3 + 10. Studies have shown that high CO2 levels are probably generated by respiratory muscle weakness associated with marked hypokalemia and potassium depletion, which almost invariably develop in these patients. This is classically seen in a baby with It may also help to obtain urine electrolytes such as urinary cl in metabolic alkalosis. We will visit an approach to urinary chloride interpretation in future episodes!
               
               

               
               

               We talked about a wide breadth of topics today! Let's summarize…

               Key objective takeaways:

               1. Trend blood gasses based on similar sampling sites, remember for a peripheral venous sample, the range for pH is approximately 0.03 to 0.04 pH units lower than in arterial blood.
               2. Have a step-wise approach for acid base disorders — we covered 1. establish alkalemia vs acidemia; 2. which value CO2 or HCO3 supports your primary disorder; 3. assess compensation
               3. In metabolic acidosis, you'll have a low pH and a low bicarb, make sure that you do an Anion gap calculation, as well as Winter's formula.
               
               

               This concludes our episode on the approach to acid base disorders. We hope you found value in our short, case-based podcast. We welcome you to share your feedback, subscribe & place a review on our podcast! Please visit our website picudoconcall.org which showcases our episodes as well as our Doc on Call management cards. PICU Doc on Call is co-hosted by myself Dr. Pradip Kamat and Dr. Rahul Damania. Stay tuned for our next episode! Thank you!

               
               

               • More information can be found
               • Berend K, de Vries AP, Gans RO. Physiological approach to the assessment of acid-base disturbances. N Engl J Med. 2014 Oct 9;371(15):1434-45. doi: 10.1056/NEJMra1003327. Erratum in: N Engl J Med. 2014 Nov 13;371(20):1948. PMID: 25295502.
               • Rose BD, Post TW. Clinical Physiology of Acid-Base and Electrolyte Disorders, 5th ed, McGraw-Hill, New York 2001. p.328.
               • Malatesha G, Singh NK, Bharija A, et al. Comparison of arterial and venous pH, bicarbonate, PCO2 and PO2 in initial emergency department assessment. Emerg Med J 2007; 24:569.
               
               

               
               

               ]]>cdcf64fc-7daa-4479-8f7b-977a2746fff1Sun, 03 Jul 2022 03:00:00 -040024:36falsefull5656Ventilation of the Ex-premie in the PICUWelcome to PICU Doc On Call, a podcast dedicated to current and aspiring intensivists. My name is Pradip Kamat

               My name is Rahul Damania, a current 3rd-year pediatric critical care fellow and we are coming to you from Children’s Healthcare of Atlanta Emory University School of Medicine

               Today's episode is dedicated to the transition between NICU & PICU. We will focus on the ventilation of the ex-premature infant who graduated from NICU care and transitioned to the PICU.

               I will turn it over to Rahul to start with our patient case.

               • Case: A 4-month-old ex-27 week baby boy is transferred to our PICU after an echo at an outside hospital showed elevated pulmonary pressures. The infant was born via a stat C-section due to maternal complications during pregnancy. His birth weight was 560 g. The patient was intubated shortly after delivery and had a protracted course in the NICU which included a sepsis rule out, increased ventilator settings, and a few weeks on inhaled nitric oxide (iNO).
               
               
               1. The intubation course was complicated pulmonary hemorrhage on day 1 after intubation. After such an extensive NICU course, thankfully, the infant survived & was sent home on 1/2 LPM NC, diuretics, albuterol, inhaled corticosteroids, Synthroid, multivitamin with iron as well as Vitamin D. The patient was able to tolerate breast milk via NG tube and had a home apnea monitor with pulse oximetry.
               
               
               • After about a week’s stay at home, the mother noted that the patient’s SPO2 was in the low 80s. The mother took the patient to the local hospital, where the patient was started on HFNC which improved his saturations. An echo done at the OSH showed elevated RV pressures (higher than the prior echo). The patient was subsequently transferred to our hospital for further management. At our hospital, the patient presented hypoxemic, tachycardic, and tachypneic. On physical exam: Baby appeared well developed, had a systolic murmur heard throughout the precordium, and there was increased WOB with significant intercostal retraction. There was no hepatosplenomegaly.
               • Due to worsening respiratory distress, and increasing FIO2 requirement despite maximum RAM cannula, the patient was intubated and placed on conventional MV. A blood gas prior to intubation revealed a pH of 7.1/PCO2 of 100. An arterial line and a central venous line were also placed for better access and monitoring. Initial vent settings post intubation PRVC ventilation: TV 32cc, (25/10), 0.7 time, rate 0 (patient sedated/paralyzed).
               
               

               To summarize, What are some of the features in H&P that are concerning for you in this case:

               • Ex-27 week prematurity with a birth weight of 560 gms
               • Prolonged MV in the NICU
               • Home O2 requirement
               • Abnormal echo showing high pulmonary pressures
               • hypercarbia despite the use of RAM cannula
               
               

               As mentioned, our patient was intubated, can you tell us pertinent diagnostics which were obtained?

               • CXR revealed: Hazy airspace opacification in the right upper lung concerning developing pneumonia. Streaky airspace opacity in the left lung base medially may represent atelectasis.
               
               

               I do want to highlight that the intubation of an ex-premie especially with elevated RV pressures is a high-risk scenario, it is best managed by a provider with experience, in a very controlled setting with optimal team dynamics. Adequate preparation to optimize the patient prior to the intubation as well as the knowledge to manage the post intubation cardiopulmonary interactions are essential. I would highly advise you to re-visit our previous podcast on intubation of the high-risk PICU patient by Dr. Heather Viamonte. Like many Peds ICU conditions, the management of the EX-NICU graduate in the PICU is a multidisciplinary team sport.

               Our patient likely has the diagnosis of Bronchopulmonary Dysplasia or BPD, Pradip, can you comment on the evolving definition of this diagnosis?

               • Let me first define BPD — Clinically, BPD is defined by a requirement of oxygen supplementation either at 28 days postnatal age or 36 weeks postmenstrual age. The literature stratifies the difference between old vs. new BPD definitions. In the old BPD, seen before the 1980s and in usually more mature infants - the pathogenesis is related to damage caused to the lungs from mechanical ventilation and/or oxygen resulting in inflammation/fibrosis. It can occur in premature as well as term infants. We see less of the old BPD due to the use of surfactant and HFOV use. In old BPD, we have e/o hyperinflation and diffuse parenchymal infiltrate -lung histology dilated distal airspace, fibrosis throughout the interstitium, and significant pulmonary arterial fibroproliferative disease
               
               

               What about the new BPD?

               New BPD: Refers to abnormal or arrest in lung development (fewer and larger alveoli) and decreased microvascular development in extremely low birth weight infants. In new BPD, we see more evidence of dilated distal lung, less evidence of fibrosis, more typically have an arrest of distal lung development, and still have vascular beds are abnormal. The key here is impaired lung surface area, decreased alveoli, and decreased vascular growth.

               It is important to note that In severely affected infants, fibrosis, bronchial smooth muscle hypertrophy, and interstitial edema (“old” BPD) may be superimposed on the characteristic reduced numbers of alveoli and capillaries

               Let's transition and speak about the pathogenesis of BPD, Rahul, what are the key risk factors?

               • The important concept here is to understand the maternal fetal interface that can lead to premature birth. Determinants of disease include-Prenatal factors such as chorio-amniotic, fetal infection, IUGR, preeclampsia, maternal smoking/drug use with interplay from epigenetic/genetic factors, hyperoxia, inflammation, infection, ventilator induced lung injury can cause disruption of growth factor signaling pathways leading to changes in vascular growth, alveolar growth, and lung function.
               • There is a 43% incidence (unchanged in the last 50 years) of BPD born < 29 weeks of age. The earlier one is born, the more severe is the BPD. At autopsy, one can see Regions of Hyperinflation, areas of atelectatic/edema and have pseudo-fissures between them, and dilated distal airways with little septae (”alveolar simplification).
               
               

               Pradip, as it seems the histological architecture of the lung is altered, can you comment on the persistent respiratory disease seen in BPD?

               Patients with BPD can have persistent respiratory disease, which can be seen as prolonged respiratory support/NICU hospitalization, chronic respiratory distress, recurrent exacerbations, re-hospitalizations, exercise intolerance, wheezing, and increased susceptibility to chronic lung disease in adulthood. These patients may require long-term ventilatory support via an ETT or tracheostomy.

               To highlight epidemiology, did you know that 58% of preterm infants are readmitted to the hospital within the first year of life. 20% of these were admitted to the PICU and 12% ended up on MV.

               Pradip, we mentioned the use of mechanical ventilation in BPD. Let’s pivot today’s episode and focus on management, understanding how to invasively ventilate a patient with BPD. How can we use our understanding of ARDS (say in an adolescent) to understand the ventilation strategies in BPD?

               If we look at the lungs of a teenager with ARDS and hypoxemia, we may see diffuse parenchymal infiltrates. In these patients, the CT is will show a heterogeneous disease. There is a portion of the lung which may be susceptible to atelectasis, gravity dependent, and is edematous. It is this baby lung that we want to ventilate and recruit without overstretching. It’s balance. This is why we use the ARDSnet protocol which involves low tidal volumes, typically 6-8 mL/kg. We use prone positioning and increased PEEP to help recruit the lungs.

               Great, let's contrast this with BPD, what are the radiographic and physiologic considerations in our patient who is now intubated in the PICU?

               In BPD, the CT may show hyperinflation, diffuse infiltrates,...]]>Welcome to PICU Doc On Call, a podcast dedicated to current and aspiring intensivists. My name is Pradip Kamat

               My name is Rahul Damania, a current 3rd-year pediatric critical care fellow and we are coming to you from Children’s Healthcare of Atlanta Emory University School of Medicine

               Today's episode is dedicated to the transition between NICU & PICU. We will focus on the ventilation of the ex-premature infant who graduated from NICU care and transitioned to the PICU.

               I will turn it over to Rahul to start with our patient case.

               • Case: A 4-month-old ex-27 week baby boy is transferred to our PICU after an echo at an outside hospital showed elevated pulmonary pressures. The infant was born via a stat C-section due to maternal complications during pregnancy. His birth weight was 560 g. The patient was intubated shortly after delivery and had a protracted course in the NICU which included a sepsis rule out, increased ventilator settings, and a few weeks on inhaled nitric oxide (iNO).
               
               
               1. The intubation course was complicated pulmonary hemorrhage on day 1 after intubation. After such an extensive NICU course, thankfully, the infant survived & was sent home on 1/2 LPM NC, diuretics, albuterol, inhaled corticosteroids, Synthroid, multivitamin with iron as well as Vitamin D. The patient was able to tolerate breast milk via NG tube and had a home apnea monitor with pulse oximetry.
               
               
               • After about a week’s stay at home, the mother noted that the patient’s SPO2 was in the low 80s. The mother took the patient to the local hospital, where the patient was started on HFNC which improved his saturations. An echo done at the OSH showed elevated RV pressures (higher than the prior echo). The patient was subsequently transferred to our hospital for further management. At our hospital, the patient presented hypoxemic, tachycardic, and tachypneic. On physical exam: Baby appeared well developed, had a systolic murmur heard throughout the precordium, and there was increased WOB with significant intercostal retraction. There was no hepatosplenomegaly.
               • Due to worsening respiratory distress, and increasing FIO2 requirement despite maximum RAM cannula, the patient was intubated and placed on conventional MV. A blood gas prior to intubation revealed a pH of 7.1/PCO2 of 100. An arterial line and a central venous line were also placed for better access and monitoring. Initial vent settings post intubation PRVC ventilation: TV 32cc, (25/10), 0.7 time, rate 0 (patient sedated/paralyzed).
               
               

               To summarize, What are some of the features in H&P that are concerning for you in this case:

               • Ex-27 week prematurity with a birth weight of 560 gms
               • Prolonged MV in the NICU
               • Home O2 requirement
               • Abnormal echo showing high pulmonary pressures
               • hypercarbia despite the use of RAM cannula
               
               

               As mentioned, our patient was intubated, can you tell us pertinent diagnostics which were obtained?

               • CXR revealed: Hazy airspace opacification in the right upper lung concerning developing pneumonia. Streaky airspace opacity in the left lung base medially may represent atelectasis.
               
               

               I do want to highlight that the intubation of an ex-premie especially with elevated RV pressures is a high-risk scenario, it is best managed by a provider with experience, in a very controlled setting with optimal team dynamics. Adequate preparation to optimize the patient prior to the intubation as well as the knowledge to manage the post intubation cardiopulmonary interactions are essential. I would highly advise you to re-visit our previous podcast on intubation of the high-risk PICU patient by Dr. Heather Viamonte. Like many Peds ICU conditions, the management of the EX-NICU graduate in the PICU is a multidisciplinary team sport.

               Our patient likely has the diagnosis of Bronchopulmonary Dysplasia or BPD, Pradip, can you comment on the evolving definition of this diagnosis?

               • Let me first define BPD — Clinically, BPD is defined by a requirement of oxygen supplementation either at 28 days postnatal age or 36 weeks postmenstrual age. The literature stratifies the difference between old vs. new BPD definitions. In the old BPD, seen before the 1980s and in usually more mature infants - the pathogenesis is related to damage caused to the lungs from mechanical ventilation and/or oxygen resulting in inflammation/fibrosis. It can occur in premature as well as term infants. We see less of the old BPD due to the use of surfactant and HFOV use. In old BPD, we have e/o hyperinflation and diffuse parenchymal infiltrate -lung histology dilated distal airspace, fibrosis throughout the interstitium, and significant pulmonary arterial fibroproliferative disease
               
               

               What about the new BPD?

               New BPD: Refers to abnormal or arrest in lung development (fewer and larger alveoli) and decreased microvascular development in extremely low birth weight infants. In new BPD, we see more evidence of dilated distal lung, less evidence of fibrosis, more typically have an arrest of distal lung development, and still have vascular beds are abnormal. The key here is impaired lung surface area, decreased alveoli, and decreased vascular growth.

               It is important to note that In severely affected infants, fibrosis, bronchial smooth muscle hypertrophy, and interstitial edema (“old” BPD) may be superimposed on the characteristic reduced numbers of alveoli and capillaries

               Let's transition and speak about the pathogenesis of BPD, Rahul, what are the key risk factors?

               • The important concept here is to understand the maternal fetal interface that can lead to premature birth. Determinants of disease include-Prenatal factors such as chorio-amniotic, fetal infection, IUGR, preeclampsia, maternal smoking/drug use with interplay from epigenetic/genetic factors, hyperoxia, inflammation, infection, ventilator induced lung injury can cause disruption of growth factor signaling pathways leading to changes in vascular growth, alveolar growth, and lung function.
               • There is a 43% incidence (unchanged in the last 50 years) of BPD born < 29 weeks of age. The earlier one is born, the more severe is the BPD. At autopsy, one can see Regions of Hyperinflation, areas of atelectatic/edema and have pseudo-fissures between them, and dilated distal airways with little septae (”alveolar simplification).
               
               

               Pradip, as it seems the histological architecture of the lung is altered, can you comment on the persistent respiratory disease seen in BPD?

               Patients with BPD can have persistent respiratory disease, which can be seen as prolonged respiratory support/NICU hospitalization, chronic respiratory distress, recurrent exacerbations, re-hospitalizations, exercise intolerance, wheezing, and increased susceptibility to chronic lung disease in adulthood. These patients may require long-term ventilatory support via an ETT or tracheostomy.

               To highlight epidemiology, did you know that 58% of preterm infants are readmitted to the hospital within the first year of life. 20% of these were admitted to the PICU and 12% ended up on MV.

               Pradip, we mentioned the use of mechanical ventilation in BPD. Let’s pivot today’s episode and focus on management, understanding how to invasively ventilate a patient with BPD. How can we use our understanding of ARDS (say in an adolescent) to understand the ventilation strategies in BPD?

               If we look at the lungs of a teenager with ARDS and hypoxemia, we may see diffuse parenchymal infiltrates. In these patients, the CT is will show a heterogeneous disease. There is a portion of the lung which may be susceptible to atelectasis, gravity dependent, and is edematous. It is this baby lung that we want to ventilate and recruit without overstretching. It’s balance. This is why we use the ARDSnet protocol which involves low tidal volumes, typically 6-8 mL/kg. We use prone positioning and increased PEEP to help recruit the lungs.

               Great, let's contrast this with BPD, what are the radiographic and physiologic considerations in our patient who is now intubated in the PICU?

               In BPD, the CT may show hyperinflation, diffuse infiltrates, peri-bronchial lesions, ground glass lesions, cystic lesions, etc. This is a stark contrast with ARDS. They can have large central airway diseases like tracheobronchomalacia, or subglottic or bronchial stenosis, and even granulomas. Patients with severe BPD can have small airway structural remodeling such as mucus gland hyperplasia and clinically we will see more secretions that are not cleared well due to ciliary dysfunction. These airways have an epithelial injury, edema, smooth muscle proliferation, broncho-constriction, and hyper-reactivity. The patients with BPD also have decreased alveolarization, decreased vascular growth (i.e. fewer vessels), abnormal vascular remodeling, tone, and reactivity as well as impaired lymphatic function. As these infants age, they can have sleep-disordered breathing, diaphragm dysfunction, and chest-wall instability. In summary, BPD affects not only the lung parenchyma, but the whole respiratory unit — pulmonary vessels, lymphatics, chest wall, and diaphragm!

               Yes, it seems the take home is that the patient with severe BPD who is intubated in the PICU has vastly different physiologic and radiographic lesions compared to the run-of-the-mill teenager with acute ARDS. Hence a different ventilation and oxygenation strategy is required for the intubated BPD patient in the PICU. BPD subtypes include those with parenchymal lung disease, those with vascular disease (pulmonary arterial hypertension-evaluated at least initially with an echo), and those with airways disease (tracheo-bronchomalacia-evaluated by bronchoscopy). Additionally, a single patient may have more than one BPD subtype for example 28% can have all the above 3 subtypes. (Wu K et al. AJRCC Med 2020).

               Before we dive deep into management how do you evaluate the underlying lung disease in patients with severe BPD?

               We typically get CXR, blood gas, +/-Chest CT scan (may not require acutely), target SPO2 and PCO2, evaluate for chronic aspiration (ph probe, barium swallow, swallow study, etc.), sleep study, flexible bronchoscopy to evaluate structural airway disease as well as EKG, echocardiography, cardiac catheterization, etc may be required.

               In terms of labs, lactates, BNP, and NT-pro BNP may be required on a case-by-case basis. Additionally, an Interstitial lung disease panel may also be required on a case-by-case basis. The management of the patient with severe BPD in the PICU is really a team sport, which involves the intensivist, the cardiologist, the pulmonologist, gastroenterologists, and support staff such as the speech therapist and the rehabilitation team. It also involves open discussions with family as these patients are hospitalized long term not infrequently. Family conferences at periodic intervals in collaboration with social workers can help optimize decision making, set goals of care, and allow for facilitation amongst teams.

               Absolutely, it is a team sport!

               Now Pradip, you mentioned the radiographic and lab evaluation of these patients who have chronic lung disease. As we think about continuous monitoring in the PICU, do you have some management pearls?

               It is important to prevent hyperoxia by targeting an SPO2 of 92-94%. We also should avoid accepting an SPO2 of 90% as that can cause pulmonary hyper-vascular reactivity and these children can have marked vasospasm. We allow for permissive hypercapnia but avoid marked spikes or swings in PCO2 as long as pH is buffered. If PCO2 is chronically elevated its effect on PHTN is unclear. Elevated PCO2 may be a biomarker for severe parenchymal lung disease.

               Rahul, we mentioned in the pathogenesis the abnormal vascular development in the pulmonary circuit, can you comment on the cardiopulmonary interactions seen in a patient with BPD?

               In patients with severe BPD, we have High pulmonary artery pressures due to lung disease. Remember these children will have hyperinflation in some areas, atelectasis, and fluctuations in O2 and CO2. This can create chronic heart disease as well. Particularly RV dysfunction. Patients downstream can have issues with LV contractility as we have at times an exaggerated systolic interdependence which can affect LV contractility. The LV diastolic dysfunction may be due to persistent pulmonary edema. As these children are premature, it is also important to assess for abnormalities in cardiac development. These children will frequently have shunts. ASD, VSD, PDAs for example. The L to R shunting may create over-circulation, and in times of crises, these shunts may reverse leading to hypoxemia. Fortunately, when children have these shunts, they serve as “pop-offs” during times of increased pulmonary pressure. As we mentioned cath as one of our diagnostics it is important to assess for pulmonary vein stenosis as this fixed anatomic defect can further contribute to high pulmonary artery pressures.

               In a summary, remember that the RV is relatively afterload sensitive and the LV is more sensitive to changes in preload!

               As we set titrate the ventilator in our patient with BPD, Pradip, what strategies are you going to use for effective oxygenation and ventilation?

               The biggest point before we go into the specific ventilator strategies is the heterogeneity of lung disease. This is not a two-compartment model as seen in ARDS. There is marked variability of regional time constants, and as mentioned, airway secretions, and pulmonary hypertension in many cases. Some areas of the lung may have normal compliance and resistance, whereas others may have poor compliance and high resistance. In this heterogeneous disease, there are also significant areas of high compliance and low resistance. So if we ventilate these patients with BPD with low tidal volumes, rapid rates, and low iTimes (similar to ARDS), we run the risk of having worse distribution of gas, increased dead space ventilation, hypercarbia, the need for higher FiO2 and radiographically progressive atelectasis.

               As such, it is important for users to manage the patient with severe, chronic BPD with high TV. This allows for more gas to fill the lungs. Couple this high tidal volume, usually 8-10 mL/kg with higher iTimes and low rates to decrease the risk of atelectasis.

               Ok, to summarize here, BPD patients, in general, have higher iTimes, higher tidal volumes, and low rates. This is to especially account for the areas of the lungs with higher time constants.

               Rahul, real quick what is the definition of a time constant?

               • The time constant is the time required for inflation of alveoli up to 63% of the final volume, or deflation by 63%. It is the product of resistance and compliance. For a normal set of lungs as a whole, the normal time constant is 0.1-0.2 seconds. In BPD, these children have varied, heterogenous time constants.
               
               

               Rahul what about PEEP use in the intubated BPD patient?

               • These patients in general require higher PEEP. It opens the airways and along with larger lung volumes has a tethering effect. This stretching effect with high peep may favor airflow and improves gas exchange. Like you frequently preach on rounds Pradip, PEEP is your friend! High PEEP with high rates can lead to air trapping and dynamic hyperinflation, so continue to reassess your patient, serial gas, x-rays, and ventilator scalars to determine the optimal rate to set on the ventilator in addition to the PEEP.
               
               

               Let's take a holistic picture now, Pradip, beyond the ventilator, what do we have to consider?

               • Don't rush towards extubation, but work to reduce distress, retractions, and “dyspnea”; at times growth with optimal nutrition is very beneficial. We need to optimize therapies such as OT and PT. but also consider the desaturations/increased PVR which may ensue during this hands-on care. We should focus on weaning sedation and NMB as tolerated.
               • These children are in the PICU at times for long periods, so optimize day night cycles, sleep hygiene, lab schedules, and most importantly bonding with family & caregivers. Don’t forget to catch up on immunizations and ROP care. Remember Rahul, we are pediatricians first!!
               
               

               I love these points, it is really a team effort. As we conclude this episode, in your opinion what does successful care of the BPD patient in the PICU look like?

               • Successful treatment with BPD is synonymous with good supportive care — we want to do no harm. In this setting, we want ”minimal impact respiratory support”. Prevention of harm, prevention of infection, prevention of right heart failure, excellent nutrition for growth and repair as well as developmental assistance. You will frequently be coordinating care with your NICU or PICU...]]>965b6ef8-8f63-439b-8b35-52df4aeda38cSun, 05 Jun 2022 03:00:00 -040028:17falsefull5555Providing Kidney Support in the PICUWelcome to PICU Doc On Call, a podcast dedicated to current and aspiring intensivists. I am Pradip Kamat.

                 I am Rahul Damania, a current 3rd year pediatric critical care fellow.

                 I am Kate Phelps- a second year pediatric critical care medicine. We come to you from Children's Healthcare of Atlanta Emory University School of Medicine.

                 We are delighted to be joined by guest expert Dr Stephanie Jernigan Assistant Professor of Pediatric-Pediatric nephrology, Medical Director of the Pediatric Dialysis Program at Children’s Healthcare of Atlanta. She is the Chief of Medicine and Campus Medical Director at Children’s Healthcare of Atlanta, Egleston Campus. Her research interests include chronic kidney disease, and dialysis. She is on twitter @stephaniejern13

                 I will turn it over to Rahul to start with our patient case...

                 • A 3 year old previously healthy male presents with periorbital edema. Patient was initially seen by a pediatrician who prescribed anti-histamines for allergy. After no improvement in the eye swelling after a two week anti-histamine course, the patient was given a short course of steroids, which also did not improve his periorbital edema. The patient progressed to having abdominal distention and was prescribed miralax for constipation. Grandparents subsequently noticed worsening edema in his face, eyes, and feet. The patient subsequently had low urine output, low appetite and lack of energy patient was subsequently brought to an ED and labs were obtained. Grandparents denied any illness prior to presentation, fever, congestion, sore throat, cough, nausea, vomiting, gross hematuria, or diarrhea. In ED patient was noted to be hypertensive (Average systolic 135-highest 159mm HG), tachycardic (HR 130s-140s), breathing ~20-30 times per minute on RA with SpO2 92%. Admission weight was recorded at 16.5Kg. Physical exam showed periorbital edema, edema of ankles, there was mild abdominal distention (no tenderness and no hepatosplenomegaly), heart and lung exams were normal. There were no rashes on extremities.
                 
                 

                 Labs at the time of transfer to the PICU: WBC 10 (62% neutrophils, 26% lymphocytes) Hgb 7.2, Hct 21, Platelets 276. BMP: Na 142/K 8.4/Cl 102/HCO3 19/BUN 173/creatinine 5.8. Serum phosphorus was 10.5, Total Ca 6.4 (ionized Ca= 3.4), Mag 2.0, albumin 2.6, AST/ALT were normal. An urine analysis showed: 1015, ph 7.5, urine protein 300 and rest negative. Chest radiograph revealed small bilateral pleural effusions. After initial stabilization of his hyperkalemia-patient was admitted to the PICU. PTH intact 295 (range 8.5-22pg/mL). Respiratory viral panel including for SARS-COV-2 was negative. C3 and C4 were normal. A nephrotic syndrome/FSGS genetic panel was sent. A renal US showed: bilateral echogenic kidneys and ascites (small volume).

                 Pradip: Dr Phelps what are the salient features of the above case presented?

                 Kate Phelps: This patient has a subacute illness characterized by edema, anemia, and proteinuria. His labs show that he has severe acute kidney injury with significantly elevated BUN and Creatinine, hyperkalemia, hyperphosphatemia, and hypocalemia.

                 Rahul: Dr Jernigan welcome to PICU Doc on Call Podcast.

                 Thanks Kate, Rahul and Pradip for inviting me to your podcast. This is a such a great way to provide education and it is my pleasure to come today to speak about one of my favorite topics, pediatric dialysis. I have no financial disclosures or conflicts of interest and am ready to get started.

                 Rahul: Dr Jernigan as you get that call from the ED and then subsequently from the PCCM docs, as a nephrologists whats going on in your mind ?

                 When I get the call from the outside hospital my first job is to make sure the patient is safe and stable for transfer to a tertiary care center. This includes concern about airway, breathing and level of alertness. From a renal standpoint, I am worried about elevated blood pressure, electrolyte abnormalities, in this case primarily the hyperkalemia, and fluid overload, especially given the low oxygen saturation. It is important that children are transported to an appropriate center early, but still safely, to allow for diagnostic work up and intervention. This is particularly true in the case of renal replacement therapy which most community hospitals are reticent or unable to offer to our pediatric patients.

                 Our episode today will be divided into a few broad categories: INDICATIONS/PRINCIPLES of KIDNEY REPLACEMENT, TECHNICAL ASPECTS of RRT, Anticoagulation, and a comparison of various types of RRT and their complications.

                 Let’s start with INDICATIONS/PRINCIPLES of KIDNEY REPLACEMENT

                 Kate Phelps: What are in general indications for renal replacement in pediatric patients?

                 Indications for renal replacement therapy are similar for acute vs chronic dialysis however differ in their urgency. As we know, our kidneys are important for waste product elimination, a primary measurement of this is blood urea nitrogen, acid base and electrolyte balance and of course maintaining fluid balance. When these functions fail acutely so as to be dangerous to a patient or when they are chronically inadequate despite medical management, then renal replacement is indicated. Acute indications tend to be significant uremia which can have consequences on multiple systems (CNS, heart, coagulation), symptomatic fluid overload (affecting breathing and cardiac function), and/or hyperkalemia and intractable acidosis not responsive to medical intervention. Medical management includes for fluid overload the use of diuretics and the use of bicarb in order to correct acidosis and shift potassium intracellularly. Additional therapy for hyperkalemia – membrane stabilization with calcium, further increase of uptake of potassium by cells with glucose, insulin and Beta agonists and elimination of potassium in the gut with ion exchange resin (kayexlate). Not related to the kidney directly, dialysis may also be needed in toxic overdose (salicylates and acetaminophen, lithium, metformin to name a few) or inborn errors of metabolism resulting in hyperammonemia.

                 This has led to the mnemonic AEIOU – acidosis, electrolytes, ingestions, overload and uremia.

                 Uremia with a BUN of greater than 100 and symptomatic or greater than 150 even without current symptoms are concerning and in most cases indication for dialysis.

                 Less acute indication but no less important is need for dialysis when treatment and caloric nutrition are impeded by fluid issues and dialysis allows for these to be maximized without regard the secondary consequences of fluid imbalance.

                 Of note, while creatinine gives us a stable measurement of glomerular filtration rate, it’s value is not in and of itself an indicator for renal replacement therapy.

                 🎯 Just to summarize, acidosis – metabolic acidosis with a pH <7.1; electrolyte refractory hyperkalemia with a serum potassium >6.5 mEq/L or rapidly rising potassium levels; Intoxications

                  – use the mnemonic SLIME to remember the drugs and toxins that can be removed with dialysis: salicylates, lithium, isopropyl alcohol, methanol, ethylene glycol; Overload

                  – volume overload refractory to diuresis; Uremia

                  – elevated BUN with signs or symptoms of uremia, including pericarditis, neuropathy, uremic bleeding, or an otherwise unexplained decline in mental status

                 Rahul: Dr Jernigan what physical principles are used in dialysis and what are the properties of the substances we can dialyze?

                 Let’s start with the principles of dialysis. Important here is understanding the laws governing movement of molecules between solutions and across a semipermeable membrane.

                 First is diffusion which is movement of molecules from a solution of higher concentration to lower concentration. This is much like “tea” where tea in the bag diffuses out into the water based on a concentration gradient. In diffusion, equilibrium will eventually occur and all things equal diffusion will slow and then stop. Smaller molecules will diffuse faster than larger molecules so this modality does better with smaller molecules.

                 Next is convection. Convection is movement across the membrane due to a pressure gradient, sometimes called solute drag. This can be compared to the making of coffee where water passed through the coffee grounds “pulling” or “dragging” the coffee (flavor and caffeine thank goodness) with it. This can be a pressure gradient (CVVH) or an osmotic gradient (PD)Convective therapies are better for larger molecular weight substances but removes small molecules as well.

                 Hemofiltration is movement of fluid across the membrane due to a gradient.

                 I believe we will talk more specifically about the different types of dialysis later however in brief, Hemodialysis utilizes primarily diffusion with the blood flow rate and the dialyzer being the factors that increases or decreases clearance.

                 PD uses both diffusion and convection equally but is not the most common modality seen in the ICU setting.

                 CVVH (continuous veno-venous hemofiltration) in its classic form uses primarily convection but has different modes which also allows for convection , diffusion and a combination of both.

                 So for best clearance molecules are smaller <10000 Daltons have high water solubility and small volume of distribution and low protein binding (most are greater than 10K Dalton, albumin is 66K Dalton)

                 To summarize, dialysis systems operate either via diffusion (i.e movement of...]]>Welcome to PICU Doc On Call, a podcast dedicated to current and aspiring intensivists. I am Pradip Kamat.

                 I am Rahul Damania, a current 3rd year pediatric critical care fellow.

                 I am Kate Phelps- a second year pediatric critical care medicine. We come to you from Children's Healthcare of Atlanta Emory University School of Medicine.

                 We are delighted to be joined by guest expert Dr Stephanie Jernigan Assistant Professor of Pediatric-Pediatric nephrology, Medical Director of the Pediatric Dialysis Program at Children’s Healthcare of Atlanta. She is the Chief of Medicine and Campus Medical Director at Children’s Healthcare of Atlanta, Egleston Campus. Her research interests include chronic kidney disease, and dialysis. She is on twitter @stephaniejern13

                 I will turn it over to Rahul to start with our patient case...

                 • A 3 year old previously healthy male presents with periorbital edema. Patient was initially seen by a pediatrician who prescribed anti-histamines for allergy. After no improvement in the eye swelling after a two week anti-histamine course, the patient was given a short course of steroids, which also did not improve his periorbital edema. The patient progressed to having abdominal distention and was prescribed miralax for constipation. Grandparents subsequently noticed worsening edema in his face, eyes, and feet. The patient subsequently had low urine output, low appetite and lack of energy patient was subsequently brought to an ED and labs were obtained. Grandparents denied any illness prior to presentation, fever, congestion, sore throat, cough, nausea, vomiting, gross hematuria, or diarrhea. In ED patient was noted to be hypertensive (Average systolic 135-highest 159mm HG), tachycardic (HR 130s-140s), breathing ~20-30 times per minute on RA with SpO2 92%. Admission weight was recorded at 16.5Kg. Physical exam showed periorbital edema, edema of ankles, there was mild abdominal distention (no tenderness and no hepatosplenomegaly), heart and lung exams were normal. There were no rashes on extremities.
                 
                 

                 Labs at the time of transfer to the PICU: WBC 10 (62% neutrophils, 26% lymphocytes) Hgb 7.2, Hct 21, Platelets 276. BMP: Na 142/K 8.4/Cl 102/HCO3 19/BUN 173/creatinine 5.8. Serum phosphorus was 10.5, Total Ca 6.4 (ionized Ca= 3.4), Mag 2.0, albumin 2.6, AST/ALT were normal. An urine analysis showed: 1015, ph 7.5, urine protein 300 and rest negative. Chest radiograph revealed small bilateral pleural effusions. After initial stabilization of his hyperkalemia-patient was admitted to the PICU. PTH intact 295 (range 8.5-22pg/mL). Respiratory viral panel including for SARS-COV-2 was negative. C3 and C4 were normal. A nephrotic syndrome/FSGS genetic panel was sent. A renal US showed: bilateral echogenic kidneys and ascites (small volume).

                 Pradip: Dr Phelps what are the salient features of the above case presented?

                 Kate Phelps: This patient has a subacute illness characterized by edema, anemia, and proteinuria. His labs show that he has severe acute kidney injury with significantly elevated BUN and Creatinine, hyperkalemia, hyperphosphatemia, and hypocalemia.

                 Rahul: Dr Jernigan welcome to PICU Doc on Call Podcast.

                 Thanks Kate, Rahul and Pradip for inviting me to your podcast. This is a such a great way to provide education and it is my pleasure to come today to speak about one of my favorite topics, pediatric dialysis. I have no financial disclosures or conflicts of interest and am ready to get started.

                 Rahul: Dr Jernigan as you get that call from the ED and then subsequently from the PCCM docs, as a nephrologists whats going on in your mind ?

                 When I get the call from the outside hospital my first job is to make sure the patient is safe and stable for transfer to a tertiary care center. This includes concern about airway, breathing and level of alertness. From a renal standpoint, I am worried about elevated blood pressure, electrolyte abnormalities, in this case primarily the hyperkalemia, and fluid overload, especially given the low oxygen saturation. It is important that children are transported to an appropriate center early, but still safely, to allow for diagnostic work up and intervention. This is particularly true in the case of renal replacement therapy which most community hospitals are reticent or unable to offer to our pediatric patients.

                 Our episode today will be divided into a few broad categories: INDICATIONS/PRINCIPLES of KIDNEY REPLACEMENT, TECHNICAL ASPECTS of RRT, Anticoagulation, and a comparison of various types of RRT and their complications.

                 Let’s start with INDICATIONS/PRINCIPLES of KIDNEY REPLACEMENT

                 Kate Phelps: What are in general indications for renal replacement in pediatric patients?

                 Indications for renal replacement therapy are similar for acute vs chronic dialysis however differ in their urgency. As we know, our kidneys are important for waste product elimination, a primary measurement of this is blood urea nitrogen, acid base and electrolyte balance and of course maintaining fluid balance. When these functions fail acutely so as to be dangerous to a patient or when they are chronically inadequate despite medical management, then renal replacement is indicated. Acute indications tend to be significant uremia which can have consequences on multiple systems (CNS, heart, coagulation), symptomatic fluid overload (affecting breathing and cardiac function), and/or hyperkalemia and intractable acidosis not responsive to medical intervention. Medical management includes for fluid overload the use of diuretics and the use of bicarb in order to correct acidosis and shift potassium intracellularly. Additional therapy for hyperkalemia – membrane stabilization with calcium, further increase of uptake of potassium by cells with glucose, insulin and Beta agonists and elimination of potassium in the gut with ion exchange resin (kayexlate). Not related to the kidney directly, dialysis may also be needed in toxic overdose (salicylates and acetaminophen, lithium, metformin to name a few) or inborn errors of metabolism resulting in hyperammonemia.

                 This has led to the mnemonic AEIOU – acidosis, electrolytes, ingestions, overload and uremia.

                 Uremia with a BUN of greater than 100 and symptomatic or greater than 150 even without current symptoms are concerning and in most cases indication for dialysis.

                 Less acute indication but no less important is need for dialysis when treatment and caloric nutrition are impeded by fluid issues and dialysis allows for these to be maximized without regard the secondary consequences of fluid imbalance.

                 Of note, while creatinine gives us a stable measurement of glomerular filtration rate, it’s value is not in and of itself an indicator for renal replacement therapy.

                 🎯 Just to summarize, acidosis – metabolic acidosis with a pH <7.1; electrolyte refractory hyperkalemia with a serum potassium >6.5 mEq/L or rapidly rising potassium levels; Intoxications

                  – use the mnemonic SLIME to remember the drugs and toxins that can be removed with dialysis: salicylates, lithium, isopropyl alcohol, methanol, ethylene glycol; Overload

                  – volume overload refractory to diuresis; Uremia

                  – elevated BUN with signs or symptoms of uremia, including pericarditis, neuropathy, uremic bleeding, or an otherwise unexplained decline in mental status

                 Rahul: Dr Jernigan what physical principles are used in dialysis and what are the properties of the substances we can dialyze?

                 Let’s start with the principles of dialysis. Important here is understanding the laws governing movement of molecules between solutions and across a semipermeable membrane.

                 First is diffusion which is movement of molecules from a solution of higher concentration to lower concentration. This is much like “tea” where tea in the bag diffuses out into the water based on a concentration gradient. In diffusion, equilibrium will eventually occur and all things equal diffusion will slow and then stop. Smaller molecules will diffuse faster than larger molecules so this modality does better with smaller molecules.

                 Next is convection. Convection is movement across the membrane due to a pressure gradient, sometimes called solute drag. This can be compared to the making of coffee where water passed through the coffee grounds “pulling” or “dragging” the coffee (flavor and caffeine thank goodness) with it. This can be a pressure gradient (CVVH) or an osmotic gradient (PD)Convective therapies are better for larger molecular weight substances but removes small molecules as well.

                 Hemofiltration is movement of fluid across the membrane due to a gradient.

                 I believe we will talk more specifically about the different types of dialysis later however in brief, Hemodialysis utilizes primarily diffusion with the blood flow rate and the dialyzer being the factors that increases or decreases clearance.

                 PD uses both diffusion and convection equally but is not the most common modality seen in the ICU setting.

                 CVVH (continuous veno-venous hemofiltration) in its classic form uses primarily convection but has different modes which also allows for convection , diffusion and a combination of both.

                 So for best clearance molecules are smaller <10000 Daltons have high water solubility and small volume of distribution and low protein binding (most are greater than 10K Dalton, albumin is 66K Dalton)

                 To summarize, dialysis systems operate either via diffusion (i.e movement of molecules across a semipermeable membrane using a concentration gradient OR via convection where solutes move across a semipermeable membrane using a pressure gradient. In some modalities ultrafiltration occurs due to an osmotic pressure gradient. Lets transition to the next portion of our podcast which will cover vascular access & anticoagulation

                 VASCULAR ACCESS

                 Rahul: Dr Jernigan before we go into each modality, should we discuss the access required for RRT in the PICU?

                 Before we can begin dialysis we need access to the vasculature (HD and CRRT) and the peritoneal cavity (PD). Vascular access can be placed by you, our ICU colleagues, as well as interventional radiologists and surgeons. In general, we need a large gage vascular catheter. The smallest catheter utilized is 8 gage up to 14 gage. It is best placed in the internal jugular. The subclavian (the location of old) has been changed as complications during placement and vessel stenosis are problematic. This is especially true if future need of arteriovenous fistulas. If there is urgency of placement and especially in larger individuals (greater than 28 BMI) then femoral access may be needed but this has a higher infection risk and we worry about future vascular access for renal transplantation.

                 While old terminology included vas cath (temporary) and permcath (longer term), we have a system move to terminology that better describes the type of catheter placed. This includes single vs double lumen, low flow vs high flow, tunneled and cuffed (permanent) vs non tunneled. For dialysis we require double lumen and high flow. For long term, the catheter is tunneled and cuffed to allow for lesser infection and movement risk.

                 Peritoneal catheters are placed by surgeons. These are silicone or polyurethane and in best practice are double cuffed. The first cuff is placed under the skin and then the catheter is tunneled with the second cuff in the rectus muscle. The catheter then enters the peritoneal cavity where the coiled tip is placed in the pericolic gutter or pelvis. While they can be used urgently, the preference is to allow them to sit and heal for two weeks to avoid leakage and infection. The exception is in infants where this is the best option for many situations due to patient size.

                 ANTICOAGULATION

                 Kate: Dr Jernigan can you shed some light on the type of anticoagulation required during RRT?

                 Any time blood is circulated outside the body, it is at risk for clotting which leads to blood loss. For this reason, anticoagulation is required.

                 This original anticoagulation for blood dialysis is heparin and this is still the mainstay in hemodialysis. This is given as a bolus and thin continuous infusion until some point before discontinuation of dialysis as this is systemic anticoagulation (turned off sooner for fistula’s due to bleeding) Monitoring is through ACT’s however standard dosing is fairly well established and act’s used less often and not in the chronic unit. Starting bolus 20-50 units/kg and infusion of 10-30 units/kg/hr over remaining time.

                 Side effects are HIT (heparin induced thrombocytopenia) and bleeding risk due to systemic anticoagulation.

                 Citrate: This is used as regional anticoagulation meaning it only anticoagulates the circuit and not the patient. Citrate binds to calcium in the circuit and prevents activation of both coagulation cascades and platelet aggregation. The majority of the calcium–citrate complex is moves across the membrane by diffusion during dialysis and is lost in the ultrafiltrate. A systemic calcium infusion is necessary post filter to replace the calcium lost with citrate. Any calcium–citrate complex is not filtered and returns to the patient has a very short half life and is metabolized to bicarb by the liver, kidney and skeletal muscle. This citrate is titrated to blood flow to maintain low iCa in the circuit. The Calcium infusion is adjusted to keep iCa normal in the patient.

                 There are several advantages to citrate. First and foremost is the regional anticoagulation and less systemic bleeding, especially for those at high risk. It can be used in patients with HIT and in some patients, the additional bicarb from the citrate metabolism is helpful. The disadvantages are that in some patients the additional bicarb is not helpful and there can be other metabolic complications related to acid/base and calcium loss. In addition, with citrate there are the more complex protocols for the varying infusion rates and frequent calcium measurements. Citrate is relatively contraindicated in patient with hepatic failure and inborn errors of metabolism related to mitochondrial disorders.

                 Flolan: Epoprostenol, a naturally occurring prostaglandin with potent vasodilatory activity and inhibitory activity of platelet aggregation and thrombus generation which is it’s mechanism to prevent clotting. For this reason it is avoided in patients with thrombocytopenia and should be used with caution in patients with hypotension. It has a short half-life and like other anticoagulants for CVVH is a continuous infusion of 2-8 ng/kg/min. Monitoring is simple and in addition to the above is circuit longevity.

                 🎯 Summary time — citrate binds calcium, be careful in patients with liver failure. With Flolan, watch for thrombocytopenia.

                 MEMBRANE

                 Pradip: Dr Jernigan what are the types of dialyzers used during RRT?

                 Hemodialysis dialyzers are primarily made of synthetic material. (polysulfone , poly mix) Synthetic membranes have less complement activation and systemic “allergic” reaction. They are made of multiple hollow semi permeable membrane fibers through which blood is flows with dialysate moving counter current outside the fibers. The effectiveness of the dialyzer is based on the thinness of the material and the number and size of the pores. There is a large surface area which in HD should approximate the patients BSA.

                 For prismaflex/CVVH we use two synthetic catheters the HF 20 and the HF1000 which are determined by patient size and clearance capability. HF 20 allows CRRT more safely on the small child weighing 8-20 kg.The volume of the dialyzer and tubing is important as in there is limit to the volume of blood that can be in the extracorporeal circuit. This is less than 10% of estimated blood volume and if more needs a blood prime. Keeping in mind that the extracorporeal tubing is also part of this calculation.

                 Although vascular access for dialysis in the PICU is easily attained by the intensivists, we have to be cautious about infants < 1 year of age. Due to fluid overload, platelet dysfunction (from uremia) etc., these are best done by the surgeon or interventional colleagues in a controlled setting. Pediatric Intensivists should be well versed with anti-coagulation choices during RRT.

                 RENAL REPLACEMENT MODALITIES

                 Dr. Phelps: Dr Jernigan what are modalities of renal replacement therapies typically used in children?

                 In children we can used peritoneal dialysis, hemodialysis, and continuous veno-venous hemofiltration (CVVH), CVVHD, or CVVHDF.

                 Rahul: Dr. Jernigan Lets start with peritoneal dialysis

                 After placement of the catheter, Peritoneal dialysis takes advantage of the large surface area of the peritoneal lining, a semi permeable bidirectional membrane to do dialysis by diffusion and convection.

                 PD is perfomed by instilling fluid, dianeal, into the peritoneal cavity which is then allowed to dwell for a prescribed amount of time (allowing solute movement via diffusion) and then drained. This is repeated for a prescribed number of cycles or time. Dianeal contains calcium, magnesium, sodium chloride and sodium lactate as a buffer. The variable in dianeal is dextrose which creates the osmolarity to allow for fluid removal and secondary solute drag (convection). The dextrose concentrations include 1.5%, 2.5% and 4.25% with higher dextrose pulling more fluid. As the peritoneal membrane is bidirectional, equilibration will occur so the fine art is to find the right dwell time to remove waste and fluid and drain before equilibration happens. Volumes range from 10-40 ml/kg and dialysis improves with increased volume and thus more membrane exposure to dianeal and by increasing time on dialysis.

                 In general PD is well tolerated and is the best dialysis for young babies with catheters being able to be placed in children weighing as little as 1.8 to 2kg without needing blood exposure as in hemodialysis. While inpatient, PD can be done with a manual exchange set for very small volumes and once appropriate volumes obtained transitioned to an automated cycler.

                 In addition to its advantage in the smallest patients, other advantages of PD include less need for specialized equipment and highly trained extracorporeal personnel. It does not require vascular access or anticoagulation. Electrolyte shifts are gentle and slow. In the outpatient world, PD is done at home and daily so has advantages to quality of life. Concerns include that waste and fluid removal are variable and may not be acute or aggressive enough for some ill children (fluid overload or hyperkalemia) and PD is not great acute therapy due to concerns for leakage with a fresh catheter. Instilling fluid into the abdomen may impinge on respiratory excursion could be an issue for some patients and as this modality does rely on adequate blood pressure to perfuse the peritoneum, it hypotension present, if may be less effective. Recent or impending abdominal surgery or gastroschisis /omphalocele are contraindications however VP shunts, ostomies and Eagle Barret...]]>bceaaf1b-c999-48b5-9c07-423e7607a945Sun, 29 May 2022 03:00:00 -040043:10falsefull5454GI HemorrhageWelcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.

                 I'm Pradip Kamat

                 I'm Rahul Damania, a third-year PICU fellow.

                 I’m Kate Phelps, a second-year PICU fellow and we are all coming to you from Children's Healthcare of Atlanta - Emory University School of Medicine, joining Pradip and Rahul today. Welcome to our episode, where will be discussing gastrointestinal bleeding.

                 Kate: Let’s start with a case:

                 A 4-year-old, previously healthy male presents to the emergency room after a large, bloody stool at home. He notably had an episode of dark emesis and an episode of blood-tinged emesis on the day prior. In triage, he is altered and unable to answer questions coherently. Initial vital signs are temperature 36.1 C, RR 24, HR 146, BP 110/54. Point-of-care labs show hemoglobin to be 5.1 with hematocrit 15. His venous blood gas is reassuring against respiratory disease, and he is in no respiratory distress. Further labs are sent and a massive transfusion protocol is initiated before transfer to the PICU. Before arrival in the PICU, he receives two aliquots of RBCs, 1 aliquot of FFP, and 1 aliquot of platelets. Additional labs are sent from the PICU, post-transfusion. His post-transfusion hemoglobin is 8.8. Other labs are notable for normal MCV, elevated total bilirubin to 4.1 (with direct component 3.4), and elevated AST and ALT to 309 and 495 respectively.

                 Rahul: To summarize key elements from this case, this patient has:

                 • An undifferentiated gastrointestinal bleed with both hematemesis and hematochezia.
                 • He has symptomatic anemia, as evidenced by tachycardia
                 • Altered mental status.
                 • He is initially stabilized via transfusion of several blood products and liver function labs are shown to be very abnormal — which we will get more into later!
                 
                 

                 PK: Let’s get into important parts of the history and physical. Kate, can you tell me what some key history items in this patient are — and what are some areas to make sure to touch on when a patient has a GI bleed?

                 Kate: Yeah! I’d love to.

                 First - in our patient, some important elements are his rather acute onset. His parents mention he has had one day of bleeding symptoms - first with emesis yesterday, with components of old, partially digested blood, as well as some fresh blood. Second, he has a frankly bloody stool at home. Given his clinical instability, history taking was probably limited at first, so it’s important to ask follow-up questions and really dig into the case after stabilization!

                 I like to put my questions about gastrointestinal bleeding into buckets based on the questions I need to answer. I need to answer: is this active bleeding or old blood? Is this slow, insidious bleeding or fast, life-threatening bleeding? Is this an upper GI bleed or a lower GI bleed? Bright red blood in emesis tells us that bleeding is active, whereas coffee-ground or dark emesis tells us that, while recent, the blood has been partially digested in the stomach and may not be ongoing. Similarly, melena (dark, tarry stool), tells us blood has come through the colon. While coffee-ground emesis and melena don’t rule out an active bleed, they do tell us the bleeding may be slower, as large volume, active bleedy is irritating to the stomach and gastrointestinal tracks and moves through the system quickly.

                 The next question I want to answer is: what is the cause of this bleed? Easy bruising, petechiae and mucosal bleeding may point to a coagulation disorder. Abdominal cramping, frequent stooling, and weight loss may point to inflammatory bowel disease. Past medical history, family history, and a thorough review of systems are key here.

                 Rahul: Yeah, that’s great! Let’s talk about your question of upper GI vs lower GI bleed.

                 First, a definition: an upper GI bleed is bleeding that occurs above the ligament of Treitz — which is ligamentous tissue that supports the end of the duodenum and beginning of the jejunum at their junction. While not 100% specific, some symptoms that point to an upper GI bleed are: hematemesis, coffee-ground or dark emesis, and melena. Symptoms that lend themselves to the diagnosis of a lower GI bleed are hematochezia (bright red blood in the stool) and melena (which may represent a more bleed more proximal to Treitz). However, with a brisk, heavy upper GI bleed — say from the duodenum — patients can also have hematochezia.

                 OK to summarize, when we think of GI bleeding, first stratify your patient into slow vs. fast bleeding, identify whether it is upper or lower GI bleeding, and dive deeper into an underlying cause after your patient is stabilized.

                 Pradip: Relatively little data exists about the prevalence of GI bleeds in the PICU. In a study by Chaibou, et al., they reported that approx 10% of PICU children have upper GI bleeding with only 1/5 of those with UGIB having clinically relevant bleeding (characterized by significant hemoglobin drop, need for transfusion, hypotension, multi-organ failure, or death). Incidence of lower GI bleeding is even less well characterized in current available evidence.

                 Kate: Thanks, Pradip. Given our patient’s symptoms, I would be most concerned for an upper GI bleed, given the bloody emesis — but a significant one if it’s leading to hematochezia.

                 Rahul: Yeah, that’s exactly what I was thinking, KP. Pradip, in the literature we see they mention that NG saline lavage can be used diagnostically to help confirm if bleeding is occurring in the upper GI tract vs a pulmonary source. Further, NG lavage has been advocated as a therapeutic practices, however, this may be outdated now as we push for more timely endoscopy. In fact, studies show: ice water lavage is not recommended; this older practice does not slow bleeding and may induce iatrogenic hypothermia, particularly in infants and small children.

                 Kate: Ok, let’s back up for a second — let’s talk about red flag symptoms! ABCs should always come first for every patient who arrives anywhere in the hospital. In this patient, concerning symptoms in this scenario, are his tachycardia and his altered mental status. These symptoms tell us that anemia is symptomatic and likely more acute. Hypotension and tachycardia indicate that bleeding is significant enough to cause hypovolemia. Altered mental status indicates that the brain is hypoxic, in this case, due to inadequate hemoglobin. Other red flags symptoms in GI bleeding include: orthostatic changes, delayed capillary refill and other signs of poor perfusion, currant jelly stools (which may indicate bowel ischemia), and of course anything that points to a large volume of blood in emesis or stool (for example, “the whole toilet bowl was red”) — as these may precede hypotension. Rahul will fill us in later about how to treat patients with red flag symptoms!

                 Absolutely, the identification of hypovolemic shock is essential in GI bleeding. Notice subtle data trends and optimize O2 delivery. Please check out our prior episode entitled Oxygen Content & Delivery.

                 Pradip: To switch gears, tell me how you think about the differential in patients with bleeding?

                 Kate: Sure, the differential will be different for upper vs lower but will also be relevant to the age of the patient. The differential for clinically relevant GI bleeding in an infant includes hemorrhagic disease of the newborn (in those who did not receive Vit K at birth), necrotizing enterocolitis, and Hirschprung’s enterocolitis (which interestingly can occur after repair), and volvulus. For children >1 year, the differential includes esophageal varices, gastric or duodenal ulcers, volvulus, intussusception, Meckel’s diverticulum, Mallory Weiss tears, IgA vasculitis, hemolytic uremic syndrome, and several infectious etiologies. Adolescents and young adults have a similar differential but now we begin to think more about inflammatory bowel disease and NSAIDs. Of course, there is a lot of overlap between school-age children and adolescents. In the oncology population, we have to think about graft-versus-host disease and typhlitis.

                 Rahul: So really — the differential is broad. Let’s talk about initial and ongoing work up to narrow our differential.

                 Initial labs should include a complete blood count, a comprehensive metabolic panel with a fractionated bilirubin, coagulation studies, and — perhaps most importantly — a type & screen! Initial imaging might include a two-view abdominal X-ray to evaluate for obstruction or perforation. Ultrasound can help rule in intussusception. Later imaging might include CT with angiography or even MRI.

                 Remember when it comes to liver function tests: alkaline phosphatase and GGT give us info about the biliary ducts, AST and ALT tell us about hepatocellular function, and albumin and PT/INR give us info about hepatic synthetic function.

                 Pradip: Great — now let’s get into treatment.

                 Rahul: As Kate eluded to earlier, if any red flag symptoms are present, we need to think about resuscitation and stabilization. Initial stabilization for patients should include attention to the airway, breathing, and circulation. For serious upper GI bleeds, intubation should be considered for repeated bloody emesis, to control the airway and prevent aspiration. Hypotension can be initially managed with judicious fluid resuscitation to temporize but should be followed by blood products as soon as possible. Most hospital centers have a massive transfusion protocol, so consider this in hemorrhage states before you have signs of end-organ hypo-perfusion! Kate, can you touch on additional specific treatment for ongoing bleeding?

                 Kate: Yeah - we really have two avenues for intervention: medical and...]]>Welcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.

                 I'm Pradip Kamat

                 I'm Rahul Damania, a third-year PICU fellow.

                 I’m Kate Phelps, a second-year PICU fellow and we are all coming to you from Children's Healthcare of Atlanta - Emory University School of Medicine, joining Pradip and Rahul today. Welcome to our episode, where will be discussing gastrointestinal bleeding.

                 Kate: Let’s start with a case:

                 A 4-year-old, previously healthy male presents to the emergency room after a large, bloody stool at home. He notably had an episode of dark emesis and an episode of blood-tinged emesis on the day prior. In triage, he is altered and unable to answer questions coherently. Initial vital signs are temperature 36.1 C, RR 24, HR 146, BP 110/54. Point-of-care labs show hemoglobin to be 5.1 with hematocrit 15. His venous blood gas is reassuring against respiratory disease, and he is in no respiratory distress. Further labs are sent and a massive transfusion protocol is initiated before transfer to the PICU. Before arrival in the PICU, he receives two aliquots of RBCs, 1 aliquot of FFP, and 1 aliquot of platelets. Additional labs are sent from the PICU, post-transfusion. His post-transfusion hemoglobin is 8.8. Other labs are notable for normal MCV, elevated total bilirubin to 4.1 (with direct component 3.4), and elevated AST and ALT to 309 and 495 respectively.

                 Rahul: To summarize key elements from this case, this patient has:

                 • An undifferentiated gastrointestinal bleed with both hematemesis and hematochezia.
                 • He has symptomatic anemia, as evidenced by tachycardia
                 • Altered mental status.
                 • He is initially stabilized via transfusion of several blood products and liver function labs are shown to be very abnormal — which we will get more into later!
                 
                 

                 PK: Let’s get into important parts of the history and physical. Kate, can you tell me what some key history items in this patient are — and what are some areas to make sure to touch on when a patient has a GI bleed?

                 Kate: Yeah! I’d love to.

                 First - in our patient, some important elements are his rather acute onset. His parents mention he has had one day of bleeding symptoms - first with emesis yesterday, with components of old, partially digested blood, as well as some fresh blood. Second, he has a frankly bloody stool at home. Given his clinical instability, history taking was probably limited at first, so it’s important to ask follow-up questions and really dig into the case after stabilization!

                 I like to put my questions about gastrointestinal bleeding into buckets based on the questions I need to answer. I need to answer: is this active bleeding or old blood? Is this slow, insidious bleeding or fast, life-threatening bleeding? Is this an upper GI bleed or a lower GI bleed? Bright red blood in emesis tells us that bleeding is active, whereas coffee-ground or dark emesis tells us that, while recent, the blood has been partially digested in the stomach and may not be ongoing. Similarly, melena (dark, tarry stool), tells us blood has come through the colon. While coffee-ground emesis and melena don’t rule out an active bleed, they do tell us the bleeding may be slower, as large volume, active bleedy is irritating to the stomach and gastrointestinal tracks and moves through the system quickly.

                 The next question I want to answer is: what is the cause of this bleed? Easy bruising, petechiae and mucosal bleeding may point to a coagulation disorder. Abdominal cramping, frequent stooling, and weight loss may point to inflammatory bowel disease. Past medical history, family history, and a thorough review of systems are key here.

                 Rahul: Yeah, that’s great! Let’s talk about your question of upper GI vs lower GI bleed.

                 First, a definition: an upper GI bleed is bleeding that occurs above the ligament of Treitz — which is ligamentous tissue that supports the end of the duodenum and beginning of the jejunum at their junction. While not 100% specific, some symptoms that point to an upper GI bleed are: hematemesis, coffee-ground or dark emesis, and melena. Symptoms that lend themselves to the diagnosis of a lower GI bleed are hematochezia (bright red blood in the stool) and melena (which may represent a more bleed more proximal to Treitz). However, with a brisk, heavy upper GI bleed — say from the duodenum — patients can also have hematochezia.

                 OK to summarize, when we think of GI bleeding, first stratify your patient into slow vs. fast bleeding, identify whether it is upper or lower GI bleeding, and dive deeper into an underlying cause after your patient is stabilized.

                 Pradip: Relatively little data exists about the prevalence of GI bleeds in the PICU. In a study by Chaibou, et al., they reported that approx 10% of PICU children have upper GI bleeding with only 1/5 of those with UGIB having clinically relevant bleeding (characterized by significant hemoglobin drop, need for transfusion, hypotension, multi-organ failure, or death). Incidence of lower GI bleeding is even less well characterized in current available evidence.

                 Kate: Thanks, Pradip. Given our patient’s symptoms, I would be most concerned for an upper GI bleed, given the bloody emesis — but a significant one if it’s leading to hematochezia.

                 Rahul: Yeah, that’s exactly what I was thinking, KP. Pradip, in the literature we see they mention that NG saline lavage can be used diagnostically to help confirm if bleeding is occurring in the upper GI tract vs a pulmonary source. Further, NG lavage has been advocated as a therapeutic practices, however, this may be outdated now as we push for more timely endoscopy. In fact, studies show: ice water lavage is not recommended; this older practice does not slow bleeding and may induce iatrogenic hypothermia, particularly in infants and small children.

                 Kate: Ok, let’s back up for a second — let’s talk about red flag symptoms! ABCs should always come first for every patient who arrives anywhere in the hospital. In this patient, concerning symptoms in this scenario, are his tachycardia and his altered mental status. These symptoms tell us that anemia is symptomatic and likely more acute. Hypotension and tachycardia indicate that bleeding is significant enough to cause hypovolemia. Altered mental status indicates that the brain is hypoxic, in this case, due to inadequate hemoglobin. Other red flags symptoms in GI bleeding include: orthostatic changes, delayed capillary refill and other signs of poor perfusion, currant jelly stools (which may indicate bowel ischemia), and of course anything that points to a large volume of blood in emesis or stool (for example, “the whole toilet bowl was red”) — as these may precede hypotension. Rahul will fill us in later about how to treat patients with red flag symptoms!

                 Absolutely, the identification of hypovolemic shock is essential in GI bleeding. Notice subtle data trends and optimize O2 delivery. Please check out our prior episode entitled Oxygen Content & Delivery.

                 Pradip: To switch gears, tell me how you think about the differential in patients with bleeding?

                 Kate: Sure, the differential will be different for upper vs lower but will also be relevant to the age of the patient. The differential for clinically relevant GI bleeding in an infant includes hemorrhagic disease of the newborn (in those who did not receive Vit K at birth), necrotizing enterocolitis, and Hirschprung’s enterocolitis (which interestingly can occur after repair), and volvulus. For children >1 year, the differential includes esophageal varices, gastric or duodenal ulcers, volvulus, intussusception, Meckel’s diverticulum, Mallory Weiss tears, IgA vasculitis, hemolytic uremic syndrome, and several infectious etiologies. Adolescents and young adults have a similar differential but now we begin to think more about inflammatory bowel disease and NSAIDs. Of course, there is a lot of overlap between school-age children and adolescents. In the oncology population, we have to think about graft-versus-host disease and typhlitis.

                 Rahul: So really — the differential is broad. Let’s talk about initial and ongoing work up to narrow our differential.

                 Initial labs should include a complete blood count, a comprehensive metabolic panel with a fractionated bilirubin, coagulation studies, and — perhaps most importantly — a type & screen! Initial imaging might include a two-view abdominal X-ray to evaluate for obstruction or perforation. Ultrasound can help rule in intussusception. Later imaging might include CT with angiography or even MRI.

                 Remember when it comes to liver function tests: alkaline phosphatase and GGT give us info about the biliary ducts, AST and ALT tell us about hepatocellular function, and albumin and PT/INR give us info about hepatic synthetic function.

                 Pradip: Great — now let’s get into treatment.

                 Rahul: As Kate eluded to earlier, if any red flag symptoms are present, we need to think about resuscitation and stabilization. Initial stabilization for patients should include attention to the airway, breathing, and circulation. For serious upper GI bleeds, intubation should be considered for repeated bloody emesis, to control the airway and prevent aspiration. Hypotension can be initially managed with judicious fluid resuscitation to temporize but should be followed by blood products as soon as possible. Most hospital centers have a massive transfusion protocol, so consider this in hemorrhage states before you have signs of end-organ hypo-perfusion! Kate, can you touch on additional specific treatment for ongoing bleeding?

                 Kate: Yeah - we really have two avenues for intervention: medical and surgical. Medical treatment can be tailored to the etiology but can include an IV proton pump inhibitor (or PPI) as first like during workup, followed by an octreotide infusion. Rahul, can you tell us about octreotide before I continue?

                 Rahul:

                 • Octreotide is a Long-acting somatostatin-analog: that reduces splanchnic blood flow and inhibits gastric acid secretion.
                 • Dosing: an initial bonus of 1 mcg/kg followed by a maximum infusion of 10 mcg/kg/hr, which can be titrated down as bleeding improves and resolves.
                 • Side effect: hyperglycemia as we inhibit the effects of insulin.
                 
                 

                 Kate: Perfect- thanks! An additional medication sometimes used in GI bleeding is vasopressin, though octreotide has been shown to be as efficacious and does not carry the same daunting side effect profile. Most management strategies have shifted to using octreotide over vasopressin. If intermittent PPI dosing plus octreotide doesn’t control bleeding, a continuous infusion of a proton pump inhibitor can be considered though no data has shown this.

                 Let’s summarize the medical therapies, PPI, octreotide, and in some cases vasopressin.

                 Pradip: For surgical intervention, we’re first talking about upper endoscopy (esophagogastroduodenoscopy) or a colonoscopy — which can be both diagnostic and therapeutic. Endoscopy should ideally occur after hemodynamic stabilization but within 12 hours of admission for variceal bleeding and within 24 hours of admission for non-variceal bleeding in the case of upper gastrointestinal sources. Endoscopic interventions may include: adhesive cyanoacrylate applied to the bleeding lesion, band ligation applied to varix, injection sclerotherapy, and epinephrine injection, among other things. Interventional radiology may be able to perform arterial embolization.

                 Kate: I think this is the perfect point to follow up with our case, initial labs point toward normocytic anemia biliary duct obstruction without coagulopathy. During the hospital admission, bleeding stabilized after the initial massive transfusion. EGD showed acute clot formation near the ampulla of Vater in the duodenum. The eventual MRI showed a choledochal cyst with arterial erosion leading to the acute hemorrhage. An angiogram and percutaneous biliary drain placement were accomplished with IR.

                 OK Kate, do you mind summarizing our takeaways for today?

                 Kate: Key objective takeaways:

                 1. Clinical relevant GI bleeds are uncommon in the PICU, but the skills to stabilize are crucial in the setting of a life-threatening hemorrhage.
                 2. The differential for a GI bleed is broad but can be narrowed through careful and thorough history taking, physical examination, laboratory data, and imaging.
                 3. Endoscopy should occur in a timely fashion in the setting of clinically significant upper GI bleeding.
                 
                 
                 • For more reading, information can be found in:
                 • Pediatrics in Review, “Gastrointestinal Bleeds” by Baker, et. al in the October 2021 edition.
                 • Chapter 95 of the most recent edition of Fuhrman & Zimmerman’s Pediatric Critical Care, with sections on many of the differential diagnoses, included today.
                 
                 

                 This concludes our episode on GI hemorrhage. We hope you found value in our short, case-based podcast. We welcome you to share your feedback, subscribe & place a review on our podcast! Please visit our website picudoconcall.org which showcases our episodes as well as our Doc on Call management cards. PICU Doc on Call is hosted by myself Dr. Pradip Kamat, and my dream cohosts Dr. Rahul Damania and Dr. Kate Phelps. Stay tuned for our next episode! Thank you!

                 ]]>b6e5f6b0-139b-4256-bdb3-2375146daf82Sun, 15 May 2022 03:00:00 -040016:19falsefull5353RhabdomyolysisWelcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.

                 I'm Pradip Kama and I'm Rahul Damania, a third-year PICU fellow. I’m Kate Phelps, a second-year PICU fellow and we are all coming to you from Children's Healthcare of Atlanta, Emory University School of Medicine, joining Pradip and Rahul today. Welcome to our episode, where will be discussing rhabdomyolysis and associated acute kidney injury in the ICU.

                 Rahul: Here's the case, a 7-year-old female presents to the ED with three days of fever, poor PO, and diffuse myalgia. In the ED, her vital signs are T 39.1C, HR 139, BP 82/44, RR 32. She is pale and diaphoretic, complaining weakly about how much her legs hurt. Her parents note that she has not been peeing very well since yesterday, and when she does pee it is “very concentrated, almost brown.” She’s also been spending all her time on the couch and has asked to be carried to the bathroom when she does need to go.

                 An IV is placed by the emergency room team, and she is given a fluid bolus, acetaminophen, and initial labs are drawn (CMP, CBC, RSV/Flu swab) before she is admitted to the PICU. In the PICU, her fever is better and her vitals have improved to T 37.7, HR 119, BP 115/70, and RR 25. Her respiratory swab has just resulted positive for Influenza A. Further labs are sent, including creatine kinase (CK), coagulation studies, and a urinalysis. Labs are notable for K 3.9, Bicarb 22, BUN 15, Cr 0.8, and CK 5768 IU/L. Her urinalysis is notable for 1 WBC, 2 RBC, +3 blood, negative nitrites, and leukocyte esterase.

                 Kate: To summarize key elements from this case, this patient has:

                 • Influenza A, as evidenced by her respiratory swab, as well as her clinical prodrome.
                 • She has diffuse myalgias, as well as fevers, diaphoresis, and hypotension.
                 • Labs are most notable for elevated creatinine and elevated creatine kinase, as well as an abnormal urinalysis.
                 • All of which brings up a concern for rhabdomyolysis and myoglobin-induced acute kidney injury.
                 
                 

                 Before we get into this episode — let's create a mental framework for this episode — we will dissect our case by highlighting key H&P components, visit a differential diagnosis, pivot to speaking about pathophysiology, and finally, speak about management!

                 • Rahul: Let's transition into some history and physical exam components of this case.
                 • The classic presentation of rhabdomyolysis is myalgias, muscle weakness, and tea-colored urine, all of which our patient has. Decreased urinary output can also accompany, a variety of reasons, but most notably if the patient has myoglobin-induced acute kidney injury. In our patient, poor PO is also probably contributing to her decrease in urine output. Red flag signs or symptoms will include anuria, hypotension, and altered mental status (which is rare but may indicate severe acidemia and deterioration)
                 • Pradip: As we think about our case, what other disease processes might be in our differential? As we dive in a bit more, we’ll come up with ways to distinguish between rhabdo and other things!
                 • Viral myositis - inflammation in the muscles in the setting of a viral illness, which can definitely happen with influenza and other common viruses
                 • Some other things which may cause reddish-brown urine, including hematuria, hemoglobinuria, porphyria, some specific foods or drugs (like rifampin, beets, food coloring — even ibuprofen)
                 • We also have to investigate a bit more to convince ourselves that our patient’s AKI is due to rhabdomyolysis, as it could be from dehydration, sepsis, NSAIDS, etc.
                 
                 

                 Kate: Let’s dive further into rhabdomyolysis!

                 Rhabdomyolysis affects over 25,000 adults and children every year. While toxins (including prescription drugs, alcohol, and illicit drugs) and trauma are two common causes of rhabdo in adults (and teens), infections, especially viruses, are the most common cause in young children. Influenza, EBV, and CMV are three most commonly reported.

                 What’s the pathophysiology of Rhabdomyolysis?

                 Rhabdomyolysis is the injury of skeletal muscle, which leads to cellular damage, apoptosis, and necrosis. As a result, skeletal muscle cells lyse and release their intracellular contents. Insult directly to the cell membrane and ATP-depletion are two mechanisms that can start the chain reaction leading to this cell death.

                 When the cell membrane itself is injured (as may happen in trauma or crush injury, metabolic conditions, or toxins), ionized calcium can freely enter the cell, leading to activation of proteases and phospholipases, which further injure the cell membrane, as well as mitochondria. As a result, the cell undergoes apoptosis and necrosis. When there is an ATP-depletion, pumps on the cell membrane important for maintaining sodium and calcium homeostasis between the intracellular and extracellular components become compromised. Intracellular calcium levels build, and the same process of cell and mitochondrial injury leads to apoptosis and necrosis.

                 To summarize, Rhabdomyolysis is an index example of cell adaptations, injury, and death. The key here is cell membrane damage which leads to downstream apoptosis.

                 Absolutely Rahul, the danger of this is that other intracellular contents are released into the extracellular space, including myoglobin, potassium, uric acid, intracellular enzymes, and many other things. Creatine kinase, or CK, released from cells is relatively indicative of rhabdo. Though no consensus criteria for rhabdo exist, most experts agree that serum CK level >1000 IU/L combined with the history and physical findings we will discuss is consistent with rhabdomyolysis.

                 This is especially important as there is are a multitude of pathologies that can cause a mild, transient increase in CK levels usually < 1000.

                 Pradip: One of the most common and most dangerous complications of rhabdomyolysis is acute kidney injury. While more common in adults, AKI occurs in ~5% of children with rhabdomyolysis. Let’s take a brief moment to discuss rhabdomyolysis-induced, or more specifically myoglobin-induced, acute kidney injury. While the mechanisms for myoglobin injury to the nephron aren’t entirely clear, most experts believe one of three things or, more likely, a combination of three things occur. Rahul, can you walk us through those?

                 Rahul: Sure, I’d love to!

                 • First, myoglobin is directly nephrotoxic, though notably only in an acidic environment!
                 • Second, it causes oxidation of ferrous oxide, leading to free radicals and reactive oxygen species, unregulated by usual intracellular processes.
                 • Third, myoglobin, through protein-binding, can precipitate in the tubule, leading to obstructive nephropathy.
                 
                 

                 Kate: Whew! That is a lot! Let’s take a break and review what we just learned:

                 Rhabdomyolysis is the injury of skeletal muscle leading to calcium influx into cells, which cascades into eventual apoptosis and necrosis. This leads to a massive release of intracellular components that upsets the overall homeostasis of the intra- and extracellular spaces. Myoglobin released from cells can directly injure the kidneys, leading to AKI. Potassium and hydrogen proton leakage, combined with AKI, can lead to life-threatening hyperkalemia and acidosis. CK is a serum measurement that can help confirm the diagnosis of rhabdomyolysis.

                 Rahul: Fun Fact Myoglobinuria usually only occurs in rhabdomyolysis (BUT not all rhabdomyolysis has myoglobinuria as it only spills out in urine above certain serum concentrations). Myoglobinuria can be inferred from a urine dipstick when there is moderate or large blood but few or no red blood cells. This is because the dipstick test for blood is non-specific for hemoglobin vs myoglobin! Myoglobin is also the reason the urine turns reddish-brown or “tea-colored.”

                 Pradip: Let’s change gears and talk about management. Kate, can you tell us about the management of rhabdomyolysis?

                 • Kate: With this patient, our first step should be resuscitation — always ABCs first! After initial fluid resuscitation and stabilization, we can begin to think about further workup and screening. Labs should include a comprehensive metabolic panel (CMP), urinalysis with dipstick, complete blood count, and creatine kinase. Depending on the severity of clinical illness, coagulation studies can be sent, as DIC is a rare complication of rhabdomyolysis, as well as sepsis, which is on our differential! In rhabdo, labs will show an elevated CK, possible hyperkalemia, acidosis, hyperphosphatemia, and hyperuricemia. If kidney injury is present, hyperkalemia is more likely, in addition to elevated creatinine.
                 • Once rhabdomyolysis is confirmed, treatment should focus on hydration, hydration, hydration! Additionally any complications of abnormal electrolytes, etc, should be monitored for and addressed. This includes telemetry monitoring or EKG in the setting of hyperkalemia.
                 
                 

                 Rahul: Remember, symptomatic hyperkalemia as evidenced by EKG changes, including wide QRS, absent P waves, or arrhythmias, including ventricular fibrillation, should be treated immediately. IV calcium administration will stabilize the cardiac membrane. Bicarbonate, insulin + glucose, and albuterol can quickly but only temporarily shift potassium into cells. Kayexalate and diuretics can remove potassium from the body.

                 • Pradip: Hydration is the most important treatment in rhabdomyolysis. There is a paucity of data, but most expert consensus suggests targeting a urine output of 3-4 ml/kg/hr while administering 2x maintenance fluids for children with rhabdo. Which fluid is the right fluid is still...]]>Welcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.

                   I'm Pradip Kama and I'm Rahul Damania, a third-year PICU fellow. I’m Kate Phelps, a second-year PICU fellow and we are all coming to you from Children's Healthcare of Atlanta, Emory University School of Medicine, joining Pradip and Rahul today. Welcome to our episode, where will be discussing rhabdomyolysis and associated acute kidney injury in the ICU.

                   Rahul: Here's the case, a 7-year-old female presents to the ED with three days of fever, poor PO, and diffuse myalgia. In the ED, her vital signs are T 39.1C, HR 139, BP 82/44, RR 32. She is pale and diaphoretic, complaining weakly about how much her legs hurt. Her parents note that she has not been peeing very well since yesterday, and when she does pee it is “very concentrated, almost brown.” She’s also been spending all her time on the couch and has asked to be carried to the bathroom when she does need to go.

                   An IV is placed by the emergency room team, and she is given a fluid bolus, acetaminophen, and initial labs are drawn (CMP, CBC, RSV/Flu swab) before she is admitted to the PICU. In the PICU, her fever is better and her vitals have improved to T 37.7, HR 119, BP 115/70, and RR 25. Her respiratory swab has just resulted positive for Influenza A. Further labs are sent, including creatine kinase (CK), coagulation studies, and a urinalysis. Labs are notable for K 3.9, Bicarb 22, BUN 15, Cr 0.8, and CK 5768 IU/L. Her urinalysis is notable for 1 WBC, 2 RBC, +3 blood, negative nitrites, and leukocyte esterase.

                   Kate: To summarize key elements from this case, this patient has:

                   • Influenza A, as evidenced by her respiratory swab, as well as her clinical prodrome.
                   • She has diffuse myalgias, as well as fevers, diaphoresis, and hypotension.
                   • Labs are most notable for elevated creatinine and elevated creatine kinase, as well as an abnormal urinalysis.
                   • All of which brings up a concern for rhabdomyolysis and myoglobin-induced acute kidney injury.
                   
                   

                   Before we get into this episode — let's create a mental framework for this episode — we will dissect our case by highlighting key H&P components, visit a differential diagnosis, pivot to speaking about pathophysiology, and finally, speak about management!

                   • Rahul: Let's transition into some history and physical exam components of this case.
                   • The classic presentation of rhabdomyolysis is myalgias, muscle weakness, and tea-colored urine, all of which our patient has. Decreased urinary output can also accompany, a variety of reasons, but most notably if the patient has myoglobin-induced acute kidney injury. In our patient, poor PO is also probably contributing to her decrease in urine output. Red flag signs or symptoms will include anuria, hypotension, and altered mental status (which is rare but may indicate severe acidemia and deterioration)
                   • Pradip: As we think about our case, what other disease processes might be in our differential? As we dive in a bit more, we’ll come up with ways to distinguish between rhabdo and other things!
                   • Viral myositis - inflammation in the muscles in the setting of a viral illness, which can definitely happen with influenza and other common viruses
                   • Some other things which may cause reddish-brown urine, including hematuria, hemoglobinuria, porphyria, some specific foods or drugs (like rifampin, beets, food coloring — even ibuprofen)
                   • We also have to investigate a bit more to convince ourselves that our patient’s AKI is due to rhabdomyolysis, as it could be from dehydration, sepsis, NSAIDS, etc.
                   
                   

                   Kate: Let’s dive further into rhabdomyolysis!

                   Rhabdomyolysis affects over 25,000 adults and children every year. While toxins (including prescription drugs, alcohol, and illicit drugs) and trauma are two common causes of rhabdo in adults (and teens), infections, especially viruses, are the most common cause in young children. Influenza, EBV, and CMV are three most commonly reported.

                   What’s the pathophysiology of Rhabdomyolysis?

                   Rhabdomyolysis is the injury of skeletal muscle, which leads to cellular damage, apoptosis, and necrosis. As a result, skeletal muscle cells lyse and release their intracellular contents. Insult directly to the cell membrane and ATP-depletion are two mechanisms that can start the chain reaction leading to this cell death.

                   When the cell membrane itself is injured (as may happen in trauma or crush injury, metabolic conditions, or toxins), ionized calcium can freely enter the cell, leading to activation of proteases and phospholipases, which further injure the cell membrane, as well as mitochondria. As a result, the cell undergoes apoptosis and necrosis. When there is an ATP-depletion, pumps on the cell membrane important for maintaining sodium and calcium homeostasis between the intracellular and extracellular components become compromised. Intracellular calcium levels build, and the same process of cell and mitochondrial injury leads to apoptosis and necrosis.

                   To summarize, Rhabdomyolysis is an index example of cell adaptations, injury, and death. The key here is cell membrane damage which leads to downstream apoptosis.

                   Absolutely Rahul, the danger of this is that other intracellular contents are released into the extracellular space, including myoglobin, potassium, uric acid, intracellular enzymes, and many other things. Creatine kinase, or CK, released from cells is relatively indicative of rhabdo. Though no consensus criteria for rhabdo exist, most experts agree that serum CK level >1000 IU/L combined with the history and physical findings we will discuss is consistent with rhabdomyolysis.

                   This is especially important as there is are a multitude of pathologies that can cause a mild, transient increase in CK levels usually < 1000.

                   Pradip: One of the most common and most dangerous complications of rhabdomyolysis is acute kidney injury. While more common in adults, AKI occurs in ~5% of children with rhabdomyolysis. Let’s take a brief moment to discuss rhabdomyolysis-induced, or more specifically myoglobin-induced, acute kidney injury. While the mechanisms for myoglobin injury to the nephron aren’t entirely clear, most experts believe one of three things or, more likely, a combination of three things occur. Rahul, can you walk us through those?

                   Rahul: Sure, I’d love to!

                   • First, myoglobin is directly nephrotoxic, though notably only in an acidic environment!
                   • Second, it causes oxidation of ferrous oxide, leading to free radicals and reactive oxygen species, unregulated by usual intracellular processes.
                   • Third, myoglobin, through protein-binding, can precipitate in the tubule, leading to obstructive nephropathy.
                   
                   

                   Kate: Whew! That is a lot! Let’s take a break and review what we just learned:

                   Rhabdomyolysis is the injury of skeletal muscle leading to calcium influx into cells, which cascades into eventual apoptosis and necrosis. This leads to a massive release of intracellular components that upsets the overall homeostasis of the intra- and extracellular spaces. Myoglobin released from cells can directly injure the kidneys, leading to AKI. Potassium and hydrogen proton leakage, combined with AKI, can lead to life-threatening hyperkalemia and acidosis. CK is a serum measurement that can help confirm the diagnosis of rhabdomyolysis.

                   Rahul: Fun Fact Myoglobinuria usually only occurs in rhabdomyolysis (BUT not all rhabdomyolysis has myoglobinuria as it only spills out in urine above certain serum concentrations). Myoglobinuria can be inferred from a urine dipstick when there is moderate or large blood but few or no red blood cells. This is because the dipstick test for blood is non-specific for hemoglobin vs myoglobin! Myoglobin is also the reason the urine turns reddish-brown or “tea-colored.”

                   Pradip: Let’s change gears and talk about management. Kate, can you tell us about the management of rhabdomyolysis?

                   • Kate: With this patient, our first step should be resuscitation — always ABCs first! After initial fluid resuscitation and stabilization, we can begin to think about further workup and screening. Labs should include a comprehensive metabolic panel (CMP), urinalysis with dipstick, complete blood count, and creatine kinase. Depending on the severity of clinical illness, coagulation studies can be sent, as DIC is a rare complication of rhabdomyolysis, as well as sepsis, which is on our differential! In rhabdo, labs will show an elevated CK, possible hyperkalemia, acidosis, hyperphosphatemia, and hyperuricemia. If kidney injury is present, hyperkalemia is more likely, in addition to elevated creatinine.
                   • Once rhabdomyolysis is confirmed, treatment should focus on hydration, hydration, hydration! Additionally any complications of abnormal electrolytes, etc, should be monitored for and addressed. This includes telemetry monitoring or EKG in the setting of hyperkalemia.
                   
                   

                   Rahul: Remember, symptomatic hyperkalemia as evidenced by EKG changes, including wide QRS, absent P waves, or arrhythmias, including ventricular fibrillation, should be treated immediately. IV calcium administration will stabilize the cardiac membrane. Bicarbonate, insulin + glucose, and albuterol can quickly but only temporarily shift potassium into cells. Kayexalate and diuretics can remove potassium from the body.

                   • Pradip: Hydration is the most important treatment in rhabdomyolysis. There is a paucity of data, but most expert consensus suggests targeting a urine output of 3-4 ml/kg/hr while administering 2x maintenance fluids for children with rhabdo. Which fluid is the right fluid is still an area for more research, as studies have shown conflicting data about the benefits of NS vs LR vs bicarb-fluids. Normal saline without potassium can be used. Bicarbonate-containing fluids can be considered to buffer the urine on a case-by-case basis.
                   • Kate: And treatment of AKI should include avoidance of nephrotoxic medications and treatment of the underlying etiology. Renal replacement therapy should be considered for refractory fluid overload in the setting of oliguria or anuria, refractory acidosis (with pH<7.1), and refractory or life-threatening hyperkalemia. Remember those AEIOU reasons for RRT!
                   • With the resolution of the underlying cause, CK should peak in 3-5 days and then start to down-trend. Patients can be considered safe for discharge with the return of kidney function, normalization of electrolytes, and resolution of myoglobinuria.
                   
                   

                   We should note here that underlying metabolic myopathies can cause recurrent, mild rhabdomyolysis, though these children do not usually need critical care unless the cause for an exacerbation is sepsis or other potentially life-threatening illness!

                   • Kate: To wrap up, here are some take-away points:
                   • The key is hydration, hydration, hydration for the treatment and prevention of life-threatening electrolyte abnormalities and acute kidney injury in the setting of rhabdomyolysis
                   • If present, myoglobinuria indicates rhabdomyolysis.
                   • In children, viral illness is the most common cause of rhabdomyolysis, while toxins and trauma are more common in older teens and adults.
                   • Rahul: More information can be found
                   • “Rhabdomyolysis and acute kidney injury” from Bosch, et al, in the July 2009 issue of the New England Journal of Medicine and,
                   • “Pediatric rhabdomyolysis” in the June 2020 Pediatrics in Review
                   • References: (don't read these)
                   • Szugye HS. Pediatric Rhabdomyolysis. Pediatr Rev. 2020 Jun;41(6):265-275. doi: 10.1542/pir.2018-0300. PMID: 32482689.
                   • Nance JR, Mammen AL. Diagnostic evaluation of rhabdomyolysis. Muscle Nerve. 2015 un;51(6):793-810. doi: 10.1002/mus.24606. Epub 2015 Mar 14. PMID: 25678154; PMCID: PMC4437836.
                   • Bosch X, Poch E, Grau JM. Rhabdomyolysis and acute kidney injury. N Engl J Med. 2009 Jul 2;361(1):62-72. doi: 10.1056/NEJMra0801327. Erratum in: N Engl J Med. 2011 May 19;364(20):1982. PMID: 19571284.
                   
                   

                   Pradip: This concludes our episode on rhabdomyolysis. We hope you found value in our short, case-based podcast. We welcome you to share your feedback, subscribe & place a review on our podcast! Please visit our website picudoconcall.org which showcases our episodes as well as our Doc on Call management cards. PICU Doc on Call is co-hosted by myself Dr. Pradip Kamat and Dr. Rahul Damania — with special guest Kate Phelps today. Stay tuned for our next episode! Thank you!

                   ]]>7b9cf960-bacb-4409-b88a-6d50006f8f9eSun, 08 May 2022 01:00:00 -040014:47falsefull5252Approach to Calcium Channel Blocker OverdoseWelcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.

                   I'm Pradip Kamat and I'm Rahul Damania. We are coming to you from Children's Healthcare of Atlanta - Emory University School of Medicine.

                   Welcome to our Episode about a 14- year- old female who presented with hypotension after a suicide attempt.

                   Here's the case:

                   A 14 yo F with PMH of depression and oppositional defiant disorder presents with dizziness. Her mother states she was in her normal state of health when on the day of admission she noticed the patient to be dizzy, slurring speech, and pale. The mother became very concerned about the dizziness as the patient was stumbling and a few hours prior to presentation, became increasingly sleepy. The patient does have a history of depression and is controlled on sertraline. Other medications in the home include Metformin, Amlodipine, and Clonidine. The patient denies ingesting any substance. She does have a prior attempt two years prior, after an argument with her mother; however, her mother was able to “stop” her prior to the attempt. She presents to the ER via EMS. Her vital signs are notable for HR 50 bpm with occasional PACs and non-conducted QRS complexes on telemetry; BP of 75/40. A physical exam is notable for AMS and GCS of 10. She is noted to have clear breath sounds, with a cardiac exam notable for slowed and delayed pulses. Initial laboratory work is notable for serum glucose 180 mg/dL and B HCG negative. Initial resuscitation is begun with IV fluids and atropine. Serum acetaminophen and ASA levels are sent and upon stabilization, the patient presents to the PICU for admission.

                   
                   

                   To summarize key elements from this case, this patient has:

                   • A history of depression with prior attempt
                   • An acute bout of altered mental status
                   • Bradycardia, hypotension, and hyperglycemia.
                   • All of which brings up a concern for an acute ingestion
                   • Let’s take a step back and talk about the approach to ingestions in the PICU.
                   
                   
                   1. What are key aspects to consider in the work-up of these patients?
                   
                   
                   • History and physical are key:
                   • Stratifying acute or chronic ingestions
                   • Baseline prescription medications a patient may be taking or have access to in the household
                   • Whether the ingestion involves a single drug or co-ingestants are all first steps in evaluating your patient.
                   • In an undifferentiated patient, management is paramount. Initial management is focused on pattern recognition and acute stabilization.
                   • A brief initial screening examination should be performed on all patients to identify immediate measures required to stabilize and prevent deterioration of the patient. Assess the airway, vital signs, mental status, pupil size, and skin temperature and moisture.
                   
                   

                   These components of your physical exam should help allude to a toxidrome, and these syndromes are frequently tested on board examinations. Any time a patient has hypotension and bradycardia other drugs that should be considered include beta blockers, digoxin, clonidine, as well as ingestion of barbiturates, opioids, and even benzodiazepines.

                   
                   

                   1. What are some diagnostic studies you will want to send immediately in a patient with suspected ingestion?
                   2. Immediate diagnostic studies to be performed include pulse oximetry, continuous cardiac monitoring, an electrocardiogram (ECG), and a capillary glucose measurement (in altered patients). Intravenous (IV) access should be obtained in all cases of serious ingestion.
                   3. You also want to send beta-hcg and acetaminophen and salicylate levels. an extended toxicology screen may be required on a case-by-case basis.
                   
                   

                   One study found detectable serum acetaminophen concentrations in 9.6 percent of all overdose patients; almost one-third of this subset denied ingestion of acetaminophen.

                   
                   

                   1. Now that you’ve focused on ABCs are there more detailed laboratory studies to send in patients with toxidromes?
                   2. Symptomatic patients and those with an unreliable or unknown history should, at a minimum, undergo urinalysis and measurement of serum electrolytes, blood urea nitrogen (BUN), creatinine, and glucose. Measurements of serum ketones, creatine kinase, liver function tests, lipase, ionized calcium, and magnesium should also be performed in most significantly ill patients.
                   3. Additional testing may be useful in specific circumstances, such as serum osmolality in suspected toxic alcohol ingestion. We will discuss these in a separate episode.
                   4. Patients who continue to be altered may also undergo head CT as head trauma is frequently associated with ingestions.
                   5. ECG, Echocardiography helps to distinguish refractory hypotension due to vasodilatation from pump failure. CXR may be needed to evaluate pulmonary edema and guide fluid management. Abdominal radiograph or US may be required in cases of suspected bowel ischemia/perforation. Ingestion of a large number of CCB tablets, especially sustained-release tablets, the pills may aggregate to form bezoars and the drug can be continuously absorbed for long periods.
                   6. To go back to our case, with history and initial diagnostics only, how are we able to stratify whether this patient took a CCB versus a beta-blocker?
                   7. This is a great question. This patient had an electrocardiogram, which showed changes associated with CCB poisoning including a PR interval prolongation and bradydysrhythmia. Importantly, our patient’s serum glucose was >150 mg/dL and thus, the presence of hyperglycemia in a non-diabetic patient may help to distinguish CCB from beta-blocker poisoning.
                   
                   

                   The mechanism of hyperglycemia in CCB involves the CCB causing inhibition of calcium-mediated insulin release; remember that the serum glucose elevation is rarely clinically significant, and is used for diagnostic purposes to stratify between bb and CCB overdose.

                   
                   

                   Per history, our patient had access to amlodipine which is the likely agent she ingested. Can you shed some light on how non-DHP CCB overdoses are different than DHP overdoses?

                   • Let’s review some basic science & pharmacology:
                   • Calcium channel blockers (CCBs) can be divided into two major categories based on their predominant physiologic effects: dihydropyridines, which preferentially block the L-type calcium channels in the vasculature; and non-dihydropyridines, such as verapamil and diltiazem which selectively block L-type calcium channels in the myocardium.
                   • L-type calcium channels are responsible for myocardial contractility and vascular smooth muscle contractility; they also affect conducting and pacemaker cells.
                   • In general DHP (which has the suffix dipine) are potent vasodilators that have little negative effect upon cardiac contractility or conduction at standard doses.
                   • In contrast, verapamil and diltiazem are relatively weak vasodilators but have a depressive effect on cardiac conduction and contractility.
                   • How does this framework help with our understanding of CCB ingestions?
                   • Overdose with dihydropyridine CCBs (amlodipine/nifedipine) causes hypotension coupled with reflex tachycardia, although severe toxicity may result in hypotension and bradycardia. This is what we saw in our patient — severe toxicity.
                   • Overdose with non-DHP CCB like verapamil or diltiazem also causes a dangerous combination of hypotension and...]]>Welcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.

                     I'm Pradip Kamat and I'm Rahul Damania. We are coming to you from Children's Healthcare of Atlanta - Emory University School of Medicine.

                     Welcome to our Episode about a 14- year- old female who presented with hypotension after a suicide attempt.

                     Here's the case:

                     A 14 yo F with PMH of depression and oppositional defiant disorder presents with dizziness. Her mother states she was in her normal state of health when on the day of admission she noticed the patient to be dizzy, slurring speech, and pale. The mother became very concerned about the dizziness as the patient was stumbling and a few hours prior to presentation, became increasingly sleepy. The patient does have a history of depression and is controlled on sertraline. Other medications in the home include Metformin, Amlodipine, and Clonidine. The patient denies ingesting any substance. She does have a prior attempt two years prior, after an argument with her mother; however, her mother was able to “stop” her prior to the attempt. She presents to the ER via EMS. Her vital signs are notable for HR 50 bpm with occasional PACs and non-conducted QRS complexes on telemetry; BP of 75/40. A physical exam is notable for AMS and GCS of 10. She is noted to have clear breath sounds, with a cardiac exam notable for slowed and delayed pulses. Initial laboratory work is notable for serum glucose 180 mg/dL and B HCG negative. Initial resuscitation is begun with IV fluids and atropine. Serum acetaminophen and ASA levels are sent and upon stabilization, the patient presents to the PICU for admission.

                     
                     

                     To summarize key elements from this case, this patient has:

                     • A history of depression with prior attempt
                     • An acute bout of altered mental status
                     • Bradycardia, hypotension, and hyperglycemia.
                     • All of which brings up a concern for an acute ingestion
                     • Let’s take a step back and talk about the approach to ingestions in the PICU.
                     
                     
                     1. What are key aspects to consider in the work-up of these patients?
                     
                     
                     • History and physical are key:
                     • Stratifying acute or chronic ingestions
                     • Baseline prescription medications a patient may be taking or have access to in the household
                     • Whether the ingestion involves a single drug or co-ingestants are all first steps in evaluating your patient.
                     • In an undifferentiated patient, management is paramount. Initial management is focused on pattern recognition and acute stabilization.
                     • A brief initial screening examination should be performed on all patients to identify immediate measures required to stabilize and prevent deterioration of the patient. Assess the airway, vital signs, mental status, pupil size, and skin temperature and moisture.
                     
                     

                     These components of your physical exam should help allude to a toxidrome, and these syndromes are frequently tested on board examinations. Any time a patient has hypotension and bradycardia other drugs that should be considered include beta blockers, digoxin, clonidine, as well as ingestion of barbiturates, opioids, and even benzodiazepines.

                     
                     

                     1. What are some diagnostic studies you will want to send immediately in a patient with suspected ingestion?
                     2. Immediate diagnostic studies to be performed include pulse oximetry, continuous cardiac monitoring, an electrocardiogram (ECG), and a capillary glucose measurement (in altered patients). Intravenous (IV) access should be obtained in all cases of serious ingestion.
                     3. You also want to send beta-hcg and acetaminophen and salicylate levels. an extended toxicology screen may be required on a case-by-case basis.
                     
                     

                     One study found detectable serum acetaminophen concentrations in 9.6 percent of all overdose patients; almost one-third of this subset denied ingestion of acetaminophen.

                     
                     

                     1. Now that you’ve focused on ABCs are there more detailed laboratory studies to send in patients with toxidromes?
                     2. Symptomatic patients and those with an unreliable or unknown history should, at a minimum, undergo urinalysis and measurement of serum electrolytes, blood urea nitrogen (BUN), creatinine, and glucose. Measurements of serum ketones, creatine kinase, liver function tests, lipase, ionized calcium, and magnesium should also be performed in most significantly ill patients.
                     3. Additional testing may be useful in specific circumstances, such as serum osmolality in suspected toxic alcohol ingestion. We will discuss these in a separate episode.
                     4. Patients who continue to be altered may also undergo head CT as head trauma is frequently associated with ingestions.
                     5. ECG, Echocardiography helps to distinguish refractory hypotension due to vasodilatation from pump failure. CXR may be needed to evaluate pulmonary edema and guide fluid management. Abdominal radiograph or US may be required in cases of suspected bowel ischemia/perforation. Ingestion of a large number of CCB tablets, especially sustained-release tablets, the pills may aggregate to form bezoars and the drug can be continuously absorbed for long periods.
                     6. To go back to our case, with history and initial diagnostics only, how are we able to stratify whether this patient took a CCB versus a beta-blocker?
                     7. This is a great question. This patient had an electrocardiogram, which showed changes associated with CCB poisoning including a PR interval prolongation and bradydysrhythmia. Importantly, our patient’s serum glucose was >150 mg/dL and thus, the presence of hyperglycemia in a non-diabetic patient may help to distinguish CCB from beta-blocker poisoning.
                     
                     

                     The mechanism of hyperglycemia in CCB involves the CCB causing inhibition of calcium-mediated insulin release; remember that the serum glucose elevation is rarely clinically significant, and is used for diagnostic purposes to stratify between bb and CCB overdose.

                     
                     

                     Per history, our patient had access to amlodipine which is the likely agent she ingested. Can you shed some light on how non-DHP CCB overdoses are different than DHP overdoses?

                     • Let’s review some basic science & pharmacology:
                     • Calcium channel blockers (CCBs) can be divided into two major categories based on their predominant physiologic effects: dihydropyridines, which preferentially block the L-type calcium channels in the vasculature; and non-dihydropyridines, such as verapamil and diltiazem which selectively block L-type calcium channels in the myocardium.
                     • L-type calcium channels are responsible for myocardial contractility and vascular smooth muscle contractility; they also affect conducting and pacemaker cells.
                     • In general DHP (which has the suffix dipine) are potent vasodilators that have little negative effect upon cardiac contractility or conduction at standard doses.
                     • In contrast, verapamil and diltiazem are relatively weak vasodilators but have a depressive effect on cardiac conduction and contractility.
                     • How does this framework help with our understanding of CCB ingestions?
                     • Overdose with dihydropyridine CCBs (amlodipine/nifedipine) causes hypotension coupled with reflex tachycardia, although severe toxicity may result in hypotension and bradycardia. This is what we saw in our patient — severe toxicity.
                     • Overdose with non-DHP CCB like verapamil or diltiazem also causes a dangerous combination of hypotension and bradycardia. As these are cardiac-specific, other findings may include signs of heart failure (eg, pulmonary crackles or jugular venous distension). In anecdotal articles, CCB-poisoned patients may maintain a surprisingly clear mental status in the setting of hypotension.
                     
                     

                     Let’s conclude our episode by focusing on the management of CCB overdose. We will break this section down into initial resuscitation, the role of gastrointestinal decontamination, and specific medial therapies.

                     Let’s start with the ABC approach and initial resuscitation. What are some key management pearls?

                     An immediate consult with Poison control center is a must: PCC can help guide monitoring, investigational studies as well as patient management.

                     Empiric use of Glucagon 5-15mg IV may be warranted when patient presents with hypotension/bradycardia. Glucagon promotes calcium entry into cells via stimulation of a receptor that is considered to be separate from adrenergic receptors.

                     • Circulation is the main focus of the treatment of calcium channel blocker (CCB) exposures. Hypotension and bradycardia can be profound and refractory even to maximal treatment.
                     • Judicious use of Intravenous (IV) fluids, as well as vasopressors, are the initial therapy for hypotension, and atropine for the initial treatment for bradycardia, but both may be insufficient.
                     
                     

                     Our patient in our case maintained clear mental status despite hypotension and bradycardia. However, we need to reassess these patients frequently, as precipitous deterioration is common, and many will eventually require intubation and mechanical ventilation. With the exception of nimodipine, calcium channel blockers have poor CNS penetration. Therefore, drowsiness, seizures, or altered mental status in the absence of hemodynamic collapse should alert the physician to the possibility of co-ingestions.

                     
                     

                     For patients with CCB overdose, is there a role for orogastric lavage?

                     • Oro-gastric lavage and activated charcoal may be necessary for patients who present within one to two hours, however, make sure to use caution in a patient who has borderline mental status and who may not be able to protect their airway.
                     • Another clinical pearl to consider is that the vagal stimulation from orogastric lavage may exacerbate CCB-induced hypotension and bradycardia.
                     
                     

                     Let’s transition and talk about specific medical therapies. In diving deep into the literature, we will talk about the role of catecholamines/vasopressors, Atropine, IV Ca, Glucagon, Insulin & Dextrose, and Lipid emulsion therapies.

                     What vasopressors/catecholamines are used in CCB?

                     • Direct-acting vasopressors such as norepinephrine/epinephrine infusion is preferred in CCB. Angiotensin II (Giapreza) -a vasoconstrictor can be considered in patients 18 years of age and above.
                     
                     

                     How does atropine help in CCB overdose?

                     • Atropine is a muscarinic antagonistic and thus should be administered to any patient with symptomatic bradycardia after CCB. Pediatric dosing is 0.02 mg/kg IV, with a minimum dose of 0.1 mg to avoid the paradoxical bradycardia that may result from very small doses of this medication.
                     • What about IV Calcium?
                     
                     

                     
                     

                     • Calcium salts are often used to overcome the cardiovascular effects of CCBs.
                     • As calcium channel blockers as the name implies, inhibit calcium it is important for us to understand that CCB poisoning interferes with both the serum concentration and the intracellular handling of calcium.
                     • Anecdotally high-dose continuous infusion of calcium should be administered — after bolus dosing, a reasonable infusion of Ca Cl to consider is 0.5 mEq of calcium/kg per hour. Close monitoring of the serum or ionized calcium concentration (measurements every two hours) and serial electrocardiograms (ECGs) are necessary to avoid clinically significant hypercalcemia, which has been reported with intensive calcium therapy. The use of an aline for serial labs and hemodynamic monitoring is essential.
                     • What about Glucose and Insulin:
                     • High dose insulin (1-10U/KG/hr after a 1U/kg bolus dose) is required in CCB along with dextrose which helps to counteract the hypoglycemia. Hypokalemia can occur due to a shift in K intracellularly and requires close monitoring. It generally takes approximately 30 minutes to see the effects from HIE. The main beneficial effect is on myocardial function (ie, ejection fraction and cardiac output), with subsequent improvement in blood pressure and perfusion although improvement in cardiac rhythm has also been reported.
                     • Investigational therapies: use of methylene blue (1-2mg/kg), lipid emulsion can be tried as a last resort in those with severe hemodynamic issues and can be used even if the patient is not in cardiac arrest.
                     • Please visit our episode entitled PICU Applications of Lipid Emulsion Therapy. The use of lipids is controversial however in general: an IV bolus of 1 to 1.5 mL/kg is given over one minute of a 20 percent lipid emulsion solution. If there is no response, the same dose may be repeated in cases of cardiac arrest every three to five minutes for a total of three bolus doses. Following the initial bolus, an infusion is started at a rate of 0.25 to 0.5 mL/kg per minute until hemodynamic recovery occurs. The infusion is generally maintained for 30 to 60 minutes. The infusion rate may be increased if the patient's blood pressure drops.
                     • 
                       
                     • 
                       
                     • Procedures that may be required in CCB include: 1) A transvenous pacemaker may be placed if the transthoracic cutaneous pacer fails to capture in the face of symptomatic bradycardia. Pacing may decrease the need for pressors in a patient who may not tolerate a positive cardiac inotrope because of cardiac ischemia, although this likely is not a concern in children. Cardiac pacing is typically required for 12-48 hours.
                     • 
                       
                     • 2) Extracorporeal membrane oxygenation (ECMO) has also been attempted in patients who have hypotension refractory to all pharmacologic therapies.
                     • 
                       
                     • Rahul what are Key objective take-aways from today’s episode:
                     
                     
                     1. Hypotension & bradycardia is a life-threatening toxidrome that is related to circulatory collapse and poor cerebral perfusion.
                     2. Differential includes:
                     3. CCB
                     4. BB
                     5. Digoxin
                     6. Clonidine
                     7. CNS depressants
                     8. A stepwise approach to CCB includes — close monitoring of ABCs, and in severely symptomatic patients: IV boluses of isotonic crystalloid, IV calcium salts, IV glucagon, IV high-dose insulin and glucose, IV vasopressor (eg, norepinephrine), and IV lipid emulsion therapy in refractory cases.
                     
                     

                     This concludes our episode on Approach to Calcium Channel Blockers. We hope you found value in our short, case-based podcast. We welcome you to share your feedback, subscribe & place a review on our podcast! Please visit our website picudoconcall.org which showcases our episodes as well as...]]>86b9fa01-c865-4074-bdf2-d8da36b1081aSun, 01 May 2022 03:00:00 -040021:06falsefull5151All Things Sodium & the Brain in the PICUWelcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.

                     I'm Pradip Kamat and I'm Rahul Damania. We are coming to you from Children's Healthcare of Atlanta - Emory University School of Medicine.

                     Here's the case:

                     A 6-year-old child with a known h/o craniopharyngioma who has been endocrinologically intact with exception of needing thyroid replacement was admitted to the PICU prior to craniotomy to proceed with further tumor resection as well as the removal of a secondary cyst impacting his brainstem. The patient is receiving Keppra for seizures and per mother, he has recently been significantly more sleepy at school.

                     On POD Op day 5: the PICU the bedside nurse notices increased urine output (6cc/kg/hr to as high as 10cc/kg/hr). Initially, there was an increase in Na to 157mEq/L within 48-72 hours the serum Na dropped to 128mEq/L

                     To summarize key elements from this case, this patient has:

                     • Increase UOP
                     • Rapidly increasing Na initially followed by a drop
                     • All of which brings up a concern for Na abnormality post craniotomy
                     
                     

                     In today’s episode, we will be breaking down all things Sodium & the Brain. We will discuss diagnostic & management frameworks related to three pathologies:

                     1. Central Diabetes Insipidus
                     2. Syndrome of inappropriate Anti-Diuretic Hormone or SIADH
                     3. Cerebral Salt Wasting
                     
                     

                     These diagnoses can certainly be seen individually inpatients or as a spectrum of diseases — as we go through each of these diagnoses, pay particular attention to patient characteristics and lab abnormalities. Namely, serum sodium, serum osm, and urine osm.

                     To build the fundamentals, lets first start with classic nephrology saying: Serum Na represents Hydration

                     This takes us into a brief review of normal physiology — talking about three important hormones:

                     1. ADH
                     2. Aldosterone
                     3. Atrial Natriuretic Peptide (ANP)
                     
                     

                     Let’s go through a quick multiple-choice question.

                     A patient is recently started on DDAVP for pan-hypopituitarism. The medication acts similarly to a hormone that is physiologically synthesized in which of the following from which are in the body?

                     A. Paraventricular Nucleus of the Hypothalamus

                     B. Supraoptic Nucleus of the Hypothalamus

                     C. Anterior Pituitary

                     D. Vascular Endothelium

                     The correct answer here is B the Supraoptic Nucleus of the Hypothalamus. Remember that ADH is synthesized in the hypothalamus and released from the posterior pituitary.

                     What are the physiologic actions of ADH?

                     ADH Increases H2O permeability by directing the insertion of aquaporin 2 (AQP2) H2O channels in the luminal membrane of the principal cells. Thus, as we will see with Central Diabetes insipidus, in the absence of ADH, the principal cells are virtually impermeable to water.

                     Let's talk about our next hormone, aldosterone. What are the important physiologic considerations?

                     • Aldosterone is secreted from the adrenal cortex as a byproduct of the RAAS.
                     • Aldosterone increases Na+ reabsorption by the renal distal tubule, thereby increasing extracellular fluid (ECF) volume, blood volume, and arterial pressure.
                     • It also helps in secreting K and H. This physiology is applied directly at the bedside when we have patients in the ICU who have a contraction alkalosis secondary to diuretics. The increase in aldosterone as these patients lose free water from their Lasix administration results in hypokalemia and metabolic alkalosis.
                     
                     

                     Alright, what about the third hormone, ANP?

                     • Atrial natriuretic peptide (ANP) is released from the atria in response to an increase in blood volume and atrial pressure.
                     • ANP causes relaxation of vascular smooth muscle, dilation of arterioles, and decreased TPR.
                     • causes increased excretion of Na+ and water by the kidney, which reduces blood volume and attempts to bring arterial pressure down to normal.
                     
                     

                     As ANP causes natriuresis, diuresis, and inhibition of renin, you can consider this hormone as having a complementary & opposite effect to ADH and aldosterone.

                     Alright, now that we have the basics, let's talk about our index case presentation, central diabetes insipidus, can you illustrate the key diagnostic features of this disease?

                     • Central diabetes insipidus (CDI) is an important cause of hypernatremia in the intensive care setting and can be seen in primary brain lesions, traumatic brain injury, or as a harbinger of brain death.
                     • CDI results from inadequate ADH secretion. Children in the intensive care setting typically present with abrupt polyuria and free water diuresis.
                     
                     

                     What are common triggers for CDI?

                     • Traumatic brain injury, brain tumors, pituitary surgery (i.e. postoperative craniopharyngioma resection), central nervous system infections, and cerebral hemorrhages or infarcts.
                     • CDI occurs most commonly in the setting of brain death.
                     
                     

                      Because patients with CDI can conserve sodium appropriately, they typically do not manifest signs of volume depletion unless the diagnosis is delayed. Thus CDI is a cause of euvolemic hypernatremia.

                     Absolutely, actually, in CDI the urine osmolality is typically less than the plasma osmolality. These patients have about >4 mL/kg/hr of urine output.

                     What is the management of CDI?

                     • CDI includes the correction of free water deficit and the administration of the ADH synthetic analog desmopressin acetate (dDAVP). In a critically-ill patient, a vasopressin infusion may be needed for the rapid increase in UOP and serum Na. An advantage of vasopressin is the “quick on-off effect”
                     • Desmopressin can be administered subcutaneously, intranasally, or intravenously. The dosing varies by the route of administration and can be thought of as the 1-10-100 rule.
                     • IV 1mcg
                     • IN 10mcg (one puff = 10mcg)
                     • PO 100mcg
                     • In critically ill patients, edema and peripheral vasoconstriction may preclude effective subcutaneous administration therefore intravenous administration of dDAVP or a continuous vasopressin infusion may be required.
                     
                     

                     Alright, so you gave the patient with presumed CDI a dose of DDAVP. What will you expect?

                     • Patients with central diabetes insipidus will typically have a reduction in urinary output and a greater than 50% increase in urine osmolality in response to the first dose of dDAVP.
                     • At times we are measuring their urine output in mL/kg/hr so if a patient is on a continuous vasopressin infusion for DI, titrating to a UOP of 1-2 mL/kg/hr can be appropriate.
                     
                     

                     Rahul why do you think in our patient with high UOP and a high serum Na, the serum Na suddenly dropped in 48 hours?

                     There are two possibilities. Either patient has received DDAVP or]]>Welcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.

                     I'm Pradip Kamat and I'm Rahul Damania. We are coming to you from Children's Healthcare of Atlanta - Emory University School of Medicine.

                     Here's the case:

                     A 6-year-old child with a known h/o craniopharyngioma who has been endocrinologically intact with exception of needing thyroid replacement was admitted to the PICU prior to craniotomy to proceed with further tumor resection as well as the removal of a secondary cyst impacting his brainstem. The patient is receiving Keppra for seizures and per mother, he has recently been significantly more sleepy at school.

                     On POD Op day 5: the PICU the bedside nurse notices increased urine output (6cc/kg/hr to as high as 10cc/kg/hr). Initially, there was an increase in Na to 157mEq/L within 48-72 hours the serum Na dropped to 128mEq/L

                     To summarize key elements from this case, this patient has:

                     • Increase UOP
                     • Rapidly increasing Na initially followed by a drop
                     • All of which brings up a concern for Na abnormality post craniotomy
                     
                     

                     In today’s episode, we will be breaking down all things Sodium & the Brain. We will discuss diagnostic & management frameworks related to three pathologies:

                     1. Central Diabetes Insipidus
                     2. Syndrome of inappropriate Anti-Diuretic Hormone or SIADH
                     3. Cerebral Salt Wasting
                     
                     

                     These diagnoses can certainly be seen individually inpatients or as a spectrum of diseases — as we go through each of these diagnoses, pay particular attention to patient characteristics and lab abnormalities. Namely, serum sodium, serum osm, and urine osm.

                     To build the fundamentals, lets first start with classic nephrology saying: Serum Na represents Hydration

                     This takes us into a brief review of normal physiology — talking about three important hormones:

                     1. ADH
                     2. Aldosterone
                     3. Atrial Natriuretic Peptide (ANP)
                     
                     

                     Let’s go through a quick multiple-choice question.

                     A patient is recently started on DDAVP for pan-hypopituitarism. The medication acts similarly to a hormone that is physiologically synthesized in which of the following from which are in the body?

                     A. Paraventricular Nucleus of the Hypothalamus

                     B. Supraoptic Nucleus of the Hypothalamus

                     C. Anterior Pituitary

                     D. Vascular Endothelium

                     The correct answer here is B the Supraoptic Nucleus of the Hypothalamus. Remember that ADH is synthesized in the hypothalamus and released from the posterior pituitary.

                     What are the physiologic actions of ADH?

                     ADH Increases H2O permeability by directing the insertion of aquaporin 2 (AQP2) H2O channels in the luminal membrane of the principal cells. Thus, as we will see with Central Diabetes insipidus, in the absence of ADH, the principal cells are virtually impermeable to water.

                     Let's talk about our next hormone, aldosterone. What are the important physiologic considerations?

                     • Aldosterone is secreted from the adrenal cortex as a byproduct of the RAAS.
                     • Aldosterone increases Na+ reabsorption by the renal distal tubule, thereby increasing extracellular fluid (ECF) volume, blood volume, and arterial pressure.
                     • It also helps in secreting K and H. This physiology is applied directly at the bedside when we have patients in the ICU who have a contraction alkalosis secondary to diuretics. The increase in aldosterone as these patients lose free water from their Lasix administration results in hypokalemia and metabolic alkalosis.
                     
                     

                     Alright, what about the third hormone, ANP?

                     • Atrial natriuretic peptide (ANP) is released from the atria in response to an increase in blood volume and atrial pressure.
                     • ANP causes relaxation of vascular smooth muscle, dilation of arterioles, and decreased TPR.
                     • causes increased excretion of Na+ and water by the kidney, which reduces blood volume and attempts to bring arterial pressure down to normal.
                     
                     

                     As ANP causes natriuresis, diuresis, and inhibition of renin, you can consider this hormone as having a complementary & opposite effect to ADH and aldosterone.

                     Alright, now that we have the basics, let's talk about our index case presentation, central diabetes insipidus, can you illustrate the key diagnostic features of this disease?

                     • Central diabetes insipidus (CDI) is an important cause of hypernatremia in the intensive care setting and can be seen in primary brain lesions, traumatic brain injury, or as a harbinger of brain death.
                     • CDI results from inadequate ADH secretion. Children in the intensive care setting typically present with abrupt polyuria and free water diuresis.
                     
                     

                     What are common triggers for CDI?

                     • Traumatic brain injury, brain tumors, pituitary surgery (i.e. postoperative craniopharyngioma resection), central nervous system infections, and cerebral hemorrhages or infarcts.
                     • CDI occurs most commonly in the setting of brain death.
                     
                     

                      Because patients with CDI can conserve sodium appropriately, they typically do not manifest signs of volume depletion unless the diagnosis is delayed. Thus CDI is a cause of euvolemic hypernatremia.

                     Absolutely, actually, in CDI the urine osmolality is typically less than the plasma osmolality. These patients have about >4 mL/kg/hr of urine output.

                     What is the management of CDI?

                     • CDI includes the correction of free water deficit and the administration of the ADH synthetic analog desmopressin acetate (dDAVP). In a critically-ill patient, a vasopressin infusion may be needed for the rapid increase in UOP and serum Na. An advantage of vasopressin is the “quick on-off effect”
                     • Desmopressin can be administered subcutaneously, intranasally, or intravenously. The dosing varies by the route of administration and can be thought of as the 1-10-100 rule.
                     • IV 1mcg
                     • IN 10mcg (one puff = 10mcg)
                     • PO 100mcg
                     • In critically ill patients, edema and peripheral vasoconstriction may preclude effective subcutaneous administration therefore intravenous administration of dDAVP or a continuous vasopressin infusion may be required.
                     
                     

                     Alright, so you gave the patient with presumed CDI a dose of DDAVP. What will you expect?

                     • Patients with central diabetes insipidus will typically have a reduction in urinary output and a greater than 50% increase in urine osmolality in response to the first dose of dDAVP.
                     • At times we are measuring their urine output in mL/kg/hr so if a patient is on a continuous vasopressin infusion for DI, titrating to a UOP of 1-2 mL/kg/hr can be appropriate.
                     
                     

                     Rahul why do you think in our patient with high UOP and a high serum Na, the serum Na suddenly dropped in 48 hours?

                     There are two possibilities. Either patient has received DDAVP or more likely patient is having a Triphasic Response as many patients undergoing pituitary surgery do (DI within 2-4 days, followed by SIADH for 2-5 days, and a return to DI), which sometimes can be difficult to treat.

                     Most patients with CP already have pituitary hormone deficiencies at the time of diagnosis, which is more common in children than adults. Approximately 70% of children had growth hormone (GH) deficiency, followed by gonadotropin deficiency (51.7%), central diabetes insipidus (CDI, 28.6%), and thyroid-stimulating hormone (TSH) deficiency (21.9%), and adrenocorticotrophic hormone (ACTH) deficiency (12.5%).

                     The course of postoperative CDI can be transient, permanent, or a component of the triphasic pattern.

                     Pradip, can you highlight the triphasic response a bit more?

                     • In the first phase of the triphasic pattern, there is an acute increase in hypo-osmolar urine output within 24–48 h following surgery due to antidiuretic hormone (ADH) deficiency resulting from traumatic edema of the neurons, axonal shock due to impairment of vascular supply, and/or pituitary stalk transection.
                     • The patients have a tendency toward hypernatremic dehydration during this phase, which lasts approximately 1–7 days. At this phase, appropriate fluid replacement is required to prevent water loss and hypernatremic dehydration.
                     • However, low-dose diamino D-arginine vasopressin (desmopressin; dDAVP) can be used to decrease fluid intake/output. dDAVP replacement dose should be titrated with caution because its long half-life during this phase may complicate the subsequent hyponatremic phase of the triphasic response.
                     
                     

                     Let’s transition to the other extreme, and that is SIADH — syndrome of too much ADH. What are some common etiologies?

                     • SIADH can occur due to a variety of illnesses, but most often occurs due to central nervous system disorders, pulmonary disorders, and medications. As this episode is all things brain and salt related, common CNS diagnosis that can lead to SIADH are:
                     • Meningitis, encephalitis
                     • Neoplasms
                     • Post-pituitary surgery
                     • Hydrocephalus
                     • Head Trauma
                     
                     

                     We will be reviewing specific electrolyte disorders in future episodes however please remember that hyponatremia like SIADH typically develops when a relative excess of free water is accompanied by an underlying condition that impairs the kidney’s ability to excrete free water. In SIADH, ADH secretion occurs independently of serum osmolality and intravascular volume status.

                     Interestingly, SIADH is essentially a diagnosis of exclusion. Before SIADH can be diagnosed, diseases causing decreased effective circulating volume, renal impairment, adrenal insufficiency, and hypothyroidism must be excluded.

                     Clinically, what will we see?

                     • The hallmarks of SIADH are:
                     • mild volume expansion with low to normal plasma concentrations of creatinine, urea, uric acid, and potassium
                     • impaired free water excretion with normal sodium excretion which reflects sodium intake
                     • hyponatremia which is relatively unresponsive to sodium administration in the absence of fluid restriction.
                     
                     

                     If left uncorrected, SIADH can lead to severe hyponatremia (plasma Na <120 mEq/L) - leading to seizures.

                     To close out this topic, how would you approach the management of SIADH?

                     • SIADH is usually of short duration and resolves with treatment of the underlying disorder and discontinuation of the offending medication.
                     • Additionally, fluid restriction is the cornerstone of therapy for SIADH.
                     • However, fluid restriction results in slow correction of hyponatremia and is frequently impractical in infants who receive most of their nutrition as liquids.
                     
                     

                     Finally, let’s talk about Cerebral salt wasting. How can we compare and contrast CSW and SIADH?

                     • In the setting of CNS injury or following a neurosurgical procedure, hyponatremia is usually attributed to SIADH, a condition whose hallmark is euvolemia to mild hypervolemia, with the cornerstone of management being fluid restriction.
                     • More recently it has become apparent that an increasing number of neurosurgical patients with hyponatremia can have CSW a condition whose hallmark is renal sodium loss leading to extracellular volume depletion.
                     
                     

                     So to summarize patients with CSW and SIADH can both be hypoNa in the setting of brain injury however patients with CSW are hypovolemic relative to patients with SIADH who have a euvolemic hypoNa.

                     What is the pathogenesis of CSW?

                     • The pathogenesis of CSW is not completely understood, but it appears to be due to the release of natriuretic peptides, such as an atrial natriuretic peptide. As we reviewed in our physiology discussion, ANP helps us with three things:
                     • hemodynamic effects leading to an increased GFR
                     • inhibition of the renin
                     • Inhibition of the secretion and action of ADH
                     • And, just to summarize, the key distinguishing feature between CSW and SIADH is extracellular volume depletion. You can establish this assessment via serial monitoring of UOP, clinical exam, and CVPs.
                     
                     

                     Pradip, any other clinical pearl regarding CSW?

                     • Yes, so when you provide NS infusion to a patient, let's say with SIADH — it should be adequate prophylaxis to prevent hypoNa (i.e. a sodium <130 meQ/L)
                     • However, If clinically significant hyponatremia develops inpatient with a CNS disorder receiving only normal saline, then the diagnosis of CSW should be strongly considered.
                     
                     

                     How do we manage these patients?

                     • The hallmark pearl is to expand their intravascular space.
                     • This can be achieved by normal saline, followed by sufficient quantities of normal saline and 3% NaCl to main fluid balance and normal serum sodium. There have been studies that have advocated the administration of fludrocortisone as aldosterone production is relatively decreased in CSW.
                     
                     

                     Ok, Rahul, do you mind summarizing today’s episode?

                     This concludes our episode on All Things Sodium & the Brain in the PICU. We hope you found value in our short, case-based podcast. We welcome you to share your feedback, subscribe & place a review on our podcast! Please visit our website picudoconcall.org which showcases our episodes as well as our Doc on Call management cards. PICU Doc on Call is co-hosted by myself Dr. Pradip Kamat and Dr. Rahul Damania. Stay tuned for our next episode! Thank you!

                     • References:
                     • Bereket A: Postoperative and Long-Term Endocrinologic Complications of Craniopharyngioma. Horm Res Paediatr 2020;93:497-509. doi: 10.1159/000515347
                     • Prete A, Corsello SM, Salvatori R. Current best practice in the management of patients after pituitary surgery. Therapeutic Advances in Endocrinology and Metabolism. March 2017:33-48. doi:10.1177/2042018816687240
                     
                     ]]>467e1df6-732d-4152-98a2-c1bbca6dd40fSun, 17 Apr 2022 03:00:00 -040021:11falsefull5050Necrotizing Enterocolitis (NEC)Welcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.

                     I'm Pradip Kamat. I’m Dr. Ali Towne, a rising 3rd-year pediatrics resident interested in a neonatology fellowship, and I'm Rahul Damania and we are coming to you from Children's Healthcare of Atlanta - Emory University School of Medicine.

                     Welcome to our Episode a 5-month-old, ex-28 week female with abdominal distention.

                     Here's the case:

                     A 5-month-old, ex 28 week, female with a past medical history of severe BPD, pulmonary hypertension, home oxygen requirement, and G-tube dependence presents with hypoxemia and increased work of breathing.

                     The patient has a history of prolonged NICU stay with 8 weeks of intubation. The patient developed worsening respiratory distress requiring increased support and eventual intubation for hypoxemic respiratory failure. Echo showed worsened pulmonary hypertension with severe systolic flattening of the ventricular septum and a markedly elevated TR jet. The patient had poor peripheral perfusion, and upon intubation was started on milrinone and epinephrine. The patient improved, but the patient then developed abdominal distention and increasing FiO2 requirements prompting an abdominal x-ray. X-ray showed diffuse pneumatosis with portal venous gas. The patient was made NPO and antibiotic therapy was initiated.

                     To summarize key elements from this case, this patient has NEC.

                     • NEC is not a homogenous disease, but rather a collection of diseases with similar phenotypes.
                     • Some people split NEC into two categories: Cardiac NEC and Inflammatory NEC.
                     • Babies who develop cardiac NEC tend to be significantly older than babies who develop inflammatory NEC (about 1 month vs 2 weeks).
                     • There are three main contributory factors to the development of NEC: gut prematurity, abnormal bacterial colonization, and ischemia-reperfusion injury.
                     • Many cases result from an ischemic insult to the bowel, resulting in translocation of intra-luminal bacteria into the wall of the bowel, but the etiology and course of NEC can be very variable.
                     • This translocation can cause sepsis and death; the ischemia of the bowel can result in intestinal perforation and/or necrosis.
                     
                     

                     Necrotizing enterocolitis (NEC) is one of the most common gastrointestinal emergencies in the newborn infant. It is estimated to occur in 1 to 3 per 1000 live births. More than 90 percent of cases occur in very low birth weight (VLBW) infants (BW <1500 g) born at <32 weeks gestation, and the incidence of NEC decreases with increasing gestational age (GA) and BW.

                     What are key risk factors for the development of NEC?

                     • Prematurity and Birth Weight
                     • NEC incidence is inversely proportional to gestational age.
                     • Congenital Heart Disease
                     • Puts children at risk for NEC due to (1) decreased stroke volume, and (2) improperly oxygenated blood which reduced oxygen supply to the SMA and decreases intestinal wall perfusion.
                     • On the repair of the cardiac lesion, patients develop reperfusion injury due to their now improved perfusion to their gut. This reperfusion causes hyper inflammation via neutrophil activation resulting in NEC.
                     •  NEC primarily occurs in healthy, growing, and feeding VLBW preterm infants. It presents with sudden changes in feeding tolerance (increase in gastric residuals) with both nonspecific systemic signs (eg, apnea, respiratory failure, poor feeding, lethargy, or temperature instability) and abdominal signs (eg, abdominal distension, bilious gastric retention and/or vomiting, tenderness, rectal bleeding, and diarrhea). Physical findings may include abdominal wall erythema, crepitus, and induration.
                     
                     

                     Other than the immediate risk of death, what are some consequences of NEC long-term?

                     • Higher risk of malnutrition and short gut.
                     • BPD
                     • Developmental delay.
                     
                     

                     What are some areas of current research and development on the topic of NEC?

                     • Improved biomarkers for early recognition of NEC prior to the development of radiographic findings.
                     • Preventative measures.
                     • Immune modulators of NEC development.
                     • Underdeveloped adaptive immunity of the premature infant may be contributory.
                     • The normal passive sharing of immune compounds between mother and babies (IgG via the placenta and secretory IgA from breastmilk) is disrupted in premature infants, particularly those that are formula-fed.
                     • The majority of IgG transfer occurs in the last 4 weeks of pregnancy.
                     • Several additional cellular and cytokine-based changes may increase the risk of NEC.
                     
                     

                     A clinical diagnosis of NEC is based on the presence of the characteristic clinical features of abdominal distension, bilious vomiting or gastric aspirate, rectal bleeding (hematochezia), and the abdominal radiographic finding of pneumatosis intestinalis, pneumoperitoneum, or sentinel loops. The definite diagnosis of NEC is made from either surgical or postmortem intestinal specimens that demonstrate the histological findings of inflammation, infarction, and necrosis. However, a pathologic diagnosis is not always possible.

                     What are some of the currently favored preventative measures used to decrease the risk of NEC?

                     • Probiotics – research has found that babies with NEC have a different underlying gut microbiome than infants without NEC.
                     • The underlying suggestion is that “good bacteria” prevent the overgrowth of gram-negative enteric pathogens that may lead to NEC.
                     • Associated with increased risk in the development of NEC between 30-32 weeks where there is a concomitant change in microbiome colonization.
                     • Also, some suggestions that “good bacteria” downregulate the inflammatory response in the gut.
                     • Dosing, type of probiotic, and other details of usage are still yet to be decided on.
                     • Still not the standard of care in the US.
                     • Human Milk over Formula – a 1990 study demonstrated that the risk of NEC is 6-10 times greater in formula-fed infants.
                     • Secretory IgA from breastmilk may be protected as the adaptive immune system develops.
                     
                     

                     How is NEC managed?

                     • NEC is typically managed with gut rest (NPO with mIVF), gut decompression (Anderson tube to LIS), and broad-spectrum antibiotic coverage (we use Vanc and Zosyn at CHOA).
                     • Typically is managed in conjunction with pediatric surgery to evaluate the need for surgical resection.
                     • Otherwise, management includes supportive care including increased respiratory support as needed and typically TPN given the length of NPO time required.
                     • Pradip, we talked a great deal about NEC however can you provide some key differentials to consider?
                     • The differential diagnosis of NEC includes other conditions that cause rectal bleeding, abdominal distension, or intestinal perforation. These include spontaneous intestinal perforation of the newborn, infectious enterocolitis, and other causes of the surgical abdomen. NEC is usually differentiated...]]>Welcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.

                       I'm Pradip Kamat. I’m Dr. Ali Towne, a rising 3rd-year pediatrics resident interested in a neonatology fellowship, and I'm Rahul Damania and we are coming to you from Children's Healthcare of Atlanta - Emory University School of Medicine.

                       Welcome to our Episode a 5-month-old, ex-28 week female with abdominal distention.

                       Here's the case:

                       A 5-month-old, ex 28 week, female with a past medical history of severe BPD, pulmonary hypertension, home oxygen requirement, and G-tube dependence presents with hypoxemia and increased work of breathing.

                       The patient has a history of prolonged NICU stay with 8 weeks of intubation. The patient developed worsening respiratory distress requiring increased support and eventual intubation for hypoxemic respiratory failure. Echo showed worsened pulmonary hypertension with severe systolic flattening of the ventricular septum and a markedly elevated TR jet. The patient had poor peripheral perfusion, and upon intubation was started on milrinone and epinephrine. The patient improved, but the patient then developed abdominal distention and increasing FiO2 requirements prompting an abdominal x-ray. X-ray showed diffuse pneumatosis with portal venous gas. The patient was made NPO and antibiotic therapy was initiated.

                       To summarize key elements from this case, this patient has NEC.

                       • NEC is not a homogenous disease, but rather a collection of diseases with similar phenotypes.
                       • Some people split NEC into two categories: Cardiac NEC and Inflammatory NEC.
                       • Babies who develop cardiac NEC tend to be significantly older than babies who develop inflammatory NEC (about 1 month vs 2 weeks).
                       • There are three main contributory factors to the development of NEC: gut prematurity, abnormal bacterial colonization, and ischemia-reperfusion injury.
                       • Many cases result from an ischemic insult to the bowel, resulting in translocation of intra-luminal bacteria into the wall of the bowel, but the etiology and course of NEC can be very variable.
                       • This translocation can cause sepsis and death; the ischemia of the bowel can result in intestinal perforation and/or necrosis.
                       
                       

                       Necrotizing enterocolitis (NEC) is one of the most common gastrointestinal emergencies in the newborn infant. It is estimated to occur in 1 to 3 per 1000 live births. More than 90 percent of cases occur in very low birth weight (VLBW) infants (BW <1500 g) born at <32 weeks gestation, and the incidence of NEC decreases with increasing gestational age (GA) and BW.

                       What are key risk factors for the development of NEC?

                       • Prematurity and Birth Weight
                       • NEC incidence is inversely proportional to gestational age.
                       • Congenital Heart Disease
                       • Puts children at risk for NEC due to (1) decreased stroke volume, and (2) improperly oxygenated blood which reduced oxygen supply to the SMA and decreases intestinal wall perfusion.
                       • On the repair of the cardiac lesion, patients develop reperfusion injury due to their now improved perfusion to their gut. This reperfusion causes hyper inflammation via neutrophil activation resulting in NEC.
                       •  NEC primarily occurs in healthy, growing, and feeding VLBW preterm infants. It presents with sudden changes in feeding tolerance (increase in gastric residuals) with both nonspecific systemic signs (eg, apnea, respiratory failure, poor feeding, lethargy, or temperature instability) and abdominal signs (eg, abdominal distension, bilious gastric retention and/or vomiting, tenderness, rectal bleeding, and diarrhea). Physical findings may include abdominal wall erythema, crepitus, and induration.
                       
                       

                       Other than the immediate risk of death, what are some consequences of NEC long-term?

                       • Higher risk of malnutrition and short gut.
                       • BPD
                       • Developmental delay.
                       
                       

                       What are some areas of current research and development on the topic of NEC?

                       • Improved biomarkers for early recognition of NEC prior to the development of radiographic findings.
                       • Preventative measures.
                       • Immune modulators of NEC development.
                       • Underdeveloped adaptive immunity of the premature infant may be contributory.
                       • The normal passive sharing of immune compounds between mother and babies (IgG via the placenta and secretory IgA from breastmilk) is disrupted in premature infants, particularly those that are formula-fed.
                       • The majority of IgG transfer occurs in the last 4 weeks of pregnancy.
                       • Several additional cellular and cytokine-based changes may increase the risk of NEC.
                       
                       

                       A clinical diagnosis of NEC is based on the presence of the characteristic clinical features of abdominal distension, bilious vomiting or gastric aspirate, rectal bleeding (hematochezia), and the abdominal radiographic finding of pneumatosis intestinalis, pneumoperitoneum, or sentinel loops. The definite diagnosis of NEC is made from either surgical or postmortem intestinal specimens that demonstrate the histological findings of inflammation, infarction, and necrosis. However, a pathologic diagnosis is not always possible.

                       What are some of the currently favored preventative measures used to decrease the risk of NEC?

                       • Probiotics – research has found that babies with NEC have a different underlying gut microbiome than infants without NEC.
                       • The underlying suggestion is that “good bacteria” prevent the overgrowth of gram-negative enteric pathogens that may lead to NEC.
                       • Associated with increased risk in the development of NEC between 30-32 weeks where there is a concomitant change in microbiome colonization.
                       • Also, some suggestions that “good bacteria” downregulate the inflammatory response in the gut.
                       • Dosing, type of probiotic, and other details of usage are still yet to be decided on.
                       • Still not the standard of care in the US.
                       • Human Milk over Formula – a 1990 study demonstrated that the risk of NEC is 6-10 times greater in formula-fed infants.
                       • Secretory IgA from breastmilk may be protected as the adaptive immune system develops.
                       
                       

                       How is NEC managed?

                       • NEC is typically managed with gut rest (NPO with mIVF), gut decompression (Anderson tube to LIS), and broad-spectrum antibiotic coverage (we use Vanc and Zosyn at CHOA).
                       • Typically is managed in conjunction with pediatric surgery to evaluate the need for surgical resection.
                       • Otherwise, management includes supportive care including increased respiratory support as needed and typically TPN given the length of NPO time required.
                       • Pradip, we talked a great deal about NEC however can you provide some key differentials to consider?
                       • The differential diagnosis of NEC includes other conditions that cause rectal bleeding, abdominal distension, or intestinal perforation. These include spontaneous intestinal perforation of the newborn, infectious enterocolitis, and other causes of the surgical abdomen. NEC is usually differentiated from these conditions by its characteristic clinical features (healthy, growing, and feeding VLBW preterm infants who present with feeding intolerance and evidence of rectal bleeding) and abdominal radiographic findings (eg, pneumatosis intestinalis).
                       
                       

                       To Summarize:

                       • Medical management should be initiated promptly when NEC is suspected and in all infants with proven NEC. It includes the following:
                       • Supportive care – Supportive care includes bowel rest with discontinuation of enteral intake, gastric decompression with intermittent nasogastric suction, initiation of parenteral nutrition, correction of metabolic, fluid/electrolyte, and hematologic abnormalities, and stabilization of the cardiac and respiratory function.
                       • Antibiotic therapy – After obtaining appropriate specimens for culture, a course of parenteral antibiotics that cover a broad range of aerobic and anaerobic intestinal bacteria should be started:
                       • Ampicillin, gentamicin, and metronidazole could be options.
                       • Vancomycin can be used in areas of high MRSA and can be coupled with Zosyn.
                       • The clinical status is monitored to see if the patient responds to medical management, or if NEC continues to progress, and to determine if (and when) surgical intervention is required. Monitoring entails serial physical examinations and abdominal radiographs, and ongoing laboratory testing (eg, white cell and platelet count, and serum bicarbonate and glucose measurements).
                       • Surgical intervention is required either when intestinal perforation occurs or when there is unremitting clinical deterioration despite medical management, which suggests extensive and irreversible necrosis.
                       
                       

                       This concludes our episode on NEC.Special thanks to Dr. Ali Towne for her deep dive into this topic.

                       We hope you found value in our short, case-based podcast. We welcome you to share your feedback, subscribe & place a review on our podcast! Please visit our website picudoconcall.org which showcases our episodes as well as our Doc on Call management cards. PICU Doc on Call is co-hosted by myself Dr. Pradip Kamat and Dr. Rahul Damania. . Stay tuned for our next episode! Thank you!

                       References:

                       1. Klinke M, Wiskemann H, Bay B, et al. Cardiac and Inflammatory Necrotizing Enterocolitis in Newborns Are Not the Same Entity. Front Pediatr. 2020;8:593926.
                       2. Alison Chu M. Necrotizing Enterocolitis: Predictive Markers and Preventive Strategies. NeoReviews. 2013;14.
                       3. Denning TL, Bhatia AM, Kane AF, Patel RM, Denning PW. Pathogenesis of NEC: Role of the innate and adaptive immune response. Semin Perinatol. 2017;41(1):15-28.
                       
                       
                       ]]>4e952519-caa8-4fce-9690-f25b4c0e930cSun, 10 Apr 2022 03:00:00 -040016:07falsefull4949Pediatric Pain, Agitation, Neuromuscular Blockade, and Delirium in Critically Ill Pediatric Patients (PANDEM)Welcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.

                       I'm Pradip Kamat and I’m Kate Phelps, a second-year pediatric critical care fellow joining Pradip and Rahul today!

                       I'm Rahul Damania and we are coming to you from Children's Healthcare of Atlanta - Emory University School of Medicine.

                       Today we are honored to have Dr. John Berkenbosch- senior author of the Prevention and Management of Pain, Agitation, Neuromuscular Blockade, and Delirium in Critically Ill Pediatric Patients with consideration of the ICU Environment and Early Mobility (PANDEM) guidelines recently published in February 2022 issue of the Pediatric Critical Care journal.

                       Dr. Berkenbosch is a Professor of Pediatrics and Pediatric Critical Care at the University of Louisville School of Medicine, and continues to be nationally recognized as an expert in pediatric procedural sedation with multiple publications relating to sedation practices, particularly novel uses of procedural sedation medications and regimens. He currently also serves as co-chair for the American College of Critical Care Medicine’s Task Force guidelines for sedation and analgesia in critically ill children which we will be discussing in today’s episode. Dr. Berkenbosch’s research interests have primarily focused on pediatric procedural sedation and implementation of technology advances in Pediatric Critical Care and have resulted in 57 publications as well as several book chapters

                       Rahul: Dr. Berkenbosch welcome to the PICU Doc ON call podcast. I would also like to point out that the free full access to the PANDEM guidelines is available online at pccmjournal.org

                       Dr. Berkenbosch: Thanks Rahul and Pradip. I am excited to be on the PICU Doc on Call Podcast to discuss the PANDEM guidelines. I want to first start by giving a huge shout-out to all the team members who contributed to these guidelines’ development. This is a topic about which I am quite passionate but also one that provides much-needed guidance regarding pain/agitation/delirium to our entire pediatric critical care community!

                       KATE: Dr. Berkenbosch, the rationale for the development of the PANDEM guidelines was the high variability in pediatric sedation and analgesia. Can you speak to this variability and why it was important to address that variability?

                       That is a great question, the variability has been one of the key motivators in the creation of these guidelines. We also wanted to develop a guideline that was broader in scope than what was currently available. The ICU Liberation bundle provided a paradigm for liberating critically ill patients from mechanical ventilation and the ICU environment and as we delved into developing these guidelines, we realized that many elements of the ICU liberation bundle aligned very closely with PICU sedation and analgesia so it made imminent sense to incorporate all of these topics into the guidelines, an acknowledgment if you will, that PICU liberation & sedation go hand in hand!

                       Absolutely, as we have stated in our prior episodes, the paradigm is: intubate → ventilate → liberate, and sedation/analgesia is intertwined in each of these processes.

                       Dr. Berkenbosch, as we get into the guidelines, can you please highlight how the search strategy for these guidelines were derived?

                       Of course, this was a remarkable group effort solicited by the Society of Critical Care Medicine. We were initially modeled after the adult PAD (pain, agitation, and delirium) guidelines task force but, as described already, extended beyond that to include Pediatric Pain, Agitation, Neuromuscular Blockade, and Delirium in addition to the PICU Environment and Early Mobility. It was comprised of 29 national experts who collaborated over a ten-year period. The full task force gathered annually in person during the Society of Critical Care Medicine Congress for progress reports and further strategizing with the final face-to-face meeting occurring in February 2020, in addition to periodic teleconferences to keep us on track between congresses. Throughout this process, the Society of Critical Care Medicine standard operating procedures Manual for Guidelines development was adhered to.

                       KATE: Dr. Berkenbosch, what a robust process, what were some research principles you can highlight in the development of this content?

                       We created a created descriptive and actionable Population, Intervention, Comparison, and Outcome set of questions. An experienced medical information specialist developed search strategies to identify relevant literature between January 1990 and January 2020. Controlled vocabulary was incorporated (such as, “ICUs, Pediatric,” “Critical Illness,” “Ventilators,” “Mechanical”) along with keywords (e.g., “PICU,” “critically ill,” “intubation”) in addition to a sensitive pediatric filter to identify records specific to this population.

                       Dr. Berkenbosch, as we look into the guidelines, we see the term conditional cited frequently. Do you mind highlighting how this term relates to the strength of recommendation as well as the quality of evidence?

                       This relates heavily to the available literature addressing each question we asked. Based on the quality of available evidence, recommendations were considered strong where the available evidence made additional data unlikely to alter our recommendations, conditional where we felt that new data might alter recommendations. Where evidence was inadequate to make a formal recommendation but we felt a practice was very low risk and likely beneficial, we made what we referred to as Good Practice statements.

                       How should a resident or a fellow in training approach these guidelines? There are almost 37 pages worth of content as well as a large very informative supplement.

                       Add an initial glance, this document can look daunting. We placed a table with all of the recommendations alone at the beginning of the guidelines for quick reference. We also created an infographic, also found near the beginning of the article which graphically shows how all the domains we discuss are related and highlights specific recommendations. We really felt that this diagram put the recommendations themselves into a picture that makes clinical and intuitive sense. Additional discussing guidelines at a Divisional level -especially fellow conferences, examining your institutional practices, etc. may additionally be valuable to aid trainees in unpacking everything.

                       If you have not checked out our most recent episode, role & reach of the Librarian in Pediatric Critical Care Medicine, please definitely check this out!

                       Let's transition and talk about the PANDEM Guidelines: We will divide up the recommendations into broad categories, namely: Analgesia, Sedation, Neuromuscular blockade, ICU delirium, Withdrawal, and Environment Optimization. Let’s start with Analgesia. This Portion of the guidelines addresses The utility of developmentally appropriate pain scores as well as certain analgesics.

                       What pain assessment tools do the PANDEM guidelines recommend? why not vitals signs as a way to assess postoperative pain in the critically-ill pediatric patient?

                       Let me start with what we don’t recommend here, that being reliance on vital signs alone. As we all know, vital sign abnormalities are common in PICU patients and these abnormalities can have multiple causes including the underlying medical or surgical reason for PICU admission, medications we use to treat the diseases kids admitted to our PICUs, or pain and/or agitation. Hence, while helpful, vital sign changes are just not very sensitive to pain or agitation. Now to tools. First off, we wanted to recommend the use of tools validated within PICU patients as we discovered literature describing multiple tools, many of which had not been formally validated. As kids' developmental capacities also change over time, we wanted to make sure that the tools we recommend cover the spectrum of age and developmental capabilities. Ultimately, we came to recommend the use of 4 self-report scales for children over 6 years of age who can communicate their pain and 2 observational scales which cover kids unable to communicate their pain for whatever reason (being intubated, underlying diseases with mental status changes, developmental inability for example). These 2 categories of tools also do not have to be mutually exclusive and can be used concurrently.

                       RAHUL: As a follow-up, what about non-opioid analgesia - I see a huge push from surgeons to focus more on nonopioid adjuncts, rather than opioid infusions—whereas the PANDEM guidelines say that for...]]>Welcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.

                       I'm Pradip Kamat and I’m Kate Phelps, a second-year pediatric critical care fellow joining Pradip and Rahul today!

                       I'm Rahul Damania and we are coming to you from Children's Healthcare of Atlanta - Emory University School of Medicine.

                       Today we are honored to have Dr. John Berkenbosch- senior author of the Prevention and Management of Pain, Agitation, Neuromuscular Blockade, and Delirium in Critically Ill Pediatric Patients with consideration of the ICU Environment and Early Mobility (PANDEM) guidelines recently published in February 2022 issue of the Pediatric Critical Care journal.

                       Dr. Berkenbosch is a Professor of Pediatrics and Pediatric Critical Care at the University of Louisville School of Medicine, and continues to be nationally recognized as an expert in pediatric procedural sedation with multiple publications relating to sedation practices, particularly novel uses of procedural sedation medications and regimens. He currently also serves as co-chair for the American College of Critical Care Medicine’s Task Force guidelines for sedation and analgesia in critically ill children which we will be discussing in today’s episode. Dr. Berkenbosch’s research interests have primarily focused on pediatric procedural sedation and implementation of technology advances in Pediatric Critical Care and have resulted in 57 publications as well as several book chapters

                       Rahul: Dr. Berkenbosch welcome to the PICU Doc ON call podcast. I would also like to point out that the free full access to the PANDEM guidelines is available online at pccmjournal.org

                       Dr. Berkenbosch: Thanks Rahul and Pradip. I am excited to be on the PICU Doc on Call Podcast to discuss the PANDEM guidelines. I want to first start by giving a huge shout-out to all the team members who contributed to these guidelines’ development. This is a topic about which I am quite passionate but also one that provides much-needed guidance regarding pain/agitation/delirium to our entire pediatric critical care community!

                       KATE: Dr. Berkenbosch, the rationale for the development of the PANDEM guidelines was the high variability in pediatric sedation and analgesia. Can you speak to this variability and why it was important to address that variability?

                       That is a great question, the variability has been one of the key motivators in the creation of these guidelines. We also wanted to develop a guideline that was broader in scope than what was currently available. The ICU Liberation bundle provided a paradigm for liberating critically ill patients from mechanical ventilation and the ICU environment and as we delved into developing these guidelines, we realized that many elements of the ICU liberation bundle aligned very closely with PICU sedation and analgesia so it made imminent sense to incorporate all of these topics into the guidelines, an acknowledgment if you will, that PICU liberation & sedation go hand in hand!

                       Absolutely, as we have stated in our prior episodes, the paradigm is: intubate → ventilate → liberate, and sedation/analgesia is intertwined in each of these processes.

                       Dr. Berkenbosch, as we get into the guidelines, can you please highlight how the search strategy for these guidelines were derived?

                       Of course, this was a remarkable group effort solicited by the Society of Critical Care Medicine. We were initially modeled after the adult PAD (pain, agitation, and delirium) guidelines task force but, as described already, extended beyond that to include Pediatric Pain, Agitation, Neuromuscular Blockade, and Delirium in addition to the PICU Environment and Early Mobility. It was comprised of 29 national experts who collaborated over a ten-year period. The full task force gathered annually in person during the Society of Critical Care Medicine Congress for progress reports and further strategizing with the final face-to-face meeting occurring in February 2020, in addition to periodic teleconferences to keep us on track between congresses. Throughout this process, the Society of Critical Care Medicine standard operating procedures Manual for Guidelines development was adhered to.

                       KATE: Dr. Berkenbosch, what a robust process, what were some research principles you can highlight in the development of this content?

                       We created a created descriptive and actionable Population, Intervention, Comparison, and Outcome set of questions. An experienced medical information specialist developed search strategies to identify relevant literature between January 1990 and January 2020. Controlled vocabulary was incorporated (such as, “ICUs, Pediatric,” “Critical Illness,” “Ventilators,” “Mechanical”) along with keywords (e.g., “PICU,” “critically ill,” “intubation”) in addition to a sensitive pediatric filter to identify records specific to this population.

                       Dr. Berkenbosch, as we look into the guidelines, we see the term conditional cited frequently. Do you mind highlighting how this term relates to the strength of recommendation as well as the quality of evidence?

                       This relates heavily to the available literature addressing each question we asked. Based on the quality of available evidence, recommendations were considered strong where the available evidence made additional data unlikely to alter our recommendations, conditional where we felt that new data might alter recommendations. Where evidence was inadequate to make a formal recommendation but we felt a practice was very low risk and likely beneficial, we made what we referred to as Good Practice statements.

                       How should a resident or a fellow in training approach these guidelines? There are almost 37 pages worth of content as well as a large very informative supplement.

                       Add an initial glance, this document can look daunting. We placed a table with all of the recommendations alone at the beginning of the guidelines for quick reference. We also created an infographic, also found near the beginning of the article which graphically shows how all the domains we discuss are related and highlights specific recommendations. We really felt that this diagram put the recommendations themselves into a picture that makes clinical and intuitive sense. Additional discussing guidelines at a Divisional level -especially fellow conferences, examining your institutional practices, etc. may additionally be valuable to aid trainees in unpacking everything.

                       If you have not checked out our most recent episode, role & reach of the Librarian in Pediatric Critical Care Medicine, please definitely check this out!

                       Let's transition and talk about the PANDEM Guidelines: We will divide up the recommendations into broad categories, namely: Analgesia, Sedation, Neuromuscular blockade, ICU delirium, Withdrawal, and Environment Optimization. Let’s start with Analgesia. This Portion of the guidelines addresses The utility of developmentally appropriate pain scores as well as certain analgesics.

                       What pain assessment tools do the PANDEM guidelines recommend? why not vitals signs as a way to assess postoperative pain in the critically-ill pediatric patient?

                       Let me start with what we don’t recommend here, that being reliance on vital signs alone. As we all know, vital sign abnormalities are common in PICU patients and these abnormalities can have multiple causes including the underlying medical or surgical reason for PICU admission, medications we use to treat the diseases kids admitted to our PICUs, or pain and/or agitation. Hence, while helpful, vital sign changes are just not very sensitive to pain or agitation. Now to tools. First off, we wanted to recommend the use of tools validated within PICU patients as we discovered literature describing multiple tools, many of which had not been formally validated. As kids' developmental capacities also change over time, we wanted to make sure that the tools we recommend cover the spectrum of age and developmental capabilities. Ultimately, we came to recommend the use of 4 self-report scales for children over 6 years of age who can communicate their pain and 2 observational scales which cover kids unable to communicate their pain for whatever reason (being intubated, underlying diseases with mental status changes, developmental inability for example). These 2 categories of tools also do not have to be mutually exclusive and can be used concurrently.

                       RAHUL: As a follow-up, what about non-opioid analgesia - I see a huge push from surgeons to focus more on nonopioid adjuncts, rather than opioid infusions—whereas the PANDEM guidelines say that for moderate to severe pain opioid infusions are recommended (strong):

                       Thanks for the question - and we agreed with the importance of this question as opioids are not benign drugs for multiple reasons. We extensively evaluated the literature discussing adjunct use of acetaminophen or non-steroidal agents and, in the end, made strong or conditional recommendations supporting the use of both of these agents/classes of analgesics to aid in postoperative analgesia and to decrease opioid exposure. Due to inadequate literature, we were not able to extend these recommendations to patients admitted with medical diseases. Similarly, due to a lack of adequate evidence, we did not differentiate between the use of IV versus enteral formulations of these adjunct medications. Related to this, I think it is important to also mention that the guidelines also address non-pharmacologic adjuncts or interventions that can further aid in pain control. 2 such areas where we were able to make recommendations were the addition of music therapy which is applicable to the entire age range we admit to the PICU and non-nutritive sucking with or without sucrose to aid in analgesia for infants undergoing painful procedures. And I want to make it clear, these non-pharmacologic interventions are adjuncts, and should not be viewed as replacements for analgesic medications – they’re complimentary.

                       RAHUL: Lets now discuss Sedation:

                       We noticed that use of a scale to assess the depth of sedation such as comfort-B or state behavioral scale or Richmond agitation sedation Scale received a strong recommendation. What is the rationale for this? How does this help decrease the use of sedatives especially benzodiazepines in the PICU?

                       So, just as with analgesia assessment tools, we wanted to only recommend sedation scales that have been formally validated, hence the 3 you just listed. While we only made a conditional recommendation for use of the RASS scale, we felt it important to include it as it is the scale used to determine the appropriateness of a patient for delirium screening. These tools allow us as bedside providers to have a more objective means with which to assess patient comfort which should, then, guide when and if patients require additional sedation. This is important as a follow-up to the need for doing periodic sedation screening is our recommendation that each patient has a target level of sedation defined at least once a day. This represents a recognition that the sedation needs of a patient in the PICU change over the course of their disease evolution, perhaps requiring deeper sedation early on when they are at their highest acuity but with needs reducing as they improve and move towards a transition to extubation for example. Deeper sedation may also be required early on to protect lines and devices, especially endotracheal tubes, which may not be as critical or may be removed as the child improves and, again, sedation can be lightened. Without this reassessment, patients run the risk of oversedation or prolonged exposure to sedative medications. As we have also emphasized the value of early mobility, it also stands to reason that sedation targets should lighten as it becomes appropriate to mobilize patients more and more – it’s hard for a deeply sedated patient to do much of this on their own. That said, it is really important for providers to find a proper balance between over-and under-sedation. Over sedation increases the risk of delirium, lengthens time on the ventilator, and limits things like mobility whereas undersedation can, in addition to what we just discussed, contribute to adverse psychological effects which may not manifest until after the child has left the PICU and even the hospital, such as post-intensive care syndrome.

                       We see that guidelines suggest the use of protocolized sedation although the RESTORE study found no difference between the institutions, which used protocolized vs non protocolized sedation for MV patients?

                       This is true although data in addition to the Restore trial informed our suggestion to use protocolized sedation. The main advantages of protocolization are that medications can be given or infusions adjusted based on the desired sedation target automatically without calling a physician for every change. In most reports available, including the RESTORE trial, this person was the bedside nurse and this makes the most intuitive sense to me as that is the provider who is most frequently at the bedside and, therefore, has the best idea of what the patient is doing from a comfort perspective throughout their shift. When tied to a target sedation level, protocols also should aid in ensuring that patients are less likely to be exposed to excessive amounts of medications although, as a task force, we certainly recognize that this is a topic for which further study is definitely needed. Related to this, while I think most of us think about sedation protocols being useful during the acute phase of illness while the patient is intubated, we were also able to find a reasonable amount of literature describing the use of protocolized weaning of sedatives and that this practice resulted in more rapid discontinuation of sedative and analgesic infusions without increasing the risk of development of withdrawal syndromes. This allowed us to also make a conditional recommendation for the use of sedation wean protocols.

                       KATE: Dr. Berkenbosch so no more daily sedation holidays or daily sedation interruptions?

                       This is a great question. With the increasing desire to limit sedative exposure, for good reasons, there was a lot of early interest in the use of daily sedation interruptions and some of this initial evidence appeared to show promising advantages. However, A more recent and larger multicenter RCT found that adverse outcomes were actually increased in the arm of patients randomized to daily sedation interruptions. Additionally, since so few patients in the protocolized arm of the RESTORE trial required DSI due to oversedation, the use of protocolized sedation seems to be unnecessary as appropriately used protocols can be the mechanism whereby sedative exposure is already minimized.

                       KATE The guidelines advocate for the use of alpha2 agonists as the primary sedative class in critically ill pediatric patients requiring MV. What are the advantages of using Dexmedetomidine for sedation?

                       I suspect a lot of your listeners are already aware of the attractive properties of alpha agonists including minimal respiratory depression, mild analgesic effects which can aid in reducing opioid exposure, and they are a class of sedative that, based on EEG studies, facilitate a sedated state that closely mimics that seen in natural sleep. In head-to-head comparisons with benzodiazepines, they are equally efficacious from a sedation perspective. Given increasing data regarding the risk of delirium development with benzodiazepine exposure, these properties all tipped the scales to favor alpha-agonist-based sedation regimens. While some have expressed concerns that bradycardia and hypotension are more common with alpha-agonists, the data available suggested no difference in the occurrence of either event in the need for intervention for drug-related cardiovascular adverse events although the qualifier about the concern with alpha-agonist addition to patients already on heart rate reducing medications remains relevant.

                       Dexmedetomidine is also recommended as the primary agent for sedation in critically ill pediatric postoperative cardiac surgical patients with expected early extubation. They also recommend the use of dexmedetomidine for sedation in critically ill pediatric postoperative cardiac surgical patients to decrease the risk of tachyarrhythmias.

                       An important transition period for the critically-ill patient is the peri-extubation period. We see that PANDEM has a bundle approach along with the use of propofol. Dr. Berkenbosch can you give us more information on the approach to sedation/analgesia during the periextubation period.

                       This is true. To quote the guidelines, “During the peri-extubation period when sedation is typically lightened, we suggest the following bundle strategies to decrease the risk of inadvertent device removal:

                       a) Assign a target depth of sedation at an increasing frequency to adapt to changes in patient clinical status and communicate strategies to reach the titration goal.

                       b) Consider a sedation weaning protocol.

                       c) Consider unit standards for securement of endotracheal tubes and safety plan.

                       d) Restrict nursing workload to facilitate frequent patient monitoring, decrease sedation requirements, and risk of self-harm.”

                       I want to be sure that with this recommendation, it is also recognized that restricted nursing workloads may not always be feasible as many areas are experiencing nursing shortages. However,...]]>36ce6722-6140-4a5e-88e4-b571d037a0a2Mon, 04 Apr 2022 03:00:00 -040034:24falsefull4848HyperammonemiaWelcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.

                       I'm Pradip Kamat and I'm Rahul Damania. We are coming to you from Children's Healthcare of Atlanta - Emory University School of Medicine.

                       I will turn it over to Rahul to start with our patient case...

                       A 2 yo Asian M presents with difficulty feeding. He has a history of epilepsy and recently was switched to Valproic Acid for seizure control as well as OTC deficiency diagnosed at birth. He has had a 3-day history of URI, cough, which now progressed to this difficulty feeding. His parents state he was initially very fussy however in the past few hours he has been more sleepy. He has not had any fevers. They have noticed that while he is sleeping he has been breathing "fast." Prior to arrival at the emergency room, he was noted to have a large non-bloody, non-bilious emesis. Upon transfer to the trauma bay, the patient suddenly has a seizure. A quick POC glucose is normal. His care is escalated & diagnostic workup is initiated.

                       Pradip, our case had two key elements in his history, namely the h/o OTC deficiency & VPA use, which place him, particularly at high risk to have hyperammonemia. As this is our topic of discussion today, would you mind starting with a general background & definition of hyperammonemia?

                       Sure, this is a classic case of not only hyperammonemia but also a metabolic crisis in this case related to a urea cycle defect.

                       As background, the urea cycle is the metabolic pathway that transforms nitrogen to urea for excretion from the body. We get nitrogen sources from a few areas in the body:

                       • from peripheral (muscle)
                       • enteral sources (protein ingestion)
                       
                       

                       The urea cycle occurs in the liver and once the ammonia is converted to urea in the hepatocyte, it is excreted into the kidney as urea. We will dive into this deeper soon, however, pathologies that impair adequate hepatocyte function, can impair the urea cycle and thus lead to hyperammonemia.

                       This is a great basic science summary, would you mind commenting about this patient's enzyme defect — the OTC deficiency?

                       • Yes, Ornithine transcarbamylase, or OTC for short, is one of the first few enzymes in the urea cycle.
                       • As a background, the inheritance pattern of majority, all of the urea-cycle-defects (UCD) is autosomal recessive, however, OTC deficiency is different — it is X linked.
                       • In a 21-year, multi-center retrospective study, it was noted that only 34 % of patients with UCD presented during the neonatal period (<30 days of age) — and around 25% of cases present in the 2-12-year-old range. This is why I would like to drive home this clinical point to have a urea cycle defect or any inborn error of metabolism in your differential, especially in a child who presents in a critically ill, undifferentiated state.
                       
                       

                       Why do you think there are subsets of populations who present later?

                       • This is a great question and the cause may be multi-factorial — it is worth noting that patients may have partial enzyme deficiencies and this may be a major reason why patients may have atypical presentations after the newborn period. This delayed presentation is most commonly seen in patients with partial ornithine transcarbamylase (OTC) deficiency.
                       
                       

                       As we have highlighted key pathophysiologic components, do you mind highlighting the typical clinical presentation of a child with a UCD & hyperammonemia?

                       The presentation may be variable, however, let’s break down some key features which were in our case:

                       • Patients typically have a preceding illness such as a URI or gastroenteritis, which triggers a more catabolic state.
                       • As a result, patients end up having increased ammonia levels — this ends up creating a picture of somnolence, inability to maintain normal body temperature, poor feeding, vomiting, and in severe cases lethargy, and This is a similar presentation to sepsis and thus keeping your differential broad, having fine attention to trends in vitals or clinical exam, and early aggressive management with contingency planning is crucial to the care of these patients.
                       
                       

                       As we wrap up the clinical presentation, what would be some other physical exam abnormalities we will see upon initial presentation?

                       I would like to highlight some important points here:

                       • Subtle signs of elevated ammonia include behavioral modifications such as delirium, as well as neuro-developmental delay — thus it is important to recognize our aforementioned presentations of seizures & alteration of consciousness
                       
                       

                       Let’s finish this episode with management pearls, Rahul, what is your general approach to hyperammonemia?

                       Excellent, the nitrogen scavengers typically used are: sodium phenylacetate and sodium benzoate; in a study published in NEJM in 2007, these therapies along with adequate calorie intake, were reported to lower plasma ammonia levels especially in children with urea cycle disorders. A combined preparation of sodium phenylacetate-sodium benzoate (Ammonul) was approved by the US Food and Drug Administration (FDA) in February 2005 for parenteral delivery

                       Any recommendations on dosing?

                       • For patients who weigh ≤20 kg, we typically use a loading dose of 500 mg/kg (250 mg/kg of each drug) in a volume of 25 to 35 mL/kg of 10 percent dextrose solution infused over 90 minutes. For patients who weigh >20 kg, dosing is based upon body surface area; the loading dose is 11 g/m2 (ie, 5.5 g/m2 of each drug).
                       • A maintenance infusion of sodium phenylacetate-sodium benzoate (500 mg/kg per 24 hours for patients <20 kg, 11 g/m2 per 24 hours as a continuous infusion for patients >20 kg) is started when the loading dose is completed and is administered in the same volume as the loading dose (25 to 35 mL/kg).
                       • Are there some adverse events that we need to watch for in our patients?
                       • Most of the side effects for Ammonul are metabolic (eg, hypokalemia, hyperchloremia, acidosis), neurologic (eg, seizures), or respiratory (eg, respiratory distress or failure).
                       • Electrolytes should be monitored daily during loading and maintenance infusions of sodium phenylacetate-sodium benzoate because these medications contain high concentrations of sodium and chloride. Sodium phenylacetate administration may cause potassium depletion.
                       
                       

                       Going back to the NEJM trial, for children who were treated with Ammonul with recurrent admissions for hyperammonemia, the overall survival which was reported was 84 percent. It is important to note however, the neurologic outcome was not evaluated.

                       As I review the urea cycle, I see that arginine and citrulline are precursors which can help form urea, can you comment on their role in hyperammonemia?

                       • IV arginine hydrochloride is used as part of the initial management of metabolic decompensation in all forms of UCD except known arginase deficiency.
                       • Arginine is created via the urea cycle and in our case, this patient has an OTC deficiency so Arginine now becomes an essential amino acid.
                       • Blood pressure should be monitored since high doses of IV arginine can decrease blood
                       
                       

                       What about citrulline?

                       • In OTC or CPSI deficiency, small oral doses of citrulline also are provided because incorporating aspartate nitrogen may improve clearance as urea.
                       • In one retrospective study, patients treated with L-citrulline reduced ammonia levels and improved weight gain which was most likely due to increased protein intake.
                       
                       

                       When you look longitudinally,...]]>Welcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.

                       I'm Pradip Kamat and I'm Rahul Damania. We are coming to you from Children's Healthcare of Atlanta - Emory University School of Medicine.

                       I will turn it over to Rahul to start with our patient case...

                       A 2 yo Asian M presents with difficulty feeding. He has a history of epilepsy and recently was switched to Valproic Acid for seizure control as well as OTC deficiency diagnosed at birth. He has had a 3-day history of URI, cough, which now progressed to this difficulty feeding. His parents state he was initially very fussy however in the past few hours he has been more sleepy. He has not had any fevers. They have noticed that while he is sleeping he has been breathing "fast." Prior to arrival at the emergency room, he was noted to have a large non-bloody, non-bilious emesis. Upon transfer to the trauma bay, the patient suddenly has a seizure. A quick POC glucose is normal. His care is escalated & diagnostic workup is initiated.

                       Pradip, our case had two key elements in his history, namely the h/o OTC deficiency & VPA use, which place him, particularly at high risk to have hyperammonemia. As this is our topic of discussion today, would you mind starting with a general background & definition of hyperammonemia?

                       Sure, this is a classic case of not only hyperammonemia but also a metabolic crisis in this case related to a urea cycle defect.

                       As background, the urea cycle is the metabolic pathway that transforms nitrogen to urea for excretion from the body. We get nitrogen sources from a few areas in the body:

                       • from peripheral (muscle)
                       • enteral sources (protein ingestion)
                       
                       

                       The urea cycle occurs in the liver and once the ammonia is converted to urea in the hepatocyte, it is excreted into the kidney as urea. We will dive into this deeper soon, however, pathologies that impair adequate hepatocyte function, can impair the urea cycle and thus lead to hyperammonemia.

                       This is a great basic science summary, would you mind commenting about this patient's enzyme defect — the OTC deficiency?

                       • Yes, Ornithine transcarbamylase, or OTC for short, is one of the first few enzymes in the urea cycle.
                       • As a background, the inheritance pattern of majority, all of the urea-cycle-defects (UCD) is autosomal recessive, however, OTC deficiency is different — it is X linked.
                       • In a 21-year, multi-center retrospective study, it was noted that only 34 % of patients with UCD presented during the neonatal period (<30 days of age) — and around 25% of cases present in the 2-12-year-old range. This is why I would like to drive home this clinical point to have a urea cycle defect or any inborn error of metabolism in your differential, especially in a child who presents in a critically ill, undifferentiated state.
                       
                       

                       Why do you think there are subsets of populations who present later?

                       • This is a great question and the cause may be multi-factorial — it is worth noting that patients may have partial enzyme deficiencies and this may be a major reason why patients may have atypical presentations after the newborn period. This delayed presentation is most commonly seen in patients with partial ornithine transcarbamylase (OTC) deficiency.
                       
                       

                       As we have highlighted key pathophysiologic components, do you mind highlighting the typical clinical presentation of a child with a UCD & hyperammonemia?

                       The presentation may be variable, however, let’s break down some key features which were in our case:

                       • Patients typically have a preceding illness such as a URI or gastroenteritis, which triggers a more catabolic state.
                       • As a result, patients end up having increased ammonia levels — this ends up creating a picture of somnolence, inability to maintain normal body temperature, poor feeding, vomiting, and in severe cases lethargy, and This is a similar presentation to sepsis and thus keeping your differential broad, having fine attention to trends in vitals or clinical exam, and early aggressive management with contingency planning is crucial to the care of these patients.
                       
                       

                       As we wrap up the clinical presentation, what would be some other physical exam abnormalities we will see upon initial presentation?

                       I would like to highlight some important points here:

                       • Subtle signs of elevated ammonia include behavioral modifications such as delirium, as well as neuro-developmental delay — thus it is important to recognize our aforementioned presentations of seizures & alteration of consciousness
                       
                       

                       Let’s finish this episode with management pearls, Rahul, what is your general approach to hyperammonemia?

                       Excellent, the nitrogen scavengers typically used are: sodium phenylacetate and sodium benzoate; in a study published in NEJM in 2007, these therapies along with adequate calorie intake, were reported to lower plasma ammonia levels especially in children with urea cycle disorders. A combined preparation of sodium phenylacetate-sodium benzoate (Ammonul) was approved by the US Food and Drug Administration (FDA) in February 2005 for parenteral delivery

                       Any recommendations on dosing?

                       • For patients who weigh ≤20 kg, we typically use a loading dose of 500 mg/kg (250 mg/kg of each drug) in a volume of 25 to 35 mL/kg of 10 percent dextrose solution infused over 90 minutes. For patients who weigh >20 kg, dosing is based upon body surface area; the loading dose is 11 g/m2 (ie, 5.5 g/m2 of each drug).
                       • A maintenance infusion of sodium phenylacetate-sodium benzoate (500 mg/kg per 24 hours for patients <20 kg, 11 g/m2 per 24 hours as a continuous infusion for patients >20 kg) is started when the loading dose is completed and is administered in the same volume as the loading dose (25 to 35 mL/kg).
                       • Are there some adverse events that we need to watch for in our patients?
                       • Most of the side effects for Ammonul are metabolic (eg, hypokalemia, hyperchloremia, acidosis), neurologic (eg, seizures), or respiratory (eg, respiratory distress or failure).
                       • Electrolytes should be monitored daily during loading and maintenance infusions of sodium phenylacetate-sodium benzoate because these medications contain high concentrations of sodium and chloride. Sodium phenylacetate administration may cause potassium depletion.
                       
                       

                       Going back to the NEJM trial, for children who were treated with Ammonul with recurrent admissions for hyperammonemia, the overall survival which was reported was 84 percent. It is important to note however, the neurologic outcome was not evaluated.

                       As I review the urea cycle, I see that arginine and citrulline are precursors which can help form urea, can you comment on their role in hyperammonemia?

                       • IV arginine hydrochloride is used as part of the initial management of metabolic decompensation in all forms of UCD except known arginase deficiency.
                       • Arginine is created via the urea cycle and in our case, this patient has an OTC deficiency so Arginine now becomes an essential amino acid.
                       • Blood pressure should be monitored since high doses of IV arginine can decrease blood
                       
                       

                       What about citrulline?

                       • In OTC or CPSI deficiency, small oral doses of citrulline also are provided because incorporating aspartate nitrogen may improve clearance as urea.
                       • In one retrospective study, patients treated with L-citrulline reduced ammonia levels and improved weight gain which was most likely due to increased protein intake.
                       
                       

                       When you look longitudinally, and before we go into hemodialysis and its role, are there certain medications that we want to avoid?

                       • Glucocorticoids increase protein catabolism and should not be used routinely.
                       • As patients may have seizures, remembering that valproic acid inhibits urea synthesis, leading to increased serum ammonia levels. Thus, VPA should not be routinely used.
                       
                       

                       Seizures may be treated with other antiepileptic drugs, although correcting the underlying metabolic abnormality is more likely to affect seizure control.

                       • Yes, finally, Mannitol is ineffective in treating cerebral edema caused by hyperammonemia due to UCDs.
                       • Let's conclude this episode with hemodialysis; whats the appropriate timing?
                       • Hemodialysis should be started as soon as possible after hospital admission of a patient with severe hyperammonemia. Indications include an ammonia level that is rapidly increasing, acute hyperammonemia that is resistant to initial drug therapy, and/or ammonia that is persistently above the range of 350 to 400 micromol/L.
                       
                       

                       As many of our centers have CVVH readily available, it is important to consult with your nephrology team to optimize flow rates to be >40 to 60 mL/min. This method is less desirable as an initial treatment, although it can be used effectively between hemodialysis treatments to continue removing ammonia.

                       What is our endpoint usually if we are to go down the HD or CVVH route?

                       • Ammonia concentration is measured hourly during dialysis.
                       • Hemodialysis is stopped when the ammonia concentration has dropped below 200 micromol/L because it appears to have little effect below this level.
                       • What is important to recognize though is that plasma ammonia may increase again (rebound) because of the delay in the effect of nitrogen scavenging medications and the ongoing catabolism.
                       • Thus, hourly monitoring of ammonia levels is continued until ammonia levels have stabilized below 200 micromol/L for at least 24 hours → after a while to decrease iatrogenic blood draws, the frequency of measurements can be reduced to every four hours.
                       
                       

                       To summarize today's episode...

                       1. In newborns, UCDs typically present after 24 to 48 hours of age. Clinical features include somnolence and poor feeding followed by lethargy, vomiting, and coma. Other features include central hyperventilation leading to initial respiratory alkalosis, hyperammonemia, and seizures.
                       2. The initial laboratory evaluation for suspected UCD should include arterial pH and carbon dioxide; serum ammonia, lactate, glucose, electrolytes, and amino acids; and urine organic acids and orotic acid. Elevated plasma ammonia concentration combined with normal blood glucose and normal anion gap strongly suggests a UCD.
                       3. The initial approach to the treatment of UCDs consists of volume repletion, ammonia removal, protein restriction, and stimulation of anabolism. Respiratory status must be closely monitored. Pharmacologic therapy for hyperammonemia consists of initial IV administration of a combination preparation of sodium phenylacetate-sodium benzoate (Ammonul) followed by maintenance with oral glycerol phenylbutyrate (Ravicti).
                       
                       

                       This concludes our episode today on Hyperammonemia. We hope you found value in this short podcast. We welcome you to share your feedback & place a review on our podcast. PICU Doc on Call is co-hosted by me and my cohost Dr. Rahul Damania. Stay tuned for our next episode!

                       ]]>e08d99d6-3273-4147-bd2f-479176e7fe93Sun, 27 Mar 2022 03:00:00 -040018:49falsefull4747Pediatric Post Cardiac Arrest Syndrome (PCAS) Part 2Welcome to PICU Doc On Call, a podcast dedicated to current and aspiring intensivists. My name is Pradip Kamat. My name is Rahul Damania and we come to you from Children’s Healthcare of Atlanta-Emory University School of Medicine.

                       Today's episode Is part two of our pediatric post-cardiac arrest care syndrome

                       If you have not yet listened to part one, I would highly encourage you to visit that episode prior to delving into this one.

                       Part 1 addressed the epidemiology, causes, and pathophysiology of POST CARDIAC ARREST SYNDROME.

                       Part 2 Today will discuss management and complications related to post-cardiac arrest syndrome in the ICU.

                       To revisit our index case we had a:

                       • 11 yo previously healthy M who was admitted to the PICU after cardiac arrest. After stabilization: The patient was taken to head CT which showed diffuse cerebral edema and diffusely diminished grey-white differentiation most pronounced in the basal ganglia. He is now 18-24 hours post-cardiac arrest and the team is dealing with hemodynamic changes, arrhythmias, and difficulty with ventilation. The patient’s neurological exam still remains poor with fixed 5 mm pupils and upper motor neuron signs in the lower extremities.
                       
                       

                       Let’s get right into it:

                       • What are some of the principles in management of patients with post cardiac arrest syndrome (PCAS)? Where do we keep the patients blood pressure?
                       • Hypotension after ROSC is commonly encountered in children with PCAS. Early hypotension occurred in 27% of children after cardiac arrest is associated with lower survival to hospital discharge and unfavorable neurological outcome. When post-cardiac arrest hypotension is present, it is not clear whether increasing the blood pressure through administration of fluids and inotropes/vasopressors can mitigate harm, despite this 41% of patients under 18 receive vasopressor therapy within the first 6 hours after ROSC. Currently, there is no high-quality evidence to support any single specific strategy for post-cardiac arrest hemodynamic optimization in children. Treatment of post-cardiac arrest hypotension and myocardial dysfunction may be assisted by monitoring and evaluating arterial lactate and central venous oxygen saturation. Parenteral fluids, inotropes, and vasoactive drugs are to be used as needed to maintain a systolic blood pressure greater than the fifth percentile for age. Appropriate vasoactive drug therapies should be tailored to each patient and adjusted as needed.
                       • What about cardiac arrhythmia's such as Vtach seen in our patient?
                       • The rhythm disturbances observed during the post-cardiac arrest period include premature atrial and ventricular contractions, supraventricular tachycardias, and ventricular tachycardias. Heart block is unusual but can be observed as a manifestation of myocarditis. There is inadequate evidence in adults and no published studies in children to support the routine administration of prophylactic antiarrhythmics after ROSC, but rhythm disturbances during this period may warrant therapy. Treatment depends on the cause and hemodynamic consequences of the arrhythmias. Premature depolarizations, both atrial and ventricular, usually do not require therapy other than maintenance of adequate perfusion and normal fluid and electrolyte balance. Ventricular arrhythmias may signify more serious myocardial dysfunction. QT prolonging agents must be avoided. Many of the vasoactive agents used to support myocardial function can increase myocardial irritability and risk of arrhythmias. Premature atrial or ventricular depolarizations are frequently observed and can be controlled by optimizing the dose of the vasoactive drugs. Bradycardia is frequently seen in TTM and typically requires no therapy. During PCAC, mechanical circulatory support (ECMO) may be considered if significant cardiorespiratory instability persists despite appropriate volume expansion and administration of inotropes, vasopressors, and, if indicated, antiarrhythmics.In a study de Mos N et al (CCM 2006) in a PICU population, the use of ECMO within 24 hours after ROSC was associated with reduced mortality. Case series have documented the role of ECMO88 and ventricular assist device support89,90 in children with refractory cardiogenic shock or acute fulminant myocarditis (Blume Ed et al., J Heart Lung Transplant 2016).
                       • What about oxygenation and ventilation strategies in our patient with PCAS
                       • Optimal oxygenation and ventilation of children after ROSC may be hampered by the pathology that precipitated the cardiac arrest (such as drowning with resultant post-pulmonary edema) and by the ensuing post-cardiac arrest pathophysiology. Further management challenges may be caused by aspiration and lung injury occurring during resuscitation efforts as well as ventilator-induced lung injury. Additionally, use of TTM alters the relationship between arterial oxygen saturation and arterial oxygen tension such that, for a given arterial oxygen saturation, the arterial oxygen tension (Pao2) is lower than that observed when the temperature is normal. Hypothermia also decreases the metabolic rate; thus, carbon dioxide production will be lower at any given minute ventilation.
                       • Post–cardiac arrest blood gas abnormalities are common in children, particularly in the first hours after ROSC as seen in our patient case. Published evidence has failed to demonstrate a consistent effect of post-cardiac arrest hyperoxia or hypoxemia on outcome. After ROSC, it is reasonable to aim for normal PaO2 (or the value appropriate for the child’s condition if the child has, for example, cyanotic heart disease) and to use the lowest possible fraction of inspired oxygen, weaning to maintain an oxygen saturation of 94% to 99% as a guideline. Throughout PCAC, hypoxemia must be avoided whenever possible, particularly during oxygen titration. The 2010 AHA PALS guidelines recommended prompt arterial blood gas analysis as soon as possible after ROSC and within 10 to 15 minutes of establishing initial mechanical ventilation to guide oxygen administration and titration and to support mechanical ventilation.
                       • Post–cardiac arrest derangements in PaCO2 are common. On the basis of available evidence, after ROSC, it is reasonable to target normocapnia (ie, normal for the child, or PaCO2 35–45 mm Hg) or a PaCO2 specific for the patient’s condition, limiting exposure to severe hypercapnia and hypocapnia. Lung protective strategies such as low TV, high PEEP should be used to minimize VILI.
                       • Can you comment on targeted temperature management?
                       • Post–cardiac arrest pyrexia (elevated core body temperature) is common, and persistent hyperthermia is associated with unfavorable neurological outcomes in children (Bambea MM PCCM 2010).During PCAC, fever (≥38°C) should be aggressively treated. To treat the child who remains comatose after OHCA, the 2015 AHA PALS guidelines update recommended that it is reasonable either to maintain continuous normothermia (TTM to 36°C–37.5°C) for 5 days or to maintain 2 days of continuous hypothermia (TTM to 32C°–34°C) followed by 3 days of continuous normothermia (TTM to 36°C–37.5°C).2 Because increased mortality was associated with temperatures <32°C, if TTM to 32°C to 34°C is used, meticulous care must be provided to prevent temperatures <32°C.
                       
                       

                       Post–cardiac arrest derangements in PaCO2 are common. On the basis of available evidence, after ROSC, it is reasonable to target normocapnia (ie, normal for the child, or Paco2 35–45 mm Hg) or a Paco2 specific for the patient’s condition, limiting exposure to severe hypercapnia and hypocapnia. Lung protective strategies such as low TV, high PEEP should be used to minimize VILI.

                       • What about treatment of seizures in PCAS and can you also comment on sedation , analgesia and the use of NMB in these patients ?
                       • Seizures occur in 10% to 50% of children who remain encephalopathic after achieving ROSC. (Abend NS et al Neurology 2009). Furthermore, about half of children with post-ROSC seizures experience exclusively non-convulsive (subclinical, EEG only) seizures, which cannot be identified by clinical observation alone. Seizures could not be predicted from any clinical or resuscitation variables. Seizures were associated with unfavorable gross neurological outcomes at discharge but not with higher mortality. Because seizures increase metabolic demand, can worsen metabolic dysfunction, and can increase intracranial pressure, they can contribute to secondary brain injury.
                       • For these reasons, many clinicians aim to treat seizures, although the approach is generally...]]>Welcome to PICU Doc On Call, a podcast dedicated to current and aspiring intensivists. My name is Pradip Kamat. My name is Rahul Damania and we come to you from Children’s Healthcare of Atlanta-Emory University School of Medicine.

                         Today's episode Is part two of our pediatric post-cardiac arrest care syndrome

                         If you have not yet listened to part one, I would highly encourage you to visit that episode prior to delving into this one.

                         Part 1 addressed the epidemiology, causes, and pathophysiology of POST CARDIAC ARREST SYNDROME.

                         Part 2 Today will discuss management and complications related to post-cardiac arrest syndrome in the ICU.

                         To revisit our index case we had a:

                         • 11 yo previously healthy M who was admitted to the PICU after cardiac arrest. After stabilization: The patient was taken to head CT which showed diffuse cerebral edema and diffusely diminished grey-white differentiation most pronounced in the basal ganglia. He is now 18-24 hours post-cardiac arrest and the team is dealing with hemodynamic changes, arrhythmias, and difficulty with ventilation. The patient’s neurological exam still remains poor with fixed 5 mm pupils and upper motor neuron signs in the lower extremities.
                         
                         

                         Let’s get right into it:

                         • What are some of the principles in management of patients with post cardiac arrest syndrome (PCAS)? Where do we keep the patients blood pressure?
                         • Hypotension after ROSC is commonly encountered in children with PCAS. Early hypotension occurred in 27% of children after cardiac arrest is associated with lower survival to hospital discharge and unfavorable neurological outcome. When post-cardiac arrest hypotension is present, it is not clear whether increasing the blood pressure through administration of fluids and inotropes/vasopressors can mitigate harm, despite this 41% of patients under 18 receive vasopressor therapy within the first 6 hours after ROSC. Currently, there is no high-quality evidence to support any single specific strategy for post-cardiac arrest hemodynamic optimization in children. Treatment of post-cardiac arrest hypotension and myocardial dysfunction may be assisted by monitoring and evaluating arterial lactate and central venous oxygen saturation. Parenteral fluids, inotropes, and vasoactive drugs are to be used as needed to maintain a systolic blood pressure greater than the fifth percentile for age. Appropriate vasoactive drug therapies should be tailored to each patient and adjusted as needed.
                         • What about cardiac arrhythmia's such as Vtach seen in our patient?
                         • The rhythm disturbances observed during the post-cardiac arrest period include premature atrial and ventricular contractions, supraventricular tachycardias, and ventricular tachycardias. Heart block is unusual but can be observed as a manifestation of myocarditis. There is inadequate evidence in adults and no published studies in children to support the routine administration of prophylactic antiarrhythmics after ROSC, but rhythm disturbances during this period may warrant therapy. Treatment depends on the cause and hemodynamic consequences of the arrhythmias. Premature depolarizations, both atrial and ventricular, usually do not require therapy other than maintenance of adequate perfusion and normal fluid and electrolyte balance. Ventricular arrhythmias may signify more serious myocardial dysfunction. QT prolonging agents must be avoided. Many of the vasoactive agents used to support myocardial function can increase myocardial irritability and risk of arrhythmias. Premature atrial or ventricular depolarizations are frequently observed and can be controlled by optimizing the dose of the vasoactive drugs. Bradycardia is frequently seen in TTM and typically requires no therapy. During PCAC, mechanical circulatory support (ECMO) may be considered if significant cardiorespiratory instability persists despite appropriate volume expansion and administration of inotropes, vasopressors, and, if indicated, antiarrhythmics.In a study de Mos N et al (CCM 2006) in a PICU population, the use of ECMO within 24 hours after ROSC was associated with reduced mortality. Case series have documented the role of ECMO88 and ventricular assist device support89,90 in children with refractory cardiogenic shock or acute fulminant myocarditis (Blume Ed et al., J Heart Lung Transplant 2016).
                         • What about oxygenation and ventilation strategies in our patient with PCAS
                         • Optimal oxygenation and ventilation of children after ROSC may be hampered by the pathology that precipitated the cardiac arrest (such as drowning with resultant post-pulmonary edema) and by the ensuing post-cardiac arrest pathophysiology. Further management challenges may be caused by aspiration and lung injury occurring during resuscitation efforts as well as ventilator-induced lung injury. Additionally, use of TTM alters the relationship between arterial oxygen saturation and arterial oxygen tension such that, for a given arterial oxygen saturation, the arterial oxygen tension (Pao2) is lower than that observed when the temperature is normal. Hypothermia also decreases the metabolic rate; thus, carbon dioxide production will be lower at any given minute ventilation.
                         • Post–cardiac arrest blood gas abnormalities are common in children, particularly in the first hours after ROSC as seen in our patient case. Published evidence has failed to demonstrate a consistent effect of post-cardiac arrest hyperoxia or hypoxemia on outcome. After ROSC, it is reasonable to aim for normal PaO2 (or the value appropriate for the child’s condition if the child has, for example, cyanotic heart disease) and to use the lowest possible fraction of inspired oxygen, weaning to maintain an oxygen saturation of 94% to 99% as a guideline. Throughout PCAC, hypoxemia must be avoided whenever possible, particularly during oxygen titration. The 2010 AHA PALS guidelines recommended prompt arterial blood gas analysis as soon as possible after ROSC and within 10 to 15 minutes of establishing initial mechanical ventilation to guide oxygen administration and titration and to support mechanical ventilation.
                         • Post–cardiac arrest derangements in PaCO2 are common. On the basis of available evidence, after ROSC, it is reasonable to target normocapnia (ie, normal for the child, or PaCO2 35–45 mm Hg) or a PaCO2 specific for the patient’s condition, limiting exposure to severe hypercapnia and hypocapnia. Lung protective strategies such as low TV, high PEEP should be used to minimize VILI.
                         • Can you comment on targeted temperature management?
                         • Post–cardiac arrest pyrexia (elevated core body temperature) is common, and persistent hyperthermia is associated with unfavorable neurological outcomes in children (Bambea MM PCCM 2010).During PCAC, fever (≥38°C) should be aggressively treated. To treat the child who remains comatose after OHCA, the 2015 AHA PALS guidelines update recommended that it is reasonable either to maintain continuous normothermia (TTM to 36°C–37.5°C) for 5 days or to maintain 2 days of continuous hypothermia (TTM to 32C°–34°C) followed by 3 days of continuous normothermia (TTM to 36°C–37.5°C).2 Because increased mortality was associated with temperatures <32°C, if TTM to 32°C to 34°C is used, meticulous care must be provided to prevent temperatures <32°C.
                         
                         

                         Post–cardiac arrest derangements in PaCO2 are common. On the basis of available evidence, after ROSC, it is reasonable to target normocapnia (ie, normal for the child, or Paco2 35–45 mm Hg) or a Paco2 specific for the patient’s condition, limiting exposure to severe hypercapnia and hypocapnia. Lung protective strategies such as low TV, high PEEP should be used to minimize VILI.

                         • What about treatment of seizures in PCAS and can you also comment on sedation , analgesia and the use of NMB in these patients ?
                         • Seizures occur in 10% to 50% of children who remain encephalopathic after achieving ROSC. (Abend NS et al Neurology 2009). Furthermore, about half of children with post-ROSC seizures experience exclusively non-convulsive (subclinical, EEG only) seizures, which cannot be identified by clinical observation alone. Seizures could not be predicted from any clinical or resuscitation variables. Seizures were associated with unfavorable gross neurological outcomes at discharge but not with higher mortality. Because seizures increase metabolic demand, can worsen metabolic dysfunction, and can increase intracranial pressure, they can contribute to secondary brain injury.
                         • For these reasons, many clinicians aim to treat seizures, although the approach is generally guided by the child’s overall medical condition and other prognostic indicators. Typical acute clinical or electrographic seizures are often initially treated with benzodiazepines, levetiracetam, or phenytoin. Myoclonic seizures such as those reported in our patient case may be refractory to treatment. (Ostendorf AP et al PCCM 2016) Providers must be alert for potential adverse effects of anticonvulsants such as cardiac arrhythmias, hypotension, and respiratory depression. In addition, sedation induced by anti-seizure drugs may complicate the neurological examination. Pain and discomfort needs to be controlled using opioids (morphine or fentanyl) and sedatives (dexmedetomidine or benzodiazepines). Neuromuscular blocking agents (eg, vecuronium or pancuronium) with analgesia or sedation (or both) may improve oxygenation and ventilation in case of patient-ventilator dyssynchrony or severely compromised pulmonary function. Providers are cautioned, however, that NMB agents can mask seizures and impede neurological examinations.If TTM is used, practitioners must be aware that the pharmacokinetics and pharmacodynamics of sedatives/hypnotics and neuromuscular blocking agents will be altered, resulting in prolonged time to both hepatic and renal clearance.
                         • What about endocrine dysfunction in PCAS patients ? Can you comment on glucose control and treatment of adrenal dysfunction?
                         • Both hypoglycemia and hyperglycemia have been associated with unfavorable outcomes in critically ill children and adults. During PCAC, clinicians should avoid and promptly treat hypoglycemia.Severe hyperglycemia can also be problematic because it can lead to uncontrolled osmotic diuresis, which can exacerbate post–cardiac arrest volume depletion and hemodynamic instability. Therefore, it is important to monitor serum glucose concentration, to treat significant hyperglycemia, and to monitor urine volume. There is currently insufficient published evidence to determine the optimal blood glucose concentration during PCAC that will maximize neurological outcome. Approximately 30% of critically ill children have relative adrenal insufficiency, but this has not been evaluated in children resuscitated from cardiac arrest. There is insufficient evidence to support the routine use of corticosteroids after cardiac arrest. Patients should be treated per recommendations for critically ill children.
                         • How do we manage Renal failure in these patients?
                         • In a recent retrospective study of 296 children during PCAC, 37% had AKI, 11.5% had severe AKI by Acute Kidney Injury Network criteria, and 6.4% required RRT within 48 hours of ROSC.(Neumayr TM et al. PCCM 2017). Risk factors for severe AKI after cardiac arrest included abnormal baseline creatinine, lack of a chronic lung condition, in-hospital arrest location, higher number of doses of epinephrine during arrest, and worse post–cardiac arrest acidosis.Throughout PCAC, it is important to monitor kidney function, including urine output and creatinine, because patients are at risk for developing AKI, and RRT may be indicated. Nephrotoxic medications and medications excreted by the kidneys should be used with caution, and dose adjustment may be needed. Serum concentrations of nephrotoxic medications should be closely monitored.
                         • Do we need antibiotics during post cardiac arrest care (PCAC) ? Can you also comment on management of inflammation and coagulation abnormalities?
                         • Infection is common after pediatric cardiac arrest. Most studies reporting the incidence of infection during PCAC enrolled children treated with THAPCA trial. The incidence varied from < 5 infections per 100 days in IHCA to 11.1 infections per 100 days for OHCA patients. The incidence of culture-proven infection did not differ between patients treated with TTM 32-34 and those treated with TTM to 36-37.5. During ECMO therapy for PCAS, the infection rate was ~ 10%. Monitoring for signs of infection is important during PCAC. The decision to obtain cultures and to initiate empirical antimicrobial coverage should follow local PICU protocols.
                         • Inflammatory pathways are activated as part of PCAS, including disturbances of the coagulation cascade. The effects of blocking or modulation of these pathways have been studied in adults and in animal models; we identified no studies to date involving infants or children. Extensive animal research into blocking or modifying inflammatory pathways has yielded promising results. However, to date, most attempts to translate this work to humans have been unsuccessful. Because inflammation can alter the coagulation cascade, providers should monitor for signs of bleeding or coagulopathies; this is particularly important for patients receiving ECMO support. At this time, there is insufficient evidence to support specific treatments to modulate inflammatory pathways during PCAC.
                         
                         

                         To summarize, Infection is common after pediatric cardiac arrest. Inflammatory pathways are activated as part of PCAS, including disturbances of the coagulation cascade. The effects of blocking or modulation of these pathways have been studied in adults and in animal models; we identified no studies to date involving infants or children.

                         • Can you comment on rehabilitation and recovery after cardiac arrest ?
                         • Children surviving cardiac arrest are at high risk for physical, cognitive, and emotional disabilities that can affect quality of life, family function, activities of daily living, school performance, and employment. There is little evidence on specific interventions during PCAC that will improve functional outcomes of children after cardiac arrest. Small observational studies of children after critical illness or injury suggest that children with anoxic injury have more severe disability and demonstrate less improvement compared with children with traumatic brain injury. There is insufficient evidence to support specific rehabilitation interventions or the optimal timing of initiation of such interventions. However, on the basis of the benefits of rehabilitation for patients with traumatic brain injury and stroke, it is reasonable for providers to consult rehabilitation experts within the first 72 hours after cardiac arrest to tailor a plan of rehabilitation interventions for survivors of cardiac arrest.
                         • As we look into the future, What about biomarkers for post arrest prognostication?
                         • Currently, there is insufficient evidence to support the use of serum biomarker concentrations alone to predict outcome after pediatric cardiac arrest. Although specific biomarkers have shown promise, they have yet to be validated in prospective pediatric studies after cardiac arrest. After cardiac arrest, elevations in lactate concentration may reflect not only severe post–cardiac arrest systemic hypoperfusion but also severe cerebral hypoperfusion. In several pediatric cardiac arrest studies, higher serum lactate concentrations in the first 12 hours after cardiac arrest were associated with increased mortality, and higher concentrations within 12 hours of ROSC were modestly predictive of unfavorable outcome (area under the curve: for IHCA, 0.76; for OHCA, 0.75). (Meert K et al. PCCM 2009; Topjian A PCCM 2013). Numerous other promising biomarkers of neurological injury, systemic inflammation, and genetic polymorphisms are currently under evaluation. An ongoing trial is investigating concentrations of NSE, S100B, glial fibrillary acid protein, and ubiquitin carboxy-terminal hydrolase L1 in the first 72 hours after pediatric OHCA and their association with 1-year neurological outcomes. (Prout AJ et al. Curr Opin Pediatr 2017).
                         
                         

                         To summarize, In several pediatric cardiac arrest studies, higher serum lactate concentrations in the first 12 hours after cardiac arrest were associated with increased mortality, and higher concentrations within 12 hours of ROSC were modestly predictive of unfavorable outcome

                         How do we prognosticate PCAS

                         • Providers must consider multiple variables when attempting to prognosticate outcomes during and after cardiac arrest. Providers must consider multiple variables when attempting to prognosticate outcomes during and after cardiac arrest. Although there are factors associated with better or worse outcomes, no single factor studied predicts outcome with sufficient accuracy to recommend termination or continuation of CPR or to enable prognostication after ROSC (de Caen AR et al. Circulation 2015).
                         • Several prearrest conditions and therapies have been independently associated with worse survival to discharge and unfavorable neurological outcomes after pediatric cardiac arrest: Worse outcomes from OHCA are associated with decreased age and some causes of arrest, including sudden infant death syndrome and blunt trauma. (Meert KL et al. PCCM 2016. Matos RI et al. Circulation 2013). Factors associated with lower survival after IHCA include older age; presence of preexisting conditions; interventions such as tracheal intubation, mechanical ventilation, and use of vasopressors at the time of arrest; and arrests occurring...]]>f752653c-c000-4518-914d-ab85bccbc867Sun, 20 Mar 2022 03:00:00 -040036:49falsefull4646Pediatric Post Cardiac Arrest Syndrome (PCAS) Part 1Welcome to PICU Doc On Call, a podcast dedicated to current and aspiring intensivists. My name is Pradip Kamat.

                           My name is Rahul Damania, a current 2nd-year pediatric critical care fellow. We come to you from Children’s Healthcare of Atlanta-Emory University School of Medicine.

                           Today's episode is dedicated to pediatric post-cardiac arrest care.

                           We are going to split this topic into two episodes, part one of pediatric post-cardiac arrest syndrome will address the epidemiology, causes, and pathophysiology.

                           I will turn it over to Rahul to start with our patient case...

                           • 11 yo previously healthy M who is admitted to the PICU after cardiac arrest.
                           • The patient was noted to be found unresponsive and submerged in a neighborhood pool.
                           • He was pulled out by bystanders and CPR was started for 5 minutes with two rounds of epinephrine prior to achieving ROSC.
                           • During transport to the OSH, the patient developed hypotension requiring a continuous epinephrine infusion.
                           • His initial blood gas was notable for a mixed respiratory and metabolic acidosis:
                           • 7.0/60/-20
                           • His initial serum lactate was 6.8 mmol/L.
                           • He presents to the PICU with a temperature of 36.6, HR 130s, MAPs 50s on Epinephrine infusion at 0.03mcg/kg/min
                           • He is mechanically ventilated with notable settings PEEP of 10, FiO2 65%.
                           • The patient is taken to head CT which shows diffuse cerebral edema and diffusely diminished grey-white differentiation most pronounced in the basal ganglia.
                           
                           

                           Great Rahul, can you please comment on his physical exam & PMH?

                           • Important physical exam findings include an unresponsive intubated patient with a cervical collar and bilateral non-reactive pupils at 4mm. The patient received mechanical ventilation with coarse breath sounds. A heart exam revealed tachycardia with no murmur or gallop. The patient does not respond to stimuli, intermittent jerking movements of arms and legs were observed. There was no evidence of rash or trauma. No past medical history of seizures or any heart disease. No home medications or toxic ingestions are suspected.
                           
                           

                           So now he is transferred to the ICU, what did we do?

                           • An arterial line, central venous line, urinary catheter, esophageal temperature probe was placed. The patient was ventilated using a TV of 6cc/kg and a PEEP of 10 (FIO2 ~65%) to keep SPO2 >94%. The patient initially had runs of ventricular tachycardia for which lidocaine was used. Although the initial EKG showed mild QTc prolongation, it subsequently normalized and was considered to be due to his cardiac arrest and resuscitation. An echocardiogram revealed normal biventricular systolic function (on epinephrine) and also showed normal origins of the coronary arteries. Comprehensive Arrhythmia Panel did not identify a specific genetic cause for the patient's sudden cardiac arrest. The patient was placed on continuous EEG, which demonstrated severe diffuse encephalopathy with myoclonic status likely from anoxic brain injury Patient was also started on Levetiracetam and valproic acid. Initial portable CT scan done on day # of admission showed diffuse cerebral edema and diffusely diminished gray-white differentiation (most pronounced in the basal ganglia). MRI was deferred due to patient instability.
                           
                           

                           The case we talked about highlights a patient who had a trigger that then resulted in cardiac arrest is common is one of the common reasons for admission to the PICU at Children's hospitals whether from submersion injury, trauma, ingestion, cardiac arrhythmia, sepsis, etc. Can we start by defining post-cardiac arrest syndrome?

                           • Successful resuscitation from cardiac arrest results in a post-cardiac arrest syndrome, which can evolve in the days to weeks after the return of spontaneous circulation. The components of post-cardiac arrest syndrome are brain injury, myocardial dysfunction, systemic ischemia/reperfusion response, and persistent precipitating pathophysiology. Prior to 2008, the AHA pediatric advanced life support (PALS) guidelines focused chiefly on the prevention of cardiac arrest, immediate recognition of cardiac arrest, and provision of early CPR because outcomes of pediatric cardiac arrest were poor. The past decade has led to focused efforts by resuscitation experts to address specific pediatric post-cardiac arrest knowledge gaps. In the 2019 Aug issue of Circulation (Vol 140, issue 6) published a scientific statement from the American Heart Association, which summarizes the epidemiology, pathophysiology, management, and prognostication after the return of sustained circulation after cardiac arrest, and it provides consensus on the current evidence supporting elements of pediatric post-cardiac arrest care.
                           • In order to provide post-cardiac arrest care (PCAC), caregivers need to understand the phases of cardiac arrest. Can you give us more information on the phases of cardiac arrest care?
                           • Let me start by defining ROSC or return of spontaneous circulation: ROSC refers to a return of sustained circulation, which can include circulation that results either from a perfusing spontaneous heart rhythm or from the establishment of extracorporeal circulation with extracorporeal membrane oxygenation (ECMO).
                           • The immediate phase: the first 0 to 20 minutes after ROSC
                           • The early phase: the period after ROSC from 20 minutes up to 6 to 12 hours
                           • The intermediate phase: 12 to 72 hours
                           • The recovery phase: approximately 72 hours to day 7. Starts at different times for different patients; the timing may be influenced by factors such as cardiovascular function or use of targeted temperature management (TTM)
                           • The rehabilitation phase: traditionally began with the application of care after discharge from the acute care hospital, but rehabilitation services are now often initiated during the intermediate phase or the recovery phase.
                           • What is the epidemiology of post-cardiac arrest syndrome (PCAS)?
                           • The timing and severity of the phases of post-cardiac arrest syndrome (PCAS) may differ between patients with out-of-hospital cardiac arrest (OHCA) and those with in-hospital cardiac arrest (IHCA) because witnessed status, preexisting conditions, cause of arrest, and timing and quality of bystander actions, such as immediate administration of high-quality CPR, may differ between OHCA and IHCA.
                           • It is estimated that >5000 children experience OHCA annually in the United States with an estimated incidence of non-traumatic OHCA of 8.04 per 100 000 person-years.11 With current ROSC rates of ≈36%. The reported survival to discharge in OHCA remains poor- 6.7-10.2% although favorable neurological outcome has been reported in 77% of pediatric OHCA survivors. One study using PECARN data (Moler FW et al. CCM 2011) of TTM in comatose children who survived OHCA to be admitted to a pediatric intensive care unit (ICU), reported that 38% survived to hospital discharge.
                           
                           

                           An estimated 6000 infants and children develop IHCA annually. Non–risk-adjusted ICU ROSC occurred in 78%, with 45% surviving to discharge; 89% of survivors had a favorable neurological outcome (Berg RA et al. CCM 2016)

                           Approximately 6500 children per year in the US have PCAS. The goal of PCAC is to increase not only survival to hospital discharge but also survival with favorable neurological outcomes.

                           • Can we take a deeper dive into the pathophysiology of PCAS? Let's start with brain injury
                           • Post–cardiac arrest brain injury remains a leading cause of morbidity and mortality in adults and children because the brain has limited tolerance of ischemia, hyperemia, or edema. The first 3 phases of PCAS involve hypoxemic-hypotensive perfusion with energy deprivation. With ROSC, there is a burst of reactive oxygen species, and oxidative stress may ensue in tissue that is depleted of antioxidants. As a result, reperfusion is associated with excitotoxicity, calcium accumulation, and free radical-mediated cell injury or death. The myoclonic status seen in your case is...]]>Welcome to PICU Doc On Call, a podcast dedicated to current and aspiring intensivists. My name is Pradip Kamat.

                             My name is Rahul Damania, a current 2nd-year pediatric critical care fellow. We come to you from Children’s Healthcare of Atlanta-Emory University School of Medicine.

                             Today's episode is dedicated to pediatric post-cardiac arrest care.

                             We are going to split this topic into two episodes, part one of pediatric post-cardiac arrest syndrome will address the epidemiology, causes, and pathophysiology.

                             I will turn it over to Rahul to start with our patient case...

                             • 11 yo previously healthy M who is admitted to the PICU after cardiac arrest.
                             • The patient was noted to be found unresponsive and submerged in a neighborhood pool.
                             • He was pulled out by bystanders and CPR was started for 5 minutes with two rounds of epinephrine prior to achieving ROSC.
                             • During transport to the OSH, the patient developed hypotension requiring a continuous epinephrine infusion.
                             • His initial blood gas was notable for a mixed respiratory and metabolic acidosis:
                             • 7.0/60/-20
                             • His initial serum lactate was 6.8 mmol/L.
                             • He presents to the PICU with a temperature of 36.6, HR 130s, MAPs 50s on Epinephrine infusion at 0.03mcg/kg/min
                             • He is mechanically ventilated with notable settings PEEP of 10, FiO2 65%.
                             • The patient is taken to head CT which shows diffuse cerebral edema and diffusely diminished grey-white differentiation most pronounced in the basal ganglia.
                             
                             

                             Great Rahul, can you please comment on his physical exam & PMH?

                             • Important physical exam findings include an unresponsive intubated patient with a cervical collar and bilateral non-reactive pupils at 4mm. The patient received mechanical ventilation with coarse breath sounds. A heart exam revealed tachycardia with no murmur or gallop. The patient does not respond to stimuli, intermittent jerking movements of arms and legs were observed. There was no evidence of rash or trauma. No past medical history of seizures or any heart disease. No home medications or toxic ingestions are suspected.
                             
                             

                             So now he is transferred to the ICU, what did we do?

                             • An arterial line, central venous line, urinary catheter, esophageal temperature probe was placed. The patient was ventilated using a TV of 6cc/kg and a PEEP of 10 (FIO2 ~65%) to keep SPO2 >94%. The patient initially had runs of ventricular tachycardia for which lidocaine was used. Although the initial EKG showed mild QTc prolongation, it subsequently normalized and was considered to be due to his cardiac arrest and resuscitation. An echocardiogram revealed normal biventricular systolic function (on epinephrine) and also showed normal origins of the coronary arteries. Comprehensive Arrhythmia Panel did not identify a specific genetic cause for the patient's sudden cardiac arrest. The patient was placed on continuous EEG, which demonstrated severe diffuse encephalopathy with myoclonic status likely from anoxic brain injury Patient was also started on Levetiracetam and valproic acid. Initial portable CT scan done on day # of admission showed diffuse cerebral edema and diffusely diminished gray-white differentiation (most pronounced in the basal ganglia). MRI was deferred due to patient instability.
                             
                             

                             The case we talked about highlights a patient who had a trigger that then resulted in cardiac arrest is common is one of the common reasons for admission to the PICU at Children's hospitals whether from submersion injury, trauma, ingestion, cardiac arrhythmia, sepsis, etc. Can we start by defining post-cardiac arrest syndrome?

                             • Successful resuscitation from cardiac arrest results in a post-cardiac arrest syndrome, which can evolve in the days to weeks after the return of spontaneous circulation. The components of post-cardiac arrest syndrome are brain injury, myocardial dysfunction, systemic ischemia/reperfusion response, and persistent precipitating pathophysiology. Prior to 2008, the AHA pediatric advanced life support (PALS) guidelines focused chiefly on the prevention of cardiac arrest, immediate recognition of cardiac arrest, and provision of early CPR because outcomes of pediatric cardiac arrest were poor. The past decade has led to focused efforts by resuscitation experts to address specific pediatric post-cardiac arrest knowledge gaps. In the 2019 Aug issue of Circulation (Vol 140, issue 6) published a scientific statement from the American Heart Association, which summarizes the epidemiology, pathophysiology, management, and prognostication after the return of sustained circulation after cardiac arrest, and it provides consensus on the current evidence supporting elements of pediatric post-cardiac arrest care.
                             • In order to provide post-cardiac arrest care (PCAC), caregivers need to understand the phases of cardiac arrest. Can you give us more information on the phases of cardiac arrest care?
                             • Let me start by defining ROSC or return of spontaneous circulation: ROSC refers to a return of sustained circulation, which can include circulation that results either from a perfusing spontaneous heart rhythm or from the establishment of extracorporeal circulation with extracorporeal membrane oxygenation (ECMO).
                             • The immediate phase: the first 0 to 20 minutes after ROSC
                             • The early phase: the period after ROSC from 20 minutes up to 6 to 12 hours
                             • The intermediate phase: 12 to 72 hours
                             • The recovery phase: approximately 72 hours to day 7. Starts at different times for different patients; the timing may be influenced by factors such as cardiovascular function or use of targeted temperature management (TTM)
                             • The rehabilitation phase: traditionally began with the application of care after discharge from the acute care hospital, but rehabilitation services are now often initiated during the intermediate phase or the recovery phase.
                             • What is the epidemiology of post-cardiac arrest syndrome (PCAS)?
                             • The timing and severity of the phases of post-cardiac arrest syndrome (PCAS) may differ between patients with out-of-hospital cardiac arrest (OHCA) and those with in-hospital cardiac arrest (IHCA) because witnessed status, preexisting conditions, cause of arrest, and timing and quality of bystander actions, such as immediate administration of high-quality CPR, may differ between OHCA and IHCA.
                             • It is estimated that >5000 children experience OHCA annually in the United States with an estimated incidence of non-traumatic OHCA of 8.04 per 100 000 person-years.11 With current ROSC rates of ≈36%. The reported survival to discharge in OHCA remains poor- 6.7-10.2% although favorable neurological outcome has been reported in 77% of pediatric OHCA survivors. One study using PECARN data (Moler FW et al. CCM 2011) of TTM in comatose children who survived OHCA to be admitted to a pediatric intensive care unit (ICU), reported that 38% survived to hospital discharge.
                             
                             

                             An estimated 6000 infants and children develop IHCA annually. Non–risk-adjusted ICU ROSC occurred in 78%, with 45% surviving to discharge; 89% of survivors had a favorable neurological outcome (Berg RA et al. CCM 2016)

                             Approximately 6500 children per year in the US have PCAS. The goal of PCAC is to increase not only survival to hospital discharge but also survival with favorable neurological outcomes.

                             • Can we take a deeper dive into the pathophysiology of PCAS? Let's start with brain injury
                             • Post–cardiac arrest brain injury remains a leading cause of morbidity and mortality in adults and children because the brain has limited tolerance of ischemia, hyperemia, or edema. The first 3 phases of PCAS involve hypoxemic-hypotensive perfusion with energy deprivation. With ROSC, there is a burst of reactive oxygen species, and oxidative stress may ensue in tissue that is depleted of antioxidants. As a result, reperfusion is associated with excitotoxicity, calcium accumulation, and free radical-mediated cell injury or death. The myoclonic status seen in your case is probably due to this excitotoxicity. Both neuronal cellular necrosis and apoptosis result from this cascading injury and can continue in the days to weeks after ROSC. 
                             • A variety of post-cardiac arrest clinical conditions, including hyperoxia, hypoxemia, and hypotension, can exacerbate the neuronal injury.
                             • What about cardiac injury in PCAS?
                             • Global myocardial dysfunction occurs even in the absence of a cardiac cause of the arrest, and the severity of the myocardial dysfunction may be related to the duration of no-flow time during cardiac arrest. Myocardial dysfunction has been associated with early mortality despite successful initial resuscitation in children and adults. The onset of post-cardiac arrest myocardial dysfunction begins within hours of the arrest, peaks at ≈8 hours, begins to improve at 24 hours, and typically resolves within 48 to 72 hours. The pathophysiology contributing to this frequently reversible deterioration of cardiac function after cardiac arrest is not fully understood but is associated with cardiovascular ischemia/reperfusion injury, cytokine-mediated cardiovascular dysfunction, and induced myocardial injury secondary to catecholamines or electric shocks. (Adrie C et al. Circulation 2002).Children may initially demonstrate a hyperdynamic state and then develop cardiac dysfunction over time. Because myocardial dysfunction is likely to develop in approximately two-thirds of patients after ROSC and subsequently improve, it is thought to be a modifiable risk factor.
                             
                             

                             Clinical manifestations of myocardial dysfunction include hypotension, left ventricular and RV systolic or diastolic dysfunction resulting in reduced cardiac output, arrhythmias, and pulmonary edema, which can result in recurrent cardiac arrest. Cardiac arrhythmias such as Vtach noted in the patient in your case are common during PCAC and may be exacerbated by catecholamine administration, which is required to maintain adequate cardiac output.

                             • Rahul**: What about systemic ischemia/reperfusion ?**
                             • The combination of systemic ischemia/reperfusion produces a state similar to the sepsis syndrome, with elevated cytokines, the presence of endotoxin in plasma, activation of coagulation pathways, and inhibition of anticoagulant pathways. Transient critical illness hyperglycemia occurs after cardiac arrest from a relative insulin-resistant state that is associated with high levels of endogenous catecholamines and cortisol secretion, with resulting gluconeogenesis and glycogenolysis. In children, the serum glucose is typically elevated in the first 12 to 18 hours after the insult and then falls to normal. Clinical manifestations of systemic ischemia/reperfusion include capillary leak with intravascular hypovolemia, vasoplegia, coagulopathy, hyperglycemia, adrenal insufficiency, and impaired oxygen utilization and delivery, contributing to multisystem organ dysfunction. I would like to advise our listeners that management of the child after cardiac arrest includes diagnosis and treatment of the precipitating cause of cardiac arrest. Failure to identify and correct the original cause of cardiac arrest leaves the patient at risk for secondary injury and even recurrence of cardiac arrest. A team approach using experts from cardiology, genetics, infectious disease, radiologists and toxicologists, etc., may be required to investigate the cause of cardiac arrest.
                             
                             

                             To summarize, the combination of systemic ischemia/reperfusion produces a state similar to the sepsis syndrome, with elevated cytokines, the presence of endotoxin in plasma, activation of coagulation pathways, and inhibition of anticoagulant pathways. Transient critical illness hyperglycemia occurs after cardiac arrest from a relative insulin-resistant state that is associated with high levels of endogenous catecholamines and cortisol secretion, with resulting gluconeogenesis and glycogenolysis. In children, the serum glucose is typically elevated in the first 12 to 18 hours after the insult and then falls to normal.

                             • Let's discuss monitoring typically used in patients with PCAS?
                             • In the post-cardiac arrest period, it is important for the healthcare team to anticipate and assess for evolving systemic and organ dysfunction and to proactively support organ function. This requires ongoing monitoring to guide intensive care therapies. Monitoring in the field continues through transport and includes ECG, pulse oximetry, capnography, noninvasive blood pressure measurement, and point-of-care glucose testing.
                             • General monitoring: General intensive care monitoring includes continuous cardiac telemetry, pulse oximetry, continuous capnography, continuous temperature monitoring, and measurement of blood pressure and urine output. Monitoring includes laboratory analysis of venous or arterial blood gases, serum electrolytes, and glucose and calcium concentration. Arterial lactate and central venous oxygen saturation assist in evaluation of the adequacy of tissue oxygen delivery. A chest x-ray aids evaluation of endotracheal tube position, heart size, and pulmonary status.52 Additional monitoring includes evaluation of renal function, measurement of hemoglobin concentration, monitoring of coagulation function, and assessment for signs of inflammation and infection.
                             • Hemodynamic monitoring includes: arterial line placement for intra-arterial blood pressure monitoring to facilitate the identification and treatment of hypotension. In addition, central venous catheters may be useful to monitor central venous oxygen saturation and to provide a route for the administration of fluids and medications. Pulmonary artery catheters are now rarely used in pediatrics. An echo and ECG should be performed. The optimal timing or frequency of echo acquisition remains unknown.
                             • Neuro-monitoring: Serial neurological examinations may help identify evolving hypoxic-ischemic brain injury. Given the high incidence of electrographic seizures after ROSC(Abend NS et al. Neurology 2011) monitoring with an electroencephalogram (EEG) is increasing in pediatric PCAC. Neuroimaging can be helpful to identify a cerebral cause of cardiac arrest and the presence of severe brain injury. One small pediatric study (36 patients) by Lee JK et al (Resuscitation 2014) evaluated the role of cerebral autoregulation in guiding hemodynamic management and oxygen delivery and assisting in neuroprognostication in comatose children after cardiac arrest, but more studies are needed.
                             
                             

                             This concludes our episode today on PCAS. We hope you found value in this short podcast. We welcome you to share your feedback & place a review on our podcast. PICU Doc on Call is co-hosted by Dr. Pradip Kamat, and my cohost Dr. Rahul Damania.

                             Stay tuned for our next episode which covers Part 2 of PCAS focused on Management! Thank you

                             ]]>65469840-8de2-4f5b-9b43-1e51c33dc21aSun, 13 Mar 2022 03:00:00 -040021:38falsefull4545Approach to Critical Iron Deficiency AnemiaWelcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.

                             I'm Pradip Kamat and I'm Rahul Damania. We are coming to you from Children's Healthcare of Atlanta - Emory University School of Medicine.

                             Welcome to our Episode a 2-year-old with severe pallor and O2 desaturation.

                             Here's the case presented by Rahul:

                             A two-year-old presents to the PICU with severe pallor + O2 requirement. The patient went for a routine check with her primary care who noted the patient appeared severely pale. He sent the patient to the ED. An initial Hgb check revealed a Hgb of 1.5gm/dL. Per mother, she is otherwise healthy but a very picky eater. She also reports the patient drinks milk as a soothing adjunct at night, consuming between 12 - 36oz a day. No family h/o of anemia or any other blood disorders.

                             No h/o recent illness. Mother had a normal spontaneous full-term delivery. The patient is up to date on her immunizations. Per mother, developmental milestones are normal. The mother also denies any history of decreased activity in the child. Given the low Hgb, the patient was admitted to the PICU.

                             Let's transition into some history and physical exam components of this case?

                             What are key history features in this child?

                             • Severe pallor in a 2-year-old
                             • H/o being a picky eater
                             • H/o excessive milk consumption
                             • Pertinent negatives include: No obvious blood loss, No petechia, bruising, or jaundice
                             
                             

                             What did the physical exam show?

                             • The patient was hypertensive, tachycardic to the 140s, and 10th% weight for growth percentiles
                             • On physical exam, the patient was in no acute distress. Her lips, gums, and conjunctiva were pale. She had a systolic ejection murmur. As a pertinent negative, she had no hepatosplenomegaly. She also has no rash, bruising, or petechiae.
                             
                             

                             The lack of hepatosplenomegaly may indicate that the patient has no signs of extramedullary hematopoiesis. Patients with hemolytic processes resulting in anemia may present with signs of scleral icterus, jaundice, and hepatosplenomegaly resulting from increased red cell destruction. In fact, in an emergency department setting, the clinical detection of jaundice was found to have sensitivity and specificity of only approximately 70 percent.

                             To continue with our case, then what were the patient's labs consistent with:

                             • Initial CBC showed: WBC 8.5K, RBC 1.14 (L), Hgb 1.5gm/dL; Hct 6.1, MCV 53.5, and an elevated RDW 37.7. Initial platelet count was 50K, reticulocyte count 1.1%
                             • Peripheral smear revealed no blasts, thrombocytopenia - with occasional medium-sized platelets - ghost cells and anisocytosis/poikilocytosis- which appears most consistent with iron deficiency.
                             • It was interesting that the patient had thrombocytopenia
                             
                             

                             Absolutely, typically with Iron deficiency, there is thrombocytosis (erythropoietin is increased which closely mimics thrombopoietin stimulates platelets). In fact, both act via the non-TK, JAK-STAT pathway.

                             OK, to summarize, we have:

                             • Two year old with severe anemia most likely secondary to iron deficiency.
                             • As you think about our case, what would be your differential?
                             • For any patient with acute severe anemia presenting to the PICU- One has to think in terms of blood loss, decreased or impaired production (i.e bone marrow failure), or peripheral blood destruction (i.e hemolysis).
                             • Here would be the organizations:
                             • Blood loss
                             • Decreased or impaired production
                             • Increased destruction
                             
                             

                             Let’s go into detail for each:

                             • Blood loss can be internal or external (due to trauma, excessive blood draws, due to surgery)-typically gives rise to normochromic normocytic anemia.
                             • Decreased or impaired production: Deficiency of substances needed for Hgb & RBC production such as iron Vit B12 etc. Depression of BM due to infection (parvo B), chemicals, pharmacologic agents or immune mechanisms. Bone marrow aplasia can be idiopathic with or without congenital anomalies. Infiltration of BM due to malignancies such as leukemia, Hodgkin disease, neuroblastoma, etc.
                             
                             

                             Increased blood destruction:

                             • Can be due to intrinsic defects of the RBC such as hereditary spherocytosis, defects of Hgb such as sickle cell disease, thalassemia syndromes, enzyme defects.
                             • Extrinsic factors include immune mechanisms which can be related to drugs, infections, and non-immune mechanisms such as drugs, toxins, sepsis, HUS, TTP.
                             • Also a combination of intrinsic and extrinsic defects such as PNH, Favism, G-6PD. Patients with peripheral destruction in addition to pallor, typically have evidence of hemolysis such as jaundice, red cell breakdown (erythrocyte fragmentation) on the peripheral smear is seen typically in microangiopathic hemolytic anemias.
                             • There is typically an increase in the reticulocyte count, which keeps the MCV in the macrocytic range. Bone marrow will typically reveal erythroid hyperplasia. The sine qua non of immune hemolysis is the demonstration of the presence of antibodies or complement components bound to the erythrocyte membrane using the Direct Coombs test.
                             
                             

                             A prospective study by Bateman ST et al (Am J Respir Crit Care Med. 178:26-33 2008) reported 73% of blood loss in the PICU is attributable to blood draws. We need to limit both the number as well as the frequency of blood tests in our patients especially if these are not helping make a change in patient management. Conservative blood draws will help reduce blood transfusions in patients in the PICU. The SCCM’s “Choose Wisely” campaign recommendations from 2015 advises us not to order diagnostic tests at regular intervals (such as every day) but rather in response to specific clinical questions.

                             Rahul, can you give us a brief synopsis on the physiology of iron metabolism in the human body?

                             • Iron metabolism is unique in that iron balance is achieved by control of absorption rather than by excretion.
                             • About 1.5mg/day of iron is lost due to cell exfoliation from the skin, gut, and urinary tract.
                             • About twice this amount is lost by menstruating women and about three one-half times lost during pregnancy.
                             • Dietary iron is either in form of heme iron (from hemoglobin and myoglobin of animal sources) or non-heme iron from salts of non-animal sources. The mucosal cell of the small intestine (mostly duodenum and ileum) ultimately controls the absorption of iron in the body. Once taken up by the mucosal cell the iron is either incorporated into the ferritin of the mucosal cell (sloughed off in 3-4 days) or transferred to the portal circulation of the liver with help of mucosal cell transferrin.
                             
                             

                             The cellular metabolism of iron is mediated by three proteins:

                             • Transferrin, transferrin receptor, and ferritin.
                             • Transferrin production is increased in iron deficiency states. Iron storage exists in the soluble easily available form ferritin or insoluble more stable fraction hemosiderin. Ferritin is widely distributed in all cells whereas hemosiderin is deposited primarily in the liver, spleen, and bone marrow. Serum ferritin < 10 or 12 microgm/ml indicated...]]>Welcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.

                               I'm Pradip Kamat and I'm Rahul Damania. We are coming to you from Children's Healthcare of Atlanta - Emory University School of Medicine.

                               Welcome to our Episode a 2-year-old with severe pallor and O2 desaturation.

                               Here's the case presented by Rahul:

                               A two-year-old presents to the PICU with severe pallor + O2 requirement. The patient went for a routine check with her primary care who noted the patient appeared severely pale. He sent the patient to the ED. An initial Hgb check revealed a Hgb of 1.5gm/dL. Per mother, she is otherwise healthy but a very picky eater. She also reports the patient drinks milk as a soothing adjunct at night, consuming between 12 - 36oz a day. No family h/o of anemia or any other blood disorders.

                               No h/o recent illness. Mother had a normal spontaneous full-term delivery. The patient is up to date on her immunizations. Per mother, developmental milestones are normal. The mother also denies any history of decreased activity in the child. Given the low Hgb, the patient was admitted to the PICU.

                               Let's transition into some history and physical exam components of this case?

                               What are key history features in this child?

                               • Severe pallor in a 2-year-old
                               • H/o being a picky eater
                               • H/o excessive milk consumption
                               • Pertinent negatives include: No obvious blood loss, No petechia, bruising, or jaundice
                               
                               

                               What did the physical exam show?

                               • The patient was hypertensive, tachycardic to the 140s, and 10th% weight for growth percentiles
                               • On physical exam, the patient was in no acute distress. Her lips, gums, and conjunctiva were pale. She had a systolic ejection murmur. As a pertinent negative, she had no hepatosplenomegaly. She also has no rash, bruising, or petechiae.
                               
                               

                               The lack of hepatosplenomegaly may indicate that the patient has no signs of extramedullary hematopoiesis. Patients with hemolytic processes resulting in anemia may present with signs of scleral icterus, jaundice, and hepatosplenomegaly resulting from increased red cell destruction. In fact, in an emergency department setting, the clinical detection of jaundice was found to have sensitivity and specificity of only approximately 70 percent.

                               To continue with our case, then what were the patient's labs consistent with:

                               • Initial CBC showed: WBC 8.5K, RBC 1.14 (L), Hgb 1.5gm/dL; Hct 6.1, MCV 53.5, and an elevated RDW 37.7. Initial platelet count was 50K, reticulocyte count 1.1%
                               • Peripheral smear revealed no blasts, thrombocytopenia - with occasional medium-sized platelets - ghost cells and anisocytosis/poikilocytosis- which appears most consistent with iron deficiency.
                               • It was interesting that the patient had thrombocytopenia
                               
                               

                               Absolutely, typically with Iron deficiency, there is thrombocytosis (erythropoietin is increased which closely mimics thrombopoietin stimulates platelets). In fact, both act via the non-TK, JAK-STAT pathway.

                               OK, to summarize, we have:

                               • Two year old with severe anemia most likely secondary to iron deficiency.
                               • As you think about our case, what would be your differential?
                               • For any patient with acute severe anemia presenting to the PICU- One has to think in terms of blood loss, decreased or impaired production (i.e bone marrow failure), or peripheral blood destruction (i.e hemolysis).
                               • Here would be the organizations:
                               • Blood loss
                               • Decreased or impaired production
                               • Increased destruction
                               
                               

                               Let’s go into detail for each:

                               • Blood loss can be internal or external (due to trauma, excessive blood draws, due to surgery)-typically gives rise to normochromic normocytic anemia.
                               • Decreased or impaired production: Deficiency of substances needed for Hgb & RBC production such as iron Vit B12 etc. Depression of BM due to infection (parvo B), chemicals, pharmacologic agents or immune mechanisms. Bone marrow aplasia can be idiopathic with or without congenital anomalies. Infiltration of BM due to malignancies such as leukemia, Hodgkin disease, neuroblastoma, etc.
                               
                               

                               Increased blood destruction:

                               • Can be due to intrinsic defects of the RBC such as hereditary spherocytosis, defects of Hgb such as sickle cell disease, thalassemia syndromes, enzyme defects.
                               • Extrinsic factors include immune mechanisms which can be related to drugs, infections, and non-immune mechanisms such as drugs, toxins, sepsis, HUS, TTP.
                               • Also a combination of intrinsic and extrinsic defects such as PNH, Favism, G-6PD. Patients with peripheral destruction in addition to pallor, typically have evidence of hemolysis such as jaundice, red cell breakdown (erythrocyte fragmentation) on the peripheral smear is seen typically in microangiopathic hemolytic anemias.
                               • There is typically an increase in the reticulocyte count, which keeps the MCV in the macrocytic range. Bone marrow will typically reveal erythroid hyperplasia. The sine qua non of immune hemolysis is the demonstration of the presence of antibodies or complement components bound to the erythrocyte membrane using the Direct Coombs test.
                               
                               

                               A prospective study by Bateman ST et al (Am J Respir Crit Care Med. 178:26-33 2008) reported 73% of blood loss in the PICU is attributable to blood draws. We need to limit both the number as well as the frequency of blood tests in our patients especially if these are not helping make a change in patient management. Conservative blood draws will help reduce blood transfusions in patients in the PICU. The SCCM’s “Choose Wisely” campaign recommendations from 2015 advises us not to order diagnostic tests at regular intervals (such as every day) but rather in response to specific clinical questions.

                               Rahul, can you give us a brief synopsis on the physiology of iron metabolism in the human body?

                               • Iron metabolism is unique in that iron balance is achieved by control of absorption rather than by excretion.
                               • About 1.5mg/day of iron is lost due to cell exfoliation from the skin, gut, and urinary tract.
                               • About twice this amount is lost by menstruating women and about three one-half times lost during pregnancy.
                               • Dietary iron is either in form of heme iron (from hemoglobin and myoglobin of animal sources) or non-heme iron from salts of non-animal sources. The mucosal cell of the small intestine (mostly duodenum and ileum) ultimately controls the absorption of iron in the body. Once taken up by the mucosal cell the iron is either incorporated into the ferritin of the mucosal cell (sloughed off in 3-4 days) or transferred to the portal circulation of the liver with help of mucosal cell transferrin.
                               
                               

                               The cellular metabolism of iron is mediated by three proteins:

                               • Transferrin, transferrin receptor, and ferritin.
                               • Transferrin production is increased in iron deficiency states. Iron storage exists in the soluble easily available form ferritin or insoluble more stable fraction hemosiderin. Ferritin is widely distributed in all cells whereas hemosiderin is deposited primarily in the liver, spleen, and bone marrow. Serum ferritin < 10 or 12 microgm/ml indicated depletion of iron reserves.
                               
                               

                               To summarize, iron metabolism uptake occurs primarily in the duodenum. Thus, always watch out for patients with duodenal disease, for example, short gut, celiac, IBD, etc. Also, transferrin transports iron, and ferritin represents your stores

                               Rahul, a frequently asked question on the Peds CCM boards is about oxygen content and oxygen delivery. Can you shed some light on this with the respect to this case?

                               We have discussed this in detail in episode 33: Oxygen Content and Oxygen Delivery. Definitely worth a listen.

                               • As a review, the formula for O2 content is 1.34 X Hgb X O2 saturation +0.003X PaO2.
                               • If we assume PaO2 is 100 and O2 saturation is 100%, our O2 content for this patient = (1.34 X 1.5 X 1) +0.003 X 100 = 2.01+ 0.3 = 2.31 ml O2/dL
                               • If patient is transfused to a Hgb of 6, O2 content = 8.04+0.3 = 8.34
                               • Conversely, If patient is given 100% O2, the PaO2 = 713, The O2 content of above patient is 2.10+ 0.003 X 713 =4.239,
                               • So we either have to increase the Hgb or if unable to transfuse, increase PaO2 as shown in the calculations above.
                               • What gives us more bang for our buck is increasing Hgb concentration — this will in turn increase our O2 content.
                               
                               

                               I think it is great to practice calculations of the O2 content, anytime they are faced with a patient with low Hgb or a patient for whom blood transfusion on is indicated. I would also recommend folks read the TAXI guidelines for pRBC transfusion in the Peds ICU. (PCCM)

                               If you had to work up this patient with severe anemia, what would be your diagnostic approach?

                               • CBC with differential, reticulocyte count, peripheral smear
                               • CMP, urine analysis, stool guaiac
                               • Infectious workup should include RVP, Parvovirus
                               • Hgb electrophoresis
                               • Serum lead level
                               • If the patient has pancytopenia despite PRBC replacement, she would need workup for bone marrow arrest/failure process - such as peripheral flow, BMA/Bx
                               • No single test or combination of tests reliably documents iron deficiency in all clinical situations. I would also add that review of the peripheral smear is an essential part of any anemia evaluation. Even if the patient's RBC indices are normal, a review of the blood smear may reveal abnormal cells that can help identify the cause of anemia.
                               • If our history, physical, and diagnostic investigation led us to severe most likely due to iron deficiency anemia as our diagnosis what would be your general management of framework?
                               • When a patient is admitted to the PICU with severe anemia the usual principles of good PICU care in terms of monitoring, management of airway, and hemodynamics should precede the workup and therapy. I also make sure the patient has at least two good peripheral IVs of which one can be used to send the required labs. We work very closely with our hematology colleagues and the nutritionist.
                               • When Hgb is < 5gm%, the patient should be administered a sequential small aliquot 2.5mL/kg very slowly (typically over 3-4 hours). Frequent rechecking of hgb/hct is required as well as close monitoring for any signs of heart failure. Once Hgb is > =5gm%, we can give 5ml/kg over 2-3 hours and wait at least 2 hours in between aliquots.
                               • Absolutely, Rahul, Iron supplementation should also be started at around 3mg/kg/dose BID.
                               • Nutritionists recommended limiting milk intake and encouraging iron-containing foods and eating a healthy toddler diet. iron should not be taken with Calcium but Vitamin C, which promotes its absorption.
                               • Social work referral to get family the necessary support may be needed. Especially if there is a concern for lead in the home.
                               
                               

                               It is also essential to involve the Pediatric Hematology team for appropriate workup, management and follow-up!

                               This concludes our episode on acute anemia in the PICU. We hope you found value in our short, case-based podcast. We welcome you to share your feedback, subscribe & place a review on our podcast! Please visit our website picudoconcall.org which showcases our episodes as well as our Doc on Call management cards. If you are interested in learning more regarding acute severe anemia please refer to Fuhrman & Zimmerman - Textbook of Pediatric Critical Care Chapter 91. Transfusion Medicine. PICU Doc on Call is co-hosted by myself Dr. Pradip Kamat and Dr. Rahul Damania. Stay tuned for our next episode! Thank you!

                               • Cummings BM, Shailam R, Rosales AM, Huang MS, Nardi V. Case 37-2019: A 20-Month-Old Boy with Severe Anemia. N Engl J Med. 2019 Nov 28;381(22):2158-2167. doi: 10.1056/NEJMcpc1904048. PMID: 31774963
                               • Mattiello V, Schmugge M, Hengartner H, von der Weid N, Renella R; SPOG Pediatric Hematology Working Group. Diagnosis and management of iron deficiency in children with or without anemia: consensus recommendations of the SPOG Pediatric Hematology Working Group. Eur J Pediatr. 2020 Apr;179(4):527-545. doi: 10.1007/s00431-020-03597-5. Epub 2020 Feb 4. PMID: 32020331.
                               • Powers JM, McCavit TL, Buchanan GR. Management of iron deficiency anemia: a survey of pediatric hematology/oncology specialists. Pediatr Blood Cancer. 2015 May;62(5):842-6. doi: 10.1002/pbc.25433. Epub 2015 Feb 7. PMID: 25663613; PMCID: PMC4376588.
                               • Fuhrman & Zimmerman - Textbook of Pediatric Critical Care Chapter 91. Transfusion Medicine.
                               
                               ]]>4c827c5f-58c3-485e-9660-17381609354eSun, 06 Mar 2022 03:00:00 -040019:56falsefull4444Near Fatal Asthma: Management Beyond Non-InvasiveWelcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.

                               I'm Pradip Kamat and I'm Rahul Damania. We are coming to you from Children's Healthcare of Atlanta - Emory University School of Medicine.

                               Welcome to our episode, which is Part 2 of our acute severe asthma management. Today we discuss invasive mechanical ventilation of the acute asthmatic.

                               A patient with a history of asthma presents to the PICU with decreased air entry. Somnolence. Hypercarbia and drooling. The patient is hypoxemic and has see-saw breathing.

                               Rahul: Let’s dive right into this. What are the indications for intubating a child with acute severe asthma?

                               Absolute indications include:

                               • Altered mental status which may be preceded by obtundation, agitation
                               • Cardiac and respiratory arrest
                               
                               

                               Relative indications decided on a case by case basis:

                               Progressive exhaustion-despite, despite maximal therapy. Profound hypoxemia refractory to supplemental oxygen administration, and respiratory failure.

                               The decision to intubate should not be solely determined based on blood gas results.

                               Pradip, can you shed light on how we prepare for the intubation of the patient with acute severe asthma?

                               Rahul, first and foremost- we take the intubation of an asthmatic very seriously. In fact we try the whole “kitchen sink” to avoid intubation. But there will be times when we have to intubate especially for the indications you mentioned above.

                               The intubation will worsen the patient’s bronchospasm, put the patient at risk for barotrauma as well as cardiovascular collapse.

                               Preparation is the key- A team huddle and mapping prior to proceeding to intubate is the key. Every person in the room should have clear roles and responsibilities. Scenarios of what to do if “X” happens should be clearly laid out to the team by the team leader (preferably the attending or a senior fellow). The senior-most experienced person should manage the airway. At least two dedicated RTs to provide bag-mask ventilation as well as manage the ventilator are required. Nursing roles to push meds, chart the vitals and other activities as well a role for the resource nurses to help in case of cardiac arrest should be clearly laid out. Additionally, facilities that have access to isoflurane should have that ready to go. We typically give a heads up to our ECMO team to be on stand-by.

                               Prior to Intubation: Have central access or multiple large-bore PIVs if possible. Keep crystalloids boluses ready for hypotension. We also have peri-arrest epinephrine as well as an epinephrine infusion ready for any hypotension, bradycardia, or cardiac arrest. For intubation, we typically use Ketamine, fentanyl, and rocuronium (some centers may use succinylcholine). We use cuffed endotracheal tube. We don't bag-mask at fast rates but rather wait for a full expiration prior to the next breath being delivered. These patients require slow respiratory rates with very prolonged expiratory times to allow for adequate gas exchange and lung volumes. A helpful technique is to use a stethoscope to auscultate at the lower neck for the disappearance of expiratory wheezes prior to starting the next inspiration. We sometimes place a nasogastric tube to prevent gastric distension.

                               If there is hypoxemia, hypotension, not improving with fluids, ventilator manipulation, - A consideration for tension pneumothorax should be given especially if there is asymmetric chest rise. Bedside POCUS can be used to make a diagnosis.

                               Intubation of an asthmatic is a high-risk procedure and requires a team approach, proactiveness, and anticipation. Intubation should be approached cautiously in patients with severe acute asthma exacerbations because manipulation of the airway can cause laryngospasm and worsening bronchoconstriction.

                               Rahul, what are some of the principles we should all follow prior to initiation of mechanical ventilation in an asthmatic after intubation?

                               It is important to note that most complications of intubating an asthmatic happen in the immediate post-intubation period. Hypoxemia, hypotension, tension PTX/air leaks as well as cardiac arrest can happen immediately upon initiation of positive pressure ventilation. An important cause of hypotension is hyperinflation and decreased venous return. So slowing down manual bag-mask ventilation of even disconnecting the bag and allowing for a brief period of apnea while applying manual pressure to the rib cage may help decrease hyperinflation. Hypotension should respond to fluid boluses and decrease manual bagging.

                               Dynamic Hyperinflation: Severe airflow obstruction results in incomplete exhalation resulting in dynamic hyperinflation (DHI). Progressive DHI leads to an end-expiratory lung volume reaching a new equilibrium that exceeds the functional residual capacity. In the early stages of asthma, the increased lung volume increases pulmonary elastic recoil pressure thus increasing pulmonary expiratory flow and expanding small airways thus decreasing expiratory resistance. Thus lung volume will reach a point where the entire tidal volume can be expired during the available exhalation time. However, this process becomes maladaptive in severe asthmatic such that hyperinflation required to maintain normocapnia cannot be maintained as it would expand total lung capacity

                               Positive pressure ventilation worsens DHI especially if ventilator settings are aimed at normocapnia. This will also increase the risk of hypotension and pneumothorax. The initial rule of thumb would be to use low Tidal volumes and low respiratory rates to allow for controlled hypoventilation and permissive hypercapnia.

                               Pradip, with the above is mind what are your initial ventilator settings?

                               We typically use pressure regulated volume control (PRVC) to set a TV of 8-12m//kg (reduce to generate a plateau pressure of ~30 cm H2O), respiratory rate of 6-10/minute time of 1-1.5 seconds, which allows for an expiratory time of 4-9seconds. in the patient with NMB, we set PEEP initially at zero. Peak pressures in the 50s are expected initially due to airflow obstruction but plateau pressures of 30 or below should be reassuring.

                               An inspiratory hold will determine the plateau pressure whereas an expiratory hold will give us information about the auto-PEEP. The applied PEEP should be set below the auto peep in a spontaneously breathing patient in order to decrease the trigger work.

                               Another ventilation strategy, which is comfortable for the patient is the use of pressure support ventilation with PEEP. PEEP narrows the gap between proximal and distal airway pressures during the hyperinflated obstructed state. Pressure support facilitates inspiration while decreasing the work of breathing. The patient determines the time, respiratory rate, and depth. of each breath.

                               In summary: RR 10-12/min; Tidal volume: 6 to 8 mL/kg; set the sensitivity for triggering a ventilator-assisted breath at -2. Allow increased expiratory time by decreasing the I:E ratio (1:3 or 1:4 up to 1:5).

                               Rahul, What are the variables you closely monitor during the ventilation of a child with acute severe asthma?

                               Frequent auscultation of the patients’s chest at the bedside, observing vital signs including hemodynamics is helpful. Watching flow volume, PV loops gives useful information about patient’s condition. Monitoring peak-to-plateau pressure differences tell us about improvement in airway resistance. in response to therapy.

                               Following the capnography waveform can give us information about lung emptying.

                               Rahul, what are the sedation-analgesia-neuromuscular blockade therapies used in the child intubated for Near-fatal asthma.

                               We prefer to use ketamine with low-dose benzodiazepines such as midazolam. We initially chemically paralyze the patient using rocuronium to abolish spontaneous respirations which can add to the DHI and hypercapnia. If we use isoflurane gas we D/C all other sedatives a, analgesics and NMBs. The use of steroids along with NMB can add to the neuromuscular weakness in such critically ill patients. Consideration for early stooping of NMB should be given.

                               Welcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.

                               I'm Pradip Kamat and I'm Rahul Damania. We are coming to you from Children's Healthcare of Atlanta - Emory University School of Medicine.

                               Welcome to our episode, which is Part 2 of our acute severe asthma management. Today we discuss invasive mechanical ventilation of the acute asthmatic.

                               A patient with a history of asthma presents to the PICU with decreased air entry. Somnolence. Hypercarbia and drooling. The patient is hypoxemic and has see-saw breathing.

                               Rahul: Let’s dive right into this. What are the indications for intubating a child with acute severe asthma?

                               Absolute indications include:

                               • Altered mental status which may be preceded by obtundation, agitation
                               • Cardiac and respiratory arrest
                               
                               

                               Relative indications decided on a case by case basis:

                               Progressive exhaustion-despite, despite maximal therapy. Profound hypoxemia refractory to supplemental oxygen administration, and respiratory failure.

                               The decision to intubate should not be solely determined based on blood gas results.

                               Pradip, can you shed light on how we prepare for the intubation of the patient with acute severe asthma?

                               Rahul, first and foremost- we take the intubation of an asthmatic very seriously. In fact we try the whole “kitchen sink” to avoid intubation. But there will be times when we have to intubate especially for the indications you mentioned above.

                               The intubation will worsen the patient’s bronchospasm, put the patient at risk for barotrauma as well as cardiovascular collapse.

                               Preparation is the key- A team huddle and mapping prior to proceeding to intubate is the key. Every person in the room should have clear roles and responsibilities. Scenarios of what to do if “X” happens should be clearly laid out to the team by the team leader (preferably the attending or a senior fellow). The senior-most experienced person should manage the airway. At least two dedicated RTs to provide bag-mask ventilation as well as manage the ventilator are required. Nursing roles to push meds, chart the vitals and other activities as well a role for the resource nurses to help in case of cardiac arrest should be clearly laid out. Additionally, facilities that have access to isoflurane should have that ready to go. We typically give a heads up to our ECMO team to be on stand-by.

                               Prior to Intubation: Have central access or multiple large-bore PIVs if possible. Keep crystalloids boluses ready for hypotension. We also have peri-arrest epinephrine as well as an epinephrine infusion ready for any hypotension, bradycardia, or cardiac arrest. For intubation, we typically use Ketamine, fentanyl, and rocuronium (some centers may use succinylcholine). We use cuffed endotracheal tube. We don't bag-mask at fast rates but rather wait for a full expiration prior to the next breath being delivered. These patients require slow respiratory rates with very prolonged expiratory times to allow for adequate gas exchange and lung volumes. A helpful technique is to use a stethoscope to auscultate at the lower neck for the disappearance of expiratory wheezes prior to starting the next inspiration. We sometimes place a nasogastric tube to prevent gastric distension.

                               If there is hypoxemia, hypotension, not improving with fluids, ventilator manipulation, - A consideration for tension pneumothorax should be given especially if there is asymmetric chest rise. Bedside POCUS can be used to make a diagnosis.

                               Intubation of an asthmatic is a high-risk procedure and requires a team approach, proactiveness, and anticipation. Intubation should be approached cautiously in patients with severe acute asthma exacerbations because manipulation of the airway can cause laryngospasm and worsening bronchoconstriction.

                               Rahul, what are some of the principles we should all follow prior to initiation of mechanical ventilation in an asthmatic after intubation?

                               It is important to note that most complications of intubating an asthmatic happen in the immediate post-intubation period. Hypoxemia, hypotension, tension PTX/air leaks as well as cardiac arrest can happen immediately upon initiation of positive pressure ventilation. An important cause of hypotension is hyperinflation and decreased venous return. So slowing down manual bag-mask ventilation of even disconnecting the bag and allowing for a brief period of apnea while applying manual pressure to the rib cage may help decrease hyperinflation. Hypotension should respond to fluid boluses and decrease manual bagging.

                               Dynamic Hyperinflation: Severe airflow obstruction results in incomplete exhalation resulting in dynamic hyperinflation (DHI). Progressive DHI leads to an end-expiratory lung volume reaching a new equilibrium that exceeds the functional residual capacity. In the early stages of asthma, the increased lung volume increases pulmonary elastic recoil pressure thus increasing pulmonary expiratory flow and expanding small airways thus decreasing expiratory resistance. Thus lung volume will reach a point where the entire tidal volume can be expired during the available exhalation time. However, this process becomes maladaptive in severe asthmatic such that hyperinflation required to maintain normocapnia cannot be maintained as it would expand total lung capacity

                               Positive pressure ventilation worsens DHI especially if ventilator settings are aimed at normocapnia. This will also increase the risk of hypotension and pneumothorax. The initial rule of thumb would be to use low Tidal volumes and low respiratory rates to allow for controlled hypoventilation and permissive hypercapnia.

                               Pradip, with the above is mind what are your initial ventilator settings?

                               We typically use pressure regulated volume control (PRVC) to set a TV of 8-12m//kg (reduce to generate a plateau pressure of ~30 cm H2O), respiratory rate of 6-10/minute time of 1-1.5 seconds, which allows for an expiratory time of 4-9seconds. in the patient with NMB, we set PEEP initially at zero. Peak pressures in the 50s are expected initially due to airflow obstruction but plateau pressures of 30 or below should be reassuring.

                               An inspiratory hold will determine the plateau pressure whereas an expiratory hold will give us information about the auto-PEEP. The applied PEEP should be set below the auto peep in a spontaneously breathing patient in order to decrease the trigger work.

                               Another ventilation strategy, which is comfortable for the patient is the use of pressure support ventilation with PEEP. PEEP narrows the gap between proximal and distal airway pressures during the hyperinflated obstructed state. Pressure support facilitates inspiration while decreasing the work of breathing. The patient determines the time, respiratory rate, and depth. of each breath.

                               In summary: RR 10-12/min; Tidal volume: 6 to 8 mL/kg; set the sensitivity for triggering a ventilator-assisted breath at -2. Allow increased expiratory time by decreasing the I:E ratio (1:3 or 1:4 up to 1:5).

                               Rahul, What are the variables you closely monitor during the ventilation of a child with acute severe asthma?

                               Frequent auscultation of the patients’s chest at the bedside, observing vital signs including hemodynamics is helpful. Watching flow volume, PV loops gives useful information about patient’s condition. Monitoring peak-to-plateau pressure differences tell us about improvement in airway resistance. in response to therapy.

                               Following the capnography waveform can give us information about lung emptying.

                               Rahul, what are the sedation-analgesia-neuromuscular blockade therapies used in the child intubated for Near-fatal asthma.

                               We prefer to use ketamine with low-dose benzodiazepines such as midazolam. We initially chemically paralyze the patient using rocuronium to abolish spontaneous respirations which can add to the DHI and hypercapnia. If we use isoflurane gas we D/C all other sedatives a, analgesics and NMBs. The use of steroids along with NMB can add to the neuromuscular weakness in such critically ill patients. Consideration for early stooping of NMB should be given.

                               Pradip, can you talk about the use of isoflurane in a child with NEAR fatal asthma?

                               Inhalational anesthetics such as isoflurane can be delivered by means of an anesthesia machine that feeds into the low-pressure gas port of a conventional mechanical ventilator or via a dedicated anesthesia ventilator with its own vaporizer. Isoflurane is preferred over others has it has no negative inotropic effects although it can cause hypotension due to peripheral vasodilatation. Typical concentration used is 0.5-2%. Appropriate scavenging of the waste gas is important so as to not expose the staff. The exact mechanism of action remains unclear. although studies indicate that inhaled anesthetics reduce vagal tone and reflexes as well as alter circulating catecholamines and ß receptor sensitivity. Inhaled anesthetics may also have a direct relaxation effect on the airway smooth muscle. Potential neurotoxicity especially in the very young is a concern and withdrawal with prolonged use has been seen. Improvement is seen as early as within 30 minutes of initiation of isoflurane and typically by 12 hours. Some refractory cases may need isoflurane for 2-3 days. Inhaled anesthetics should not be used in patients at risk for malignant hyperthermia.

                               To summarize, isoflurane is an inhaled anesthetic that can be employed in near-fatal asthma by creating smooth muscle relaxation in the respiratory tree. As isoflurane is a potent anesthetic that has a smooth muscle relaxation effect, we must be mindful of the 

                               Rahul, what is the role of ECMO in NEAR Fatal asthma?

                               Some refractory cases of NFA that do not respond to isoflurane or have severe air leaks, cardiac arrest may be candidates for ECMO. Mechanical ventilation of patients with NFA is challenging, and high ventilator settings may cause lung injury and hemodynamic instability secondary to barotrauma and dynamic hyperinflation.

                               A more recent ELSO registry query (Crit Care. 2017;21(1):297.) for ECMO support for adults with asthma found successful decannulation in 86.7% and survival to discharge of 83.5%, with nonsurvivors being older in age, with lower pH and higher PEEP, higher post-ECMO oxygen requirement, and post ECMO driving pressures significantly associated with in-hospital mortality. The use of full-flow VV ECMO for refractory asthma in children is not uncommon and has been described previously as case reports and small studies. An ELSO registry report (published in CCM 2009) on ECMO use in children with SA reported a median time of ECMO support of 94 hours and was associated with 94% survival. Nine percent of the children placed on ECMO had a cardiorespiratory arrest before ECMO initiation. The presence of cardiorespiratory arrest or neurological injury was not associated with higher mortality.

                               A more recent study of children with rhinovirus (Pediatric pulmonology 2020) reported a survival rate of 100%.

                               Pradip, as these patients have hypoventilation due to obstruction, what are some of the cutting-edge therapies recently highlighted in the literature?

                               ECCO2R (or AVCCO2R-requires double lumen cannula) is a more recent strategy and is designed to remove CO2, but, unlike ECMO, does not provide significant oxygenation. Essentially, ECCO2R consists of a drainage cannula placed in a large central vein, a pump, a membrane lung, and a return cannula, or a double lumen VV cannula. Blood is pumped through the membrane and CO2 is removed by diffusion. In contrast to ECMO, where the need for oxygenation requires high blood flow rates, ECCO2R allows much lower blood flow rates. ECCO2R does not provide for oxygenation which ultimately most NFA patients require due to viral or bacterial infection, as well as doesn't provide hemodynamic support as ECMO would. There are no randomized controlled trials or large studies to compare the outcomes of ECMO versus ECCO2R in children with asthma to assess the superiority or benefit of one over the other.

                               In Chapter 50 in Furhman, Zimmerman’s textbook of Pediatric Critical Care, Dr. Steve Shein, and colleagues highlight that the use of extracorporeal life support (ECLS) has been reported in the management of the very few patients with near-fatal asthma who continue to exhibit a profound degree of clinical instability despite maximal therapy. Moreover, only 4% of patients in the Extracorporeal Life Support Organization registry have had runs for near-fatal Asthma. The survival rate for persons with near-fatal asthma necessitating ECLS is approximately 81%, which is remarkable considering that the vast majority of these patients were extraordinarily sick and had failed to respond to very aggressive treatment.

                               To Summarize:

                               1. Intubation of an asthmatic is a high-risk procedure and requires a team approach, proactiveness, and anticipation.
                               2. Ventilator strategies include allowing time for expiration by modulating the I:E ratio and decreasing the RR and TV.
                               3. Isoflurane & ECMO are last-ditch efforts in near-fatal asthma and should be performed in quaternary care facilities.
                               
                               
                               • References:
                               • Medar SS, Peek GJ, Rastogi D. Extracorporeal and advanced therapies for progressive refractory near-fatal acute severe asthma in children. Pediatr Pulmonol. 2020 Jun;55(6):1311-1319. doi: 10.1002/ppul.24751. Epub 2020 Mar 30. PMID: 32227683.
                               • Werner HA. Status asthmaticus in children: a review. Chest. 2001 Jun;119(6):1913-29. doi: 10.1378/chest.119.6.1913. PMID: 11399724.
                               • Demoule A, Brochard L, Dres M, Heunks L, Jubran A, Laghi F, Mekontso-Dessap A, Nava S, Ouanes-Besbes L, Peñuelas O, Piquilloud L, Vassilakopoulos T, Mancebo J. How to ventilate obstructive and asthmatic patients. Intensive Care Med. 2020 Dec;46(12):2436-2449. doi: 10.1007/s00134-020-06291-0. Epub 2020 Nov 9. PMID: 33169215; PMCID: PMC7652057.
                               
                               

                               More information can be found

                               • Fuhrman & Zimmerman - Textbook of Pediatric Critical Care Chapter 50 entitled Asthma
                               
                               

                               This concludes our episode on Near-Fatal Asthma. We hope you found value in our short, case-based podcast. We welcome you to share your feedback, subscribe & place a review on our podcast! Please visit our website picudoconcall.org which showcases our episodes as well as our Doc on Call management cards. PICU Doc on Call is co-hosted by myself Dr. Pradip Kamat and Dr. Rahul Damania. Stay tuned for our next episode! Thank you!

                               ]]>47c9897e-35ca-45ed-8723-b1ab26a1d180Sun, 13 Feb 2022 03:00:00 -040019:50falsefull4343Principles of Non-Invasive Positive Pressure Ventilation (niPPV)Welcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.

                               I'm Pradip Kamat and I'm Rahul Damania. We are coming to you from Children's Healthcare of Atlanta - Emory University School of Medicine.

                               Welcome to our Episode a 15 mo F with respiratory distress and runny nose.

                               Here's the case:

                               A 15 mo F presents to the ED with cough, runny nose, and increased work of breathing. Her mother states that the patient has had these symptoms for the past three days, however, the work of breathing progressed. The patient has had 2 fevers during this course, with the highest 101F. She says that her 3 yo cousin who she visited for the holidays had similar symptoms. Mother notes decreased PO and wet diapers. The patient presented to the ED with the following vital signs: T 38.5C, HR 155, BP 70/48 (MAP 50), RR 48, 92% on RA. The patient on the exam was noted to be tachypneic with abdominal retractions, grunting, and nasal flaring. The patient was nasally suctioned and initiated on 12 L 40% of HFNC. The patient was then transferred to the PICU for further management.

                               To summarize key elements from this case, this patient has:

                               • Increased work of breathing indicates respiratory distress.
                               • She has a prodrome of symptoms that worsened prior to presentation
                               • And a sick contact.
                               • All of which brings up a concern for acute respiratory failure requiring non-invasive positive pressure ventilation in the form of HFNC.
                               • Let's transition into some history and physical exam components of this case?
                               
                               
                               1. What are key history features in this child who presents with respiratory distress & URI sx?
                               
                               
                               • Usually, children under the age of two with bronchiolitis will present with cough, respiratory distress, and crackles on lung exam.
                               • The crackles indicate atelectatic alveoli that are filled with fluid which occurs due to inflammatory processes in the lung triggered by respiratory viruses.
                               • Respiratory distress, increased work of breathing, respiratory rate, and oxygenation all can change rapidly with crying, coughing, and agitation.
                               
                               
                               1. Are there some red-flag symptoms or physical exam components in a child with acute respiratory distress which you could highlight?
                               
                               
                               • That is a great question. We really want to highlight the distinction between respiratory distress and respiratory failure.
                               • Children with respiratory failure in our case may have issues with oxygenation or ventilation as well as increased work of breathing that necessitates higher levels of respiratory support like HFNC.
                               • In a 2003 Journal of Pediatrics study, infants who were most severely affected with bronchiolitis were born prematurely, <12 weeks of age, or who have underlying cardiopulmonary disease or immunodeficiency. These children are at risk for apnea and respiratory failure which may require escalation to mechanical ventilation.
                               • Finally, Infants with bronchiolitis may have difficulty maintaining adequate hydration because of increased fluid needs and metabolic demand. Remember these children will have increased insensible losses due to fever and tachypnea, as well as decreased oral intake related to their systemic illness.
                               
                               

                               To continue with our case, the patient's labs were consistent with:

                               • Mild hyper NA 149
                               • All other electrolytes were within normal limits.
                               • The patient had a respiratory viral panel which was positive for Rhino/Entero and RSV. Her COVID PCR was negative.
                               • A CXR was performed and showed alveolar airspace disease consistent with I would like to highlight an important point, with the exception of otitis media, a secondary bacterial infection is uncommon among infants and young children with bronchiolitis. In a nine-year prospective study of 565 children (<3 yo) hospitalized with documented RSV infection published in the Journal of Pediatrics, subsequent bacterial pneumonia was present in only 0.9 percent of these. 
                               
                               

                               Yes, Rahul, that is a great point. The risk of secondary bacterial pneumonia is increased among children who require admission to the intensive care unit, particularly those who require intubation.

                               Ok to summarize, we have:

                               • A 15 mo F who presented with URI symptoms and respiratory distress was admitted to the PICU with Rhino/Entero, & RSV+ bronchiolitis with concurrent community-acquired PNA. We would like to focus the rest of this podcast on discussing the use of HFNC, its principles of action, and the data surrounding its use in the PICU.
                               • Before we get into this topic, let’s start with a short multiple-choice question:
                               • A 13 mo ex-34 week infant presents to the ED with increased work of breathing, tachypnea, and hyperthermia. The patient is on a home 1/8 L nasal cannula and has no echocardiographic evidence of pulmonary hypertension on prior follow-up. HFNC is initiated at 1.5 L per kg. Which of the following responses best describes the MOA of HFNC?
                               • A. Increased nasopharyngeal dead space
                               • B. Decreased humidification of gas
                               • C. Negative distending pressure
                               • D. Reduction in upper airway resistance.
                               
                               

                               The correct answer here is D. Reduction in upper airway resistance. By providing gas flows that match or exceed spontaneous inspiratory flow rates, HFNC minimizes inspiratory resistance across the nasopharynx. The resultant reduction in work of breathing has been demonstrated in studies in neonates and infants by measuring diaphragmatic electrical activity and respiratory plethysmography.

                               Rahul, what does the literature say regarding positive distending pressure with the use of HFNC?

                               The data is definitely mixed but leans towards not HFNC not providing clinically significant PEEP. In a study of infants with bronchiolitis published in 2013 in Intensive Care Medicine, a flow rate of 2 L/kg per minute resulted in mean pharyngeal pressures >4 cm H2O as measured by transesophageal probes and improved breathing.

                               Subsequent studies have documented a difference in increased pharyngeal pressure during HFNC when the mouth is closed compared with when it is open. So if you are going to use HFNC to promote distending pressure concurrent use of a pacifier may be helpful in achieving the full benefit of HFNC.

                               To summarize key principles of how HFNC let’s review some respiratory physiology:

                               1. Rahul, what is Dead Space?
                               2. Dead space is the volume of air that is inhaled that does not take part in the gas exchange, because it either remains in the conducting airways or reaches alveoli that are not perfused or poorly perfused.
                               3. This means that not all the air in each breath is available for the exchange of oxygen and carbon dioxide.
                               4. HFNC creates a washout of nasopharyngeal dead space and creates a richly oxygenated reservoir of air. This reserve in the upper airway is what the patient draws from with each breath, minimizing the entrainment of room air and also decreasing the amount of CO2 in the anatomic zone of the respiratory tree.
                               5. What are key concepts related to Airway Resistance in Pulmonary Dynamics?
                               6. West Physiology defines airway...]]>Welcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.

                                  I'm Pradip Kamat and I'm Rahul Damania. We are coming to you from Children's Healthcare of Atlanta - Emory University School of Medicine.

                                  Welcome to our Episode a 15 mo F with respiratory distress and runny nose.

                                  Here's the case:

                                  A 15 mo F presents to the ED with cough, runny nose, and increased work of breathing. Her mother states that the patient has had these symptoms for the past three days, however, the work of breathing progressed. The patient has had 2 fevers during this course, with the highest 101F. She says that her 3 yo cousin who she visited for the holidays had similar symptoms. Mother notes decreased PO and wet diapers. The patient presented to the ED with the following vital signs: T 38.5C, HR 155, BP 70/48 (MAP 50), RR 48, 92% on RA. The patient on the exam was noted to be tachypneic with abdominal retractions, grunting, and nasal flaring. The patient was nasally suctioned and initiated on 12 L 40% of HFNC. The patient was then transferred to the PICU for further management.

                                  To summarize key elements from this case, this patient has:

                                  • Increased work of breathing indicates respiratory distress.
                                  • She has a prodrome of symptoms that worsened prior to presentation
                                  • And a sick contact.
                                  • All of which brings up a concern for acute respiratory failure requiring non-invasive positive pressure ventilation in the form of HFNC.
                                  • Let's transition into some history and physical exam components of this case?
                                  
                                  
                                  1. What are key history features in this child who presents with respiratory distress & URI sx?
                                  
                                  
                                  • Usually, children under the age of two with bronchiolitis will present with cough, respiratory distress, and crackles on lung exam.
                                  • The crackles indicate atelectatic alveoli that are filled with fluid which occurs due to inflammatory processes in the lung triggered by respiratory viruses.
                                  • Respiratory distress, increased work of breathing, respiratory rate, and oxygenation all can change rapidly with crying, coughing, and agitation.
                                  
                                  
                                  1. Are there some red-flag symptoms or physical exam components in a child with acute respiratory distress which you could highlight?
                                  
                                  
                                  • That is a great question. We really want to highlight the distinction between respiratory distress and respiratory failure.
                                  • Children with respiratory failure in our case may have issues with oxygenation or ventilation as well as increased work of breathing that necessitates higher levels of respiratory support like HFNC.
                                  • In a 2003 Journal of Pediatrics study, infants who were most severely affected with bronchiolitis were born prematurely, <12 weeks of age, or who have underlying cardiopulmonary disease or immunodeficiency. These children are at risk for apnea and respiratory failure which may require escalation to mechanical ventilation.
                                  • Finally, Infants with bronchiolitis may have difficulty maintaining adequate hydration because of increased fluid needs and metabolic demand. Remember these children will have increased insensible losses due to fever and tachypnea, as well as decreased oral intake related to their systemic illness.
                                  
                                  

                                  To continue with our case, the patient's labs were consistent with:

                                  • Mild hyper NA 149
                                  • All other electrolytes were within normal limits.
                                  • The patient had a respiratory viral panel which was positive for Rhino/Entero and RSV. Her COVID PCR was negative.
                                  • A CXR was performed and showed alveolar airspace disease consistent with I would like to highlight an important point, with the exception of otitis media, a secondary bacterial infection is uncommon among infants and young children with bronchiolitis. In a nine-year prospective study of 565 children (<3 yo) hospitalized with documented RSV infection published in the Journal of Pediatrics, subsequent bacterial pneumonia was present in only 0.9 percent of these. 
                                  
                                  

                                  Yes, Rahul, that is a great point. The risk of secondary bacterial pneumonia is increased among children who require admission to the intensive care unit, particularly those who require intubation.

                                  Ok to summarize, we have:

                                  • A 15 mo F who presented with URI symptoms and respiratory distress was admitted to the PICU with Rhino/Entero, & RSV+ bronchiolitis with concurrent community-acquired PNA. We would like to focus the rest of this podcast on discussing the use of HFNC, its principles of action, and the data surrounding its use in the PICU.
                                  • Before we get into this topic, let’s start with a short multiple-choice question:
                                  • A 13 mo ex-34 week infant presents to the ED with increased work of breathing, tachypnea, and hyperthermia. The patient is on a home 1/8 L nasal cannula and has no echocardiographic evidence of pulmonary hypertension on prior follow-up. HFNC is initiated at 1.5 L per kg. Which of the following responses best describes the MOA of HFNC?
                                  • A. Increased nasopharyngeal dead space
                                  • B. Decreased humidification of gas
                                  • C. Negative distending pressure
                                  • D. Reduction in upper airway resistance.
                                  
                                  

                                  The correct answer here is D. Reduction in upper airway resistance. By providing gas flows that match or exceed spontaneous inspiratory flow rates, HFNC minimizes inspiratory resistance across the nasopharynx. The resultant reduction in work of breathing has been demonstrated in studies in neonates and infants by measuring diaphragmatic electrical activity and respiratory plethysmography.

                                  Rahul, what does the literature say regarding positive distending pressure with the use of HFNC?

                                  The data is definitely mixed but leans towards not HFNC not providing clinically significant PEEP. In a study of infants with bronchiolitis published in 2013 in Intensive Care Medicine, a flow rate of 2 L/kg per minute resulted in mean pharyngeal pressures >4 cm H2O as measured by transesophageal probes and improved breathing.

                                  Subsequent studies have documented a difference in increased pharyngeal pressure during HFNC when the mouth is closed compared with when it is open. So if you are going to use HFNC to promote distending pressure concurrent use of a pacifier may be helpful in achieving the full benefit of HFNC.

                                  To summarize key principles of how HFNC let’s review some respiratory physiology:

                                  1. Rahul, what is Dead Space?
                                  2. Dead space is the volume of air that is inhaled that does not take part in the gas exchange, because it either remains in the conducting airways or reaches alveoli that are not perfused or poorly perfused.
                                  3. This means that not all the air in each breath is available for the exchange of oxygen and carbon dioxide.
                                  4. HFNC creates a washout of nasopharyngeal dead space and creates a richly oxygenated reservoir of air. This reserve in the upper airway is what the patient draws from with each breath, minimizing the entrainment of room air and also decreasing the amount of CO2 in the anatomic zone of the respiratory tree.
                                  5. What are key concepts related to Airway Resistance in Pulmonary Dynamics?
                                  6. West Physiology defines airway resistance as the change in transpulmonary pressure needed to produce a unit flow of gas through the airways of the lung.
                                  7. More simply put, it is the pressure difference between the mouth and alveoli of the lung, divided by airflow. Bronchiolitis creates a decrease in airflow thus increasing airway resistance. As HFNC increases flow, i.e. the denominator of our equation, It reduces resistance in the airway tree.
                                  8. By providing gas flows that match or exceed spontaneous inspiratory flow rates, HFNC minimizes inspiratory resistance across the nasopharynx.
                                  9. In a study published in 2009 in Respiratory Care, it was hypothesized that the resultant reduction in airway resistance which high flow provides the decrease in WOB. This was especially studied by measuring infant diaphragmatic electrical activity.
                                  
                                  

                                  Rahul, what is the last major mechanism of a high-flow nasal cannula?

                                  1. HFNC reduces the energy expenditure required by the body to condition air. It does this by delivering heated and humidified gas. This also promotes less bronchospasm which would occur with the delivery of cold air.
                                  
                                  

                                  Pradip, in your experience, what are disease states we see in the PICU that are most amenable to HFNC?

                                  1. Many causes of respiratory distress can respond to the use of HFNC. In this state, I would recommend that providers start HFNC, and then ensure close monitoring and frequent reassessment of these patients to ensure response as well as the need to escalate respiratory support.
                                  2. Conditions for which HFNC can be used to include conditions such as Asthma, Tracheomalacia, Apneic Oxygenation, and Bronchiolitis.
                                  
                                  

                                  HFNC should not delay advanced airway management in a patient deemed to require immediate endotracheal intubation. This may include patients with acutely impaired mental status, risk of aspiration, or other needs for airway protection

                                  Yes, thank you for highlighting this, HFNC should be avoided in patients who have facial anomalies that preclude appropriate nasal cannula fit (like choanal atresia). Children who have active vomiting, bowel obstruction, or even sensory issues which may create Agitation may be some relative contraindications for HFNC. Lastly, I would also not delay escalation in invasive respiratory support especially if the patient does not have a significant change in hemodynamic (such as a decrease in HR) or oxygenation parameters after about 4 hrs on HFNC therapy.

                                  Finally, HFNC oxygen therapy is considered an aerosol-generating procedure. Thus, appropriate infection control precautions are required when it is being administered to patients with unknown or positive coronavirus disease 2019.

                                  This concludes our episode on bronchiolitis and HFNC. We hope you found value in our short, case-based podcast. We welcome you to share your feedback, subscribe & place a review on our podcast! Please visit our website picudoconcall.org which showcases our episodes as well as our Doc on Call management cards. PICU Doc on Call is co-hosted by myself Dr. Pradip Kamat and Dr. Rahul Damania. Stay tuned for our next episode! Thank you!

                                  ]]>8f1c2e64-f8d4-415e-9f9a-4e92bf9c148bSun, 30 Jan 2022 03:00:00 -040016:37falsefull4242Airway Clearance Techniques in the PICUWelcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.

                                  I'm Pradip Kamat and I'm Rahul Damania. We are coming to you from Children's Healthcare of Atlanta - Emory University School of Medicine.

                                  Welcome to our discussion today on airway clearance in the critically-ill patient in the PICU. We will focus on the use of pharmacological as well as non-pharmacological techniques in critically ill children admitted to the ICU. This episode will be a general overview as specific clinical scenarios such as NM disease may warrant specific therapeutics.

                                  Let’s get started with the case:

                                  We have an 8-month old ex-34 week premie intubated for acute respiratory failure secondary to RSV bronchiolitis. The patient is on a conventional mechanical ventilator receiving a TV of 6ml/kg, rate of 20, PEEP 6, 40% FiO2 inspiratory time of 0.7

                                  CXR shows a pattern suggestive of viral pneumonia with minimal hyperinflation and atelectasis of the right middle lobe. The patient has excessive secretions when the suction catheter is assessed. The patient is hemodynamically stable and is on feeds via a NG tube.

                                  Rahul, Can you comment on how a child clears his/her pulmonary secretions normally when not ill?

                                  That's an excellent question. Normally some baseline secretions are produced by all humans. Normal bronchial secretions are made up of contributions from mucus-secreting (goblet)cells as well as cells secreting serous fluid. The ciliary epithelium made of columnar cells line the entire tracheobronchial tree up to the alveolar ducts. This ciliary epithelium provides the coordinated rhythmic force that propels the overlying “mucus blanket” towards the central airways and upper respiratory tract.

                                  Primary mechanisms of tracheobronchial clearance of these secretions consist of (1) The mucociliary (MC) escalator in the smaller airways and (2) Cough in central and larger airways. The co-ordinating activity of the beating cilia and their interaction with the overlying viscoelastic layer of mucus makes up the mucociliary escalator. The MC escalator helps remove both healthy and pathologic secretions from the airways as well as the removal of inhaled particles. This MC transport can be affected by mycoplasma, influenza and other viruses as well as exposure to toxins (cigarette smoke, vaping) as well as in CF, asthma, COPD, and ciliary dyskinesia just to name a few.

                                  Once the secretions are in large or central airways they are coughed out or swallowed.

                                  Let’s transition and talk a little on how one generates an effective cough:

                                  1. For an effective cough one needs firstly to take a sufficiently deep breath in.
                                  2. The glottis needs to close briefly to allow an increase in intrathoracic pressure
                                  3. This is followed by expulsive glottic opening together with abdominal contraction, which results in air being forcibly expelled.
                                  
                                  

                                   Individuals with neuromuscular disease, bulbar insufficiency, obtunded patients, those on MV with chemical neuromuscular blockade, severe skeletal deformity may have decreased cough expiratory airflow. Reduced ability to cough results in secretion retention, mucus plugging, atelectasis and pre-disposition to infection even if the MC escalator function is normal.

                                  Q2. Pradip can you tell us about atelectasis

                                  This is a great question. The term atelectasis means “imperfect expansion” and indicates reversible loss of aerated lung with otherwise normal lung parenchyma.

                                  Thats a nice concise definition, so if atelectasis reperesents imperfect expansion, what are mechanisms which keep our lungs open?

                                  There are three major mechanisms:

                                  1. Pulmonary Surfactant 

                                  2. Collateral Ventilation 

                                  3. Lung & Chest Wall Balance

                                  Let’s go into each of these in more detail:

                                  A pulmonary surfactant that covers the large alveolar surface is composed of phospholipids (mostly phosphatidylcholine), neutral lipids, and surfactant-specific apoproteins (termed surfactant proteins A , B , C , and D ). By reducing alveolar surface tension, pulmonary surfactant stabilizes the alveoli and prevents alveolar collapse.

                                  There is a collateral ventilating mechanism (intra-alveolar pores & bronchiole-alveolar communications) that prevents alveolar collapse. Inter-alveolar pores by which alveoli are connected to each other via are called the Pores of Kohn. There also exist connections between distal bronchioles and neighboring alveoli called channels of Lambert. These structures can aerate hundreds of alveoli adjacent to a bronchiole preventing the collapse of one in case there is resorption of the air from that alveolus. Resorption occurs when an airway becomes occluded, the air is trapped in lung units ventilated by that airway, and the trapped gases are absorbed by the blood perfusing that part of the lung. Oxygen is absorbed faster than nitrogen from the alveolus into the blood resulting in collapsed lungs postoperatively especially if high O2 concentrations are used.

                                  The balance between Inward recoil of lung tissue and outward expansion of the chest wall (myo-elastic element: smooth muscle fibers interwoven with elastic fibers in distal airways and alveolar sacs) is is opposed by an outward recoil of the chest wall. An exact balance of these forces is essentially FRC at end of exhalAnion. An imbalance of these forces which keep lungs open can predispose to atelectasis. An example of chest wall inability to provide outward recoil is the reason a patient with pneumothorax develops lung collapse

                                  Awesome, let’s quickly summarize, atelectasis represents airway collapse, in order to keep alveoli open, our body’s mechanisms include pulmonary surfactant, collateral ventilation, and FRC.

                                  Let's transition and talk about the various types of atelectasis and the diseases we encounter in the PICU which can create an imperfect expansion of the alveoli?

                                   Surfactant deficiency or dysfunction: Infant with surfactant deficiency or neonate with prematurity.

                                  • Children with ARDS or Near drowning, as well as hydrocarbon ingestion, can all have surfactant dysfunction which can lead to atelectasis.
                                  
                                  

                                  Resorption atelectasis (most common): high FIO2 concentration, intra-bronchial obstruction due to inflammation, infection, mucus plugs, and foreign body.

                                  Another mechanism is an extrinsic compression of the small airways. c) Compression of normal lung tissue: Pleural effusion, chylothorax, cardiac enlargement or tumors, Extra bronchial compression: vascular ring, lobar emphysema or by lymph nodes

                                  All in all, when you have atelectasis you run the risk of having decreased lung compliance, impairment of oxygenation, increased pulmonary vascular resistance, and development of lung injury.

                                  In asthma and bronchiolitis, the right middle lobe and the lingula segment are the most common localization of the atelectasis and this is called the middle lobe syndrome. It is possible that hilar Lymph node enlargement due to viral infection and subsequent compression of middle lobe bronchus may be a cause of its preferred location.

                                  Pradip, what are the clinical consequences of atelectasis?

                                  This is a great question, and like many processes, clinical consequences Depend on the patient’s age, rate of formation, extent and of course the underlying cause of the atelectasis, however, let’s talk in general:

                                  Going back to our case, a critically -ill patient such as an intubated infant with bronchiolitis on moderate ventilator settings, development of atelectasis can lead to rapid deterioration....]]>Welcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.

                                  I'm Pradip Kamat and I'm Rahul Damania. We are coming to you from Children's Healthcare of Atlanta - Emory University School of Medicine.

                                  Welcome to our discussion today on airway clearance in the critically-ill patient in the PICU. We will focus on the use of pharmacological as well as non-pharmacological techniques in critically ill children admitted to the ICU. This episode will be a general overview as specific clinical scenarios such as NM disease may warrant specific therapeutics.

                                  Let’s get started with the case:

                                  We have an 8-month old ex-34 week premie intubated for acute respiratory failure secondary to RSV bronchiolitis. The patient is on a conventional mechanical ventilator receiving a TV of 6ml/kg, rate of 20, PEEP 6, 40% FiO2 inspiratory time of 0.7

                                  CXR shows a pattern suggestive of viral pneumonia with minimal hyperinflation and atelectasis of the right middle lobe. The patient has excessive secretions when the suction catheter is assessed. The patient is hemodynamically stable and is on feeds via a NG tube.

                                  Rahul, Can you comment on how a child clears his/her pulmonary secretions normally when not ill?

                                  That's an excellent question. Normally some baseline secretions are produced by all humans. Normal bronchial secretions are made up of contributions from mucus-secreting (goblet)cells as well as cells secreting serous fluid. The ciliary epithelium made of columnar cells line the entire tracheobronchial tree up to the alveolar ducts. This ciliary epithelium provides the coordinated rhythmic force that propels the overlying “mucus blanket” towards the central airways and upper respiratory tract.

                                  Primary mechanisms of tracheobronchial clearance of these secretions consist of (1) The mucociliary (MC) escalator in the smaller airways and (2) Cough in central and larger airways. The co-ordinating activity of the beating cilia and their interaction with the overlying viscoelastic layer of mucus makes up the mucociliary escalator. The MC escalator helps remove both healthy and pathologic secretions from the airways as well as the removal of inhaled particles. This MC transport can be affected by mycoplasma, influenza and other viruses as well as exposure to toxins (cigarette smoke, vaping) as well as in CF, asthma, COPD, and ciliary dyskinesia just to name a few.

                                  Once the secretions are in large or central airways they are coughed out or swallowed.

                                  Let’s transition and talk a little on how one generates an effective cough:

                                  1. For an effective cough one needs firstly to take a sufficiently deep breath in.
                                  2. The glottis needs to close briefly to allow an increase in intrathoracic pressure
                                  3. This is followed by expulsive glottic opening together with abdominal contraction, which results in air being forcibly expelled.
                                  
                                  

                                   Individuals with neuromuscular disease, bulbar insufficiency, obtunded patients, those on MV with chemical neuromuscular blockade, severe skeletal deformity may have decreased cough expiratory airflow. Reduced ability to cough results in secretion retention, mucus plugging, atelectasis and pre-disposition to infection even if the MC escalator function is normal.

                                  Q2. Pradip can you tell us about atelectasis

                                  This is a great question. The term atelectasis means “imperfect expansion” and indicates reversible loss of aerated lung with otherwise normal lung parenchyma.

                                  Thats a nice concise definition, so if atelectasis reperesents imperfect expansion, what are mechanisms which keep our lungs open?

                                  There are three major mechanisms:

                                  1. Pulmonary Surfactant 

                                  2. Collateral Ventilation 

                                  3. Lung & Chest Wall Balance

                                  Let’s go into each of these in more detail:

                                  A pulmonary surfactant that covers the large alveolar surface is composed of phospholipids (mostly phosphatidylcholine), neutral lipids, and surfactant-specific apoproteins (termed surfactant proteins A , B , C , and D ). By reducing alveolar surface tension, pulmonary surfactant stabilizes the alveoli and prevents alveolar collapse.

                                  There is a collateral ventilating mechanism (intra-alveolar pores & bronchiole-alveolar communications) that prevents alveolar collapse. Inter-alveolar pores by which alveoli are connected to each other via are called the Pores of Kohn. There also exist connections between distal bronchioles and neighboring alveoli called channels of Lambert. These structures can aerate hundreds of alveoli adjacent to a bronchiole preventing the collapse of one in case there is resorption of the air from that alveolus. Resorption occurs when an airway becomes occluded, the air is trapped in lung units ventilated by that airway, and the trapped gases are absorbed by the blood perfusing that part of the lung. Oxygen is absorbed faster than nitrogen from the alveolus into the blood resulting in collapsed lungs postoperatively especially if high O2 concentrations are used.

                                  The balance between Inward recoil of lung tissue and outward expansion of the chest wall (myo-elastic element: smooth muscle fibers interwoven with elastic fibers in distal airways and alveolar sacs) is is opposed by an outward recoil of the chest wall. An exact balance of these forces is essentially FRC at end of exhalAnion. An imbalance of these forces which keep lungs open can predispose to atelectasis. An example of chest wall inability to provide outward recoil is the reason a patient with pneumothorax develops lung collapse

                                  Awesome, let’s quickly summarize, atelectasis represents airway collapse, in order to keep alveoli open, our body’s mechanisms include pulmonary surfactant, collateral ventilation, and FRC.

                                  Let's transition and talk about the various types of atelectasis and the diseases we encounter in the PICU which can create an imperfect expansion of the alveoli?

                                   Surfactant deficiency or dysfunction: Infant with surfactant deficiency or neonate with prematurity.

                                  • Children with ARDS or Near drowning, as well as hydrocarbon ingestion, can all have surfactant dysfunction which can lead to atelectasis.
                                  
                                  

                                  Resorption atelectasis (most common): high FIO2 concentration, intra-bronchial obstruction due to inflammation, infection, mucus plugs, and foreign body.

                                  Another mechanism is an extrinsic compression of the small airways. c) Compression of normal lung tissue: Pleural effusion, chylothorax, cardiac enlargement or tumors, Extra bronchial compression: vascular ring, lobar emphysema or by lymph nodes

                                  All in all, when you have atelectasis you run the risk of having decreased lung compliance, impairment of oxygenation, increased pulmonary vascular resistance, and development of lung injury.

                                  In asthma and bronchiolitis, the right middle lobe and the lingula segment are the most common localization of the atelectasis and this is called the middle lobe syndrome. It is possible that hilar Lymph node enlargement due to viral infection and subsequent compression of middle lobe bronchus may be a cause of its preferred location.

                                  Pradip, what are the clinical consequences of atelectasis?

                                  This is a great question, and like many processes, clinical consequences Depend on the patient’s age, rate of formation, extent and of course the underlying cause of the atelectasis, however, let’s talk in general:

                                  Going back to our case, a critically -ill patient such as an intubated infant with bronchiolitis on moderate ventilator settings, development of atelectasis can lead to rapid deterioration. This is contrasted, In a clinically stable child admittedly postoperatively for a non-pulmonary reason who is on RA, a significant atelectasis may go completely unnoticed and detected only on a chest radiograph.

                                  5) Rahul how is atelectasis treated in the PICU patient admitted for acute illness (i.e without chronic neuromuscular condition)?

                                  One of the primary approaches to tackle atelectasis involves Airway clearance or chest physiotherapy or pulmonary toilet (an outdated term) refers to a spectrum of physical and mechanical interventions aimed at interacting therapeutically with acute and chronic respiratory disorders.

                                  Over the next few minutes we will cover some primary approaches, ranging from suctioning to manual CPT. To start,

                                  One of the simplest modality is suctioning. In infants and toddlers with small ETT tubes transport of secretions may be hampered by the size of the ETT. Sedation/NMB use may diminish the cough reflex. So the suction acts like a cough substitute. Type of catheter, its size, depth of insertion are all standardized and moist centers gave their own policies/procedures. Pre-oxygenation prior to suctioning or mechanical hyperinflation post suctioning can also be used.

                                  Another useful technique is postural drainage which is easily achieved in intubated patients: Gravity helps mobilize and transport secretions. If the atelectasis is in the right lung, then placing the patient in a left lateral decubitus position so that the right side is up will help open the right lung. This can be helped with chest percussion (RTs cupped hands or small cushioned mask or mechanical percussion devices), vibration, and even compression. I use this technique in small infants, and toddlers especially if they are intubated.

                                  That’s great and I should add that it is important to have a sedation management plan or algorithm adequately balanced to the patient’s needs during these interventions.

                                  Additionally, gentle bagging-(sometimes with saline lavage)-leading to an increase in lung volume and manual hyperinflation may help open a lung segment up. We need to be careful not to de-recruit the lung by frequent disconnection of the ventilator to do bag-lavage.

                                  Pradip what are some of the mechanical devices you use in the PICU to help conventional chest physiotherapy?

                                  This is a great question and to be honest, each type of chest PT has its risks and benefits, lets's review the most common. We will talk about:

                                  1. IS
                                  2. IPV
                                  3. Mechanical In Ex (Cough Assist)
                                  4. Flutter/Acapella
                                  5. Vest therapy
                                  
                                  

                                  Incentive spirometry (IS): The basis of incentive spirometry involves having the patient take a sustained, maximal inspiration (SMI). An SMI is a slow, deep inspiration from the FRC up to the total lung capacity (TLC) followed by ≥5 seconds breath hold. An incentive spirometer is a medical device that facilitates SMI. The device gives the individual visual feedback regarding flow and volume and also prevent and reverse atelectasis when used appropriately and regularly.

                                  Patients who are at risk for developing atelectasis due to immobility especially post-operatively may be helped by the use of incentive spirometer. It can help improve lung volume, optimize oxygenation and maintain inspiratory muscle strength. One study by Fahd et al (Journal of Pediatric Hematology/Oncology) reported that mandatory IS for sickle cell disease patients admitted without respiratory complaints reduces transfusions and acute chest syndrome, particularly for those presenting with back pain.

                                  IPV: Intrapulmonary percussive ventilator: The IPV device delivers high-flow jets of air to the airways by a pneumatic flow interrupter at a rate of 100 to 300 cycles/min through a mouthpiece. The patient controls variables such as inspiratory time, peak pressure, and delivery rates. IPV has been shown to be beneficial for secretion clearance (particularly for cystic fibrosis patients) and improvement in atelectasis in intubated patients.

                                  Mechanical insufflator-exsufflator: CoughAssist is a portable, electric mechanical insufflation-exsufflation device that attempts to simulate a cough by using a blower and valve to alternately apply a positive and then a negative pressure to a patient’s airway to assist the patient in clearing retained bronchopulmonary secretions.

                                  Flutter and Acapella devices are small, handheld devices that provide positive expiratory pressure (PEP). Exhaling through the device creates oscillations in the airway, resulting in loosening of mucus.

                                  Percussive vests: A high-frequency chest wall vibrating/oscillating vest device has been shown to mobilize secretions in patients with cystic fibrosis and is commonly used as an adjunct airway clearance device in children with a reduced ability to clear secretions due to neuromuscular abnormalities

                                  Rahul can you comment on some pharmacological approaches in the PICU?

                                  Saline: 0.9% saline enables clearance of secretions, especially in an intubated patient. 0.9% saline loosens secretions, lubricates the ETT, enhances cough as well as decreases viscosity of the secretions. Studies are mixed as to the benefit of using saline instillation prior to suctioning in intubated patients.

                                  One pediatric RCT (Riddling DA et. al. Am J Crit Care 2003) in postoperative patients with congenital heart disease showed no benefit with regard to incidence of VAP or mucus plugging. They also found (similar to adult studies) a drop in SpO2 from baseline in the group that used saline.

                                  Hypertonic Saline: Although shown to be beneficial in children with cystic fibrosis who are > 6 years of age, One study showed no benefit in children under 6 years of age.

                                  In bronchiolitis HS is believed to help by decreasing airway edema and thinning of mucus to alleviate plugging via the osmotic effect of HS. Literature about 3% HS has been conflicting at best with some studies showing benefit with regards to the length of stay and symptom score and others showing no benefit.

                                  A 2017 Cochrane database review published by Zhang et al reported that nebulised hypertonic saline may modestly reduce length of stay among infants hospitalised with acute bronchiolitis and improve clinical severity score. Treatment with nebulised hypertonic saline may also reduce the risk of hospitalisation among outpatients and emergency department patients. However, we assessed the quality of the evidence as low to moderate. Quality of evidence is moderate due to substantial clinical heterogeneity between studies and large multicenter trials are still warranted.

                                  Yes, Pradip, actually — One PICU randomized study by Shein et al (2016) reported on 18 intubated patients (9 in each group)- receiving either hypertonic saline or 0.9%NS used 4 times a day for 7 days. They found no difference in any outcomes measures between the two group after adjustment for baseline differences in respiratory parameters.

                                  So Pradip, I have heard of N-Acetylcysteine or Mucomyst used as a pharmacological — how does it work?

                                  N-acetylcysteine (mucomyst) : It hydrolyzes the disulfide bonds of mucins and other proteins. The sodium salts of NAC may also disrupt DNA. Animal studies suggest there may be some benefit to the airway due to its antioxidant effect, its use in ARDS has not shown any benefit although in one study in pediatric burn patients, the combination NAC and heparin resulted in lower rates of reintubation, atelectasis, and mortality. (Desai MH et al. J burn care rehabilitation).

                                  What about Dornase Alpha?

                                  Dornase alfa: is a recombinant human DNAase, which degrades DNA of the neutrophils, which migrate to the airway in inflammatory conditions. DNA from neutrophils increases the viscosity of the sputum and mucus plugging in the airway. Dornase decreases mucus viscosity and helps its clearance from the airway.

                                  A Cochrane database review from 2018 (Yang et al)reported improved lung function in patients with cystic fibrosis in trials lasting from one month to two years. There was a decrease in pulmonary exacerbations in trials of six months or longer. A meta-analysis from 2012 (Enriquez et al.) reported no benefit with respect to clinical scores in patients with bronchiolitis but longer duration of...]]>10349489-e9f2-48b5-8af2-90aea46500bdSun, 23 Jan 2022 03:00:00 -040028:19falsefull4141Toddler with Cough and Difficulty BreathingWelcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.

                                  I'm Pradip Kamat and I'm Rahul Damania. We are coming to you from Children's Healthcare of Atlanta - Emory University School of Medicine.

                                  Welcome to our episode of a three-year-old girl presenting with a cough and difficulty breathing

                                  Here's the case presented by Rahul:

                                  A previously healthy 3-year-old girl presented to the OSH for difficulty breathing. She had a two-day h/o of cough (worse at night) and congestion but no fever. She has no h/o of emesis, h/o recent travel, or exposure to some/toxins. Initially, she received steroids, albuterol, and O2 but due to continued worsening of breathing and hypoxia-She was transferred to our PICU for initiation of High Flow Nasal Cannula. She has no allergies and her immunizations are up to date. There is a strong family history of asthma and atopic dermatitis. The mother also noted that the patient has h/o of coughing episodes while playing outside with her siblings.

                                  Initial Vitals: Temp 37.9, HR 100, BP 97/73, respiratory rate 49, SPO2 98% on 15LPM HFNC at 60% FIO2 , weight 17.5kg

                                  On PE: The child is awake, playful. she is tachycardic with no murmur. She has subcostal, intercostal, supra-sternal retractions. There is bilateral symmetric chest expansion. The air entry is decreased with diffuse (B) wheeze. There is atopic dermatitis in the flexor areas of the elbows/knees. The rest of the physical examination was normal. No hepatosplenomegaly.

                                  Viral panel: positive for HMP, SARS COV-2 negative

                                  CXR: Atelectasis superimposed upon viral pneumonitis versus multifocal bronchopneumonia. No evidence of parapneumonic effusion or air leak.

                                  CBC and BMP are normal.

                                  To summarize key elements from this case, this 3-year-old girl has:

                                  • Cough and congestion
                                  • Increased WOB and difficulty breathing
                                  • Hypoxia
                                  • No fever or rash
                                  • No recent ingestions or exposure to tobacco smoke
                                  • All of which brings up a concern for a lower airway obstructive process most likely acute asthma
                                  
                                  

                                  Let's transition into some history and physical exam components of this case?

                                  Rahul, what are key history features in this child who presents with increased work of breathing?

                                  • Cough and congestion
                                  • Difficulty breathing
                                  • No h/o suggestive of atopic dermatitis
                                  • Increased WOB: retractions (subcostal, intercostal, suprasternal). Important to note there is no nasal flaring, head bobbing or grunting.
                                  • Decreased AE
                                  • Diffuse (B) wheezing. No subcutaneous emphysema on palpation of the chest or cervical region.
                                  • Hypoxia needing oxygen
                                  • Atopic dermatitis
                                  • No crackles
                                  • No hepatomegaly
                                  • No altered mental status
                                  
                                  

                                  Not all respiratory distress arises within the respiratory tract. Important physical examination to note in any infant or toddler with increased work of breathing is to palpate for hepatomegaly as well as carefully listen for bilateral inspiratory crackles. The presence of hepatomegaly or (B) crackles should raise concern for myocarditis or congestive heart failure. In Newborns with respiratory distress-always make a habit to feel femoral pulses. Acidosis, intracranial hemorrhage, foreign body, panic attacks can also present as respiratory distress.

                                  To continue with our case, Pradip, the patient’s labs/diagnostic were consistent with:

                                  • CBC, BMP were normal
                                  • Respiratory viral panel positive for HMP virus, Negative for SARS-COV-2
                                  • Chest radiograph: Atelectasis superimposed upon viral pneumonitis versus multifocal bronchopneumonia
                                  
                                  

                                  OK, to summarize, we have: A 3-year-old with acute respiratory distress, wheezing, hypoxia after 2 days h/o of cough/congestion.

                                  Rahul, let's start with a short multiple-choice question:

                                  A 15-year-old teenager with know h/o asthma presents to the ED in severe respiratory distress, increased work of breathing, hypoxia, and diffuse wheezing. Of the following the presentation that would most likely require intubation in this teenager include-

                                  • A) Inability to talk in complete sentences
                                  • B) A blood gas that shows hypocapnia and mild respiratory alkalosis
                                  • C) Presence of pulsus paradoxus
                                  • D) Deteriorating mental status
                                  
                                  

                                  Rahul, this is an excellent question. The correct answer here is D-Deteriorating mental status. While choice A-inability to talk in complete sentences as well as Choice C-presence of pulsus paradoxus in a patient with asthma correlate with severity of acute asthma, those choices are not indications for intubation. In early asthma -in a patient who is tachypneic and breathing hard the blood gas should have hypocapnia and a mild respiratory alkalosis. I would be more worried about a normal gas or a rising PCO2 in a patient with status asthmaticus.

                                  So just for our listeners, indications for intubation and mechanical ventilation in a child with asthma should be based on clinical judgment and include: cardiac and respiratory arrest; severe hypoxia as well as rapid deterioration in the child’s mental status. Progressive exhaustion despite maximal therapy constitutes a relative indication for intubation on a case-by-case basis. The traditional rule that respiratory acidosis dictates intubation has become outdated.

                                  Rahul, can you comment on the commonly used Clinical Respiratory Score (CRS) ?

                                  The Clinical Respiratory Score (CRS) is a tool that was developed based on the National Asthma Education Program’s guidelines for the diagnosis and management of asthma. The CRS contains six equally weighted variables. It uses both objective and subjective criteria when evaluating a child with asthma to calculate a score. A CRS assessment requires a member of the care team to calculate a respiratory rate and record the room air oxygen saturation using a pulse oximeter. Auscultation of the lung fields, assessing the use of accessory muscles, mental status, and the child’s color also contribute to the CRS. Respiratory rate scores are differentiated by normal values for age. Each of the 6 categories are then categorized as mild (score = 0), moderate (score = 1), or severe distress (score = 2), and the total score is calculated from 0 to 12. The CRS is a reliable asthma severity scoring tool for pediatric patients presenting with an acute asthma exacerbation when utilized across care team members. (McLaughlin P. et al Journal of Asthma 2021).

                                  Rahul also what are risk factors for severe acute asthma?

                                  In a review by Werner H (Chest 2001; 119:1913-1929), risk factors for acute severe asthma were classified as medical factors include: Previous attack with severe, unexpected, rapid deterioration, respiratory failure, seizure or LOC, attacks precipitated by food.

                                  Psychosocial factors: denial or failure to perceive the severity of illness associated depression or psychiatric disorders, non-compliance, dysfunctional family unit, inner-city residents

                                  Ethnic factors:...]]>Welcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.

                                  I'm Pradip Kamat and I'm Rahul Damania. We are coming to you from Children's Healthcare of Atlanta - Emory University School of Medicine.

                                  Welcome to our episode of a three-year-old girl presenting with a cough and difficulty breathing

                                  Here's the case presented by Rahul:

                                  A previously healthy 3-year-old girl presented to the OSH for difficulty breathing. She had a two-day h/o of cough (worse at night) and congestion but no fever. She has no h/o of emesis, h/o recent travel, or exposure to some/toxins. Initially, she received steroids, albuterol, and O2 but due to continued worsening of breathing and hypoxia-She was transferred to our PICU for initiation of High Flow Nasal Cannula. She has no allergies and her immunizations are up to date. There is a strong family history of asthma and atopic dermatitis. The mother also noted that the patient has h/o of coughing episodes while playing outside with her siblings.

                                  Initial Vitals: Temp 37.9, HR 100, BP 97/73, respiratory rate 49, SPO2 98% on 15LPM HFNC at 60% FIO2 , weight 17.5kg

                                  On PE: The child is awake, playful. she is tachycardic with no murmur. She has subcostal, intercostal, supra-sternal retractions. There is bilateral symmetric chest expansion. The air entry is decreased with diffuse (B) wheeze. There is atopic dermatitis in the flexor areas of the elbows/knees. The rest of the physical examination was normal. No hepatosplenomegaly.

                                  Viral panel: positive for HMP, SARS COV-2 negative

                                  CXR: Atelectasis superimposed upon viral pneumonitis versus multifocal bronchopneumonia. No evidence of parapneumonic effusion or air leak.

                                  CBC and BMP are normal.

                                  To summarize key elements from this case, this 3-year-old girl has:

                                  • Cough and congestion
                                  • Increased WOB and difficulty breathing
                                  • Hypoxia
                                  • No fever or rash
                                  • No recent ingestions or exposure to tobacco smoke
                                  • All of which brings up a concern for a lower airway obstructive process most likely acute asthma
                                  
                                  

                                  Let's transition into some history and physical exam components of this case?

                                  Rahul, what are key history features in this child who presents with increased work of breathing?

                                  • Cough and congestion
                                  • Difficulty breathing
                                  • No h/o suggestive of atopic dermatitis
                                  • Increased WOB: retractions (subcostal, intercostal, suprasternal). Important to note there is no nasal flaring, head bobbing or grunting.
                                  • Decreased AE
                                  • Diffuse (B) wheezing. No subcutaneous emphysema on palpation of the chest or cervical region.
                                  • Hypoxia needing oxygen
                                  • Atopic dermatitis
                                  • No crackles
                                  • No hepatomegaly
                                  • No altered mental status
                                  
                                  

                                  Not all respiratory distress arises within the respiratory tract. Important physical examination to note in any infant or toddler with increased work of breathing is to palpate for hepatomegaly as well as carefully listen for bilateral inspiratory crackles. The presence of hepatomegaly or (B) crackles should raise concern for myocarditis or congestive heart failure. In Newborns with respiratory distress-always make a habit to feel femoral pulses. Acidosis, intracranial hemorrhage, foreign body, panic attacks can also present as respiratory distress.

                                  To continue with our case, Pradip, the patient’s labs/diagnostic were consistent with:

                                  • CBC, BMP were normal
                                  • Respiratory viral panel positive for HMP virus, Negative for SARS-COV-2
                                  • Chest radiograph: Atelectasis superimposed upon viral pneumonitis versus multifocal bronchopneumonia
                                  
                                  

                                  OK, to summarize, we have: A 3-year-old with acute respiratory distress, wheezing, hypoxia after 2 days h/o of cough/congestion.

                                  Rahul, let's start with a short multiple-choice question:

                                  A 15-year-old teenager with know h/o asthma presents to the ED in severe respiratory distress, increased work of breathing, hypoxia, and diffuse wheezing. Of the following the presentation that would most likely require intubation in this teenager include-

                                  • A) Inability to talk in complete sentences
                                  • B) A blood gas that shows hypocapnia and mild respiratory alkalosis
                                  • C) Presence of pulsus paradoxus
                                  • D) Deteriorating mental status
                                  
                                  

                                  Rahul, this is an excellent question. The correct answer here is D-Deteriorating mental status. While choice A-inability to talk in complete sentences as well as Choice C-presence of pulsus paradoxus in a patient with asthma correlate with severity of acute asthma, those choices are not indications for intubation. In early asthma -in a patient who is tachypneic and breathing hard the blood gas should have hypocapnia and a mild respiratory alkalosis. I would be more worried about a normal gas or a rising PCO2 in a patient with status asthmaticus.

                                  So just for our listeners, indications for intubation and mechanical ventilation in a child with asthma should be based on clinical judgment and include: cardiac and respiratory arrest; severe hypoxia as well as rapid deterioration in the child’s mental status. Progressive exhaustion despite maximal therapy constitutes a relative indication for intubation on a case-by-case basis. The traditional rule that respiratory acidosis dictates intubation has become outdated.

                                  Rahul, can you comment on the commonly used Clinical Respiratory Score (CRS) ?

                                  The Clinical Respiratory Score (CRS) is a tool that was developed based on the National Asthma Education Program’s guidelines for the diagnosis and management of asthma. The CRS contains six equally weighted variables. It uses both objective and subjective criteria when evaluating a child with asthma to calculate a score. A CRS assessment requires a member of the care team to calculate a respiratory rate and record the room air oxygen saturation using a pulse oximeter. Auscultation of the lung fields, assessing the use of accessory muscles, mental status, and the child’s color also contribute to the CRS. Respiratory rate scores are differentiated by normal values for age. Each of the 6 categories are then categorized as mild (score = 0), moderate (score = 1), or severe distress (score = 2), and the total score is calculated from 0 to 12. The CRS is a reliable asthma severity scoring tool for pediatric patients presenting with an acute asthma exacerbation when utilized across care team members. (McLaughlin P. et al Journal of Asthma 2021).

                                  Rahul also what are risk factors for severe acute asthma?

                                  In a review by Werner H (Chest 2001; 119:1913-1929), risk factors for acute severe asthma were classified as medical factors include: Previous attack with severe, unexpected, rapid deterioration, respiratory failure, seizure or LOC, attacks precipitated by food.

                                  Psychosocial factors: denial or failure to perceive the severity of illness associated depression or psychiatric disorders, non-compliance, dysfunctional family unit, inner-city residents

                                  Ethnic factors: Nonwhite children.

                                  A study by Grunwell et al (PCCM 2018) reports risk factors for PICU admission, with or without intubation. These include hospitalization in past 12months, a h/o pneumonia, chronic asthma severity on high dose ICS, a father with asthma, living in a region with a high burden of poverty, and being of black race.

                                  In a more recent study, Grunwell J. et al ( J Allergy Clin Immunol Pract. 2021) reported on school Age children at risk for asthma exacerbation. The authors identified Four latent classes with differing demographic features, sensitization and Type-2 inflammatory markers, prior exacerbation severity and healthcare utilization, and lung function. They found that children with exacerbation-prone asthma were present in each latent class, but were most strongly represented in the latent classes with multiple sensitization and airflow limitation.

                                  Rahul, can you explain the pathophysiology of acute asthma in terms of lung mechanics/gas exchange and cardiopulmonary interactions.

                                  Acute asthma there is (1) Inflammation is triggered by a respiratory virus, cigarette smoke, air pollution, allergens, etc. IL-4, IL-5, IL-8, IL-13 primarily mediate inflammation, amplified by increased production of IgE by B cells. There is bronchospasm due to airway hyper-responsiveness, (3) Hyper-secretion of mucous plugging the airways (worsened by dehydration due to increased insensible

                                  Airway obstruction leads to hyperinflation with resultant dead space ventilation. In fact, hyperinflation results in the conversion of lung segments from West zone 3 and two to West zone 1, thus increasing the V/Q mismatch. The Increase in respiratory rates in response to impaired ventilation results in dynamic hyperinflation and air trapping due to prolonged expiratory times.

                                  Hyperinflation leads to the flattened diaphragm, which becomes inefficient for optimal respiratory function. Diaphragmatic fatigue is further exacerbated by acidosis, hypoxia, and dehydration.

                                  VQ mismatching: Mucus plugging results in VQ mismatching due to atelectasis and intrapulmonary shunting

                                  PVR is elevated due to increased lung volumes worsened by acidosis and hypoxia, adding to the VQ mismatch by decreasing blood flow(Q). The use of albuterol can further worsen VQ mismatch

                                  In spontaneously breathing children with acute severe asthma, the pleural pressures can be as negative as -35cm H2O. The negative pleural pressure increases the (L) ventricular afterload, which favors the trans-capillary filtration of edema fluid into the airspaces resulting in a high risk for the development of pulmonary edema. Due to hypoxic pulmonary vasoconstriction, acidosis, and increased lung volume, the RV afterload is also increased.

                                  Pulsus paradoxus is not specific for acute asthma. It can also be seen in cardiac tamponade, pulmonary embolus, and tension PTC. Fall in arterial systolic blood pressure with inspiration of > 10mm Hg (normal <10 mmHg). Hyperinflation leads to the expansion of vascular beds. During inspiration, the increased RV preload leads to the septum bowing into the LV thus decreasing LV preload and exacerbating the normal physiologic drop in BP with inspiration. LV preload may be further compromised by increased pulmonary vascular bed compliance and increased (L) ventricular afterload.

                                  As you think about our case, what would be your differential in a patient with respiratory distress and/or wheezing?

                                  • Foreign body (unilateral wheezing, h/o choking/coughing while eating or playing).
                                  • Non-respiratory causes of respiratory distress include: CNS causes such as intracranial hemorrhage, airway obstruction, air leaks, acidosis, panic attacks, cardiac causes such as myocarditis, congestive heart failure. A detailed h/o and physical examination with pertinent imaging will help with the diagnosis in the above conditions.
                                  
                                  

                                  Wheezing in asthmatics occurs due to turbulent airflow in the intrathoracic airways and bilateral. NOT all wheezing is Asthma! If wheezing is asymmetric caregivers should consider the diagnosis of a foreign body, PTX, mucous plugging, or atelectasis. The degree of wheezing correlates poorly with asthma severity. If there is no airflow, no wheezing will be heard and the patient may have a silent chest, which is an ominous sign. If a patient who previously had loud wheezing but has now worsening work of breathing, a reduction in wheezing may be a harbinger of respiratory failure.

                                  • Pradip If you had to work up this patient with acute asthma what would be your diagnostic approach?
                                  • Really don’t need a lot of investigations in the routine asthma admission to the PICU. Some may not even get a chest radiograph or a viral panel. CXR may be indicated if the clinical exam suggests an air leak (such as crepitus or asymmetry of chest rise).
                                  • Frequent repeat assessments at the bedside after an intervention is the most important. Close observation of respiratory effort, pulse oximetry, and alertness serve as continuous clinical correlates of pulmonary gas exchange.
                                  • Blood gas: Typically in early asthma we see hypocarbia with mild respiratory alkalosis. If the patient clinically worsens one may see initially a normal PCO2 followed by hypercarbia and hypoxemia. Routine blood gases are not indicated in acute severe asthma and one single abnormal blood gas should not be used as an indicator to decide the need for mechanical ventilation. As the patient worsens, one may see a mixed picture of respiratory acidosis with metabolic acidosis.
                                  • Lactic acidosis: Serum lactates should not be routinely obtained in acute severe asthma as some degree of lactic acidosis is common in acute severe asthma due to the use of albuterol and adrenergic stimulation (Type B lactic acidosis(associated with adrenergic stimulation and occurring with normal oxygen delivery)) Meert K et al (PCCM 2012).
                                  • Routine BMP/CBC is not required. Hypokalemia may be seen due to continuous albuterol use. If there is dehydration, BUN may be elevated. If a CBC is obtained- there may be leucocytosis from stress or use of steroids. rarely eosinophil count may be elevated in atopic patients.
                                  • Rahul If our history, physical, and diagnostic investigation led us to acute severe asthma as our diagnosis what would be your general management of framework?
                                  • Status asthmaticus is now replaced by the term acute severe asthma and is defined as an asthma attack unresponsive to repeated doses of beta-agonists and requiring hospital admission. Critical asthma is defined as acute severe asthma which requires intensive care admission. Near-Fatal asthma is defined as critical asthma that requires endotracheal tube intubation and mechanical ventilation. General principles of good PICU care should be followed. O2, albuterol, and steroids are the mainstays of therapy in acute severe asthma.
                                  • O2 for hypoxia. Can be given with nebulizer treatments and continuously between the treatments.
                                  • Fluids: Patients with acute severe asthma have dehydration (insensible losses or decreased PO intake). Fluids also help loosen the mucus in the airways.
                                  • Corticosteroids: IV methylprednisolone 0.5-1mg/kg/dose Q6 followed by PO when the patient is able to take PO. Continue for 5-7days. It is not necessary to continue home ICS when the patient is acutely ill and on IV steroids in the PICU.
                                  • Albuterol nebulizer therapy is used initially over 20minutes at 0.05-0.15mg/kg. less than 10% of the inhaled drug is deposited in the lungs. After initial series of 3 albuterol treatments, continuous albuterol nebulization is started at a dose range of 0.15-0.45mg/kg/hr (maximum of 20mg/hr). albuterol is a 50:50 mixture of R-albuterol and S-albuterol. The R-albuterol, also called levalbuterol, is the enantiomer that causes broncho-dilation, whereas the S-albuterol is the inert form and may contribute to adverse events. We do not recommend the use of Levalbuterol as there is no advantage of its use over albuterol. Levalbuterol doesn’t cause less tachycardia than racemic albuterol and continues to have a higher cost compared to R-albuterol. In patients who do not improve with albuterol or have poor air entry, to begin with, I start IV terbutaline. I give 5-10mcg/kg IV bolus followed by an infusion at 0.1-4mcg/kg/min. I do not use IV epinephrine due to its greater affinity for beta-1 compared to terbutaline.
                                  
                                  

                                  So let's summarize A, B, C — in parallel, we optimize anti-inflammatory &...]]>95e96df4-f766-49b7-b66a-c360f3ecba1fSun, 16 Jan 2022 03:00:00 -040030:50falsefull4040Seizure and Altered Mental Status in Patient with MIS-CWelcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.

                                  I'm Pradip Kamat and I'm Rahul Damania. We are coming to you from Children's Healthcare of Atlanta - Emory University School of Medicine.

                                  Welcome to our Episode an 8-year-old admitted for PRESS syndrome with altered mental status secondary to seizures.

                                  Here's the case presented by Rahul:

                                  Our patient today is an eight-year-old who was admitted to the floor with a diagnosis of MIS-C. On his initial echo, his EF had mildly depressed systolic function, dilatation of coronaries, and worsening of inflammatory markers. As a result, the care team increased the dosing of the methylprednisolone administered to this patient. Since the initiation of methylprednisone, The patient's SBP had been steadily increasing with the latest systolic values approaching 140s-150s.

                                  On hospital day 3 patient had a generalized tonic-clonic seizure and became unresponsive for which a rapid response on the floor was called. The patient was emergently bagged and brought to the PICU for airway protection and intubation

                                  Initial vitals on PICU admission: He was afebrile, mildly tachycardic, and hypertensive to 160s even after sedation.

                                  In the PICU an initial head CT scan done after intubation and stabilization of the patient showed no bleeding or mass. cEEG monitoring was initiated, neurology consulted and an MRI was ordered for the following day. As his AMS was thought to be related to his BP, the team pursued BP control with Nicardipine.

                                  To summarize key elements from this case, this patient has:

                                  • Seizure
                                  • Altered mental status
                                  • Hypertension
                                  • Acute respiratory failure
                                  • All of which brings up a concern for an acute CNS pathology.
                                  
                                  

                                  Absolutely, the differential is broad, however, right now I am thinking of an acute stroke categorized as hemorrhagic, ischemic, or venous thrombotic; a meningoencephalitis, CNS vasculitis, acute demyelinating encephalomyelitis, metabolic encephalopathy, tumor, or AMS related to hypertension.

                                  Pradip, let's transition into some history and physical exam components of this case?

                                  What are key history features in this child?

                                  • MIS-C with cardiac dysfunction and coronary anomalies
                                  • Increase in steroid dosage
                                  • Progressive increase in BP as a result of this increase
                                  
                                  

                                  Rahul, are there some red-flag symptoms or physical exam components which you could highlight?

                                  • The patient's physical exam was relatively normal. Of note, the fundoscopic exam did not reveal papilledema and no renal bruit was auscultated.
                                  • His Pupils were equal, round, and reactive to light. The face was symmetric. Normal bulk and tone. The patient was sedated and did not withdraw extremities to noxious stimuli. Tendon reflexes were equal throughout. and no clonus is noted. Fundoscopic exam revealed no papilledema which may rule out increased ICP as a cause for our AMS.
                                  
                                  

                                  To continue with our case, Rahul ,what were the patient’s labs were consistent with:

                                  • Down trending CRP, ESR, BNP, and troponin
                                  • ECHO is consistent with improved cardiac function as well as improvement of coronary dilatation.
                                  • CT scan with no bleed
                                  • MRI suggestive of changes in the posterior brain with distinct edema pattern
                                  
                                  

                                  OK to summarize, we have:

                                  An eight-year-old, with acute severe hypertension, seizure altered mental status, and MRI changes suggestive of vasogenic edema in the posterior part of the brain -all this brings up the concern for posterior reversible encephalopathy syndrome (PRES) the topic of our discussion today.

                                  Rahul ,Let's start with a short multiple-choice question:

                                  A 19-year-old with h/o of renal transplant on tacrolimus and recent initiation of steroids for rejection presents with acute severe hypertension and a GTC seizure. The patient is afebrile with no rash. CT scan at OSH reveals no mass or hemorrhage. After stabilization and initiation of antihypertensive therapy, the next study of choice for diagnosis is

                                  • A) Continuous EEG
                                  • B) MRI
                                  • C) Lumbar puncture
                                  • D) Positron emission test (PET scan) of the brain
                                  
                                  

                                  Rahul, the correct answer is B) MRI. Patients such as the one described in the above question are at high risk to develop PRES. MRI will show classic changes associated with PRES- Involvement of the parieto-occipital region of the brain. Vasogenic edema (typically affecting the brain white matter) is characterized by hyperintensity on FLAIR and T2-weighted MRI sequences. As seizure is a presentation of PRES as in our case above, cEEG monitoring especially if intubated is indicated but may not be helpful in diagnosis. An LP also will not help with the diagnosis of PRES and the patient in this question is afebrile. PET scan may have a role in unusual or atypical cases of PRES mainly to distinguish it from the tumor. There is decreased fluorodeoxyglucose (FDG) and Methionine(MET) uptake in most PRES cases compared to tumors such as gliomas or lymphomas.

                                  To summarize:

                                  The diagnosis of PRES relies on a combination of clinical presentation and neuroimaging. Acute or subacute presentation with encephalopathy, generalized tonic-clonic seizures (60-75% patients), headaches, visual field deficits, cortical blindness, hallucinations, or rarely focal findings such as aphasia or hemiparesis should raise suspicion for PRES. Headache+visual disturbances+generalized tonic-clonic seizures =PRES unless proven otherwise.

                                  Rahul, as you think about our case, what would be your differential?

                                  • Infectious encephalitis (CSF is abnormal, CSF gram stain, CX or PCR)
                                  • CNS vasculitis (CSF pleocytosis, cytotoxic edema in a non-PRES like pattern)
                                  • Acute demyelinating encephalomyelitis (ADEM): H/o URI/bacterial infection, fever, usually asymmetric involvement of supratentorial regions on imaging
                                  • malignancy or tumor (glioma or lymphoma)-Typically subacute-chronic presentation, h/o malignancy, absence of quick resolution, abnormal CSF or blood work
                                  • Another important grouping I would consider is a toxidrome — some of these we mention in our prior podcast episodes so listeners please check them out!
                                  
                                  

                                  Rahul, can you comment on the pathogenesis of PRES**

                                  It is hypothesized that when the patient’s mean arterial BP exceeds the upper limits of cerebral autoregulation it leads to hyper-perfusion and the breakdown of the blood-brain barrier allowing interstitial extravasation of plasma and macromolecules and subsequently vasogenic edema. 

                                  • PRES can also develop in patients (15-20%) with normal BP or hypotension, which does not exceed the auto-regulatory capacity of the cerebral blood flow.
                                  • In these patients, the endothelial dysfunction and breakdown of the blood-brain barrier could be from the cytokines and inflammatory mediators from systemic toxic effects of medications, etc. resulting in vasogenic edema. The posterior regions of the brain are more susceptible to vasogenic edema because little sympathetic innervation...]]>Welcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.

                                    I'm Pradip Kamat and I'm Rahul Damania. We are coming to you from Children's Healthcare of Atlanta - Emory University School of Medicine.

                                    Welcome to our Episode an 8-year-old admitted for PRESS syndrome with altered mental status secondary to seizures.

                                    Here's the case presented by Rahul:

                                    Our patient today is an eight-year-old who was admitted to the floor with a diagnosis of MIS-C. On his initial echo, his EF had mildly depressed systolic function, dilatation of coronaries, and worsening of inflammatory markers. As a result, the care team increased the dosing of the methylprednisolone administered to this patient. Since the initiation of methylprednisone, The patient's SBP had been steadily increasing with the latest systolic values approaching 140s-150s.

                                    On hospital day 3 patient had a generalized tonic-clonic seizure and became unresponsive for which a rapid response on the floor was called. The patient was emergently bagged and brought to the PICU for airway protection and intubation

                                    Initial vitals on PICU admission: He was afebrile, mildly tachycardic, and hypertensive to 160s even after sedation.

                                    In the PICU an initial head CT scan done after intubation and stabilization of the patient showed no bleeding or mass. cEEG monitoring was initiated, neurology consulted and an MRI was ordered for the following day. As his AMS was thought to be related to his BP, the team pursued BP control with Nicardipine.

                                    To summarize key elements from this case, this patient has:

                                    • Seizure
                                    • Altered mental status
                                    • Hypertension
                                    • Acute respiratory failure
                                    • All of which brings up a concern for an acute CNS pathology.
                                    
                                    

                                    Absolutely, the differential is broad, however, right now I am thinking of an acute stroke categorized as hemorrhagic, ischemic, or venous thrombotic; a meningoencephalitis, CNS vasculitis, acute demyelinating encephalomyelitis, metabolic encephalopathy, tumor, or AMS related to hypertension.

                                    Pradip, let's transition into some history and physical exam components of this case?

                                    What are key history features in this child?

                                    • MIS-C with cardiac dysfunction and coronary anomalies
                                    • Increase in steroid dosage
                                    • Progressive increase in BP as a result of this increase
                                    
                                    

                                    Rahul, are there some red-flag symptoms or physical exam components which you could highlight?

                                    • The patient's physical exam was relatively normal. Of note, the fundoscopic exam did not reveal papilledema and no renal bruit was auscultated.
                                    • His Pupils were equal, round, and reactive to light. The face was symmetric. Normal bulk and tone. The patient was sedated and did not withdraw extremities to noxious stimuli. Tendon reflexes were equal throughout. and no clonus is noted. Fundoscopic exam revealed no papilledema which may rule out increased ICP as a cause for our AMS.
                                    
                                    

                                    To continue with our case, Rahul ,what were the patient’s labs were consistent with:

                                    • Down trending CRP, ESR, BNP, and troponin
                                    • ECHO is consistent with improved cardiac function as well as improvement of coronary dilatation.
                                    • CT scan with no bleed
                                    • MRI suggestive of changes in the posterior brain with distinct edema pattern
                                    
                                    

                                    OK to summarize, we have:

                                    An eight-year-old, with acute severe hypertension, seizure altered mental status, and MRI changes suggestive of vasogenic edema in the posterior part of the brain -all this brings up the concern for posterior reversible encephalopathy syndrome (PRES) the topic of our discussion today.

                                    Rahul ,Let's start with a short multiple-choice question:

                                    A 19-year-old with h/o of renal transplant on tacrolimus and recent initiation of steroids for rejection presents with acute severe hypertension and a GTC seizure. The patient is afebrile with no rash. CT scan at OSH reveals no mass or hemorrhage. After stabilization and initiation of antihypertensive therapy, the next study of choice for diagnosis is

                                    • A) Continuous EEG
                                    • B) MRI
                                    • C) Lumbar puncture
                                    • D) Positron emission test (PET scan) of the brain
                                    
                                    

                                    Rahul, the correct answer is B) MRI. Patients such as the one described in the above question are at high risk to develop PRES. MRI will show classic changes associated with PRES- Involvement of the parieto-occipital region of the brain. Vasogenic edema (typically affecting the brain white matter) is characterized by hyperintensity on FLAIR and T2-weighted MRI sequences. As seizure is a presentation of PRES as in our case above, cEEG monitoring especially if intubated is indicated but may not be helpful in diagnosis. An LP also will not help with the diagnosis of PRES and the patient in this question is afebrile. PET scan may have a role in unusual or atypical cases of PRES mainly to distinguish it from the tumor. There is decreased fluorodeoxyglucose (FDG) and Methionine(MET) uptake in most PRES cases compared to tumors such as gliomas or lymphomas.

                                    To summarize:

                                    The diagnosis of PRES relies on a combination of clinical presentation and neuroimaging. Acute or subacute presentation with encephalopathy, generalized tonic-clonic seizures (60-75% patients), headaches, visual field deficits, cortical blindness, hallucinations, or rarely focal findings such as aphasia or hemiparesis should raise suspicion for PRES. Headache+visual disturbances+generalized tonic-clonic seizures =PRES unless proven otherwise.

                                    Rahul, as you think about our case, what would be your differential?

                                    • Infectious encephalitis (CSF is abnormal, CSF gram stain, CX or PCR)
                                    • CNS vasculitis (CSF pleocytosis, cytotoxic edema in a non-PRES like pattern)
                                    • Acute demyelinating encephalomyelitis (ADEM): H/o URI/bacterial infection, fever, usually asymmetric involvement of supratentorial regions on imaging
                                    • malignancy or tumor (glioma or lymphoma)-Typically subacute-chronic presentation, h/o malignancy, absence of quick resolution, abnormal CSF or blood work
                                    • Another important grouping I would consider is a toxidrome — some of these we mention in our prior podcast episodes so listeners please check them out!
                                    
                                    

                                    Rahul, can you comment on the pathogenesis of PRES**

                                    It is hypothesized that when the patient’s mean arterial BP exceeds the upper limits of cerebral autoregulation it leads to hyper-perfusion and the breakdown of the blood-brain barrier allowing interstitial extravasation of plasma and macromolecules and subsequently vasogenic edema. 

                                    • PRES can also develop in patients (15-20%) with normal BP or hypotension, which does not exceed the auto-regulatory capacity of the cerebral blood flow.
                                    • In these patients, the endothelial dysfunction and breakdown of the blood-brain barrier could be from the cytokines and inflammatory mediators from systemic toxic effects of medications, etc. resulting in vasogenic edema. The posterior regions of the brain are more susceptible to vasogenic edema because little sympathetic innervation exists in the posterior fossa.
                                    
                                    

                                    Pradip, which patients are at risk for PRES?

                                    Apart from acute severe hypertension, a number of other conditions are associated with PRES. PRES is seen in patients receiving immune suppression, especially calcineurin inhibitors (tacrolimus or cyclosporine) after a stem cell or solid organ transplantation. Higher incidence is seen in BM or stem cell transplant as the dose of immunosuppression is higher in these patients compared to solid organ transplant patients. Autoimmune disorders, pregnancy with pre-eclampsia, eclampsia as well as those with renal disease have been linked to PRES.

                                    Here's a summary point when you see progressive hypertension in a patient post-transplant, after doing due diligence to pain control and diagnostic workup, pay close attention to mental status as these patients (especially if they are immunosuppression) are at high risk for developing press.

                                    Pradip If you had to work up this patient, what would be your diagnostic approach?

                                    • Acute-subacute symptoms such as confusion, seizures, visual, headache, and visual symptoms in the presence of hypertension, immune suppression, auto-immune disorders, transplant, or pre-eclampsia are highly suggestive of PRES.
                                    • Brain imaging is the most important diagnostic test typically used to exclude other diagnoses. The presence of vasogenic edema affecting the white matter in the parieto-occipital regions of both hemispheres (rarely asymmetric) on MRI FLAIR is highly sensitive. Although vasogenic edema can be seen in other areas of the brain there is always concomitant involvement of the parieto-occipital regions. Some patients with PRES may have restricted diffusion (15-30%) seen in larger areas of vasogenic edema, some patients (10-25%) may have intracranial or subarachnoid hemorrhage, especially in allogeneic BMT patients.
                                    • Other investigations which need to be decided on a case-by-case basis include obtaining LP, looking for CSF pleocytosis, gram-stain/Cx, PCR for viruses as well as cytology for malignancy.
                                    • Baseline blood gas, CBC, CMP, DIC may be required depending on the severity of the presentation
                                    • EEG: As 60-75% of patients with PRES can present with generalized tonic-clonic seizures and PRES can be suspected as the underlying cause of status epilepticus (especially when bilateral occipital sharp waves are present) continuous EEG monitoring especially in an intubated patient must be initiated.
                                    
                                    

                                    The presence of vasogenic edema affecting white matter in the parieto-occipital regions of both hemispheres (rarely asymmetric) on MRI FLAIR in the appropriate clinical context is highly sensitive for PRES. Neuroimaging helps to exclude alternative diagnoses such as brain tumor or acute demyelinating syndromes as well as detection of intracranial hemorrhage.

                                    Rahul, if our history, physical, and diagnostic investigation led us to PRES as our diagnosis what would be your general management of framework?

                                    • There is no specific management for PRES.
                                    • Treatment is supportive and basic principles of good ICU care are paramount for optimal outcomes.
                                    • Any treatable underlying cause such as severe hypertension must be managed appropriately. The anti-epileptic agent should be initiated and may be required for 3-12months (Morris EB et al. Pediatr Blood Cancer 2007). In our case, the patient's high BP was triggered by high-dose steroids used for MIS-C. The steroid dose was reduced as the patient's BP was controlled using IV nicardipine. A collaborative approach with rheumatology, infectious diseases, and ICU helped make decisions that allowed lowering of the steroid dose and titrating the BP. Magnesium has been used in PRES due to pre-eclampsia and eclampsia for seizure prophylaxis/treatment. The management of PRES from induction chemotherapy is difficult as deciding which meds to halt in a patient receiving multiple agents may not be easy. If PRES is caused by anti-rejection meds in a transplant patient, that medication may need to be discontinued at least temporarily. Listeners are encouraged to listen to our podcast on acute severe hypertension on how to safely lower BP in patients with acute severe hypertension.
                                    • Can you also comment on the prognosis of PRES?
                                    • Overall the prognosis of PRES is excellent although some severe forms may not be fully reversible and can have a mortality rate of 3-6%. Mortality is due to intracranial bleeding, cerebral edema in posterior fossa, hydrocephalous or diffuse cerebral edema, or raised ICP. In 10-20% of patients with PRES there can be neurological sequelae in the form of seizures, neuro-deficits such as hemiparesis, decreased visual activity, and dizziness. In 5-10% of patients PRES can be recurrent especially in patients with difficult to treat hypertension or who are on medications for their organ transplant.
                                    • Key objective take-aways from today's episodes:
                                    
                                    
                                    1. Acute or subacute presentation in a patient with the constellation of headache+seizures+visual disturbances should give rise to the suspicion of PRES especially in the clinical context of induction chemotherapy, immunotherapy, preeclampsia or eclampsia or acute severe hypertension
                                    2. MRI showing vasogenic edema in the parieto-occipital white matter regions on FLAIR (seen as hyperintensity) is typical for patients with PRES
                                    
                                    

                                    This concludes our episode on posterior reversible encephalopathy (PRES) We hope you found value in our short, case-based podcast. We welcome you to share your feedback, subscribe & place a review on our podcast! Please visit our website picudoconcall.org which showcases our episodes as well as our Doc on Call management cards. PICU Doc on Call is hosted by me Pradip Kamat and my co-host Dr. Rahul Damania. Stay tuned for our next episode! Thank you!

                                    References

                                    • Fugate JE, Rabinstein AA. Posterior reversible encephalopathy syndrome: clinical and radiological manifestations, pathophysiology, and outstanding questions. Lancet Neurol. 2015 Sep;14(9):914-925. doi: 10.1016/S1474-4422(15)00111-8. Epub 2015 Jul 13. Erratum in: Lancet Neurol. 2015 Sep;14(9):874. PMID: 26184985.
                                    • Ghali MGZ, Davanzo J, Leo M, Rizk E. Posterior reversible encephalopathy syndrome in pediatric patients: pathophysiology, diagnosis, and management. Leuk Lymphoma. 2019 Oct;60(10):2365-2372. doi: 10.1080/10428194.2019.1594210. Epub 2019 Sep 26. PMID: 31556774.
                                    • Fischer M, Schmutzhard E. Posterior reversible encephalopathy syndrome. J Neurol. 2017 Aug;264(8):1608-1616. doi: 10.1007/s00415-016-8377-8. Epub 2017 Jan 4. PMID: 28054130; PMCID: PMC5533845.
                                    
                                    

                                    More information can be found

                                    • Fuhrman & Zimmerman - Textbook of Pediatric Critical Care Chapter 61 (page 749-750); Chapter 64 (page 781); Chapter 78 (page 951); Chapter 92 (page 1111)
                                    • Key objective takeaways:
                                    
                                    
                                    1. Acute or subacute presentation in a patient with the constellation of headache+seizures+visual disturbances should give rise to the suspicion of PRES especially in the clinical context of induction chemotherapy, immunotherapy, preeclampsia or eclampsia or acute severe hypertension
                                    2. MRI showing vasogenic edema in the parieto-occipital white matter regions on FLAIR (seen as hyper-intensity) is typical for patients with PRES
                                    
                                    
                                    ]]>3c5b0ed4-b544-4d53-bdfe-c4f6edd7e4c9Sun, 09 Jan 2022 03:00:00 -040017:39falsefull3939Status EpilepticusWelcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.

                                    I'm Pradip Kamat and I'm Rahul Damania, and we are coming to you from Children's Healthcare of Atlanta - Emory University School of Medicine.

                                    Welcome to our Episode a 24-month-old girl with increased seizure frequency.

                                    Here's the case:

                                    A 24-month old girl presents to the ED with h/o shaking/jerking episodes in her sleep. The patient was in the care of her aunt when this acute episode occurred. When the father arrived from work, he saw his daughter having episodes of her body shaking alternating with heavy breathing. The patient would not wake up in between episodes. There was pertinently no history of trauma. 911 was called and when EMS arrived, she was starting to arouse and respond to stimuli. The patient was transported to the ED. In the ambulance, the patient continued to have similar shaking and jerking episodes and was given rectal diazepam. On arrival to ED, the patient had a fever of 38.5 Centigrade. Due to ongoing seizures, the patient was loaded with Fosphenytoin, after having been given a total of two doses of IV Lorazepam. The patient was subsequently intubated for airway protection and respiratory failure. A respiratory viral panel was negative for SARS-COV-2 but positive for Rhino-enterovirus. The patient was admitted to the PICU with cEEG monitoring and placed on mechanical ventilation with fentanyl + dexmedetomidine infusions with as needed Midazolam administrations

                                    Her physical examination on arrival to the PICU was unremarkable. She wasn't interactive as she had just received sedation after intubation. On her neuro-examination, Pupils are equal and punctiform. The face is symmetric. The tongue is midline. Normal bulk and tone. No spontaneous movements were noted. No withdrawal to painful stimuli. Tendon reflexes were equal throughout. No clonus is noted.

                                    Rahul, to summarize key elements from this case, this patient has:

                                    • Fever
                                    • Viral infection with Rhinoentero virus
                                    • Generalized Tonic clonic seizure lasting > 5minutes
                                    • Acute respiratory failure
                                    • All of which brings up a concern for status epilepticus
                                    
                                    

                                    Absolutely, we will get to this later on in the episode; however, remember that Status epilepticus is historically defined as single epileptic seizure of >30 minutes duration or a series of epileptic seizures during which function is not regained between ictal events in a 30-minute period

                                    • Let's transition into some history and physical exam components of this case?
                                    
                                    
                                    1. What are key history features in this child who presents with status epilepticus?
                                    
                                    
                                    • Prolonged Seizures
                                    • Fever with viral symptomatology which may act as a trigger
                                    • A pertinent negative is that this patient had no history of trauma or co-morbid conditions such as a genetic syndrome.
                                    • The patient also had no presumed ingestions as well.
                                    
                                    
                                    1. Are there some red-flag symptoms or physical exam components which you could highlight?
                                    
                                    
                                    • Important to look for rash (darkening of the skin = adrenoleukodystrophy), genetic facies, evidence of trauma —-all of which are absent in this girl
                                    • To continue with our case, the patients labs were consistent with:
                                    • Initial Labs: WBC 27K, with neutrophilic predominance, Hgb and platelets were normal. Initial CMP was normal except for a glucose of 233. Gas prior to intubation in the ED was 6.9/102/85/-9. (repeat after intubation 7.19/49/40/-9). Ionized ca 4.9mg/dl. A urine analysis was unremarkable.
                                    • Head CT negative
                                    
                                    

                                    OK to summarize, we have: 24-month-old girl who presented with prolonged seizures and acute respiratory failure

                                    • All of which brings up the concern for status epilepticus the topic of our discussion today.
                                    • Let's start with a short multiple-choice question:
                                    
                                    

                                    A 14-year-old girl is brought to the PICU from the floor with new-onset status epilepticus. She was admitted to the floor on her second day after a posterior spinal fusion surgery and is still receiving intravenous fluids. Her seizure is described as generalized tonic-clonic. After initial stabilization and maintenance of her airway and hemodynamics, which of the following is most likely to reveal the cause of her seizures?

                                    • A) Serum electrolytes
                                    • B) Stat MRI brain
                                    • C) Lumbar puncture
                                    • D) cEEG
                                    
                                    

                                    Rahul, the correct answer here is A) serum electrolytes. Patients especially after posterior spinal fusion surgery are at risk for hyponatremia secondary to SIADH or even hypotonic fluids used for maintenance. Correction of hyponatremia in a child with seizures requires 3% hypertonic saline. The seizure threshold is typically a serum Na of 125meQ/L. Serum electrolytes will also reveal the serum glucose which is especially important to check in infants who have seizures. A stat MRI is not warranted in this patient especially if she is alert and awake prior to the seizure. Additionally, it would be dangerous to send an unstable patient for an MRI. As the patient is afebrile, LP is less likely to be illuminating about the cause of her seizures. LP could be needed especially if there is a strong suspicion of infection such as meningitis but can be delayed if the patient is unstable and antibiotics initiated. While a CEEG may be needed especially if the patient is intubated or comatose and there is a risk of non-clinical seizures, it is not the first-line diagnostic tool.

                                    Excellent explanation Pradip, it is of utmost importance to make sure you assess for electrolyte disturbances or glucose abnormalities in your rapid diagnostics when patients are seizing. Remember hyponatremia, hypoglycemia, and hypocalcemia. If you have a child with Seizures 

                                    • As you think about our case, what would be your differential for rhythmic jerking movements that mimic or are associated with seizures?
                                    • Movement disorders: Any abnormal involuntary movements such as Tics, tremor, chorea, athetosis, dystonia, myoclonus, ballismus, asterixis. Dyskinesia is a generalized term used for abnormal involuntary movements
                                    • Migraine (its paroxysmal nature + association with neuro-deficits or altered consciousness) may lead to confusion with seizures.
                                    • In infants paroxysmal non-epileptic disorders such as jitteriness, benign neonatal myoclonus may be confused with seizure
                                    • Myoclonus from drugs such as etomidate or post drowning due to hypoxia reperfusion injury may be mistaken for seizures
                                    
                                    

                                    Let’s transition and highlight key definitions of status epilepticus:

                                    Previously defined as a seizure lasting > than 30minutes or recurrent seizures lasting > 30minutes without patient regaining consciousness between seizures. The new definition refers to SE as 5minutes or more of either continuous seizure or 2 or more discrete seizures between which there is incomplete recovery of consciousness.

                                    Refractory SE = SE that persists despite the administration of first and second-line anti-seizure medications with different mechanisms of action.

                                    Super refractory SE refers to SE that continues 24 hours or more after the onset of anesthetic therapy for SE and includes recurrence during reduction or withdrawal of anesthetic therapy.

                                    Pradip what is the...]]>Welcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.

                                    I'm Pradip Kamat and I'm Rahul Damania, and we are coming to you from Children's Healthcare of Atlanta - Emory University School of Medicine.

                                    Welcome to our Episode a 24-month-old girl with increased seizure frequency.

                                    Here's the case:

                                    A 24-month old girl presents to the ED with h/o shaking/jerking episodes in her sleep. The patient was in the care of her aunt when this acute episode occurred. When the father arrived from work, he saw his daughter having episodes of her body shaking alternating with heavy breathing. The patient would not wake up in between episodes. There was pertinently no history of trauma. 911 was called and when EMS arrived, she was starting to arouse and respond to stimuli. The patient was transported to the ED. In the ambulance, the patient continued to have similar shaking and jerking episodes and was given rectal diazepam. On arrival to ED, the patient had a fever of 38.5 Centigrade. Due to ongoing seizures, the patient was loaded with Fosphenytoin, after having been given a total of two doses of IV Lorazepam. The patient was subsequently intubated for airway protection and respiratory failure. A respiratory viral panel was negative for SARS-COV-2 but positive for Rhino-enterovirus. The patient was admitted to the PICU with cEEG monitoring and placed on mechanical ventilation with fentanyl + dexmedetomidine infusions with as needed Midazolam administrations

                                    Her physical examination on arrival to the PICU was unremarkable. She wasn't interactive as she had just received sedation after intubation. On her neuro-examination, Pupils are equal and punctiform. The face is symmetric. The tongue is midline. Normal bulk and tone. No spontaneous movements were noted. No withdrawal to painful stimuli. Tendon reflexes were equal throughout. No clonus is noted.

                                    Rahul, to summarize key elements from this case, this patient has:

                                    • Fever
                                    • Viral infection with Rhinoentero virus
                                    • Generalized Tonic clonic seizure lasting > 5minutes
                                    • Acute respiratory failure
                                    • All of which brings up a concern for status epilepticus
                                    
                                    

                                    Absolutely, we will get to this later on in the episode; however, remember that Status epilepticus is historically defined as single epileptic seizure of >30 minutes duration or a series of epileptic seizures during which function is not regained between ictal events in a 30-minute period

                                    • Let's transition into some history and physical exam components of this case?
                                    
                                    
                                    1. What are key history features in this child who presents with status epilepticus?
                                    
                                    
                                    • Prolonged Seizures
                                    • Fever with viral symptomatology which may act as a trigger
                                    • A pertinent negative is that this patient had no history of trauma or co-morbid conditions such as a genetic syndrome.
                                    • The patient also had no presumed ingestions as well.
                                    
                                    
                                    1. Are there some red-flag symptoms or physical exam components which you could highlight?
                                    
                                    
                                    • Important to look for rash (darkening of the skin = adrenoleukodystrophy), genetic facies, evidence of trauma —-all of which are absent in this girl
                                    • To continue with our case, the patients labs were consistent with:
                                    • Initial Labs: WBC 27K, with neutrophilic predominance, Hgb and platelets were normal. Initial CMP was normal except for a glucose of 233. Gas prior to intubation in the ED was 6.9/102/85/-9. (repeat after intubation 7.19/49/40/-9). Ionized ca 4.9mg/dl. A urine analysis was unremarkable.
                                    • Head CT negative
                                    
                                    

                                    OK to summarize, we have: 24-month-old girl who presented with prolonged seizures and acute respiratory failure

                                    • All of which brings up the concern for status epilepticus the topic of our discussion today.
                                    • Let's start with a short multiple-choice question:
                                    
                                    

                                    A 14-year-old girl is brought to the PICU from the floor with new-onset status epilepticus. She was admitted to the floor on her second day after a posterior spinal fusion surgery and is still receiving intravenous fluids. Her seizure is described as generalized tonic-clonic. After initial stabilization and maintenance of her airway and hemodynamics, which of the following is most likely to reveal the cause of her seizures?

                                    • A) Serum electrolytes
                                    • B) Stat MRI brain
                                    • C) Lumbar puncture
                                    • D) cEEG
                                    
                                    

                                    Rahul, the correct answer here is A) serum electrolytes. Patients especially after posterior spinal fusion surgery are at risk for hyponatremia secondary to SIADH or even hypotonic fluids used for maintenance. Correction of hyponatremia in a child with seizures requires 3% hypertonic saline. The seizure threshold is typically a serum Na of 125meQ/L. Serum electrolytes will also reveal the serum glucose which is especially important to check in infants who have seizures. A stat MRI is not warranted in this patient especially if she is alert and awake prior to the seizure. Additionally, it would be dangerous to send an unstable patient for an MRI. As the patient is afebrile, LP is less likely to be illuminating about the cause of her seizures. LP could be needed especially if there is a strong suspicion of infection such as meningitis but can be delayed if the patient is unstable and antibiotics initiated. While a CEEG may be needed especially if the patient is intubated or comatose and there is a risk of non-clinical seizures, it is not the first-line diagnostic tool.

                                    Excellent explanation Pradip, it is of utmost importance to make sure you assess for electrolyte disturbances or glucose abnormalities in your rapid diagnostics when patients are seizing. Remember hyponatremia, hypoglycemia, and hypocalcemia. If you have a child with Seizures 

                                    • As you think about our case, what would be your differential for rhythmic jerking movements that mimic or are associated with seizures?
                                    • Movement disorders: Any abnormal involuntary movements such as Tics, tremor, chorea, athetosis, dystonia, myoclonus, ballismus, asterixis. Dyskinesia is a generalized term used for abnormal involuntary movements
                                    • Migraine (its paroxysmal nature + association with neuro-deficits or altered consciousness) may lead to confusion with seizures.
                                    • In infants paroxysmal non-epileptic disorders such as jitteriness, benign neonatal myoclonus may be confused with seizure
                                    • Myoclonus from drugs such as etomidate or post drowning due to hypoxia reperfusion injury may be mistaken for seizures
                                    
                                    

                                    Let’s transition and highlight key definitions of status epilepticus:

                                    Previously defined as a seizure lasting > than 30minutes or recurrent seizures lasting > 30minutes without patient regaining consciousness between seizures. The new definition refers to SE as 5minutes or more of either continuous seizure or 2 or more discrete seizures between which there is incomplete recovery of consciousness.

                                    Refractory SE = SE that persists despite the administration of first and second-line anti-seizure medications with different mechanisms of action.

                                    Super refractory SE refers to SE that continues 24 hours or more after the onset of anesthetic therapy for SE and includes recurrence during reduction or withdrawal of anesthetic therapy.

                                    Pradip what is the most common cause of seizures in the pediatric population?

                                    The majority of pediatric SE (30-50%) involved febrile seizures. About 9-17% involved either acute metabolic derangement or a CNS infection. 12% of first seizures in children present with status epilepticus (Shinnar, Pediatrics 1996)

                                    What is the pathophysiology of seizures and its progression to status epilepticus?

                                    There is an imbalance between excitation and inhibition. Ineffective recruitment of GABA neurons coupled with excessive excitatory NMDA neuronal stimulation leads to initiation and propagation of the electrical disturbance in SE. Prolonged seizures lead to selective neuronal loss in the hippocampus, cortex, and thalamus.

                                    There is neurotoxicity due to excitotoxicity (via excess stimulation from glutamate on NMDA and AMPA receptors) as well as hypoxic-ischemic injury (imbalance between increased metabolic demand and cerebral blood flow/oxygenation). Hypoxia, acidosis, hypotension, and hypercarbia add to the ongoing damage.

                                    There are early (< 30minutes) and late (> 30minutes) time-related complications of status epilepticus which are nicely elucidated in the LearnPICU status epilepticus-pathophysiology. (http://www.learnpicu.com/neurology/status-epilepticus)

                                    The risk of subsequent epilepsy after status epilepticus is 26-36% (Barnard, J child Neurol 1999 and Eriksson, Develop Med Child Neurol 1997).

                                    Would you also mind highlighting the way seizures are classified?

                                    Seizures are classified as Partial or generalized based on clinical presentation or EEG FINDINGS. Partial Seizures arise in specific areas of the brain and are further classified as simple, local, or focal. Generalized seizures arise from diffuse cortical areas at one time. They involve both cerebral hemispheres and consciousness is typically impaired. Generalized can present as motor movements or absence seizures during which no convulsions are seen.

                                    • If you had to work up this patient with status epilepticus what would be your diagnostic approach?
                                    • I would start with some basic labs such as glucose, serum electrolytes including magnesium and calcium. I also typically add a DIC panel and CPK for especially for prolonged seizures.
                                    • If there is concern for infection then CBC with differential, Lumbar puncture, CRP, procal, appropriate cultures (urine, blood, and CSF) should be sent. Virals studies such as HSV PCR from blood/CSF as well as a respiratory viral panel.
                                    • Another thing to look at is the drug levels of any previous anti-epileptic agents (as agent withdrawal or change can precipitate seizures).
                                    • In selected cases where inflammation is suspected- ESR, CRP, vWF antigen may be required. additionally, oligoclonal bands, testing for antibodies including neuronal and ion channel antibodies may be required from blood as well as the CSF.
                                    • Rarely evaluation for toxins, metabolic disease, ophthalmologic evaluation may be needed in selected cases.
                                    • In patients with established epilepsy- imaging is typically not necessary. Otherwise, brain imaging (either a CT or MRI) is required especially for a new status epilepsy
                                    • cEEG in the PICU is required especially if the patient is intubated or comatose as the patient could continue to have non-clinical status. The overall incidence of electrographic seizures in critically-ill patients was ~ 26%.
                                    • Yes, Rahul - I would also like to highlight a “new-age technology” with regards to EEG.
                                    • One study (Fung F. et al. Epilepsia 2020) devised a predictive model for capturing electrographic seizures in critically ill pediatric patients. The model had a sensitivity of 92% with a negative predictive value of 93%. Variables associated with increased capturing of seizures on this monitor included:
                                    • age (<1 or >1 year of age)
                                    • acute encephalopathy category
                                    • clinical seizures prior to CEEG initiation
                                    • EEG background (slow disorganized, discontinuous, or burst suppression background)
                                    • epileptiform discharges during the initial 30minutes of the recording. We should be cognizant that equipment for cEEG, as well as staffing, may not be available at all centers.
                                    
                                    

                                    To summarize, these are the common causes of seizures in the PICU — AED withdrawal or change, drug toxicity or withdrawal, electrolyte problems, hypertensive encephalopathy, tumor, TBI, vasculitis, renal/hepatic dysfunction, fever, hypoxia/ischemia, and postoperative conditions. Pre-existing epilepsy, genetic and central nervous system disorders can also present with seizures. Intensivists should be vigilant about non-convulsive status especially in children who have hypoxic injury s/p cardiac arrest, submersion injury, TBI, and stroke.

                                    • If our history, physical, and diagnostic investigation led us to status epilepticus as our diagnosis what would be your approach to general management?
                                    • In the initial phase (0-5minutes): I would focus on stabilization of the patient’s airway/breathing and hemodynamics. Establish IV/IO access and supplement patients’ oxygenation and focus on correcting any abnormal glucose or electrolytes.
                                    • Medications: Benzodiazepines (BZDs) are the first-line agents for status epilepticus.
                                    • The BZDs work by potentiating the neuro-inhibitory effects of Gamma-aminobutyric acid (GABA).
                                    • Lorazepam, diazepam and midazolam are frequently used.
                                    • Zhao ZY et al. (J Child Neurol. 2016) in a network meta-analysis of 16 RCTs including 1821 patients which compared the efficacy of midazolam, lorazepam, and diazepam in treating pediatric status epilepticus concluded that non-IV midazolam and IV lorazepam were superior to IV or non-IV diazepam, and IV lorazepam was at least as effective as non-IV midazolam.
                                    
                                    

                                    Summary: IV Ativan and IV Midazolam if your patient has good access are equally effective

                                    • Yes, All the aforementioned benzodiazepines are lipid-soluble entering the brain within 2 minutes of IV administration.
                                    • Diazepam has the highest lipid solubility and is also highly protein-bound and thus has a large volume of distribution of the unbound drug. Thus the effective duration of action for diazepam in SE is 20-30minutes resulting in rapid redistribution compared to lorazepam which has a much smaller volume of distribution of unbound drug and thus has a longer duration of action in SE. Hence lorazepam is the preferred agent in the initial management of SE.
                                    • Midazolam can be given intranasally or intramuscularly inpatient without IV access. In fact, one study (Silbergleit R et al. NEJM 2012) showed that IM midazolam was as effective and safe as IV lorazepam for prehospital seizure termination. Rectal Diazepam is an option if unable to get IV access.
                                    • How many doses of benzodiazepines would you give Rahul, and what is the pharmacokinetics to keep in mind?
                                    • More than two doses of benzodiazepines are associated with side effects without a substantial increase in efficacy. The potency of BZDs decreases 20 fold over 30 minutes of SE. Receptor trafficking of GABAa receptors resulting in movement of the receptors from the synaptic membrane into the cytoplasm where they become functionally inactive. This reduces the number of GABAa receptors available on the synaptic surface to bind BZD, and in turn, leads to a single seizure becoming self-sustaining a time-dependent resistance to BZD develops. Additionally > 2 doses increases risk of respiratory depression (43% risk compared to 13% with < 2 doses). Furthermore, only 13% of patients achieved seizure termination]]>5f455466-3a40-4bef-ac70-e71aaa76587aSun, 02 Jan 2022 03:00:00 -040030:40falsefull38383-year-Old with Cough and Leg WeaknessWelcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.

                                      I'm Pradip Kamat and I'm Rahul Damania. We are coming to you from Children's Healthcare of Atlanta - Emory University School of Medicine.

                                      Welcome to our episode, A Three-Year-Old with recent cough and leg weakness.

                                      Here's the case presented by Rahul.

                                      A 3-year-old previously healthy female presented to the hospital with a 2-week history of productive cough and congestion and the new 1-day onset of bilateral weakness. Today, the mother noticed weakness and inability to stand/walk following after shower as well as her voice becoming hoarse. She also noticed her lying more limp sitting on her lap, unable to sit up fully without her mother supporting her. She had no trouble holding up her head. The mother endorses increased fussiness but is able to be consoled. Decreased p/o intake, last meal was yesterday. About 1-2 weeks prior to this patient also had non-bloody diarrhea that resolved spontaneously after a few days.

                                      UOP normal with 2-3 wet diapers. No difficulty breathing. No history of head trauma or trauma to lower extremities, no erythema/swelling to joints. No pain associated with leg movement. No previous difficulty with walking - developing normally otherwise. No fever, recent travel, H/O sick contact at home (sibling with URI). No allergies, immunization UTD. CMP largely unremarkable. CBC with leukocytosis to 19.72 with L shift and platelets of 647. CRP 0.3, ESR 12.

                                      Afebrile, RR 24/min, HR 130, BP 140/86.

                                      On PE: Patient was coughing, had a hoarse voice heart and lung exam was normal. Normal abdominal exam. No rash

                                      Neurological exam: PERRL, (A+O) X3, 3-4/5 strength at ankles and knees and 5/5 in arms, +UE DTR's but none at patella or ankles. Has a wide-based ataxic gait and needs to hold on to the wall/furniture to ambulate.

                                      Rahul, to summarize key elements from this case, this patient has:

                                      • A cough with a hoarse voice
                                      • No fever
                                      • Inability to stand/walk (i.e. lower extremity weakness) with no DTRs in patellae or ankle
                                      • Normal mental status
                                      • Diarrhea (non-bloody) preceding neurological weakness
                                      • All of these bring up a concern for Guillain-Barré syndrome-An immune-mediated disease possibly triggered by a recent infection and targeting the peripheral nervous system.
                                      
                                      

                                      Let's transition into some history and physical exam components of this case?

                                      1. What are key history features in this 3-year-old child
                                      
                                      
                                      • Acute (B) leg weakness
                                      • Cough with hoarse
                                      • Diarrheal illness
                                      • No fever, no /o rash or trauma
                                      
                                      
                                      1. Pradip, Are there some red-flag symptoms or physical exam components which you could highlight?
                                      
                                      
                                      • Bilateral lower leg weakness with absent patellar and AJ DTRs
                                      • Normal mental status
                                      • No rash, trauma
                                      • Rahul continues with our case, the patient's initial labs and imaging were consistent with:
                                      • The CMP, CBC with differential, and blood gas were unremarkable
                                      • ESR = 12, CRP 0.29, pro-cal 0.09(all normal)
                                      • Normal CPK
                                      • Normal Urine analysis
                                      • A lumbar puncture revealed colorless CSF with 4 white cells, 0 reds, Glucose 73 (serum Glucose 90) and protein 94, Gram stain and culture-negative
                                      • MRI of the brain and lumbar spine with and without contrast was completely normal
                                      • Chest radiograph with no infiltrate or atelectasis
                                      • Nerve conduction studies were not performed
                                      
                                      

                                      Any patient with acute ascending lower extremity flaccid paralysis with CSF showing acellular protein predominance should be considered to have Guillain-Barré syndrome unless proven otherwise. MRI brain spine is necessary to rule out any other etiologies such as brain tumor or spinal pathologies. Features strongly supporting the diagnosis of Guillain-Barré syndrome include a progression of onset over several days to less than 4 weeks, symmetrical involvement, painful onset, mild/absent sensory symptoms, cranial nerve involvement, autonomic dysfunction, absence of fever, and recovery 2 to 4 weeks after the onset of peak or plateauing of symptoms.

                                      • Rahul Let's start with a short multiple-choice question:
                                      • A five-year-old girl with acute ascending bilateral lower limb weakness, normal MRI, CSF with acellular protein predominance would require immediate airway management in case the girl has
                                      • A) A chest radiograph with large atelectasis
                                      • B) A Maximum inspiratory force of -40cm H20
                                      • C) A vital capacity of > 25cc/kg
                                      • D) A strong cough
                                      • Rahul, the correct answer is A. 
                                      • Chest radiograph with large atelectasis, which suggests upper airway compromise and weakness of pharyngeal and laryngeal muscles leading to difficulty in the clearing of secretions and airway maintenance and resulting in aspiration. A maximum inspiratory force of less negative than -30cm H20 is a risk for respiratory arrest (i.e. more sub-atmospheric the better), a maximum inspiratory force of -40 is actually good (> 60% predicted). The answer C is wrong because its a vital capacity of < 20mL/kg that puts a patient at risk for respiratory failure. D) A strong cough is not an indication for intubation or suggestive of impending respiratory failure but hoarseness or a weak cough is. Remember trends are more important than a single value. In infants: inability to lift their head when supine, bulbar symptoms, tachypnea, increasing O2 requirement, and use of accessory muscles of respiration implies impending respiratory failure. Remember hypercarbia is a late finding of impending respiratory arrest.
                                      
                                      

                                      PFT measurement in GB syndrome is remembered as the 20/30/40 rule: A vital capacity < 20ml/kg, a maximum inspiratory pressure less negative than -30cm H2O, or maximum expiratory pressure of ≤ 40cm H2O. Serial measurements are required.

                                      Rahul, what is the pathogenesis of Guillain-Barré Syndrome?

                                      The exact pathogenesis is unknown. An immune trigger such as infection, vaccine, etc affects peripheral nerve components due to molecular mimicry. A gastrointestinal or upper respiratory tract illness within 4 weeks of presentation triggers the onset of Guillain-Barré Syndrome. Possible viral agents include cytomegalovirus (detected in 26%), Epstein-Barr virus, influenza, and human immunodeficiency virus, and bacterial triggers include *Mycoplasma*, *Haemophilus*, and, most commonly, *Campylobacter jejuni*, which accounts for 20% to 30% of US and European cases. Although rare, vaccination (influenza), surgery, trauma, transplant, lymphoma, and systemic lupus erythematosus have also been associated with GBS. Recently GBS after exposure to Zika virus has been described with most patients having a complete recovery.

                                      • As you think about our case, what would be your differential for Guillain-Barré syndrome and neuromuscular weakness in general?
                                      • Encephalopathy....]]>Welcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.

                                        I'm Pradip Kamat and I'm Rahul Damania. We are coming to you from Children's Healthcare of Atlanta - Emory University School of Medicine.

                                        Welcome to our episode, A Three-Year-Old with recent cough and leg weakness.

                                        Here's the case presented by Rahul.

                                        A 3-year-old previously healthy female presented to the hospital with a 2-week history of productive cough and congestion and the new 1-day onset of bilateral weakness. Today, the mother noticed weakness and inability to stand/walk following after shower as well as her voice becoming hoarse. She also noticed her lying more limp sitting on her lap, unable to sit up fully without her mother supporting her. She had no trouble holding up her head. The mother endorses increased fussiness but is able to be consoled. Decreased p/o intake, last meal was yesterday. About 1-2 weeks prior to this patient also had non-bloody diarrhea that resolved spontaneously after a few days.

                                        UOP normal with 2-3 wet diapers. No difficulty breathing. No history of head trauma or trauma to lower extremities, no erythema/swelling to joints. No pain associated with leg movement. No previous difficulty with walking - developing normally otherwise. No fever, recent travel, H/O sick contact at home (sibling with URI). No allergies, immunization UTD. CMP largely unremarkable. CBC with leukocytosis to 19.72 with L shift and platelets of 647. CRP 0.3, ESR 12.

                                        Afebrile, RR 24/min, HR 130, BP 140/86.

                                        On PE: Patient was coughing, had a hoarse voice heart and lung exam was normal. Normal abdominal exam. No rash

                                        Neurological exam: PERRL, (A+O) X3, 3-4/5 strength at ankles and knees and 5/5 in arms, +UE DTR's but none at patella or ankles. Has a wide-based ataxic gait and needs to hold on to the wall/furniture to ambulate.

                                        Rahul, to summarize key elements from this case, this patient has:

                                        • A cough with a hoarse voice
                                        • No fever
                                        • Inability to stand/walk (i.e. lower extremity weakness) with no DTRs in patellae or ankle
                                        • Normal mental status
                                        • Diarrhea (non-bloody) preceding neurological weakness
                                        • All of these bring up a concern for Guillain-Barré syndrome-An immune-mediated disease possibly triggered by a recent infection and targeting the peripheral nervous system.
                                        
                                        

                                        Let's transition into some history and physical exam components of this case?

                                        1. What are key history features in this 3-year-old child
                                        
                                        
                                        • Acute (B) leg weakness
                                        • Cough with hoarse
                                        • Diarrheal illness
                                        • No fever, no /o rash or trauma
                                        
                                        
                                        1. Pradip, Are there some red-flag symptoms or physical exam components which you could highlight?
                                        
                                        
                                        • Bilateral lower leg weakness with absent patellar and AJ DTRs
                                        • Normal mental status
                                        • No rash, trauma
                                        • Rahul continues with our case, the patient's initial labs and imaging were consistent with:
                                        • The CMP, CBC with differential, and blood gas were unremarkable
                                        • ESR = 12, CRP 0.29, pro-cal 0.09(all normal)
                                        • Normal CPK
                                        • Normal Urine analysis
                                        • A lumbar puncture revealed colorless CSF with 4 white cells, 0 reds, Glucose 73 (serum Glucose 90) and protein 94, Gram stain and culture-negative
                                        • MRI of the brain and lumbar spine with and without contrast was completely normal
                                        • Chest radiograph with no infiltrate or atelectasis
                                        • Nerve conduction studies were not performed
                                        
                                        

                                        Any patient with acute ascending lower extremity flaccid paralysis with CSF showing acellular protein predominance should be considered to have Guillain-Barré syndrome unless proven otherwise. MRI brain spine is necessary to rule out any other etiologies such as brain tumor or spinal pathologies. Features strongly supporting the diagnosis of Guillain-Barré syndrome include a progression of onset over several days to less than 4 weeks, symmetrical involvement, painful onset, mild/absent sensory symptoms, cranial nerve involvement, autonomic dysfunction, absence of fever, and recovery 2 to 4 weeks after the onset of peak or plateauing of symptoms.

                                        • Rahul Let's start with a short multiple-choice question:
                                        • A five-year-old girl with acute ascending bilateral lower limb weakness, normal MRI, CSF with acellular protein predominance would require immediate airway management in case the girl has
                                        • A) A chest radiograph with large atelectasis
                                        • B) A Maximum inspiratory force of -40cm H20
                                        • C) A vital capacity of > 25cc/kg
                                        • D) A strong cough
                                        • Rahul, the correct answer is A. 
                                        • Chest radiograph with large atelectasis, which suggests upper airway compromise and weakness of pharyngeal and laryngeal muscles leading to difficulty in the clearing of secretions and airway maintenance and resulting in aspiration. A maximum inspiratory force of less negative than -30cm H20 is a risk for respiratory arrest (i.e. more sub-atmospheric the better), a maximum inspiratory force of -40 is actually good (> 60% predicted). The answer C is wrong because its a vital capacity of < 20mL/kg that puts a patient at risk for respiratory failure. D) A strong cough is not an indication for intubation or suggestive of impending respiratory failure but hoarseness or a weak cough is. Remember trends are more important than a single value. In infants: inability to lift their head when supine, bulbar symptoms, tachypnea, increasing O2 requirement, and use of accessory muscles of respiration implies impending respiratory failure. Remember hypercarbia is a late finding of impending respiratory arrest.
                                        
                                        

                                        PFT measurement in GB syndrome is remembered as the 20/30/40 rule: A vital capacity < 20ml/kg, a maximum inspiratory pressure less negative than -30cm H2O, or maximum expiratory pressure of ≤ 40cm H2O. Serial measurements are required.

                                        Rahul, what is the pathogenesis of Guillain-Barré Syndrome?

                                        The exact pathogenesis is unknown. An immune trigger such as infection, vaccine, etc affects peripheral nerve components due to molecular mimicry. A gastrointestinal or upper respiratory tract illness within 4 weeks of presentation triggers the onset of Guillain-Barré Syndrome. Possible viral agents include cytomegalovirus (detected in 26%), Epstein-Barr virus, influenza, and human immunodeficiency virus, and bacterial triggers include *Mycoplasma*, *Haemophilus*, and, most commonly, *Campylobacter jejuni*, which accounts for 20% to 30% of US and European cases. Although rare, vaccination (influenza), surgery, trauma, transplant, lymphoma, and systemic lupus erythematosus have also been associated with GBS. Recently GBS after exposure to Zika virus has been described with most patients having a complete recovery.

                                        • As you think about our case, what would be your differential for Guillain-Barré syndrome and neuromuscular weakness in general?
                                        • Encephalopathy. Location cerebral cortex/brainstem. The patient will have altered sensorium, seizures, autonomic dysfunction, upper motor neuron findings, seizures, and movement disorder.
                                        • Cord compression or Transverse myelitis: The location of the lesion is in the spinal cord. unclear etiology, MRI reveals inflammation within the spinal cord. A sensory level is present on the back. There is bilateral, sensory, motor or autonomic spinal cord dysfunction. Bowel bladder dysfunction at presentation or that which persists should lead to questioning of the diagnosis of Guillain-Barré syndrome. Typically rectal tone is maintained in Guillain-Barré syndrome.
                                        • Acute flaccid myelitis: Lesion in anterior horn cell. Sudden onset of arm or leg weakness and loss of muscle tone and reflexes. Preceded by a viral infection such as enterovirus D68. Listeners should be vigilant for vaccine-preventable diseases that are making a come back such as poliomyelitis.
                                        • Botulism: Lesion at NMJ. Presynaptic binding of toxin prevents the release of Acetylcholine. Infants can present with constipation. Descending paralysis with early bulbar findings (weak cry, poor suck, and bilateral ptosis). Can progress to respiratory failure.
                                        • Myasthenia Gravis: Location NMJ. Autoantibodies are directed against postsynaptic AcH receptors leading to destruction. Typically ocular and bulbar muscle weakness is common. Fatigable weakness is a hallmark.
                                        • Organophosphate poisoning: Location NMJ, Inhibits Acetylcholinesterase leading to increased AcH and its action at NMJ. Muscle weakness with miosis, diarrhea, urination, lacrimation, salivation, and bronchorrhea
                                        • Tick paralysis: Location NMJ. Neurotoxin prevents the release of AcH into the NMJ. Symmetric ascending paralysis with areflexia.
                                        • Periodic paralysis. Location: muscle. Episodic muscle weakness triggered by exercise, carbohydrate-rich meal (release of insulin) a genetic mutation affecting Na, K, and Ca ion channels
                                        • Rahul: If you had to work up this patient with Guillain-Barré syndrome, what would be your diagnostic approach?
                                        • MRI brain/spine with and without contrast
                                        • LP with CSF: Typically shows elevated protein and normal cell counts (called albumino-cytological dissociation)is present in only 64% of cases with Guillain-Barré syndrome. Initially may be seen in 50% in the first three days but in 80% of patients after the first week. An elevated CSF cell count > 50 should really cast doubt on the diagnosis of Guillain-Barré syndrome.
                                        • CBC, CMP, CRP, ESR. GI PCR for campylobacter Jejuni (most common infection in the US giving rise to Guillain-Barré syndrome).
                                        • Never conduction studies (NCS): Can help diagnose in difficult cases and help differentiate between axonal and demyelinating subtypes. Nerve conduction studies peak > 2 weeks after onset of weakness. NCS in AIDP reveals features of demyelination such as reduced nerve conduction velocity, prolonged F-wave latency, and prolonged distal motor latency and conduction block. Axonal Guillain-Barré syndrome reveals decreased motor or sensory amplitudes especially with the absence of demyelination features.
                                        • Antibodies: Anti GQ1b antibodies may be detected in 90% of patients with the Miller Fisher variant of Guillain-Barré syndrome. Anti ganglioside GM1 antibodies may be seen in 50% of patients with Guillain-Barré syndrome secondary to Campylobacter jejuni infection. (relatively specific but not sensitive)
                                        
                                        

                                        Rahul, can you comment on the Guillain-Barré syndrome variants?

                                        Acute inflammatory demyelinating polyneuropathy (AIDP) is considered synonymous with Guillain-Barré syndrome and has the best prognosis. Most prevalent form in Europe and North America.

                                        AMAN (acute axonal motor neuropathy): Has no to minimal sensory symptoms and predominantly presents with progressive flaccid ascending quadriparesis complicated by respiratory failure. (slow recovery and high mortality rate). More prevalent in South East Asia

                                        ASMAN: acute motor-sensory axonal polyneuropathy. Both sensory, as well as motor fibers, are involved. It’s a form of axonal GBS and is considered a variant of AMAN.

                                        Miller Fisher Variant: The patient presents with a triad of areflexia, ataxia, and ophthalmoplegia and can progress to AIDP in some cases.

                                        Rahul can you comment on the autonomic dysfunction in Guillain-Barré syndrome

                                         1/2 patients diagnosed with **Guillain-Barré syndrome** will present with autonomic dysfunction such as diarrhea/constipation, bradycardia (15% of patients), followed by hyponatremia, SIADH. Others such as cardiomyopathy, syncope, urinary retention, BP instability syncope, reversible cardiomyopathy, and Horner syndrome are rarely seen. Cranial neuropathies (seen in 60% of patients) in form of bulbar weakness, facial palsy, ophthalmoplegia, and hypoglossal nerve palsy. Bradycardia may be difficult to treat and may require pacing. Patients can have excessive sweating and light-fixed pupils as a part of their autonomic dysfunction. A small percentage of patients can have paresthesias/numbness and pain.

                                        • If our history, physical, and diagnostic investigation led us to Guillain-Barré syndrome as our diagnosis what would be your general management of framework?
                                        • Requires a multidisciplinary collaborative effort between the intensivists, neurologists, apheresis, and the rehabilitation teams.
                                        • Patients (~25%) with risk factors for respiratory failure should be intubated early. This also helps facilitate procedures such as MRI, LP, and placement of a catheter for PLEX.
                                        • Patients with bradycardia, cardiac dysrhythmias, and hemodynamic instability can be difficult to manage. Bradycardia may require pacing. The help of the cardiologist or CICU colleagues is required.
                                        • First-line therapies include IVIG and plasmapheresis. PLEX removes neurotoxic antibodies, complement factors, and other humoral mediators of inflammation. Treatment with PLEX should be initiated in the first 2 weeks of the onset of weakness. Typically five sessions each one administered every other day are performed. IVIG improved symptoms by unknown mechanisms (inhibits Fc mediated activation of the immune cells, binding of antiganglioside antibodies to their neural targets) but may also suppress further autoantibody formation and reduces T-cell and macrophage activation of the immune system. IVIG dose is 2gm/Kg. Steroids have no role in the management of GBS. The use of eculizumab (currently in phase 2 trial) has shown promise but requires RCT.
                                        • Patients require thromboembolism prophylaxis in form of low molecular weight heparin, pain management with opioids, gabapentin, management of urinary retention, as well as constipation. Frequent turning of patients will prevent decubitus ulcers. Aggressive early physical, occupational, and speech therapies are required.
                                        
                                        

                                        Rahul, what are the Key Objectives and Takeaways?

                                        1. Guillain-Barre Syndrome is the most common cause of acute flaccid paralysis in children. Symmetric ascending paralysis, mild sensory symptoms, cranial nerve involvement, & autonomic symptoms.
                                        2. Risk Factors for acute respiratory failure in Guillain-Barre Syndrome include: Elevated CSF protein during the first week of disease, short time interval between prodrome and onset GBS symptoms, cranial involvement, and weakness that waxes and wanes.
                                        3. In the Miller Fisher variant of GBS: The patient presents with a triad of areflexia, ataxia, and ophthalmoplegia. In most cases, diplopia is the presenting symptom
                                        
                                        
                                        • References:
                                        • Malek E, Salameh J. Guillain-Barre Syndrome. Semin Neurol. 2019 Oct;39(5):589-595. doi: 10.1055/s-0039-1693005. Epub 2019 Oct 22. PMID: 31639842
                                        • van den Berg B, Walgaard C, Drenthen J, Fokke C, Jacobs BC, van Doorn PA. Guillain-Barré syndrome: pathogenesis,...]]>2d9e3166-ef28-4f14-a88c-6d435b6581e7Sun, 05 Dec 2021 03:00:00 -040028:06falsefull3737Non-invasive and Invasive Ventilation in the Pediatric BMT PopulationWelcome to PICU Doc On Call, a podcast dedicated to current and aspiring intensivists. My name is Pradip Kamat.

                                          And my name is Rahul Damania, we come to you from Children's Healthcare of Atlanta/Emory University School of Medicine. Today's episode is dedicated to Noninvasive and Invasive ventilation in children post-hematopoietic cell transplantation.

                                          We are delighted to be joined by Dr. Courtney Rowan, MD, MSCR, Associate Professor of Pediatrics, and the Director of the Pediatric Critical care Fellowship at Indiana University School of Medicine/Riley Children’s Health.

                                          Dr. Rowan's research interest is in improving the outcomes of immunocompromised children with respiratory failure. She is active in this field of research and has led and participated in multi-centered studies. She is the co-chair of the committee of the hematopoietic cell transplantation subgroup of the Pediatric acute lung injury and sepsis investigators network. In our podcast today we will be asking Dr. Rowan about the findings of her recent study published in the journal-Frontiers in Oncology reporting on the risk factors for noninvasive ventilation failure in children post hematopoietic cell transplant.

                                          She is on twitter @CmRowan.

                                          Patient Case

                                          I will turn it over to Rahul to start with our patient case...

                                          • A 15-year-old female with a history of AML s/p Allogeneic hematopoietic stem cell transplantation T+15 days presents with tachypnea and a new O2 requirement. She has been on the BMT floor for 48 hrs after being admitted for respiratory distress and fevers. Her blood cultures are negative but she is febrile intermittently. Her CXR shows nonspecific haziness, no focal opacity, and underinflation. Her weight is up 2KG in the last 48 hours. She is found to have increased work of breathing and mild desaturations to 88%. She is placed on HFNC and continued on broad-spectrum antibiotics. A respiratory viral panel and Sars-CoV-2 PCR is sent. Transfer to the Pediatric ICU is initiated.
                                          
                                          

                                          Episode Dialogue

                                          Dr. Rowan, welcome to our PICU Doc on-call podcast.

                                          Dr. Rowan: Thanks Rahul & Pradip for having me. I am delighted to be here to discuss one of my favorite topics. I have no conflicts of interest but I have funding from the NHLBI.

                                          Today we will be discussing the up-to-date evidence for NIV (HFNC and NIPPV) use in children who have had BMT. Additionally, we will also be discussing the use of invasive MV strategies including HFOV in the pediatric BMT population. To start us off, Dr. Rowan, why is the BMT cohort different from other patients admitted to the PICU?

                                          There is an increase in the # of patients undergoing BMT as indications for BMT are being expanded to different disease processes. The Etiologies for lung disease in BMT patients can be infectious (common organisms as well as opportunistic organisms). They can have lung disease from non-infectious causes and even fluid overload from renal dysfunction/medications given and there is a constant threat of alloreactivity which can manifest as GVHD or engraftment syndrome. 75% of PICU admits of immunocompromised children come from the heme-onc inpatient services. BMT patients have a higher risk to progress to ARDS. Recent reports show the incidence of ARDS in the intubated BMT population reaching upwards of 92%. These patients are also at high risk for MODS and can have a mortality rate close to 60%.

                                          💡 To summarize, the BMT population is a unique ever-growing population that represents a relatively large cohort of immunocompromised children in the PICU with a risk of high mortality. As we have set this basis, we will be focusing the rest of our episode on the need for early recognition and intervention in this special population.

                                          • Dr. Rowan: A common conundrum faced by the PICU team given limited resources and bed availability is when to transfer a patient with BMT to the PICU especially when they start requiring respiratory support on the floor. Are there any risk factors we as PICU physicians need to know which can help us transfer a child from the BMT floor to the PICU in a time-appropriate manner?
                                          
                                          

                                          Dr. Rowan: This is a great question. We have had a few studies examining this very question. In a paper we published in Pediatr Blood Cancer in 2017, we evaluated 87 allogeneic HCT recipients to investigate the association of clinical risk factors with the development of respiratory failure.

                                          Of the 87 allogeneic HCT recipients, 22 (25%) developed respiratory failure. The group with respiratory failure had a significantly higher percent weight gain increase at multiple time points.

                                          The odds ratio, (OR) for respiratory, failure increased with increasing percentage peak weight gain. We also found that the OR for respiratory failure in patients requiring more than 1 liter supplemental O2 is 25.3 (6.5, 98.7).

                                          We concluded that the percent weight gain and need for supplemental oxygen is highly associated with the development of respiratory failure in pediatric HCT recipients. Additionally, Dr. Algunik et al, have reported (PCCM 2016) that Pediatric Early Warning Score is highly correlated with the need for unplanned PICU transfer in hospitalized oncology and hematopoietic stem cell transplant patients. Additionally, the authors also reported an association between higher scores and PICU mortality. In another study, Dr. Algunik et al (Cancer 2017)reported that PEWS accurately predicted the need for unplanned PICU transfer in pediatric oncology patients in this resource-limited setting, with abnormal results beginning 24 hours before PICU admission and higher scores predicting the severity of illness at the time of PICU admission, need for PICU interventions, and mortality.

                                          Cater et al (PCCM 2018) showed that adding weight gain to PEWs (cutoff of 8) score can increase specificity as well as the AUC to predict children with BMT at risk for clinical deterioration.

                                          💡 Key points from these studies which we can clinically apply — trending of weights and attention to respiratory support and PEWS. Contingency planning and prompt recognition of when to initiate a transfer from floor to PICU is essential in intervening early.

                                          • Dr. Rowan: What are the advantages of early transfer of BMT patients to the PICU?
                                          
                                          

                                          A controlled transfer with the pediatric patient not in extremis allows for opportunities and time for in-depth multidisciplinary discussion.

                                          This also allocates time for goals of care discussions.

                                          We need to balance this with bed availability, familial stress of transitioning their stay from the floor to the PICU and introduction of a new care team being us in the PICU.

                                          Dr. Rowan: In the case above, our patient was started on non-invasive PPV and antibiotics prior to transfer to the PICU. Could you comment on the ideal interface to provide respiratory support in our patient in this case?

                                          • Little data for BMT pediatric patients for NIV compared to adults. Adult studies show that there is no difference between HFNC and standard O2 (Lemiale CCM 2017) in terms of intubation rate /mortality. Similarly, a large RCT in 776 immunocompromised adults which compared HFNC to standard O2 therapy showed no difference to 28-day mortality, LOS (ICU) stay, patient comfort or dyspnea scores (Azoulay E JAMA 2018).
                                          • As mentioned there is Limited Pediatric data on HFNC use in BMT patients however we can extrapolate that the pediatric BMT population are not merely "tiny adults" and have different respiratory mechanics as well as a physiologic reserve.
                                          • Multiple RCT of NIV vs supplemental O2 (374 organ transplant patients) (Antonelli JAMA 2015) showed no difference in intubation rates or mortality. Frat (Lancet 2016): Compared Adults on HFNC to NIV via supplemental O2 in 82 immunocompromised adults. They concluded that those on supplemental O2 had the highest risk for intubation and worst survival. A study by Squadrone V., et al in Intensive Care Med, published in 2010 Compared early 40 adults with BMT who were placed on CPAP were less likely to go to ICU, less likely to be intubated, and had better survival.
                                          • Pediatric data on NIV is limited however a study by Pancera and colleagues published in 2008 in the journal of Pediatric Heme Onc concluded that the use of BIPAP in the pediatric oncology...]]>Welcome to PICU Doc On Call, a podcast dedicated to current and aspiring intensivists. My name is Pradip Kamat.

                                            And my name is Rahul Damania, we come to you from Children's Healthcare of Atlanta/Emory University School of Medicine. Today's episode is dedicated to Noninvasive and Invasive ventilation in children post-hematopoietic cell transplantation.

                                            We are delighted to be joined by Dr. Courtney Rowan, MD, MSCR, Associate Professor of Pediatrics, and the Director of the Pediatric Critical care Fellowship at Indiana University School of Medicine/Riley Children’s Health.

                                            Dr. Rowan's research interest is in improving the outcomes of immunocompromised children with respiratory failure. She is active in this field of research and has led and participated in multi-centered studies. She is the co-chair of the committee of the hematopoietic cell transplantation subgroup of the Pediatric acute lung injury and sepsis investigators network. In our podcast today we will be asking Dr. Rowan about the findings of her recent study published in the journal-Frontiers in Oncology reporting on the risk factors for noninvasive ventilation failure in children post hematopoietic cell transplant.

                                            She is on twitter @CmRowan.

                                            Patient Case

                                            I will turn it over to Rahul to start with our patient case...

                                            • A 15-year-old female with a history of AML s/p Allogeneic hematopoietic stem cell transplantation T+15 days presents with tachypnea and a new O2 requirement. She has been on the BMT floor for 48 hrs after being admitted for respiratory distress and fevers. Her blood cultures are negative but she is febrile intermittently. Her CXR shows nonspecific haziness, no focal opacity, and underinflation. Her weight is up 2KG in the last 48 hours. She is found to have increased work of breathing and mild desaturations to 88%. She is placed on HFNC and continued on broad-spectrum antibiotics. A respiratory viral panel and Sars-CoV-2 PCR is sent. Transfer to the Pediatric ICU is initiated.
                                            
                                            

                                            Episode Dialogue

                                            Dr. Rowan, welcome to our PICU Doc on-call podcast.

                                            Dr. Rowan: Thanks Rahul & Pradip for having me. I am delighted to be here to discuss one of my favorite topics. I have no conflicts of interest but I have funding from the NHLBI.

                                            Today we will be discussing the up-to-date evidence for NIV (HFNC and NIPPV) use in children who have had BMT. Additionally, we will also be discussing the use of invasive MV strategies including HFOV in the pediatric BMT population. To start us off, Dr. Rowan, why is the BMT cohort different from other patients admitted to the PICU?

                                            There is an increase in the # of patients undergoing BMT as indications for BMT are being expanded to different disease processes. The Etiologies for lung disease in BMT patients can be infectious (common organisms as well as opportunistic organisms). They can have lung disease from non-infectious causes and even fluid overload from renal dysfunction/medications given and there is a constant threat of alloreactivity which can manifest as GVHD or engraftment syndrome. 75% of PICU admits of immunocompromised children come from the heme-onc inpatient services. BMT patients have a higher risk to progress to ARDS. Recent reports show the incidence of ARDS in the intubated BMT population reaching upwards of 92%. These patients are also at high risk for MODS and can have a mortality rate close to 60%.

                                            💡 To summarize, the BMT population is a unique ever-growing population that represents a relatively large cohort of immunocompromised children in the PICU with a risk of high mortality. As we have set this basis, we will be focusing the rest of our episode on the need for early recognition and intervention in this special population.

                                            • Dr. Rowan: A common conundrum faced by the PICU team given limited resources and bed availability is when to transfer a patient with BMT to the PICU especially when they start requiring respiratory support on the floor. Are there any risk factors we as PICU physicians need to know which can help us transfer a child from the BMT floor to the PICU in a time-appropriate manner?
                                            
                                            

                                            Dr. Rowan: This is a great question. We have had a few studies examining this very question. In a paper we published in Pediatr Blood Cancer in 2017, we evaluated 87 allogeneic HCT recipients to investigate the association of clinical risk factors with the development of respiratory failure.

                                            Of the 87 allogeneic HCT recipients, 22 (25%) developed respiratory failure. The group with respiratory failure had a significantly higher percent weight gain increase at multiple time points.

                                            The odds ratio, (OR) for respiratory, failure increased with increasing percentage peak weight gain. We also found that the OR for respiratory failure in patients requiring more than 1 liter supplemental O2 is 25.3 (6.5, 98.7).

                                            We concluded that the percent weight gain and need for supplemental oxygen is highly associated with the development of respiratory failure in pediatric HCT recipients. Additionally, Dr. Algunik et al, have reported (PCCM 2016) that Pediatric Early Warning Score is highly correlated with the need for unplanned PICU transfer in hospitalized oncology and hematopoietic stem cell transplant patients. Additionally, the authors also reported an association between higher scores and PICU mortality. In another study, Dr. Algunik et al (Cancer 2017)reported that PEWS accurately predicted the need for unplanned PICU transfer in pediatric oncology patients in this resource-limited setting, with abnormal results beginning 24 hours before PICU admission and higher scores predicting the severity of illness at the time of PICU admission, need for PICU interventions, and mortality.

                                            Cater et al (PCCM 2018) showed that adding weight gain to PEWs (cutoff of 8) score can increase specificity as well as the AUC to predict children with BMT at risk for clinical deterioration.

                                            💡 Key points from these studies which we can clinically apply — trending of weights and attention to respiratory support and PEWS. Contingency planning and prompt recognition of when to initiate a transfer from floor to PICU is essential in intervening early.

                                            • Dr. Rowan: What are the advantages of early transfer of BMT patients to the PICU?
                                            
                                            

                                            A controlled transfer with the pediatric patient not in extremis allows for opportunities and time for in-depth multidisciplinary discussion.

                                            This also allocates time for goals of care discussions.

                                            We need to balance this with bed availability, familial stress of transitioning their stay from the floor to the PICU and introduction of a new care team being us in the PICU.

                                            Dr. Rowan: In the case above, our patient was started on non-invasive PPV and antibiotics prior to transfer to the PICU. Could you comment on the ideal interface to provide respiratory support in our patient in this case?

                                            • Little data for BMT pediatric patients for NIV compared to adults. Adult studies show that there is no difference between HFNC and standard O2 (Lemiale CCM 2017) in terms of intubation rate /mortality. Similarly, a large RCT in 776 immunocompromised adults which compared HFNC to standard O2 therapy showed no difference to 28-day mortality, LOS (ICU) stay, patient comfort or dyspnea scores (Azoulay E JAMA 2018).
                                            • As mentioned there is Limited Pediatric data on HFNC use in BMT patients however we can extrapolate that the pediatric BMT population are not merely "tiny adults" and have different respiratory mechanics as well as a physiologic reserve.
                                            • Multiple RCT of NIV vs supplemental O2 (374 organ transplant patients) (Antonelli JAMA 2015) showed no difference in intubation rates or mortality. Frat (Lancet 2016): Compared Adults on HFNC to NIV via supplemental O2 in 82 immunocompromised adults. They concluded that those on supplemental O2 had the highest risk for intubation and worst survival. A study by Squadrone V., et al in Intensive Care Med, published in 2010 Compared early 40 adults with BMT who were placed on CPAP were less likely to go to ICU, less likely to be intubated, and had better survival.
                                            • Pediatric data on NIV is limited however a study by Pancera and colleagues published in 2008 in the journal of Pediatric Heme Onc concluded that the use of BIPAP in the pediatric oncology population was associated with adverse outcomes especially in patients with hemodynamic compromise.
                                            
                                            

                                            💡 Yes from both the adult and pediatric literature It seems like there is a trend towards worsened outcomes with non-invasive ventilation in a BMT patient with acute respiratory failure.

                                            • Dr. Rowan, we would love to hear more about your research interests specifically related to the pediatric BMT population. How have you addressed the challenge of limited pediatric critical care studies on the Pediatric BMT population?
                                            • As this is a growing population of interest We have created the SIRCH (Study of Intensive Care and Respiratory Support in Children Post HSCT) database to offer collaboration across institutions in efforts to optimize patient care and understand key patient trends. The search database is comprised of 12 centers across the nation. One of our unique students looked at pediatric BMT patients aged 1 month to 21 months with RF. In our population of 222 individuals, we found that patients on NIV had a higher mortality and risk of pARDS (especially at 48 hrs).
                                            • As we have commented on non-invasive PPV, let’s transition to intubation and MV. What are the risk factors for intubation in BMT patients treated with NIV?
                                            • Great question. We developed a study that looked at 153 non intubated patients who were treated with NIV: Risk factors for failure were evaluated:
                                            • RR > 40, Vasoactive use were the biggest risk for developing RF requiring intubation. matched related donor was protective. (Rowan CM, Frontiers in Oncology 2021).
                                            
                                            

                                            💡 This is a great summary point that answers the question when do these patients need to be considered for intubation:

                                            1. Tachypnea
                                            2. Vasoactive use
                                            
                                            

                                            Dr. Rowan, If a BMT patient needs intubation, what does your study using search data inform us of?

                                            • Of the 153 patients who received NIV, 63% progressed to intubation. A small subset of these patients, around 10% of the 97 who were intubated, had a cardiac arrest during intubation. And of those who arrested during intubation, only 18% survived to PICU discharge.
                                            • 24% of patients who arrested peri-intubation had a NiPPV started outside of the PICU. 8% of children who arrested upon intubation had NiPPV started in the PICU.
                                            • Our search database also -used PALICC criteria to define ARDS after these children were intubated. We found that 92% of intubated HSCT patients have ARDS in the first 3-7 days (Rowan PCCM 2017). The majority are diagnosed with PARDS on the day they are intubated.
                                            
                                            

                                            💡 This high percentage of ARDS in intubated pediatric patients with BMT is close to the incidence in adult studies.

                                            • If we take a step back, what were the characteristics of children who survived with NIPPV?
                                            • Those who were successful with NIV had better PICU survival 90%, however, hospital mortality was 41% when placed on NIV regardless of whether they were successful or failed NIPPV. My personal opinion is that we are pushing NIV too much and too long. Don't delay intubation. As we see, this may increase the risk for cardiac arrest.
                                            • If we comment on our case further, our patient on HFNC now continues to worsen and upon admission to the PICU is escalated to BIPAP and is initiated on a norepinephrine infusion for vasoplegia and shock. The PICU team decides to intubate. What would be your approach in this high-risk situation?
                                            • Intubation should be a multi-disciplinary approach. This patient in particular is high-risk not only due to her significant past medical history but also the concurrent hemodynamic instability!
                                            • Exactly. As we know, these patients are at high risk for ARDS.
                                            
                                            

                                                 Our strategy, once the patient is intubated, should be surrounding lung-protective ventilation. 

                                                          

                                            These include close attention to:

                                            • Plateau pressures
                                            • Driving pressures
                                            • Higher PEEP
                                            • and lower FiO2
                                            
                                            

                                            Our goal is to decrease ventilator-induced lung injury. (Rowan PCCM 2018).

                                            • 💡 Totally agree. And for our listeners, please refer to our prior episode on high-risk intubation to review key management principles surrounding the hemodynamically unstable patient.
                                            • This is a great overview, what specific numerical values or trends should we target in our management?
                                            • Peak inspiratory pressure (PIP) is the first value. Our studies show that PIP > 31 had an increase in mortality.
                                            • Particular attention to OI should also be a cornerstone of management. In fact, we showed a 13% increase in mortality for every 1 unit increase in OI (Rowan 2012). Patients who had an OI > 18 had upwards to 24% increase in mortality.
                                            • In line with Oxygenation limiting, FiO2 is key. In patients requiring upwards of 60% FIO2 and four times greater odds of mortality, we found that there was heterogeneity amongst centers and some centers did not use a high PEEP-low FIO2 strategy or grid. Centers that were compliant with a high-peep low FIO2 strategy had better survival.
                                            • In terms of ventilation, we need to allow for permissive hypercapnia.
                                            
                                            

                                            💡 Summary: limit peak pressures, initiate high PEEP early, and limit FiO2.

                                            Dr. Rowan: Our patient now is intubated and has an OI of 28. The patient is starting to have increased peak pressures to 35. She has saturations ~87% with high-mean airway pressures. How would you approach the management in this case?

                                            • At this time it is important to consider HFOV or APRV (Yehya PCCM 2014): If O2 gets better at 24 hrs the child will have a higher likelihood of surviving.
                                            • From our SIRCH database, 85 patients/222 received HFOV (Rowan Resp care 2018). If HFOV started after 48 hrs none of the kids survived. Lower OI at 24hrs after initiation of HFOV was correlated with increased survival. Those who didn't survive continued with higher OI past 24 hours. We showed no survival in patients who received HFOV after 1 week of conventional mechanical ventilation.
                                            
                                            

                                            Dr. Rowan, would you mind commenting on the data related to early vs. late oscillator initiation?

                                            • Using the SIRCH database, we identified children with severe pARDS.
                                            • We compared early HFOV (within the first 2 days) vs late HFOV (> 2 days start) compared to CMV. Early HFOV had better survival, whereas late HFOV only 9% survived.
                                            • Adding HFOV after a week of CMV may not offer a survival benefit.
                                            
                                            

                                             💡 The summary for our listeners here is to consider if HFOV is indicated within 48hrs from CMV to allow for peak survival.

                                            Unfortunately, the patient in the above case died during her stay in the PICU. If we reflect, were there opportunities for us to improve her outcome?

                                            This is a great question and as there are many factors that are patient-specific. Here are some general rules to consider:

                                            1. Early transfer to the PICU upon recognition of respiratory failure
                                            2. The trend of weights and optimizing diuresis in the setting of fluid overload
                                            3. A consideration to intubate early and if oxygenation continues to be poor early use of HFOV
                                            
                                            

                                            Conclusion

                                            Dr. Rowan, we appreciate your insights on today's podcasts, as we wrap up, would you mind highlighting your]]>ecdf1e98-d726-409d-9c35-97c315e62c71Sun, 21 Nov 2021 03:00:00 -040028:25falsefull3636A Teenager with Acute Psychosis in the PICUWelcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.

                                            I'm Pradip Kamat and I'm Rahul Damania and we are coming to you from Children's Healthcare of Atlanta - Emory University School of Medicine.

                                            Welcome to our episode of a 14-year-old girl with sudden acute outbursts of aggression and severe agitation.

                                            Here's the case presented by Dr. Damania:

                                            A 14-year-old previously healthy teenager with no significant past h/o presents to the PICU with a three-day h/o of aggressive behavior, agitation, and screaming. Her mother reports that her daughter has recently developed insomnia, abnormal movements and is more irritable with temper tantrums and episodic unintelligible verbal output. Parents report no recent stressors at home or at school. She has been also complaining of headaches for the past week along with things "being too loud". She denies any vertigo symptoms or tinnitus. The patient is brought to the ER due to persistent auditory/visual hallucinations followed by agitation, aggressive behavior, and catatonia. There is no h/o of recent illnesses, head trauma, fevers, rash, abdominal pain, diarrhea, or vomiting. Social history is negative for drugs of abuse in the home. Family h/o negative for seizures, and psychiatric disorders.

                                            The patient is sent to the ED and upon arrival has an unprovoked convulsive episode concerning a GTC seizure. The patient was initially admitted to the floor but transferred to the PICU for management of severe agitation, aggressive behavior, and fluctuations of blood pressure and heart rate.

                                            Initial vitals in the PICU were notable for tachycardia. The patient was found to be afebrile, normotensive for age, and SpO2 96% on RA. Her physical exam though limited by her aggressive behaviors was normal. The heart, lung, and abdominal exams are normal with no rash or bruising on her body.

                                            Initials lab work includes a negative:

                                            • U preg
                                            • Serum and Urine tox screen
                                            • CBC, CMP, and UA are all within normal limits
                                            • Inflammatory markers — including ESR CRP are unremarkable.
                                            • A head CT which was normal and an A lumbar puncture revealed colorless CSF with 8 white and 0 red cells. Serum and CSF glucose were within normal limits and protein count in CSF was negligible.
                                            • An extended multi-disciplinary work-up is initiated.
                                            
                                            

                                            To summarize key elements from this case, Rahul this teenage girl has:

                                            • Sudden outbursts of agitation, and aggression
                                            • Recent difficulty in sleeping
                                            • Irritability, and decreased verbal output
                                            • Auditory and visual hallucinations
                                            • Potential autonomic dysfunction as she has fluctuating BP and HR All of which brings up a concern for neuropsychiatric symptoms that could be organic in nature.
                                            • Let's transition into some history and physical exam components of this case?
                                            • Rahul, what are key history features in the patient presented this case.
                                            • Seizures, Agitation, and aggressive behavior which could reflect CNS dysfunction are seen in this case.
                                            • The patient additionally has concern for hallucinations which point to a primary psychiatric disturbance as well. Remember the incidence of new-onset psychosis or schizophrenia in a child <13 is increasingly rare — 1 in 40K and thus identification and thorough workup for an organic cause is increasingly important.
                                            • Rahul, are there some red-flag symptoms or physical exam components which you could highlight?
                                            • The physical examination (although limited by her behavior) in this patient is negative
                                            • I would particularly stress the need for a detailed neurological and skin exam.
                                            • For many of the differentials we will discuss, we must evaluate for rashes, changes in nails or hair, bruising or cutting marks in her arms, and even evidence of trauma to the (head and spine), and considering both an abdominal exam to r/o organomegaly as well as bi-manual pelvic exam is important to perform.
                                            • Pradip, to continue with our case, the patient’s labs were consistent with?
                                            • Rahul, actually her labs were normal. Besides the CBC, CMP being normal her presentation CRP & ESR were also normal. This was interesting as CRP and ESR are non-specific highly sensitive markers whose elevations may point to an infectious or inflammatory process.
                                            • Speaking of infection or inflammation, a lumbar puncture was done and her CSF revealed zero red cells but 8 white cells with a normal protein and glucose.
                                            
                                            
                                            1. Thyroid studies include the presence of serum thyroid (thyroid peroxidase, thyroglobulin) antibodies. All of which were negative.
                                            
                                            
                                            • As we continued to observe this patient's behavior in the PICU we expanded our CSF and serum studies. One of the panels which we sent from the CSF and serum was the auto-immune encephalopathy panel. The panel includes various Ab including:
                                            
                                            
                                            1. Glutamic Acid Decarboxylase (GAD) Ab
                                            2. Aquaporin-4 Receptor Ab,
                                            3. Gamma-Aminobutyric Acid Receptor, Type B (GABA-B-receptor) Ab, GFAP Ab,
                                            4. Voltage-Gated Potassium Channel (VGKC) Antibody, and many more.
                                            
                                            
                                            • One essential Ab that is tested in the panel, which is an important differential in our case and one that has increased in media popularity, is the N-methyl-D-Aspartate Receptor (NMDA receptor) Ab. The book Brain on Fire by Susannah Cahalan published in 2012 and the subsequent movie released in 2016 has brought this diagnosis to the public limelight.
                                            
                                            

                                            OK to summarize, we have a 14-year-old girl with acute onset of neuropsychiatric symptoms and a working diagnosis of autoimmune encephalitis — the topic of our discussion today.

                                            • Let's start with a short multiple-choice question: A patient presents with new-onset aggression, irritability, and seizures. A diagnosis of Anti-NMDA encephalitis is suspected, the subsequent test to confirm the diagnosis is:
                                            • A) MRI chest, abdomen, and pelvis
                                            • B) Serum antibodies against GLUN1 subunit of the NMDAR
                                            • C) CSF antibodies against GLUN1 subunit of the NMDAR
                                            • D) CSF antibodies against Leucine-Rich, Glioma-Inactivated Protein 1(LGI-1)
                                            • Rahul the correct Answer is C. CSF antibodies against the GLUN1 subunit of the NMDAR. Answer A (MRI chest, abdomen, and pelvis) is not required for an initial diagnosis but make be required for the detection of teratomas (58% of young females have an ovarian teratoma). ( Answer B (Serum antibodies against GLUN1 subunit of the NMDAR) is wrong because of false-negative results in 14% of cases. False-positive serum results can also be seen in patients without anti-NMDA receptor encephalitis. Answer D (CSF antibodies against Leucine-Rich, Glioma-Inactivated Protein 1(LGI-1)) are typically seen in adults with anti-LGI1 encephalitis who have faciobrachial dystonic seizures, memory loss, hyponatremia, and paroxysmal dizzy spells. In our patient antibodies against the GLUN1 subunit of the NMDAR were detected in the CSF and the serum.
                                            • As you think about our case, Pradip what would be your differential
                                            • Acute Demyelinating encephalopathies would be at the top of my differential. These would...]]>Welcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.

                                              I'm Pradip Kamat and I'm Rahul Damania and we are coming to you from Children's Healthcare of Atlanta - Emory University School of Medicine.

                                              Welcome to our episode of a 14-year-old girl with sudden acute outbursts of aggression and severe agitation.

                                              Here's the case presented by Dr. Damania:

                                              A 14-year-old previously healthy teenager with no significant past h/o presents to the PICU with a three-day h/o of aggressive behavior, agitation, and screaming. Her mother reports that her daughter has recently developed insomnia, abnormal movements and is more irritable with temper tantrums and episodic unintelligible verbal output. Parents report no recent stressors at home or at school. She has been also complaining of headaches for the past week along with things "being too loud". She denies any vertigo symptoms or tinnitus. The patient is brought to the ER due to persistent auditory/visual hallucinations followed by agitation, aggressive behavior, and catatonia. There is no h/o of recent illnesses, head trauma, fevers, rash, abdominal pain, diarrhea, or vomiting. Social history is negative for drugs of abuse in the home. Family h/o negative for seizures, and psychiatric disorders.

                                              The patient is sent to the ED and upon arrival has an unprovoked convulsive episode concerning a GTC seizure. The patient was initially admitted to the floor but transferred to the PICU for management of severe agitation, aggressive behavior, and fluctuations of blood pressure and heart rate.

                                              Initial vitals in the PICU were notable for tachycardia. The patient was found to be afebrile, normotensive for age, and SpO2 96% on RA. Her physical exam though limited by her aggressive behaviors was normal. The heart, lung, and abdominal exams are normal with no rash or bruising on her body.

                                              Initials lab work includes a negative:

                                              • U preg
                                              • Serum and Urine tox screen
                                              • CBC, CMP, and UA are all within normal limits
                                              • Inflammatory markers — including ESR CRP are unremarkable.
                                              • A head CT which was normal and an A lumbar puncture revealed colorless CSF with 8 white and 0 red cells. Serum and CSF glucose were within normal limits and protein count in CSF was negligible.
                                              • An extended multi-disciplinary work-up is initiated.
                                              
                                              

                                              To summarize key elements from this case, Rahul this teenage girl has:

                                              • Sudden outbursts of agitation, and aggression
                                              • Recent difficulty in sleeping
                                              • Irritability, and decreased verbal output
                                              • Auditory and visual hallucinations
                                              • Potential autonomic dysfunction as she has fluctuating BP and HR All of which brings up a concern for neuropsychiatric symptoms that could be organic in nature.
                                              • Let's transition into some history and physical exam components of this case?
                                              • Rahul, what are key history features in the patient presented this case.
                                              • Seizures, Agitation, and aggressive behavior which could reflect CNS dysfunction are seen in this case.
                                              • The patient additionally has concern for hallucinations which point to a primary psychiatric disturbance as well. Remember the incidence of new-onset psychosis or schizophrenia in a child <13 is increasingly rare — 1 in 40K and thus identification and thorough workup for an organic cause is increasingly important.
                                              • Rahul, are there some red-flag symptoms or physical exam components which you could highlight?
                                              • The physical examination (although limited by her behavior) in this patient is negative
                                              • I would particularly stress the need for a detailed neurological and skin exam.
                                              • For many of the differentials we will discuss, we must evaluate for rashes, changes in nails or hair, bruising or cutting marks in her arms, and even evidence of trauma to the (head and spine), and considering both an abdominal exam to r/o organomegaly as well as bi-manual pelvic exam is important to perform.
                                              • Pradip, to continue with our case, the patient’s labs were consistent with?
                                              • Rahul, actually her labs were normal. Besides the CBC, CMP being normal her presentation CRP & ESR were also normal. This was interesting as CRP and ESR are non-specific highly sensitive markers whose elevations may point to an infectious or inflammatory process.
                                              • Speaking of infection or inflammation, a lumbar puncture was done and her CSF revealed zero red cells but 8 white cells with a normal protein and glucose.
                                              
                                              
                                              1. Thyroid studies include the presence of serum thyroid (thyroid peroxidase, thyroglobulin) antibodies. All of which were negative.
                                              
                                              
                                              • As we continued to observe this patient's behavior in the PICU we expanded our CSF and serum studies. One of the panels which we sent from the CSF and serum was the auto-immune encephalopathy panel. The panel includes various Ab including:
                                              
                                              
                                              1. Glutamic Acid Decarboxylase (GAD) Ab
                                              2. Aquaporin-4 Receptor Ab,
                                              3. Gamma-Aminobutyric Acid Receptor, Type B (GABA-B-receptor) Ab, GFAP Ab,
                                              4. Voltage-Gated Potassium Channel (VGKC) Antibody, and many more.
                                              
                                              
                                              • One essential Ab that is tested in the panel, which is an important differential in our case and one that has increased in media popularity, is the N-methyl-D-Aspartate Receptor (NMDA receptor) Ab. The book Brain on Fire by Susannah Cahalan published in 2012 and the subsequent movie released in 2016 has brought this diagnosis to the public limelight.
                                              
                                              

                                              OK to summarize, we have a 14-year-old girl with acute onset of neuropsychiatric symptoms and a working diagnosis of autoimmune encephalitis — the topic of our discussion today.

                                              • Let's start with a short multiple-choice question: A patient presents with new-onset aggression, irritability, and seizures. A diagnosis of Anti-NMDA encephalitis is suspected, the subsequent test to confirm the diagnosis is:
                                              • A) MRI chest, abdomen, and pelvis
                                              • B) Serum antibodies against GLUN1 subunit of the NMDAR
                                              • C) CSF antibodies against GLUN1 subunit of the NMDAR
                                              • D) CSF antibodies against Leucine-Rich, Glioma-Inactivated Protein 1(LGI-1)
                                              • Rahul the correct Answer is C. CSF antibodies against the GLUN1 subunit of the NMDAR. Answer A (MRI chest, abdomen, and pelvis) is not required for an initial diagnosis but make be required for the detection of teratomas (58% of young females have an ovarian teratoma). ( Answer B (Serum antibodies against GLUN1 subunit of the NMDAR) is wrong because of false-negative results in 14% of cases. False-positive serum results can also be seen in patients without anti-NMDA receptor encephalitis. Answer D (CSF antibodies against Leucine-Rich, Glioma-Inactivated Protein 1(LGI-1)) are typically seen in adults with anti-LGI1 encephalitis who have faciobrachial dystonic seizures, memory loss, hyponatremia, and paroxysmal dizzy spells. In our patient antibodies against the GLUN1 subunit of the NMDAR were detected in the CSF and the serum.
                                              • As you think about our case, Pradip what would be your differential
                                              • Acute Demyelinating encephalopathies would be at the top of my differential. These would specifically be seen after an infectious trigger or vaccin
                                              • Common features on MRI would be an abnormality in gray and white matter with CSF testing suggesting Ab against myelin oligodendrocyte glycoprotein (MOG)
                                              • Another differential I would consider is the Neuromyelitis Optica spectrum. The classic Ab associated with this condition is towards the aquaporin-4. MRI abnormalities adjacent to periventricular and ependymal regions are seen in these patients.
                                              • Viral encephalitides are also going to be important to consider. Remember that encephalitis typically causes aberrations in mental status with or without meningeal signs.
                                              • To transition outside of the CNS, I would also consider Hashimotos encephalopathy (serum antithyroid Ab, absence of neuronal Ab in serum and CSF).
                                              • Autoimmune diseases like systemic lupus would be an important consideration — specifically the diagnosis of lupus cerebritis.
                                              • Other rare causes of these neuro-psychiatric disturbances include:
                                              • Bickerstaff’s brainstem encephalitis (characterized by subacute onset, in less than 4 weeks, of progressive impairment of consciousness along with ataxia and bilateral, mostly symmetrical, ophthalmoparesis). CSF pleocytosis (45%) and brain MRI is normal with brainstem abnormalities in T2- weighted FLAIR imaging is present in 23% of patients.
                                              • Limbic encephalitis (Ab against GAD, CSF oligoclonal bands)
                                              • Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) and its subset Pediatric autoimmune neuropsychiatric disorder associated with group A streptococcal infections (PANDAS)- is characterized by OCD and/or tic disorder, and a temporal relationship between symptoms and group A streptococcal (GAS) infection typically in prepubertal children. Controversy exists as to whether these conditions exist as distinct clinical entities.
                                              • 💡 Great - so for our working diagnosis in this case Anti-NMDA receptor encephalitis let’s go through the diagnostic criteria.
                                              
                                              

                                              4 of the following 6 are required for a diagnosis: 1. abnormal (psychiatric) behavior or cognitive dysfunction, 2. speech dysfunction (pressured speech, verbal reduction, mutism), 3. seizures, 4. movement disorder, dyskinesias, or rigidity/abnormal postures, 5. decreased level of consciousness, 6. autonomic dysfunction or central hypoventilation.

                                              These symptoms must be with rapid onset typically less than < 3months.

                                              Laboratory study results include abnormal electroencephalogram (EEG) showing focal or diffuse slow or disorganized activity, epileptic activity, or extreme delta brush, cerebrospinal fluid (CSF) with pleocytosis or oligoclonal bands.

                                              Rahul, If you had to work up this patient with Anti-NMDA encephalitis, what would be your diagnostic approach in the PICU?

                                              1. MRI brain and spine: In our patient case the MRI showed: hyperintense signal on T2-weighted (FLAIR) sequences highly restricted to both medial temporal lobes involving both the grey and white matter suggestive of demyelination/inflammation.
                                              2. I would also do an EGG. Her EEG showed extreme delta brush pattern (rhythmic delta activity (1–3 Hz) with superimposed beta activity riding on each delta wave)
                                              3. Serum and CSF antibodies against the GLUN1 subunit of the NMDAR as explained previously were detected in this patient.
                                              4. If Anti-NMDA Ab is detected then an MRI of the ches,t abdomen, and pelvis to detect ovarian teratoma is necessary. The frequency of an underlying tumor varies with age and sex, ranging from 0–5% in children (male and female) younger than 12 years, to 58% in women older than 18 years (usually an ovarian teratoma). Adults older than 45 years have a lower frequency of tumors (23%), and these are usually carcinomas instead of teratomas.
                                              5. It is also important to evaluate for infections like herpes simplex virus (CSF PCR), arboviral diseases which can cause infectious encephalitis. A respiratory viral panel that includes SARS COV-2 must be obtained.
                                              
                                              

                                               💡 Most patients with encephalitis undergo brain MRI at early stages of the disease. The findings could be normal or non-specific, but sometimes they might suggest an autoimmune cause. It may be necessary to repeat the MRI especially if the initial was performed early in the disease process and is normal.

                                              Additionally, a team approach with the neurologist, infectious disease, a rheumatologist is necessary prior to sending tests or obtaining imaging for optimal outcomes. The pediatric ICU fellow/attending needs to be the linchpin who updates the family on any results that are obtained from the various tests which are sent. Weekly care conferences with the family to answer the questions the family may have will help alleviate their anxiety and keep them up-to-date on their child's progress. As treatment modalities may have various responses, it is important to also focus on neuro-behavioral rehab for these patients and consider a consultation with in-patient PM&R colleagues.

                                              Rahul before we go to the management framework can you briefly inform us about the pathogenesis of anti-NMDA autoimmune encephalitis?

                                              The big picture pathophysiologic framework is simple: auto-immune attack and inflammation to neurons leading to neuro-psychiatric changes.

                                              To go into more detail:

                                              1. Antigens released from viral destruction of neurons or from tumors elicit an auto-immune reaction.
                                              2. The antigens released are transported by the dendritic cells to the regional lymph nodes, where the naive B cells become differentiated into memory B cells.
                                              3. The memory B cells enter the brain where they differentiate into antibody-producing plasma cells directed against in our case the N-methyl-D-aspartate receptor (NMDAR).
                                              4. In the case of Anti-NMDA encephalitis, there is cross-linking and internalization of the NMDAR leading to a decreased density of the NMDAR. The clinical features thus will resemble those observed with drugs like ketamine or phencyclidine, which work through non-competitive NMDAR antagonists.
                                              
                                              
                                              • If our history, physical, and diagnostic investigation led us to Anti NMDA encephalitis as our diagnosis what would be your general management of framework?
                                              • Good basic supportive care in the PICU, while maintaining patient and staff safety should be a top priority. A collaborative approach with neurologists, infectious disease, rheumatology, and neuroradiologists is necessary for an optimal outcome. The main job of the PICU team is to facilitate early diagnosis by the acquisition of MRI and other diagnostic studies. Intubation and CVL/arterial line may be required for procedure completion, and getting the blood for multiple labs draws and close follow-up labs. Neuroleptic agents such as haloperidol are best avoided in these patients but may be required in extreme agitation. Close monitoring of serum CPK and patient temperature may be required. An EKG to measure a baseline QTc. Sedation of an intubated patient may be challenging and ketamine should be avoided. Continuous EEG monitoring must be initiated if the patient is intubated.
                                              • Current therapy involves the removal of immunologic triggers such as teratoma, tumors, and immunotherapy. No large randomized trials show the efficacy of any single therapy.
                                              • In autoimmune encephalitis, most antibody production and inflammatory changes are behind the blood-brain barrier so it is not surprising that treatments that target serum immunologic triggers are rarely effective.
                                              • Patients are treated with high-dose systemic steroids (followed by a taper), intravenous immune globulin, or plasma exchange. Rituximab may be...]]>b8e03584-e06f-4370-aa0f-893443978842Sun, 14 Nov 2021 03:00:00 -040023:49falsefull3535Hemolytic Uremic SyndromeWelcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.

                                                I'm Pradip Kamatand I'm Rahul Damania. We are coming to you from Children's Healthcare of Atlanta - Emory University School of Medicine.

                                                Welcome to our Episode of a 19 month old female with bloody stool, petechiae and no urine output

                                                Here's the case presented by Rahul:

                                                A 19 month old previously healthy female was brought to the pediatric emergency department for blood in her stool. Patient was at daycare the previous day where she developed a low grade fever, congestion and URI symptoms along with non-bloody-non-bilious vomiting and diarrhea. Patient had a rapid COVID test which was negative and was sent home with instructions for oral hydration. That evening, patient began having vomiting/diarrhea which worsened. She was unable to retain anything by mouth and her parents also noted blood in her stool.

                                                Due to this, she was rushed to the Emergency Department. In the ED here, she was hypertensive for age BP of 124/103 mm Hg, febrile, and ill. Specks of blood were noted on the diarrheal stool in the diaper.

                                                On her physical exam she was noted to be pale with petechiae on neck and chest. Her abdomen was soft, ND, with some hyperactive bowel sounds, and no hepatosplenomegaly. The rest of her physical examination was normal.

                                                In the ED, initial labs were significant for WBC 19, Hgb 8.8, and Platelets 34. CMP was significant for BUN of 74mg/dL and Cr of 3.5mg/dL, Na 131 mmol/L, and K of 5.5mmol/L, Ca 8.3mg/dL (corrected for albumin of 2.2g/dL), Phosphorous 8.5 AST 413, and ALT of 227, LDH > 4000. BNP was 142 and troponin negative. She was given 1 dose of CTX 50mg/kg and a 20cc/kg NS bolus. Stool PCR was sent. She was given labetalol for her hypertension, started on maintenance IV fluids and transferred to the PICU for further management.

                                                Rahul to summarize key elements from this case, this patient has:

                                                • We have a 19-month old child with
                                                • Diarrhea and emesis X 2 days
                                                • No urine output for over 24 hours
                                                • Bloody stool
                                                • Petechiae on the neck and chest
                                                • Anemia and thrombocytopenia
                                                
                                                

                                                All of which bring up a concern for hemolytic uremic syndrome the topic of our discussion today

                                                Let's transition into some history and physical exam components of this case.

                                                What are the key historical features in this child who presents with above?

                                                • Bloody stool which alludes to an invasive diarrhea
                                                • No urine output and an ill appearing state which points to a systemic inflammatory condition and end organ dysfunction.
                                                
                                                

                                                Are there some red-flag symptoms or physical exam components which you could highlight?

                                                • Presence of petechiae which are physical exam features of thrombocytopenia
                                                • Her pallor which is a physical exam sign of anemia
                                                • Hypertension which is related to her renal dysfunction
                                                
                                                

                                                To continue with our case, the patient's labs were consistent with:

                                                • Anemia
                                                • Thrombocytopenia
                                                • Elevated BUN and creatinine
                                                • Elevated serum LDH
                                                • The patient did not have hyperkalemia, or acidosis on initial presentation
                                                
                                                

                                                OK to summarize, we have a 19 month old girl with:

                                                • Anemia, thrombocytopenia, and renal failure. This brings up the concern for Hemolytic uremic syndrome →
                                                
                                                

                                                Rahul Let's start with a short multiple choice question:

                                                A 2-year old boy is admitted to the PICU with acute respiratory failure secondary to pneumococcal pneumonia. On day # 3 of admission, the nurse reports the patient appears pale and has petechiae on his chest. The patient also has not had urine output for > 12 hours and appears to be fluid overloaded. Of the following the lab findings would be most consistent with the above clinical findings in the patient?

                                                • A) Elevation of serum haptoglobin
                                                • B) Low serum lactate dehydrogenase (LDH)
                                                • C) Negative Direct Coombs test
                                                • D) Peripheral smear showing schistocytes
                                                • The correct answer is D-Peripheral smear showing schistocytes.
                                                
                                                

                                                Patient in the above case most likely has streptococcus pneumoniae associated hemolytic uremic syndrome commonly called as pneumococcal HUS, an uncommon condition, which accounts for 5% of all cases of HUS in children. A peripheral smear will show the presence of schistocytes (which consists of fragmented, deformed, irregular red blood cells). The schistocytes represent RBCs that are partially destroyed as they traverse through the blood vessels partially occluded by microthrombi. Smear may also show giant platelets due to the rapid platelet turnover from peripheral destruction. Because HUS is an intravascular hemolysis serum haptoglobin should be low. Serum LDH along with indirect bilirubin are typically elevated. The Direct Coombs test detects antibodies that coat RBCs and may allude to this pathology. In pneumococcal HUS where there is antigen-antibody interaction on RBC cell surface, the Direct Coombs test may be positive in 90% of the cases. A direct Coombs test is highly sensitive for pneumococcal HUS, but the degree of specificity is unclear.

                                                A few points which I want to highlight classically on board exams, schistocytes look like helmet cells on blood smear. Also, presence of COOMBs positivity in the setting of hemolysis think about autoimmune hemolytic anemia (AIHA).

                                                • Rahul As you think about our case, what would be your differential?
                                                
                                                

                                                            The following may sometimes be difficult to differentiate from HUS

                                                • Bacterial sepsis (History, clinical presentation with hemodynamic compromise and feature of distributive shock, fever with elevated WBC with neutrophil predominance, multiorgan presentation, source of infection, immunocompromised host etc)
                                                • Disseminated intravascular coagulation (history of sepsis, drug, toxin eg snake venom, abnormal coagulation etc.)-In HUS the fibrinogen, PT, PTT are normal or slightly elevated and there is no active bleeding.
                                                • Acute hemolysis from any other causes (drugs, toxins, warm-antibody, cold agglutinin disease, paroxysmal nocturnal hemoglobinuria etc.) -typical history, likely older patients, PNH post-viral in children.
                                                • Hemophagocytic lymphohistiocytosis (HLH), acute macrophage activating syndrome (MAS), liver failure, TMA etc (good history, h/o JRA and other features may be helpful).
                                                • Thrombotic thrombocytopenic purpura (older patient, neurological symptoms)
                                                • The classic triad of hemolytic anemia, thrombocytopenia and renal failure is associated with hemolytic uremic syndrome can be seen on the spectrum of TTP — which adds fever and neurological symptoms to the diagnosis. In the pediatric population, TTP can be seen when children have acquired or congenital absence of ADAMS TS 13. Think of ADAMS TS 13 as a pair of scissors that cuts up vWF, an essential component of primary hemostasis. When you have a deficient or mutated ADAMS TS 13, which is a MMP, you end up having large vWF multimers which deposit in between endothelial cells which creates a consumptive thrombocytopenia and intravascular hemolysis.
                                                • Pradip, do you mind building a framework between typical HUS versus Atypical HUS?
                                                • Welcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.

                                                  I'm Pradip Kamatand I'm Rahul Damania. We are coming to you from Children's Healthcare of Atlanta - Emory University School of Medicine.

                                                  Welcome to our Episode of a 19 month old female with bloody stool, petechiae and no urine output

                                                  Here's the case presented by Rahul:

                                                  A 19 month old previously healthy female was brought to the pediatric emergency department for blood in her stool. Patient was at daycare the previous day where she developed a low grade fever, congestion and URI symptoms along with non-bloody-non-bilious vomiting and diarrhea. Patient had a rapid COVID test which was negative and was sent home with instructions for oral hydration. That evening, patient began having vomiting/diarrhea which worsened. She was unable to retain anything by mouth and her parents also noted blood in her stool.

                                                  Due to this, she was rushed to the Emergency Department. In the ED here, she was hypertensive for age BP of 124/103 mm Hg, febrile, and ill. Specks of blood were noted on the diarrheal stool in the diaper.

                                                  On her physical exam she was noted to be pale with petechiae on neck and chest. Her abdomen was soft, ND, with some hyperactive bowel sounds, and no hepatosplenomegaly. The rest of her physical examination was normal.

                                                  In the ED, initial labs were significant for WBC 19, Hgb 8.8, and Platelets 34. CMP was significant for BUN of 74mg/dL and Cr of 3.5mg/dL, Na 131 mmol/L, and K of 5.5mmol/L, Ca 8.3mg/dL (corrected for albumin of 2.2g/dL), Phosphorous 8.5 AST 413, and ALT of 227, LDH > 4000. BNP was 142 and troponin negative. She was given 1 dose of CTX 50mg/kg and a 20cc/kg NS bolus. Stool PCR was sent. She was given labetalol for her hypertension, started on maintenance IV fluids and transferred to the PICU for further management.

                                                  Rahul to summarize key elements from this case, this patient has:

                                                  • We have a 19-month old child with
                                                  • Diarrhea and emesis X 2 days
                                                  • No urine output for over 24 hours
                                                  • Bloody stool
                                                  • Petechiae on the neck and chest
                                                  • Anemia and thrombocytopenia
                                                  
                                                  

                                                  All of which bring up a concern for hemolytic uremic syndrome the topic of our discussion today

                                                  Let's transition into some history and physical exam components of this case.

                                                  What are the key historical features in this child who presents with above?

                                                  • Bloody stool which alludes to an invasive diarrhea
                                                  • No urine output and an ill appearing state which points to a systemic inflammatory condition and end organ dysfunction.
                                                  
                                                  

                                                  Are there some red-flag symptoms or physical exam components which you could highlight?

                                                  • Presence of petechiae which are physical exam features of thrombocytopenia
                                                  • Her pallor which is a physical exam sign of anemia
                                                  • Hypertension which is related to her renal dysfunction
                                                  
                                                  

                                                  To continue with our case, the patient's labs were consistent with:

                                                  • Anemia
                                                  • Thrombocytopenia
                                                  • Elevated BUN and creatinine
                                                  • Elevated serum LDH
                                                  • The patient did not have hyperkalemia, or acidosis on initial presentation
                                                  
                                                  

                                                  OK to summarize, we have a 19 month old girl with:

                                                  • Anemia, thrombocytopenia, and renal failure. This brings up the concern for Hemolytic uremic syndrome →
                                                  
                                                  

                                                  Rahul Let's start with a short multiple choice question:

                                                  A 2-year old boy is admitted to the PICU with acute respiratory failure secondary to pneumococcal pneumonia. On day # 3 of admission, the nurse reports the patient appears pale and has petechiae on his chest. The patient also has not had urine output for > 12 hours and appears to be fluid overloaded. Of the following the lab findings would be most consistent with the above clinical findings in the patient?

                                                  • A) Elevation of serum haptoglobin
                                                  • B) Low serum lactate dehydrogenase (LDH)
                                                  • C) Negative Direct Coombs test
                                                  • D) Peripheral smear showing schistocytes
                                                  • The correct answer is D-Peripheral smear showing schistocytes.
                                                  
                                                  

                                                  Patient in the above case most likely has streptococcus pneumoniae associated hemolytic uremic syndrome commonly called as pneumococcal HUS, an uncommon condition, which accounts for 5% of all cases of HUS in children. A peripheral smear will show the presence of schistocytes (which consists of fragmented, deformed, irregular red blood cells). The schistocytes represent RBCs that are partially destroyed as they traverse through the blood vessels partially occluded by microthrombi. Smear may also show giant platelets due to the rapid platelet turnover from peripheral destruction. Because HUS is an intravascular hemolysis serum haptoglobin should be low. Serum LDH along with indirect bilirubin are typically elevated. The Direct Coombs test detects antibodies that coat RBCs and may allude to this pathology. In pneumococcal HUS where there is antigen-antibody interaction on RBC cell surface, the Direct Coombs test may be positive in 90% of the cases. A direct Coombs test is highly sensitive for pneumococcal HUS, but the degree of specificity is unclear.

                                                  A few points which I want to highlight classically on board exams, schistocytes look like helmet cells on blood smear. Also, presence of COOMBs positivity in the setting of hemolysis think about autoimmune hemolytic anemia (AIHA).

                                                  • Rahul As you think about our case, what would be your differential?
                                                  
                                                  

                                                              The following may sometimes be difficult to differentiate from HUS

                                                  • Bacterial sepsis (History, clinical presentation with hemodynamic compromise and feature of distributive shock, fever with elevated WBC with neutrophil predominance, multiorgan presentation, source of infection, immunocompromised host etc)
                                                  • Disseminated intravascular coagulation (history of sepsis, drug, toxin eg snake venom, abnormal coagulation etc.)-In HUS the fibrinogen, PT, PTT are normal or slightly elevated and there is no active bleeding.
                                                  • Acute hemolysis from any other causes (drugs, toxins, warm-antibody, cold agglutinin disease, paroxysmal nocturnal hemoglobinuria etc.) -typical history, likely older patients, PNH post-viral in children.
                                                  • Hemophagocytic lymphohistiocytosis (HLH), acute macrophage activating syndrome (MAS), liver failure, TMA etc (good history, h/o JRA and other features may be helpful).
                                                  • Thrombotic thrombocytopenic purpura (older patient, neurological symptoms)
                                                  • The classic triad of hemolytic anemia, thrombocytopenia and renal failure is associated with hemolytic uremic syndrome can be seen on the spectrum of TTP — which adds fever and neurological symptoms to the diagnosis. In the pediatric population, TTP can be seen when children have acquired or congenital absence of ADAMS TS 13. Think of ADAMS TS 13 as a pair of scissors that cuts up vWF, an essential component of primary hemostasis. When you have a deficient or mutated ADAMS TS 13, which is a MMP, you end up having large vWF multimers which deposit in between endothelial cells which creates a consumptive thrombocytopenia and intravascular hemolysis.
                                                  • Pradip, do you mind building a framework between typical HUS versus Atypical HUS?
                                                  • Typical HUS is seen in patients with STEC diarrhea, or invasive pneumococcal disease, such as pneumonia. The atypical HUS is a term reserved for complement mediated HUS in which there is uncontrolled complement activation using the alternative pathway.
                                                  
                                                  

                                                  Rahul, before we go into the diagnostic and management framework can you shed some light on the pathogenesis of HUS?

                                                  The hemolytic uremic syndrome comes under an umbrella term called Thrombotic microangiopathy (TMA) syndromes. The clinical features of TMA include microangiopathic hemolytic anemia, thrombocytopenia, and organ injury. The pathological features are vascular damage that is manifested by arteriolar and capillary thrombosis with characteristic abnormalities in the endothelium and vessel wall.

                                                  Let’s breakdown the three pathogenesis or sub-diagnoses:

                                                  1. In STEC HUS (accounts for most of the HUS seen in children):
                                                  2. Enterohemorrhagic E coli expresses adhesin called intimin, allowing the Shiga Toxin to enter the bloodstream.
                                                  3. Once in the bloodstream the Shiga Toxin binds to globotriaosylceramide (Gb3, also known as CD77 or ceramide trihexoside) on endothelial cells, as well as to renal mesangial cells and epithelial cells.
                                                  4. After endocytosis, the toxin causes ribosomal inactivation leading to cell death.
                                                  5. Shiga Toxin is pro-inflammatory and pro-thrombotic and induces endothelial Von Willebrand factor resulting in thrombosis.
                                                  6. Multiple E Coli species produce the Shiga toxin but E Coli 0157:H7 is the most common in Europe and North America. S. dysenteriae Type 1 is an important cause of Shiga toxin HUS in other countries. STEC HUS is seen in younger children (3-5 years). Severe disease is seen in those with high white counts on initial presentation, female gender and younger age.
                                                  
                                                  

                                                  Pradip, what is the second subtype?

                                                  • Pneumococcal HUS (accounts for 5% of all HUS seen in children): Neuraminidase produced by the pneumococci cleaves the n-acetyl neuraminic acid from cell surface of platelets, RBC and glomerular cells and exposes the Thomsen Friedenreich (TF) crypt antigen. The TF antigen is typically hidden by the neuraminic acid. Once the TF antigen is exposed, preformed IgM antibodies bind to the TF antigen resulting in a cascade of events leading to hemolytic uremic syndrome.
                                                  
                                                  

                                                  Finally, let’s talk about atypical HUS.

                                                  Atypical HUS or complement mediated HUS accounts for approximately 10% of cases seen in children - what is the pathophysiology of this disease?

                                                  • In Atypical or complement mediated HUS the gain or loss of function mutations in complement regulatory protein results in uncontrolled activation of the alternative pathway of complement.
                                                  • Unlike the other two pathways of complement activation, the alternative pathway is constitutively active as a result of spontaneous hydrolysis of C3 to C3b.
                                                  • In the absence of normal regulation, C3b deposition on tissues may increase markedly, resulting in increased formation of the C5b-9 terminal complement complex (also called the membrane-attack complex) leading to endothelial injury and TMA.
                                                  • 30% of patients may not have any mutation in complement genes at presentation. 80% of patients present with a fulminant course (after acute URI or viral gastroenteritis). Low C3 with normal C4 indicates alternative pathway activation. Extra-renal manifestations such as seizures, hemiplegia, diplopia, blindness, coma, cardiac and lung involvement are also seen.
                                                  • Rahul: If you had to work up this patient with HUS, what would be your diagnostic approach?
                                                  • Before we get into this, lets create a mental model: 1) Show evidence of hemolysis, 2) find a source/cause and 3) determine severity of organ involvement
                                                  • Excellently said, Initial tests include CBC with differential, peripheral smear, DIC panel, Direct Coombs test.
                                                  • A comprehensive metabolic panel, serum LDH, serum haptoglobin, complement levels (C3 and C4), urinary NGAL.
                                                  • Blood culture, stool PCR/culture, respiratory culture from ETT
                                                  • Imaging and other diagnostics include: Chest radiograph, echocardiography, and renal ultrasound. Daily weights are highly recommended for the patient.
                                                  • Disease severity can be gauged by acidosis, hyperkalemia, LDH level and platelet count. Recovery of platelet count followed by decrease in LDH suggests improvement of hemolysis. Persistent hyperkalemia/acidosis suggests an urgent need for dialysis along with decreased UOP, fluid overload and weight gain.
                                                  • Other labs that may be needed on a case by case basis include ADAMTS-13 (needed for diagnosis of TTP) or complement 3 glomerulopathy (C3G) functional panel (Includes Complement Antibody Panel, Complement Biomarker Panel, Complement Pathway Panel). This will require great coordination between the nephrology, hematology, and ICU team.
                                                  • Pradip, If our history, physical, and diagnostic investigation led us to HUS as our diagnosis what would be your general management of the framework?
                                                  • After careful attention to airway, breathing circulation and good basic PICU care, supportive therapy is the cornerstone of the treatment of HUS patients admitted to the PICU.
                                                  • Let’s organize our management model into key PICU management components: fluid and electrolyte management, blood pressure control, transfusion thresholds, plasma exchange and antimicrobial
                                                  • Fluid, Electrolytes and Nutrition:
                                                  • Early volume expansion especially prior to development of acute kidney injury has been shown to have also proven to lessen the need for renal replacement therapy (RRT) as well as reduce central nervous system-associated complications.
                                                  • Once AKI develops, the intensivist will have to work with the nephrologist to provide dialysis. Typically at our institution this is done using CVVH although peritoneal dialysis can also be used.
                                                  • CVVH will help reduce volume overload, correct electrolytes, acidosis and allow provision of nutrition. We typically use citrate regional anticoagulation.
                                                  • Blood pressure control:
                                                  • Hypertension is common in HUS.
                                                  • Early use of titratable IV nicardipine especially for severe hypertension followed by transition to PO meds is recommended.
                                                  • Blood and platelet transfusion:
                                                  • Transfusion of pRBCs should be considered only in symptomatic children whose hemoglobin is < 7gm/dL.
                                                  • Platelet transfusion must be restricted to active bleeding or invasive surgical procedures.
                                                  • Transfusion of fresh frozen plasma also should be avoided unless there is active bleeding.
                                                  • You're absolutely correct, FFP which contains clotting factors & complement mediators may actually fuel your inflammatory cascade. A discussion with blood bank/hematology may be required to see if there is a role for "dextran washed RBCs" which removes more than 95% of plasma from donor pRBCs.
                                                  • Rahul, is there a role for plasma exchange in these patients?
                                                  • Plasma exchange:
                                                  • No role for...]]>4575eeda-ef00-4b02-a7a6-55ee1f0aaf73Sun, 31 Oct 2021 03:00:00 -040025:52falsefull3434Oxygen Content and Oxygen DeliveryWelcome to PICU Doc On Call, a podcast dedicated to current and aspiring intensivists. My name is Pradip Kamat

                                                    My name is Rahul Damania, a current 2nd year pediatric critical care fellow. We come to you from Emory University,School of Medicine, Children’s Healthcare of Atlanta, Atlanta, GA.

                                                    Today's episode is dedicated to O2 delivery in the PICU. We would like to highlight in this episode Stanford University School of Medicine Pediatric Critical Care's LearnPICU website. The LearnPICU.com website Is dedicated to reviewing clinical topics related to pediatric critical care, and is an open access resources which Is widely accessed worldwide. The website has over 10,000 visits each month, and is managed by Dr. Kevin Kuo - Clinical associate professor of pediatrics pediatric critical care at Stanford University. Dr. Kuo has Been featured on our prior episode entitled seven habits of highly effective Picu fellows, and we are very excited to collaborate with his educational resources to provide you the listener a comprehensive educational experience.

                                                    Rahul, let's go ahead and get into today's case.

                                                    A 17-year old boy is admitted after he was struck by a car at slow speed while crossing the street.

                                                    He is has SPO2 of 98%, HR 98 bpm with a normal capillary refill and perfusion.

                                                    His blood gas at admission to the PICU reveals a ph of 7.3/PCO2 35/PaO2 196 mm Hg on 50% NRB with 100% O2 flowing at 12LPM.

                                                    His admission hgb is 10.5 gm%.

                                                    4 hours post admission, the nurses noticed that the patient is tachycardic to 150s, with a drop in his BP, delayed capillary refill, with cool extremities and increased output from the chest tube.

                                                    His SpO2 has decreased to 86% and PaO2 on his blood gas is now 65mm HG. He is found to have a POC Hgb of 6.8 mg/dL.

                                                    Let’s take this case and highlight key components of O2 delivery and O2 consumption.

                                                    Lets focus on O2 delivery first. Rahul What are the components of O2 delivery ?

                                                     Pradip, O2 delivery is made of O2 content X Cardiac output

                                                    Simply put, O2 content is the amount of blood present in 100ml of arterial or venous blood. Its is denoted by CaO2 or CvO2 and its unit is mL O2 / dL blood or mL O2 per 100 mL of blood.

                                                    Before we introduce the complicated formula, let's just appreciate the variables within the equation.

                                                    Oxygen content is going to be a function of three variables:

                                                    This is going to be Hgb, Saturations on the hemoglobin also known as SaO2, and the amount of oxygen that is dissolved within the blood also known as your PaO2.

                                                    Pradip, Can you elucidate further about O2 content?

                                                    O2 content is given by the formula: CaO2 = (1.34X Hgb gm/dl X SaO2) + (0.003X PaO2)

                                                    Important points to remember about above formula is that the constant 1.34 (or 1.36 as given by some textbooks) is the amount of O2 in mL bound by one gm of Hgb and is called as the O2 carrying capacity of Hgb. In a healthy person say with 15gm% of Hgb, the O2 carrying capacity is about 15X1.34 = 20gm%.

                                                    Now many times amount of O2 bound to Hgb may not always reflect 100% saturation So we need to factor the % oxygen saturation into the oxygen carrying capacity of the Hgb.

                                                    The final element is to understand that some oxygen is dissolved in the plasma and is calculated using a constant 0.003 X PaO2. Typically 100ml of arterial blood with a saturation of 100 will contain 100 X 0.003 = 0.30ml of dissolved oxygen.

                                                    Rahul can you calculate the pre-decompensation oxygen content in the above case?

                                                    The above patients hgb pre-decompensation = 10.5gm%. His room air saturation 98% and his PaO2 is 196.

                                                    CaO2 = (1.34X10.5X0.98) + 0.003 X 196 = 13.7 + 0.58 = 14.2ml O2/dL blood.

                                                    Great - what is the post decompensation CaO2.?

                                                    The post decompensation CaO2 can be estimated using same formula as above: CaO2 = (1.34 X 6.8 X0.86) + (0.003 X 65) = 7.8 + 0.195 = 7.9 O2/dL blood.

                                                    Exactly So if you see the pre and post bleed O2 content just with a drop in Hgb from 10.5 to 7.5gm/dL: There is almost a 38% decrease in patients O2 content (8.83/14.2 = 62%,)

                                                    What is the best strategy to increase the patients O2 content?

                                                    First we can increase the patients FiO2 from 50% to 100% (immediate bedside action). We can get consent from family to order blood for transfusion.

                                                    Increasing FiO2 will result in an CaO2 = (1.34 X 6.8 X1 ) + (0.003 X 65) = 7.8 + 0.195 of about 9. O2/dL blood.

                                                    If we transfuse to a hgb of 10gm% with no increase in FiO2: we will get an CaO2 of (1.34X10X0.86) + (0.003 X 65) = 11.52 + 0.195 = 11.71 ml O2/dL.

                                                    The summary of this is to understand that modulating the patients hemoglobin via transfusion gives greatest bang for your buck in terms of optimizing O2 content

                                                    Exactly. Now, there is some value of increasing PaO2 in patients with acute severe hgb (say a Hgb of < 3gm/dL). Placing a child on 100% FIO2 NRB or placing child in hyperbaric chamber (diving & increasing PaO2) can increase CaO2 significantly. This is rarely used however may be indicated in patients who present with severe anemia with difficulty finding blood for transfusion due to antibody development etc.

                                                    Except for acute severe symptomatic anemia,Hgb should not be the sole criteria to transfuse to improve O2 content. In fact recent studies report that liberal policy of transfusion may be associated with increased mortality compared to a more restricted (transfused only if Hgb < 7gm/dL). So you want to assess the clinical picture fully and identify, intervene, and reassess.

                                                    Rahul, can you create a mental model related to O2 content in the blood for our listeners?

                                                    Absolutely, I would like to create 2 mental models:

                                                    As we reviewed, the variables in the oxygen content equation are:

                                                    1. Hgb
                                                    2. SaO2
                                                    3. PaO2
                                                    4. So how do we measure these clinically?
                                                    5. Well, in order to get the Hgb you order a CBC
                                                    6. In order to get your SaO2 you would place the patient on a pulse oximeter
                                                    7. In order to obtain your PaO2 to you or draw an ABG
                                                    
                                                    

                                                    Thus, your total oxygen content can be thought of as CBC, pulse ox, an ABG.

                                                    This is great - What’s another way to think about CaO2?

                                                    You can think about CAO2 by visualizing a car.

                                                    Many of us have heard that hemoglobin is the car which carries oxygen throughout our body. So the car and its frame represents hemoglobin. The wheels on the car represents the saturations. Four wheels on a car, for binding sites on hemoglobin. And finally thinking about a car needing to travel on a fluid road, helps you remember that PaO2 is the dissolved O2 in the plasma.

                                                    Pradip, we also talked about Venous oxygen content. How is that calculated?

                                                    CvO2 is similar to CaO2 and it is calculated using the formula: 1.34XHgbXSvO2 + 0.003 X PvO2

                                                    Typically, mixed venous O2 sat is used instead of SaO2 and PVO2 is used instead of PaO2. The blood gas is typically obtained from a central venous line with tip at SVC-RA...]]>Welcome to PICU Doc On Call, a podcast dedicated to current and aspiring intensivists. My name is Pradip Kamat

                                                    My name is Rahul Damania, a current 2nd year pediatric critical care fellow. We come to you from Emory University,School of Medicine, Children’s Healthcare of Atlanta, Atlanta, GA.

                                                    Today's episode is dedicated to O2 delivery in the PICU. We would like to highlight in this episode Stanford University School of Medicine Pediatric Critical Care's LearnPICU website. The LearnPICU.com website Is dedicated to reviewing clinical topics related to pediatric critical care, and is an open access resources which Is widely accessed worldwide. The website has over 10,000 visits each month, and is managed by Dr. Kevin Kuo - Clinical associate professor of pediatrics pediatric critical care at Stanford University. Dr. Kuo has Been featured on our prior episode entitled seven habits of highly effective Picu fellows, and we are very excited to collaborate with his educational resources to provide you the listener a comprehensive educational experience.

                                                    Rahul, let's go ahead and get into today's case.

                                                    A 17-year old boy is admitted after he was struck by a car at slow speed while crossing the street.

                                                    He is has SPO2 of 98%, HR 98 bpm with a normal capillary refill and perfusion.

                                                    His blood gas at admission to the PICU reveals a ph of 7.3/PCO2 35/PaO2 196 mm Hg on 50% NRB with 100% O2 flowing at 12LPM.

                                                    His admission hgb is 10.5 gm%.

                                                    4 hours post admission, the nurses noticed that the patient is tachycardic to 150s, with a drop in his BP, delayed capillary refill, with cool extremities and increased output from the chest tube.

                                                    His SpO2 has decreased to 86% and PaO2 on his blood gas is now 65mm HG. He is found to have a POC Hgb of 6.8 mg/dL.

                                                    Let’s take this case and highlight key components of O2 delivery and O2 consumption.

                                                    Lets focus on O2 delivery first. Rahul What are the components of O2 delivery ?

                                                     Pradip, O2 delivery is made of O2 content X Cardiac output

                                                    Simply put, O2 content is the amount of blood present in 100ml of arterial or venous blood. Its is denoted by CaO2 or CvO2 and its unit is mL O2 / dL blood or mL O2 per 100 mL of blood.

                                                    Before we introduce the complicated formula, let's just appreciate the variables within the equation.

                                                    Oxygen content is going to be a function of three variables:

                                                    This is going to be Hgb, Saturations on the hemoglobin also known as SaO2, and the amount of oxygen that is dissolved within the blood also known as your PaO2.

                                                    Pradip, Can you elucidate further about O2 content?

                                                    O2 content is given by the formula: CaO2 = (1.34X Hgb gm/dl X SaO2) + (0.003X PaO2)

                                                    Important points to remember about above formula is that the constant 1.34 (or 1.36 as given by some textbooks) is the amount of O2 in mL bound by one gm of Hgb and is called as the O2 carrying capacity of Hgb. In a healthy person say with 15gm% of Hgb, the O2 carrying capacity is about 15X1.34 = 20gm%.

                                                    Now many times amount of O2 bound to Hgb may not always reflect 100% saturation So we need to factor the % oxygen saturation into the oxygen carrying capacity of the Hgb.

                                                    The final element is to understand that some oxygen is dissolved in the plasma and is calculated using a constant 0.003 X PaO2. Typically 100ml of arterial blood with a saturation of 100 will contain 100 X 0.003 = 0.30ml of dissolved oxygen.

                                                    Rahul can you calculate the pre-decompensation oxygen content in the above case?

                                                    The above patients hgb pre-decompensation = 10.5gm%. His room air saturation 98% and his PaO2 is 196.

                                                    CaO2 = (1.34X10.5X0.98) + 0.003 X 196 = 13.7 + 0.58 = 14.2ml O2/dL blood.

                                                    Great - what is the post decompensation CaO2.?

                                                    The post decompensation CaO2 can be estimated using same formula as above: CaO2 = (1.34 X 6.8 X0.86) + (0.003 X 65) = 7.8 + 0.195 = 7.9 O2/dL blood.

                                                    Exactly So if you see the pre and post bleed O2 content just with a drop in Hgb from 10.5 to 7.5gm/dL: There is almost a 38% decrease in patients O2 content (8.83/14.2 = 62%,)

                                                    What is the best strategy to increase the patients O2 content?

                                                    First we can increase the patients FiO2 from 50% to 100% (immediate bedside action). We can get consent from family to order blood for transfusion.

                                                    Increasing FiO2 will result in an CaO2 = (1.34 X 6.8 X1 ) + (0.003 X 65) = 7.8 + 0.195 of about 9. O2/dL blood.

                                                    If we transfuse to a hgb of 10gm% with no increase in FiO2: we will get an CaO2 of (1.34X10X0.86) + (0.003 X 65) = 11.52 + 0.195 = 11.71 ml O2/dL.

                                                    The summary of this is to understand that modulating the patients hemoglobin via transfusion gives greatest bang for your buck in terms of optimizing O2 content

                                                    Exactly. Now, there is some value of increasing PaO2 in patients with acute severe hgb (say a Hgb of < 3gm/dL). Placing a child on 100% FIO2 NRB or placing child in hyperbaric chamber (diving & increasing PaO2) can increase CaO2 significantly. This is rarely used however may be indicated in patients who present with severe anemia with difficulty finding blood for transfusion due to antibody development etc.

                                                    Except for acute severe symptomatic anemia,Hgb should not be the sole criteria to transfuse to improve O2 content. In fact recent studies report that liberal policy of transfusion may be associated with increased mortality compared to a more restricted (transfused only if Hgb < 7gm/dL). So you want to assess the clinical picture fully and identify, intervene, and reassess.

                                                    Rahul, can you create a mental model related to O2 content in the blood for our listeners?

                                                    Absolutely, I would like to create 2 mental models:

                                                    As we reviewed, the variables in the oxygen content equation are:

                                                    1. Hgb
                                                    2. SaO2
                                                    3. PaO2
                                                    4. So how do we measure these clinically?
                                                    5. Well, in order to get the Hgb you order a CBC
                                                    6. In order to get your SaO2 you would place the patient on a pulse oximeter
                                                    7. In order to obtain your PaO2 to you or draw an ABG
                                                    
                                                    

                                                    Thus, your total oxygen content can be thought of as CBC, pulse ox, an ABG.

                                                    This is great - What’s another way to think about CaO2?

                                                    You can think about CAO2 by visualizing a car.

                                                    Many of us have heard that hemoglobin is the car which carries oxygen throughout our body. So the car and its frame represents hemoglobin. The wheels on the car represents the saturations. Four wheels on a car, for binding sites on hemoglobin. And finally thinking about a car needing to travel on a fluid road, helps you remember that PaO2 is the dissolved O2 in the plasma.

                                                    Pradip, we also talked about Venous oxygen content. How is that calculated?

                                                    CvO2 is similar to CaO2 and it is calculated using the formula: 1.34XHgbXSvO2 + 0.003 X PvO2

                                                    Typically, mixed venous O2 sat is used instead of SaO2 and PVO2 is used instead of PaO2. The blood gas is typically obtained from a central venous line with tip at SVC-RA junction.

                                                    Now thtat we have defined CaO2 and CvO2 lets talk about the other component of O2 delivery and that is CO. remember DO2 = CaO2 x CO.

                                                    Exactly, going into our Car analogy:

                                                    Hgb representing the frame SaO2 being the wheels on a car and PaO2 being the fluid road which the car travels on,

                                                    Remember that a car cannot run without a motor. SO what is that motor? It is CO.

                                                    So just to summarize DO2 = CaO2 x CO.

                                                    So Rahul, what is the AVO2 difference?

                                                    It is The difference between CaO2 and CvO2 can be used as a measure of the adequacy of O2 delivery. Typically in a normal patient the CaO2 is about 20.5 mL O2/dL and the CVO2 is about 14.5mL O2/dL giving us an AVDO2 of 5mL O2/dL. The normal range is 4-6mL O2/dL.

                                                    A decrease in DO2 will lead to higher O2 extraction and therefore a higher AV O2 difference. A lower AV O2 difference is seen when there is decreased O2 extraction such as in cyanide toxicity or sepsis.

                                                    Rahul, lets shift gears to the next heading of our talk O2 consumption or VO2 - can you introduce this to us?

                                                    VO2 is the amount of oxygen consumed by the tissues per minute. Certain condition can result in low VO2 such as hypothermia in the absence of shivering sedation/paralysis, coma, brain death, cyanide poisoning etc. Increased VO2 is seen with fever, pain, shivering, increased work of breathing, positive inotropes etc. VO2 (mL/min) is given by (CaO2-CvO2) X cardiac output, which uses the reversed Fick equation. VO2 = CI X AVDO2. IN ARDS or sepsis, VO2 may continue to increase even as DO2 increases above normal values. VO2 remains supply dependent to much higher levels of DO2 leading to pathologic supply dependency. The exact reason for this pathologic supply dependency is unknown.

                                                    Pradip, help us understand O2 Extraction a bit more?

                                                    It is important to understand that the DO2 in humans is around 620+/- 50mL/min per square meter. The O2 consumption in humans is typically in the range of 120-200mL/min per square meter. The body normally extracts only about 25% of the oxygen delivered to the tissues overall. O2 extraction (ERO2) is given by DO2/VO2 = 25%. OR AVDO2/CaO2. O2 extraction can vary by organ-the heart, brain extract a lot of oxygen but the kidneys, liver utilize little oxygen.

                                                    Global impairment in oxygen delivery can thus be determined by monitoring central venous oxygen saturation (measured at SVC-RA junction with a central venous line) or mixed venous oxygen saturation (measured with a Swan Ganz catheter at the pulmonary artery).

                                                    Normal ScvO2 = 70-75% reflecting an O2 extraction of 25%

                                                    It is important to note that in humans: O2 consumption or VO2 is independent of O2 delivery or DO2.

                                                    As the oxygen delivery decreases (or as oxygen demand increases), the body responds by extracting more oxygen and hence, the mixed venous saturation (ScvO2) or its oxygen saturation of blood at the SVC-RA junction gradually decreases to reflect this increasing oxygen extraction. However, the body can only extract so much oxygen and eventually, a critical extraction threshold (critical point of oxygen delivery) is met and cellular metabolism becomes anaerobic with the subsequent production of lactate. I would advise listeners to visit learnpicu.com to see an important graph drafting the relationship between DO2 and VO2.

                                                    An important component of oxygen delivery is Cardiac output: Rahul can you tell us the components of cardiac output?

                                                    Rahul: CO (liters per minute) = HR(beat per minute) X SV(mL). Cardiac output is typically indexed to BSA. CI is given as CO/BSA

                                                    Listeners need to remember that newborns and children with heart disease cannot increase stroke volume and are therefore heart rate dependent to increase cardiac output. Any rate or conduction anomalies can affect heart rate as in myocarditis, arrhythmias or poisoning.

                                                    SV is amount of blood pumped at each contraction and is dependent on preload, pump function and afterload.

                                                    Preload is the stretch of the cardiac myocytes just prior to contraction. Left ventricular end-diastolic volume, which is the volume of blood in the (L) ventricle just prior to contraction is the best surrogate marker of systemic preload. Preload is decreased in hypovolemia, hemorrhagic shock and cardiac tamponade.

                                                    Stroke volume is also determined by cardiac contractility which is defined as the extent of shortening that occurs in cardiac myocytes when stimulated independent of preload or afterload. It a function of cardiac muscle performance. Echocardiographic measures of shortening fraction and ejection fraction are typically used as estimates of contractility. Listeners need to remember that multiple factors affect contractility such as catecholamines as well as optimization of the so called cardiac lytes:- calcium, magnesium and potassium. contractility is decreased in cardiogenic shock, drugs/toxins or cardiomyopathy.

                                                    Afterload: is defined as the force opposing the contraction of the left ventricular myocytes during systole. Increased or decreased SVR can affect afterload in shock states

                                                    In the next section Lets us discuss the assessment of O2 delivery & consumption clinically at the bedside where it matters.:

                                                    How can you assess oxygen delivery and consumption at the bedside?

                                                    A physical exam we can assess peripheral perfusion, heart rate, blood pressure, urine output, and mental status.

                                                    Serial arterial blood gases, measures of serum lactate, SmVO2 (if available as SmvO2 requires pulmonary artery catheter), ScvO2, measure of Hgb, SaO2 can be obtained. A rise in lactate with falling ScVO2 or SmvO2 suggest anaerobic metabolism. A rising base deficit, persistent acidosis, decreasing pH may suggest declining DO2 in the right circumstances.

                                                    Blood lactate can be used as an indirect measure of perfusion. A temporal trend is more valuable than a single number. Rate of production and clearance is affected by liver metabolism.

                                                    Rahul, any serum biomarkers for assessment of cardiac function ?

                                                    Paige: B-type Brain natriuretic peptide (BNP):, troponin (specific to myocardium) Troponin increase is seen in myocarditis, pericarditis, coronary injury or occlusion, and sepsis. BNP is released in response to ventricular wall stress due to volume or pressure overload. High levels of circulating BNP have been correlated with congestive heart failure states—a trend over time is likely the most helpful for the clinician

                                                    Pradip, what can you tell us about Near-infrared spectroscopy?

                                                    NIRS helps assess the systemic and regional O2 transport. NIRS is commonly used, particularly in patients with CHD, as a means of trending regional DO2 or as a surrogate for mixed venous O2 saturation or systemic DO2. Frequently used on patients undergoing VA ECMO. Rahul, how can we improve oxygen delivery?

                                                    We can give patient a blood transfusion (although not ideal unless hgb < 7gm%) increase FIO2 to increase SAO2. We can decrease VO2 by reducing fever/catabolic states, treating infection, treating agitation with sedation/paralysis, cooling (while avoiding shivering), inducing coma etc. We can also decrease VO2 by early intubation if necessary in a patient with severe respiratory distress. Avoiding vasopressors can also decrease myocardial oxygen requirement and O2 consumption.

                                                    Pradip How can we tackle O2 consumption?

                                                    Let’s break this down in a systems based manner:

                                                    1. Resp:
                                                    2. Reduce respiratory distress by supporting using Ni or Inv MV
                                                    3. Reduce arrythmia as this can increase VO2 but also derail CO and thus DO2
                                                    4. Reduce pain agitation fever seizure or shivering. At times you may not have a great clinical assessment of subclinincal status so consider placing eeg on patient or intiating...]]>f6775402-d85e-49e0-90b0-54233c4be777Sun, 24 Oct 2021 03:00:00 -040030:07falsefull3333Pulmonary Hypertension CrisesAcute pulmonary Hypertensive Crises.

                                                       Welcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.

                                                       I'm Pradip Kamat and I'm Rahul Damania. We are coming to you from Children's Healthcare of Atlanta - Emory University School of Medicine.

                                                       Welcome to our Episode a 7 month old boy ex-26 week premature infant with acute hypoxemia, bradycardia episodes, poor perfusion

                                                       Here's the case:

                                                       A 7 month old ex-26 week male was transferred from the outside hospital to our PICU for tracheostomy evaluation. Patient was intubated on second day of life. He had a prolonged course, on inhaled Nitric Oxide for first 2-3 months of life in the setting of severe pulmonary hypertension, requiring HFOV for a prolonged period of time. Failed extubation attempts multiple times. Received steroid burst x2. BPD settings trialed (lower rate, longer iTime, high PEEP, larger TV) without improvement. At time of transfer he was in PRVC mode on the ventilator — TV ~10ml/kg, 50%, PEEP 8, rate 28 (Peak pressures 27-32). Patient received albuterol Q4 for bronchospasm/wheezing and pulmicort BID. Patient was deeply sedated with morphine and midazolam. Interstitial lung disease panel was negative. ECHO showed: systolic septal flattening, moderate RV hypertrophy with normal systolic functioning. Patient was not on any PH medications at transfer. Patient is also on furosemide, hydrochlorothiazide and spironolactone.

                                                       Patient has completed a course of antibiotics for klebsiella tracheitis from a ETT CX a week prior to admission to our picu. Patient tolerated feeds via an NJ tube.

                                                       The team continues to evaluate his case as the Patient continues to have episodes of acute desaturation, tachycardia, cool extremities and poor perfusion.

                                                       To summarize key elements from this case, we have a 7month old who is ex-26 week premie

                                                       • Patient has BPD and is on high vent settings and failing extubation
                                                       • Abnormal echocardiogram with flat septum and hypertrophied Right ventricle
                                                       • Episodes of cold shock-tachycardia, poor perfusion, and cool extremities
                                                       • Hypoxia
                                                       
                                                       

                                                       All of which bring up a concern for acute pulmonary hypertensive crisis

                                                       Rahul Let's transition into some history and physical exam components of this case?

                                                       What are key history features in this infants who presents with an acute pulmonary hypertensive crisis

                                                       • Prematurity
                                                       • BPD
                                                       
                                                       

                                                       Remember BPD is defined by a requirement of oxygen supplementation either at 28 days postnatal age or 36 weeks postmenstrual age.

                                                       Are there some red-flag symptoms or physical exam components which you could highlight?

                                                       • Presence of cold shock: tachycardia, cool extremities and poor perfusion
                                                       • Hypoxia
                                                       • Cardiac exam will reveal a bounding right ventricle, prominent loud single S2
                                                       • Although not obvious in this patient: some patients can have a palpable liver, cardiac gallop, peripheral edema and jugular venous distention
                                                       
                                                       

                                                       S2 heart sound represents the closure of the PV very close to AV — In pulmonary hypertension this PE sign is seen with equal right and left ventricular pressures.

                                                       To continue with our case, the patient's labs were consistent with:

                                                       • Respiratory acidosis (PCO2 > 100)
                                                       • CMP, CBC are normal
                                                       • BNP < 100, serum lactate normal
                                                       
                                                       

                                                       Echocardiography findings in these patients can show tricuspid regurgitation. We can estimate right ventricular systolic pressure on echo and, by extension, systolic PAP (sPAP), by using tricuspid regurgitant (TR) jet velocity in combination with other echocardiographic findings. Using the modified bernoulli principle 4 x TR jet velocity squared, we can estimate the sPAP. If sPAP >2/3 systemic sBP with severe flattening or posterior bowing of the interventricular septum the patient can be diagnosed with severe pHTN.

                                                       Pradip, what if the patient had a PDA on echo — what would you see?

                                                       Rahul, when you see Predominantly right-to-left shunting across the PDA suggests suprasystemic sPAP. And as a result these patients can be hypoxemic

                                                       Ok, to summarize, we have:

                                                       • A 7-month ex-26 week premie infant old with shock with signs of poor perfusion +bounding right ventricle and loud single second heart sound, which brings us to the concern for acute pulmonary hypertensive crises.
                                                       • Let's start with a short multiple choice question:
                                                       
                                                       

                                                       The best treatment for an acute pulmonary hypertension crises in an six month old ex-26 week with premie without congenital heart disease who is mechanically ventilated secondary to RSV bronchiolitis is

                                                       A) Sildenafil

                                                       B) Hypoventilation

                                                       C) Milrinone

                                                       D) Sedation and paralysis

                                                       Rahul the correct answer is D sedation and paralysis. Although not a choice the I would recommend giving 100% O2 which is a potent vasodilator preferably with bag-mask hyperventilation (which causes alkalemia and causes pulmonary vasculature vasodilatation). Of the choices given in the above question none will be helpful in an acute PH crises although they are frequently used to treat PH in children. Milrinone is a PDE-3 inhibitor (increases cAMP) where as sildenafil is a PDE-5 inhibitor (increases cGMP). Hypoventilation will increase PCO2 which is a potent stimulus for PH crises. If available nitric oxide could be used.

                                                       To summarize, acute pHtn you have to think about the pulmonary vasculature — which is responsive to changes in 02, pH, and Co2.

                                                       As you think about our case, what would be your differential?

                                                       • Cold shock (although the in patients without PH-the cardiac exam will not reveal a loud single S2 or hyperdynamic right ventricle
                                                       • "Tet spell"-cyanotic spells typically seen in infants with congenital heart disease with a VSD such as tetralogy of fallot. deoxygenated blood is shunted across fro the right to the left across the VSD due to increased PVR. Cardiac exam may reveal reduced intensity or no murmur (as the murmur due to right ventricular outflow tract obstruction is proportional to the blood flow to the pulmonary circuit).
                                                       • We should also be vigilant of obstruction/Kinking of ETT in a patient resulting in hypoxia, bradycardia and cardiac arrest- which may look like a PH crises
                                                       
                                                       

                                                       Remember due to inc RV afterload you are going to have impairment of forward flow thus clinically presenting with hypoxemia and signs of poor perfusion

                                                       If you had to work up this patient with what would be your diagnostic approach?

                                                       Really you don't need any investigation during an acute crises especially in a patient with h/o PHTN, h/o chronic lung disease, BPD or an infant with known cyanotic heart disease. Once patient is stable- consider chest radiograph (to check ETT tube position), blood gas for adequacy of ventilation. If patient is febrile then a CBC with differential + blood culture should be considered. An EKG may show RAH, RVH, ECHO may reveal findings...]]>Acute pulmonary Hypertensive Crises.

                                                       Welcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.

                                                       I'm Pradip Kamat and I'm Rahul Damania. We are coming to you from Children's Healthcare of Atlanta - Emory University School of Medicine.

                                                       Welcome to our Episode a 7 month old boy ex-26 week premature infant with acute hypoxemia, bradycardia episodes, poor perfusion

                                                       Here's the case:

                                                       A 7 month old ex-26 week male was transferred from the outside hospital to our PICU for tracheostomy evaluation. Patient was intubated on second day of life. He had a prolonged course, on inhaled Nitric Oxide for first 2-3 months of life in the setting of severe pulmonary hypertension, requiring HFOV for a prolonged period of time. Failed extubation attempts multiple times. Received steroid burst x2. BPD settings trialed (lower rate, longer iTime, high PEEP, larger TV) without improvement. At time of transfer he was in PRVC mode on the ventilator — TV ~10ml/kg, 50%, PEEP 8, rate 28 (Peak pressures 27-32). Patient received albuterol Q4 for bronchospasm/wheezing and pulmicort BID. Patient was deeply sedated with morphine and midazolam. Interstitial lung disease panel was negative. ECHO showed: systolic septal flattening, moderate RV hypertrophy with normal systolic functioning. Patient was not on any PH medications at transfer. Patient is also on furosemide, hydrochlorothiazide and spironolactone.

                                                       Patient has completed a course of antibiotics for klebsiella tracheitis from a ETT CX a week prior to admission to our picu. Patient tolerated feeds via an NJ tube.

                                                       The team continues to evaluate his case as the Patient continues to have episodes of acute desaturation, tachycardia, cool extremities and poor perfusion.

                                                       To summarize key elements from this case, we have a 7month old who is ex-26 week premie

                                                       • Patient has BPD and is on high vent settings and failing extubation
                                                       • Abnormal echocardiogram with flat septum and hypertrophied Right ventricle
                                                       • Episodes of cold shock-tachycardia, poor perfusion, and cool extremities
                                                       • Hypoxia
                                                       
                                                       

                                                       All of which bring up a concern for acute pulmonary hypertensive crisis

                                                       Rahul Let's transition into some history and physical exam components of this case?

                                                       What are key history features in this infants who presents with an acute pulmonary hypertensive crisis

                                                       • Prematurity
                                                       • BPD
                                                       
                                                       

                                                       Remember BPD is defined by a requirement of oxygen supplementation either at 28 days postnatal age or 36 weeks postmenstrual age.

                                                       Are there some red-flag symptoms or physical exam components which you could highlight?

                                                       • Presence of cold shock: tachycardia, cool extremities and poor perfusion
                                                       • Hypoxia
                                                       • Cardiac exam will reveal a bounding right ventricle, prominent loud single S2
                                                       • Although not obvious in this patient: some patients can have a palpable liver, cardiac gallop, peripheral edema and jugular venous distention
                                                       
                                                       

                                                       S2 heart sound represents the closure of the PV very close to AV — In pulmonary hypertension this PE sign is seen with equal right and left ventricular pressures.

                                                       To continue with our case, the patient's labs were consistent with:

                                                       • Respiratory acidosis (PCO2 > 100)
                                                       • CMP, CBC are normal
                                                       • BNP < 100, serum lactate normal
                                                       
                                                       

                                                       Echocardiography findings in these patients can show tricuspid regurgitation. We can estimate right ventricular systolic pressure on echo and, by extension, systolic PAP (sPAP), by using tricuspid regurgitant (TR) jet velocity in combination with other echocardiographic findings. Using the modified bernoulli principle 4 x TR jet velocity squared, we can estimate the sPAP. If sPAP >2/3 systemic sBP with severe flattening or posterior bowing of the interventricular septum the patient can be diagnosed with severe pHTN.

                                                       Pradip, what if the patient had a PDA on echo — what would you see?

                                                       Rahul, when you see Predominantly right-to-left shunting across the PDA suggests suprasystemic sPAP. And as a result these patients can be hypoxemic

                                                       Ok, to summarize, we have:

                                                       • A 7-month ex-26 week premie infant old with shock with signs of poor perfusion +bounding right ventricle and loud single second heart sound, which brings us to the concern for acute pulmonary hypertensive crises.
                                                       • Let's start with a short multiple choice question:
                                                       
                                                       

                                                       The best treatment for an acute pulmonary hypertension crises in an six month old ex-26 week with premie without congenital heart disease who is mechanically ventilated secondary to RSV bronchiolitis is

                                                       A) Sildenafil

                                                       B) Hypoventilation

                                                       C) Milrinone

                                                       D) Sedation and paralysis

                                                       Rahul the correct answer is D sedation and paralysis. Although not a choice the I would recommend giving 100% O2 which is a potent vasodilator preferably with bag-mask hyperventilation (which causes alkalemia and causes pulmonary vasculature vasodilatation). Of the choices given in the above question none will be helpful in an acute PH crises although they are frequently used to treat PH in children. Milrinone is a PDE-3 inhibitor (increases cAMP) where as sildenafil is a PDE-5 inhibitor (increases cGMP). Hypoventilation will increase PCO2 which is a potent stimulus for PH crises. If available nitric oxide could be used.

                                                       To summarize, acute pHtn you have to think about the pulmonary vasculature — which is responsive to changes in 02, pH, and Co2.

                                                       As you think about our case, what would be your differential?

                                                       • Cold shock (although the in patients without PH-the cardiac exam will not reveal a loud single S2 or hyperdynamic right ventricle
                                                       • "Tet spell"-cyanotic spells typically seen in infants with congenital heart disease with a VSD such as tetralogy of fallot. deoxygenated blood is shunted across fro the right to the left across the VSD due to increased PVR. Cardiac exam may reveal reduced intensity or no murmur (as the murmur due to right ventricular outflow tract obstruction is proportional to the blood flow to the pulmonary circuit).
                                                       • We should also be vigilant of obstruction/Kinking of ETT in a patient resulting in hypoxia, bradycardia and cardiac arrest- which may look like a PH crises
                                                       
                                                       

                                                       Remember due to inc RV afterload you are going to have impairment of forward flow thus clinically presenting with hypoxemia and signs of poor perfusion

                                                       If you had to work up this patient with what would be your diagnostic approach?

                                                       Really you don't need any investigation during an acute crises especially in a patient with h/o PHTN, h/o chronic lung disease, BPD or an infant with known cyanotic heart disease. Once patient is stable- consider chest radiograph (to check ETT tube position), blood gas for adequacy of ventilation. If patient is febrile then a CBC with differential + blood culture should be considered. An EKG may show RAH, RVH, ECHO may reveal findings suggestive of PH such as enlarged RA/RV, increased RV pressure, systolic flattening of the septum.

                                                       Rahul: What is the pathophysiology of an acute PHTN crises?

                                                       A pulmonary hypertensive crisis occurs when the pulmonary vasculature presents such a high resistance that there is little or no preload to the left ventricle and a massive, unsustainable afterload to the failing right ventricle. This can be triggered by multiple causes including parenchymal lung disease, Fever,pain, anxiety, tracheal suctioning, hypovolemia, increased cardiac demand, acidemia, aspiration, GE reflux, accidental interruption of prostanoid infusion. The acute massive loss of left ventricular preload and right ventricular afterload results in a drop in systemic cardiac output and coronary blood flow. Decreased coronary flow causes worsening right ventricular function. The higher than systemic right ventricular pressure pushes the interventricular septum into the left ventricle and that further worsens left ventricular filling. A vicious cycle ensues resulting in worsened left ventricular performance, syncope, bradycardia, and asystole.

                                                       • Once this point is reached, it is rare that cardiopulmonary resuscitation will successfully return sufficient cardiac output without significant multiorgan damage.
                                                       • If our history, physical, and diagnostic investigation led us to acute PH crises as our diagnosis what would be your general management of framework?
                                                       • Although PH management depends on the underlying cause-during a acute PH crises the following can be tried:
                                                       • If patient is on the ventilator-bag-mask ventilation with 100% O2 will vasodilate the pulmonary vasculature. O2 is a potent vasodilator and hyperventilation will decrease the PCO2 also causing vasodilation
                                                       • Bolus of sedation (decreases sympathetic drive) and a dose of NMB such as rocuronium will further relax the vasculature
                                                       • Nitric oxide can be used (start at 20-40ppm) if available-as it is a direct pulmonary vasodilator (works by increasing cGMP), causes selective pulmonary vasodilation (improves VQ matching as well as PVR)
                                                       • Great rahul - further, Correct metabolic acidosis using NAHCO3
                                                       • Treat bradycardia and hypotension
                                                       • Use fluid bolus if patient is dehydrated or over diuresed.
                                                       • After acute crises is mitigated - consideration for anti-reflux therapy of treatment of infection should be highly considered. A short course of steroids can also be used to decrease inflammation although these may not help in an acute crises.
                                                       • We have used epoprostenol (PGI2) infusion more to treat acute PH rather than in a crises. Typically started at 2ng/kg/min and slowly increased by 2ng/kg/min to a max of 9-11ng/kg/min.
                                                       
                                                       

                                                       OK to summarize, long term management focuses on modulating NO pathway, endothelin pathway, and prostacyclin pathway.

                                                       Are there any recent publications related to acute PH crises?

                                                       • We have posted references on our website picudoconcall.org (should NOT go through all below but just say posted in our shownotes)
                                                       • Lau EMT, Giannoulatou E, Celermajer DS, Humbert M. Epidemiology and treatment of pulmonary arterial hypertension. Nat Rev Cardiol. 2017 Oct;14(10):603-614. doi: 10.1038/nrcardio.2017.84. Epub 2017 Jun 8. PMID: 28593996.
                                                       • Hansmann G. Pulmonary Hypertension in Infants, Children, and Young Adults. J Am Coll Cardiol. 2017 May 23;69(20):2551-2569. doi: 10.1016/j.jacc.2017.03.575. PMID: 28521893.
                                                       • Krishnan U, Feinstein JA, Adatia I, Austin ED, Mullen MP, Hopper RK, Hanna B, Romer L, Keller RL, Fineman J, Steinhorn R, Kinsella JP, Ivy DD, Rosenzweig EB, Raj U, Humpl T, Abman SH; Pediatric Pulmonary Hypertension Network (PPHNet). Evaluation and Management of Pulmonary Hypertension in Children with Bronchopulmonary Dysplasia. J Pediatr. 2017 Sep;188:24-34.e1. doi: 10.1016/j.jpeds.2017.05.029. Epub 2017 Jun 20. PMID: 28645441.
                                                       • Del Pizzo J, Hanna B. Emergency Management of Pediatric Pulmonary Hypertension. Pediatr Emerg Care. 2016 Jan;32(1):49-55. doi: 10.1097/PEC.0000000000000674. PMID: 26720067.
                                                       
                                                       

                                                       Rahul, where can more information can be found:

                                                       • Fuhrman & Zimmerman - Textbook of Pediatric Critical Care Chapter 53: Diseases of the Pulmonary Circulation by Zhang H et al.
                                                       • Rahul what are the key objective take-aways:
                                                       
                                                       
                                                       1. Acute PHTN crises is a life threatening event that requires immediate therapy using oxygen, sedation+paralysis, inhaled nitric oxide, prevention of bradycardia and hypotension.
                                                       2. A multidisciplinary team approach with specialists from cardiology, pulmonary teams are needed in the management of patients with PH in the picu. Intensivists should understand the triggers for acute PH crises and try to avoid these triggers to prevent such crises.
                                                       
                                                       

                                                       This concludes our episode on acute pulmonary hypertensive crises. We hope you found value in our short, case-based podcast. We welcome you to share your feedback, subscribe & place a review on our podcast! Please visit our website picudoconcall.org which showcases our episodes as well as our Doc on Call management cards. PICU Doc on Call is hosted by myself Pradip Kamat and Dr. Rahul Damania. Stay tuned for our next episode! Thank you!

                                                       ]]>612cb5fc-7846-4b49-84ae-77da9da7b9dbSun, 17 Oct 2021 03:00:00 -040018:05falsefull32327 Habits of Highly-Effective PICU Fellows PodcastsWelcome to PICU Doc On Call, a podcast dedicated to current and aspiring intensivists. My name is Pradip Kamat.

                                                       My name is Rahul Damania, a current 3rd year pediatric critical care fellow. We come to you from Emory University School of Medicine-Children's Healthcare of Atlanta.

                                                       Today's episode is very special as we are going to be discussing 7 Habits of Highly Effective PICU fellows. As many trainees, both residents and fellows are settling into the year, We wanted to make a special podcast which highlights some key, high value habits Which can make the pediatric critical care experience very fruitful longitudinally!

                                                       We are delighted to be joined by Dr. Kevin Kuo and Dr. Paige Stevens.

                                                       Dr. Kuo is a Clinical Associate Professor, Pediatrics - Critical Care as well as the Program Director, Pediatric Critical Care Fellowship at Stanford University. Notably, Dr. Kuo is also the site creator and editor of the informational & well-known PICU website learnpicu.com- which accumulates over 10K views a month. Dr. Paige Stevens is a PCCM fellow at Stanford University and is here to provide the trainee perspective.

                                                       Dr. Kuo and Dr Stevens - we are delighted to have you. Welcome to PICU doc on call podcast.

                                                       • Dr Kuo or Stevens: Thank You Pradip and Rahul for having us on PICU Doc on Call. We have no relevant financial disclosures or conflicts of interest.
                                                       
                                                       

                                                       Our episode will be a series of actionable steps which can optimize your passion and performance in the PICU. This episode was inspired by the very famous book: The 7 Habits of Highly Effective People by Steven Covey which is an international bestseller.

                                                       To start with our episode, Dr. Kuo, do you mind highlighting the 7 Habits which we will cover:

                                                       • KK: Sure, here they are:
                                                       • From Dr. Covey's book we wanted to start with Begin with the End in Mind as the first habit
                                                       • Second, Embrace a Growth Mindset
                                                       • Third, Eat a Piece of Humble Pie Daily
                                                       • Fourth, Remember the ABCs
                                                       • Fifth, Put on Your Own Oxygen Mask First
                                                       • Sixth, Be Aware of the Meta
                                                       • Seventh, Sing in the Rain
                                                       
                                                       

                                                       Awesome, I can't wait to get into each of these. Dr. Kuo can you start us off with the first habit — Begin with the End in Mind?

                                                       • Dr. Kuo: sure
                                                       • 3 years goes by very quickly - what do you want your career to look like, what skills do you want to have gained, what things do you want to accomplish by the end of your three years, where do you want to work when you finish (academic vs community)?
                                                       • Be honest with what your interests and career goals are - i.e. not everyone needs to be an R01 funded basic scientist (although that is certainly needed and a wonderful career path).
                                                       • This is also great advice for people interviewing for fellowship. If you have a clear idea of who you want to be at the end of training, it will be easier to find a program that is going to help you get there. If you don’t know, you might want to choose a program where fellows go on to successfully do a broad range of things well.
                                                       
                                                       

                                                       Excellent approach and mindset especially for residents applying for PICU and matching in a few short months.

                                                       Dr. Stevens: What about the Growth Mindset?

                                                       • PS: Starting with the Growth Mindset is to
                                                       • Be active in the continual process of self-reflection and evaluating your strengths and areas for growth- use those ILP’s and conversations with your mentors.
                                                       • Be active in the continual process of seeking out feedback from others. You may not always be able to see the full perspective so seek it out from everyone you interact with.
                                                       • When you find areas for improvement after self-reflection or receive feedback from others, embrace a growth mindset and a desire to incorporate that feedback and enact change.
                                                       
                                                       

                                                       This habit reminds me of a great book known as Mindset: The New Psychology of Success by Carol Dwek, a PhD psychologist who has transformed the way we think about personal development, resilience, and optimism — definitely a trainee read.

                                                       Dr. Kuo, as you grow your experience as an attending what does the third habit, Eat a Piece of the Humble Pie mean to you?

                                                       • Dr Kuo:
                                                       • In the ICU we are constantly asked to be a "Jack of all Trades" ranging from a pulmonologist, to a cardiologist, to a nephrologist, to a transplant specialist, to a proceduralist... Our division chief Tim always says, "The minute you think you know it all is the day you should retire." You can't know it all and, at the end of the day, knowing and admitting what you don't know and asking for help is one of the most important things you can do.
                                                       • Additionally, even the things you think you know now (ie blood transfusion for EGDT in sepsis, looking for UTI's in RSV etc) could very well change during your years in practice.
                                                       • Approach each day with an eagerness to learn from those around you: your patients, your colleagues, your trainees, your RNs, RTs, Child Life specialists, Chaplains, etc. Ties into Covey’s “Seek first to understand, then be understood.”
                                                       
                                                       

                                                       Thank you for highlighting this invaluable characteristic — as ICU is a team sport humility and ego sublimation is paramount to success.

                                                       Lets transition to some productivity and self-compassion techniques - our next two habits are Remember the ABCs & Put your Own Oxygen Mask on — Dr. Kuo can you go into the prioritization of Airway Breathing Circulation in a bit more detail pls?

                                                       1. Dr Kuo: Remember the ABCs
                                                       
                                                       
                                                       • Just like in a resuscitation where you must prioritize the ABCs above all else, learning the art of prioritization is a skill that will go a long way in all aspects of your clinical skills and career.
                                                       • Concept of 4 quadrants (Covey): important/unimportant/urgent/nonurgent quadrants. There will always be something more that needs to be done, the real art comes in choosing your next step wisely
                                                       
                                                       
                                                       1. Dr Stevens: Put on Your Own Oxygen Mask First
                                                       
                                                       
                                                       • In order to best care for others, you need to care for yourself.
                                                       • Get in the habit of practicing self-compassion – we see and experience all sorts of challenging things in critical care- at the end of the day, we can only do our very best, continually learn, and the rest really isn’t in our hands.
                                                       • This includes building up all aspects of your life both inside and outside of medicine: relationships, finances, staying healthy: sleep, exercise, nutrition, mental health, spiritual health
                                                       • Also, surround yourself with people who can help put your oxygen mask on in case of emergencies like family/friends/spiritual community etc
                                                       
                                                       

                                                       This is great - lets do a quick re-cap thus far: End in Mind, Growth Mindset, Humble Pie, ABCs and O2 mask on first!

                                                       Lets round this episode off with our last two. Dr. Kuo what does Be Aware of the MEta mean to you?

                                                       1. Dr Kuo: Be Aware of the]]>Welcome to PICU Doc On Call, a podcast dedicated to current and aspiring intensivists. My name is Pradip Kamat.

                                                          My name is Rahul Damania, a current 3rd year pediatric critical care fellow. We come to you from Emory University School of Medicine-Children's Healthcare of Atlanta.

                                                          Today's episode is very special as we are going to be discussing 7 Habits of Highly Effective PICU fellows. As many trainees, both residents and fellows are settling into the year, We wanted to make a special podcast which highlights some key, high value habits Which can make the pediatric critical care experience very fruitful longitudinally!

                                                          We are delighted to be joined by Dr. Kevin Kuo and Dr. Paige Stevens.

                                                          Dr. Kuo is a Clinical Associate Professor, Pediatrics - Critical Care as well as the Program Director, Pediatric Critical Care Fellowship at Stanford University. Notably, Dr. Kuo is also the site creator and editor of the informational & well-known PICU website learnpicu.com- which accumulates over 10K views a month. Dr. Paige Stevens is a PCCM fellow at Stanford University and is here to provide the trainee perspective.

                                                          Dr. Kuo and Dr Stevens - we are delighted to have you. Welcome to PICU doc on call podcast.

                                                          • Dr Kuo or Stevens: Thank You Pradip and Rahul for having us on PICU Doc on Call. We have no relevant financial disclosures or conflicts of interest.
                                                          
                                                          

                                                          Our episode will be a series of actionable steps which can optimize your passion and performance in the PICU. This episode was inspired by the very famous book: The 7 Habits of Highly Effective People by Steven Covey which is an international bestseller.

                                                          To start with our episode, Dr. Kuo, do you mind highlighting the 7 Habits which we will cover:

                                                          • KK: Sure, here they are:
                                                          • From Dr. Covey's book we wanted to start with Begin with the End in Mind as the first habit
                                                          • Second, Embrace a Growth Mindset
                                                          • Third, Eat a Piece of Humble Pie Daily
                                                          • Fourth, Remember the ABCs
                                                          • Fifth, Put on Your Own Oxygen Mask First
                                                          • Sixth, Be Aware of the Meta
                                                          • Seventh, Sing in the Rain
                                                          
                                                          

                                                          Awesome, I can't wait to get into each of these. Dr. Kuo can you start us off with the first habit — Begin with the End in Mind?

                                                          • Dr. Kuo: sure
                                                          • 3 years goes by very quickly - what do you want your career to look like, what skills do you want to have gained, what things do you want to accomplish by the end of your three years, where do you want to work when you finish (academic vs community)?
                                                          • Be honest with what your interests and career goals are - i.e. not everyone needs to be an R01 funded basic scientist (although that is certainly needed and a wonderful career path).
                                                          • This is also great advice for people interviewing for fellowship. If you have a clear idea of who you want to be at the end of training, it will be easier to find a program that is going to help you get there. If you don’t know, you might want to choose a program where fellows go on to successfully do a broad range of things well.
                                                          
                                                          

                                                          Excellent approach and mindset especially for residents applying for PICU and matching in a few short months.

                                                          Dr. Stevens: What about the Growth Mindset?

                                                          • PS: Starting with the Growth Mindset is to
                                                          • Be active in the continual process of self-reflection and evaluating your strengths and areas for growth- use those ILP’s and conversations with your mentors.
                                                          • Be active in the continual process of seeking out feedback from others. You may not always be able to see the full perspective so seek it out from everyone you interact with.
                                                          • When you find areas for improvement after self-reflection or receive feedback from others, embrace a growth mindset and a desire to incorporate that feedback and enact change.
                                                          
                                                          

                                                          This habit reminds me of a great book known as Mindset: The New Psychology of Success by Carol Dwek, a PhD psychologist who has transformed the way we think about personal development, resilience, and optimism — definitely a trainee read.

                                                          Dr. Kuo, as you grow your experience as an attending what does the third habit, Eat a Piece of the Humble Pie mean to you?

                                                          • Dr Kuo:
                                                          • In the ICU we are constantly asked to be a "Jack of all Trades" ranging from a pulmonologist, to a cardiologist, to a nephrologist, to a transplant specialist, to a proceduralist... Our division chief Tim always says, "The minute you think you know it all is the day you should retire." You can't know it all and, at the end of the day, knowing and admitting what you don't know and asking for help is one of the most important things you can do.
                                                          • Additionally, even the things you think you know now (ie blood transfusion for EGDT in sepsis, looking for UTI's in RSV etc) could very well change during your years in practice.
                                                          • Approach each day with an eagerness to learn from those around you: your patients, your colleagues, your trainees, your RNs, RTs, Child Life specialists, Chaplains, etc. Ties into Covey’s “Seek first to understand, then be understood.”
                                                          
                                                          

                                                          Thank you for highlighting this invaluable characteristic — as ICU is a team sport humility and ego sublimation is paramount to success.

                                                          Lets transition to some productivity and self-compassion techniques - our next two habits are Remember the ABCs & Put your Own Oxygen Mask on — Dr. Kuo can you go into the prioritization of Airway Breathing Circulation in a bit more detail pls?

                                                          1. Dr Kuo: Remember the ABCs
                                                          
                                                          
                                                          • Just like in a resuscitation where you must prioritize the ABCs above all else, learning the art of prioritization is a skill that will go a long way in all aspects of your clinical skills and career.
                                                          • Concept of 4 quadrants (Covey): important/unimportant/urgent/nonurgent quadrants. There will always be something more that needs to be done, the real art comes in choosing your next step wisely
                                                          
                                                          
                                                          1. Dr Stevens: Put on Your Own Oxygen Mask First
                                                          
                                                          
                                                          • In order to best care for others, you need to care for yourself.
                                                          • Get in the habit of practicing self-compassion – we see and experience all sorts of challenging things in critical care- at the end of the day, we can only do our very best, continually learn, and the rest really isn’t in our hands.
                                                          • This includes building up all aspects of your life both inside and outside of medicine: relationships, finances, staying healthy: sleep, exercise, nutrition, mental health, spiritual health
                                                          • Also, surround yourself with people who can help put your oxygen mask on in case of emergencies like family/friends/spiritual community etc
                                                          
                                                          

                                                          This is great - lets do a quick re-cap thus far: End in Mind, Growth Mindset, Humble Pie, ABCs and O2 mask on first!

                                                          Lets round this episode off with our last two. Dr. Kuo what does Be Aware of the MEta mean to you?

                                                          1. Dr Kuo: Be Aware of the Meta
                                                          
                                                          
                                                          • Coming into fellowship, you’re probably worried and thinking about what induction meds to use for that intubation, how to run that code, putting in the line, when to start CRRT or cannulate for ECMO etc. -You’ll almost certainly learn that during fellowship. The “meta” is all the stuff that might not be strictly medical nor made explicit and includes things like: interpersonal interactions-ie picking up on the cue that the nurse/parent/RT etc is worried about something, team dynamics- ie facilitating autonomy for each level of learner on your team, how to run efficient yet helpful rounds, learning when/how to speak in a meeting, thinking about the meaning of the work we do, etc.) Long after you’ve learned most of the explicitly “medical” things, the meta often can be some of the most challenging and humbling parts of what we do.
                                                          • To get the most out of your training, take a step back and look at the bigger picture (“meta”) going around you. That, at least in my experience, is where more of the challenges and conflict arises and is the tougher part of the job as you get to be a more seasoned attending.
                                                          • Push yourself to see things from others' perspective and to see yourself from others' perspectives.
                                                          • Take time to recognize the “meta” of what we do. We have the privilege of taking care of children and families during the most difficult times in their lives. Take a moment to recognize the WOW factor of that privilege.
                                                          
                                                          

                                                          This is such a great point highlighting humanism in medicine - especially during this pandemic we have come to realize the meta in our care for children.

                                                          This has been an awe inspiring podcast today - Dr. Stevens - can you go into our last habit?

                                                          1. Dr. Stevens: Sing in the Rain
                                                          
                                                          
                                                          • Even though there will be challenges, remember to have fun!
                                                          • For me, these are the absolute best years of medical training. Yes, the hours may be long but you’re finally getting to do what you want to do. You’re immersed in an environment where you are constantly learning and growing. There are new challenges all the time and, even though things can be nerve wracking, you still have the backup of your attendings. You have great colleagues who you'll remember and may be friends with for the rest of your life.
                                                          • People who have fun are fun to be around. You'll be a better team leader, teacher, doctor, consultant, etc. if you find ways to make things fun.
                                                          
                                                          

                                                          This was an enlightening discussion - lets do a brief summary of each of today's habits:

                                                          • Begin with the End in Mind as the first habit
                                                          • Second, Embrace a Growth Mindset
                                                          • Third, Eat a Piece of Humble Pie Daily
                                                          • Fourth, Remember the ABCs
                                                          • Fifth, Put on Your Own Oxygen Mask First
                                                          • Sixth, Be Aware of the Meta
                                                          • Seventh, Sing in the Rain
                                                          
                                                          

                                                          Rahul-Dr Kuo Paige: What are your tips for first year fellows starting their PICU fellowship

                                                          Rahul: Especially during these challenging times due to the COVID-19 pandemic when its seems like there is no end, We advise the fellows to stay reslient and Remember these 7 habits of highly effective fellows. As budding intensivits we are on the path of life-long learning, and this episode allows for us to form a network and lead by example!

                                                          This concludes our episode today on 7 Habits of Highly Effective PICU Fellows We hope you found value in this short podcast. We welcome you to share your feedback & place a review on our podcast. PICU Doc on Call is hosted by me Pradip Kamat and my cohost Dr. Rahul Damania.

                                                          Stay tuned for our next episode! Thank you

                                                          ]]>4655be25-a865-4e9a-8ccb-0fde510d7162Sun, 03 Oct 2021 03:00:00 -040020:19falsefull3131Neurogenic ShockWelcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists. I'm Pradip Kamat and I'm Rahul Damania. We are coming to you from Children's Healthcare of Atlanta - Emory University School of Medicine.

                                                          Welcome to our Episode with a 15 year old Male having hypotension and bradycardia.

                                                          Here's the case presented by Rahul:

                                                          A 15 year old M presents to the PICU after sustaining an acute trauma. The patient was brought to the ER by his family after being on a boat and lifting a heavy object. He did not fall, sustain any head or extremity trauma, but did feel an achy non-radiating back pain shortly after the event. His grandmother states that the patient kept complaining about the back-pain and over the next few hours the patient became increasingly fatigued and flushed in the face. The patient was able to move his arms and legs and still walk, however family became concerned when the patient had abdominal fullness and was unable to urinate properly. He presents to the emergency department for further evaluation. In the emergency department he is noted to be awake however intermittently sleepy. His vital signs are notable for a HR of 58 bpm and a blood pressure of 85/60. He has 3/5 motor strength in his lower extremities with decreased sensation in his feet. Patellar reflexes are 1+ bilaterally. Rectal tone is normal. Acute resuscitation is begun for this patient.

                                                          To summarize key elements from this case, this patient has:

                                                          • Acute trigger
                                                          • Back pain
                                                          • Vital sign instability and lower motor neuron signs.
                                                          • All of which bring up a concern for a spinal cord injury.
                                                          • Let's transition and discuss some history and physical exam components of this presentation:
                                                          
                                                          
                                                          1. What are key history features in a child who presents with hypotension and bradycardia?
                                                          
                                                          
                                                          • As our worry is primarily spinal cord in etiology you would want to ask about trauma — this could be blunt or penetrating trauma
                                                          • You also would like to ask about the nature of the injury and scene. It is especially important to inquire with the pre-hospital providers about the nature of the injury and the patient course in transport. Besides our normal ABCs, it is important to ask the care taken regarding spinal cord restriction (such as use of a cervical collar or backboard)
                                                          • Another high yield history component when you think about hypotension and bradycardia is to assess for Numbness, weakness, or changes in bowel or bladder habits. In this case the patient had abdominal fullness which maybe due to bladder dysfunction.
                                                          
                                                          

                                                          This is a great summary of key history findings for patients who present with hypotension and bradycardia as it relates to spinal cord issues. Remember that patients who have Down's syndrome may have a predilection to have lax ligaments especially in the upper verterbrae. As a result, you should have an increased index of suspicion if a Down's Syndrome patient presents with hypotension and bradycardia in the presence or absence of trauma. In a study published in 2017 in Neurocrit Care it was estimated that about 20% of patients with Trisomy 21 may have atlantoaxial instability.

                                                          A great point which you just highlighted. Remember that when you approach hypotension and bradycardia, it is also important to focus on cardiac etiologies:

                                                          Bradycardia directly pulls down the cardiac output, potentially causing shock, and especially if you have a blunted vasoconstrictor response you can couple this bradycardia with hypotension.I do not want to delve too much out of the scope of today's episode but there is a wide differential for bradycardia but specifically related to history you should consider intoxication as a cause of bradycardia and hypotension.

                                                          • This includes:
                                                          • Beta-blocker or calcium-channel blocker.
                                                          • Central alpha-2 agonist (e.g., clonidine, dexmedetomidine, guanfacine).
                                                          
                                                          

                                                          Going back to our case, are there some red-flag symptoms or physical exam components which you could highlight when you approach?

                                                          Yes, in this patient who we suspect spinal cord injury, we would like to perform a comprehensive neurological exam:

                                                          • Motor strength should be tested especially in the lower extremities
                                                          • Key muscle groups should be tested to determine level of injury
                                                          • Knee extensors are at L3
                                                          • Whereas your triceps and biceps can be assessed C5-C7.
                                                          
                                                          

                                                          On physical exam, this patient had a flushed face, and this could be related to an Interruption of sympathetic chain causing a horner's syndrome like presentation.

                                                          Recall that Horner's Syndrome is a triad of ptosis, miosis, and anhidrosis which can present as facial flushing.

                                                          During this spinal cord assessment it is important to perform a rectal exam to check for perianal sensation and rectal tone

                                                          • If at least 1 is normal in the acute setting, this suggests a sacral-sparing injury and thus an incomplete injury with the potential for some motor recovery
                                                          
                                                          

                                                          Other physical exam components includes assessing for priapism in male patients. Priapism in male patients may be present from abrupt loss of sympathetic tone to pelvic vasculature, causing a high-flow arterial priapism.

                                                          This is a great review of history & physical components for hypotension and bradycardia as a presentation of spinal cord injury — I think the key point here is to remember that this presentation is related to a loss of sympathetics and thus unopposed vagal tone which leads to the acute symptamology of Distributive shock with hypotension and bradycardia

                                                          To continue with our case, the patients labs were consistent with:

                                                          • Blood gas consistent with a metabolic acidosis
                                                          • A lactic acid of 4.6 mg/dL
                                                          • His coagulation panel and basic metabolic panel was within normal limits
                                                          • EKG was notable for sinus bradycardia with no evidence of heart block.
                                                          
                                                          

                                                          I would also like listeners to note that in patient with high cervical spinal cord injuries, the presence of hypercarbia suggesting hypoventilation may prompt for the need for early intubation

                                                          What did the imaging show in this patient?

                                                          • After stabilization, our patient underwent CT showing an T2 spinal cord injury. There was an associated T5 vertebral fracture.
                                                          
                                                          

                                                          Interesting this may have been related to his boat trauma. Remember listeners, that CT is very sensitive for defining bone fractures in the spine. Because CT is more sensitive than plain films, patients who are suspected to have a spinal injury and have normal plain films should also undergo CT. CT also has advantages over plain films in assessing the patency of the spinal canal. CT also provides some assessment of the paravertebral soft tissues and perhaps of the spinal cord as well, but is inferior in that regard to MRI.

                                                          OK, to summarize, we have:

                                                          • A 15 yo M who presents after trauma with hypotension, bradycardia, facial flushing and bladder dysfunction. This brings up the concern for spinal or neurogenic shock, the topic of our discussion today.
                                                          • Let's start with a short multiple choice question:
                                                          • After a MVA, a 16 yo M presents with a HR 50 and MAP 45. Patient is obtunded, gurgling, and resuscitation efforts are begun. His hypotension does not improve with fluid resuscitation. A diagnosis of neurogenic shock is suspected. Stimulation of which of the following receptors is most likely to benefit this patient acutely?
                                                          
                                                          
                                                          1. nicotinic ach receptors
                                                          2. muscarinic ach receptors
                                                          3. vasopressin -2 receptors
                                                          4. alpha-1 receptors.
                                                          
                                                          

                                                          The correct answer is D. alpha-1 receptors. Remember that patients with neurogenic shock are devoid of sympathetics. Thus, you want to initiate sympathomimetics early. Some patients may require continuous infusion of norepinephrine, phyenlephrine, or dopamine.

                                                          As you think about our case, what would be your differential?

                                                          • First off I would make a distinction between Conus medullaris syndrome & Cauda Equina Syndrome.
                                                          • To start, the Conus medullaris is the terminal end of the spinal cord. If damaged, these children will have UMN weakness.
                                                          • They make have impaired sphincter control early, and Disturbances in urination
                                                          • Older children may be able to communicate a feeling of saddle anesthesia.
                                                          
                                                          

                                                          Pradip, what about cauda eqina syndrome?

                                                          Great question. So the Cauda equina is the lumbar and sacral roots caudal from the conus medullaris. These patients are going to have multiple nerves affected and may also have progressive incontinence.

                                                          In fact, studies have shown that Finding of urinary retention (post void residual > 100-200 mL) has 90% sensitivity for cauda equina syndrome.

                                                          A key distinction between the two is that cauda equaina syndrome in general has an asymmetric weakness with primarily LMN signs. These patient are going to have urinary retention that presents later from the onset of injury.

                                                          OK, to summarize, Conus medullaris syndrome you damage spinal cord, think early onset issues of bowel and bladder with UMN vs CE syndrome you have more damage of peripheral nerve roots and you in general will have a progressive inconitence with UMN signs.

                                                          RAHUL, I have also heard of this acronym, SCIWORA. What is this clinical entity?

                                                          SCIWORA stands for Spinal Cord Injury WithOut Radiographic Abnormality (SCIWORA)

                                                          In the pediatric population this differential is greater concern in pediatric population due to laxity of ligaments and weaker muscles

                                                          In this disorder, there is...]]>Welcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists. I'm Pradip Kamat and I'm Rahul Damania. We are coming to you from Children's Healthcare of Atlanta - Emory University School of Medicine.

                                                          Welcome to our Episode with a 15 year old Male having hypotension and bradycardia.

                                                          Here's the case presented by Rahul:

                                                          A 15 year old M presents to the PICU after sustaining an acute trauma. The patient was brought to the ER by his family after being on a boat and lifting a heavy object. He did not fall, sustain any head or extremity trauma, but did feel an achy non-radiating back pain shortly after the event. His grandmother states that the patient kept complaining about the back-pain and over the next few hours the patient became increasingly fatigued and flushed in the face. The patient was able to move his arms and legs and still walk, however family became concerned when the patient had abdominal fullness and was unable to urinate properly. He presents to the emergency department for further evaluation. In the emergency department he is noted to be awake however intermittently sleepy. His vital signs are notable for a HR of 58 bpm and a blood pressure of 85/60. He has 3/5 motor strength in his lower extremities with decreased sensation in his feet. Patellar reflexes are 1+ bilaterally. Rectal tone is normal. Acute resuscitation is begun for this patient.

                                                          To summarize key elements from this case, this patient has:

                                                          • Acute trigger
                                                          • Back pain
                                                          • Vital sign instability and lower motor neuron signs.
                                                          • All of which bring up a concern for a spinal cord injury.
                                                          • Let's transition and discuss some history and physical exam components of this presentation:
                                                          
                                                          
                                                          1. What are key history features in a child who presents with hypotension and bradycardia?
                                                          
                                                          
                                                          • As our worry is primarily spinal cord in etiology you would want to ask about trauma — this could be blunt or penetrating trauma
                                                          • You also would like to ask about the nature of the injury and scene. It is especially important to inquire with the pre-hospital providers about the nature of the injury and the patient course in transport. Besides our normal ABCs, it is important to ask the care taken regarding spinal cord restriction (such as use of a cervical collar or backboard)
                                                          • Another high yield history component when you think about hypotension and bradycardia is to assess for Numbness, weakness, or changes in bowel or bladder habits. In this case the patient had abdominal fullness which maybe due to bladder dysfunction.
                                                          
                                                          

                                                          This is a great summary of key history findings for patients who present with hypotension and bradycardia as it relates to spinal cord issues. Remember that patients who have Down's syndrome may have a predilection to have lax ligaments especially in the upper verterbrae. As a result, you should have an increased index of suspicion if a Down's Syndrome patient presents with hypotension and bradycardia in the presence or absence of trauma. In a study published in 2017 in Neurocrit Care it was estimated that about 20% of patients with Trisomy 21 may have atlantoaxial instability.

                                                          A great point which you just highlighted. Remember that when you approach hypotension and bradycardia, it is also important to focus on cardiac etiologies:

                                                          Bradycardia directly pulls down the cardiac output, potentially causing shock, and especially if you have a blunted vasoconstrictor response you can couple this bradycardia with hypotension.I do not want to delve too much out of the scope of today's episode but there is a wide differential for bradycardia but specifically related to history you should consider intoxication as a cause of bradycardia and hypotension.

                                                          • This includes:
                                                          • Beta-blocker or calcium-channel blocker.
                                                          • Central alpha-2 agonist (e.g., clonidine, dexmedetomidine, guanfacine).
                                                          
                                                          

                                                          Going back to our case, are there some red-flag symptoms or physical exam components which you could highlight when you approach?

                                                          Yes, in this patient who we suspect spinal cord injury, we would like to perform a comprehensive neurological exam:

                                                          • Motor strength should be tested especially in the lower extremities
                                                          • Key muscle groups should be tested to determine level of injury
                                                          • Knee extensors are at L3
                                                          • Whereas your triceps and biceps can be assessed C5-C7.
                                                          
                                                          

                                                          On physical exam, this patient had a flushed face, and this could be related to an Interruption of sympathetic chain causing a horner's syndrome like presentation.

                                                          Recall that Horner's Syndrome is a triad of ptosis, miosis, and anhidrosis which can present as facial flushing.

                                                          During this spinal cord assessment it is important to perform a rectal exam to check for perianal sensation and rectal tone

                                                          • If at least 1 is normal in the acute setting, this suggests a sacral-sparing injury and thus an incomplete injury with the potential for some motor recovery
                                                          
                                                          

                                                          Other physical exam components includes assessing for priapism in male patients. Priapism in male patients may be present from abrupt loss of sympathetic tone to pelvic vasculature, causing a high-flow arterial priapism.

                                                          This is a great review of history & physical components for hypotension and bradycardia as a presentation of spinal cord injury — I think the key point here is to remember that this presentation is related to a loss of sympathetics and thus unopposed vagal tone which leads to the acute symptamology of Distributive shock with hypotension and bradycardia

                                                          To continue with our case, the patients labs were consistent with:

                                                          • Blood gas consistent with a metabolic acidosis
                                                          • A lactic acid of 4.6 mg/dL
                                                          • His coagulation panel and basic metabolic panel was within normal limits
                                                          • EKG was notable for sinus bradycardia with no evidence of heart block.
                                                          
                                                          

                                                          I would also like listeners to note that in patient with high cervical spinal cord injuries, the presence of hypercarbia suggesting hypoventilation may prompt for the need for early intubation

                                                          What did the imaging show in this patient?

                                                          • After stabilization, our patient underwent CT showing an T2 spinal cord injury. There was an associated T5 vertebral fracture.
                                                          
                                                          

                                                          Interesting this may have been related to his boat trauma. Remember listeners, that CT is very sensitive for defining bone fractures in the spine. Because CT is more sensitive than plain films, patients who are suspected to have a spinal injury and have normal plain films should also undergo CT. CT also has advantages over plain films in assessing the patency of the spinal canal. CT also provides some assessment of the paravertebral soft tissues and perhaps of the spinal cord as well, but is inferior in that regard to MRI.

                                                          OK, to summarize, we have:

                                                          • A 15 yo M who presents after trauma with hypotension, bradycardia, facial flushing and bladder dysfunction. This brings up the concern for spinal or neurogenic shock, the topic of our discussion today.
                                                          • Let's start with a short multiple choice question:
                                                          • After a MVA, a 16 yo M presents with a HR 50 and MAP 45. Patient is obtunded, gurgling, and resuscitation efforts are begun. His hypotension does not improve with fluid resuscitation. A diagnosis of neurogenic shock is suspected. Stimulation of which of the following receptors is most likely to benefit this patient acutely?
                                                          
                                                          
                                                          1. nicotinic ach receptors
                                                          2. muscarinic ach receptors
                                                          3. vasopressin -2 receptors
                                                          4. alpha-1 receptors.
                                                          
                                                          

                                                          The correct answer is D. alpha-1 receptors. Remember that patients with neurogenic shock are devoid of sympathetics. Thus, you want to initiate sympathomimetics early. Some patients may require continuous infusion of norepinephrine, phyenlephrine, or dopamine.

                                                          As you think about our case, what would be your differential?

                                                          • First off I would make a distinction between Conus medullaris syndrome & Cauda Equina Syndrome.
                                                          • To start, the Conus medullaris is the terminal end of the spinal cord. If damaged, these children will have UMN weakness.
                                                          • They make have impaired sphincter control early, and Disturbances in urination
                                                          • Older children may be able to communicate a feeling of saddle anesthesia.
                                                          
                                                          

                                                          Pradip, what about cauda eqina syndrome?

                                                          Great question. So the Cauda equina is the lumbar and sacral roots caudal from the conus medullaris. These patients are going to have multiple nerves affected and may also have progressive incontinence.

                                                          In fact, studies have shown that Finding of urinary retention (post void residual > 100-200 mL) has 90% sensitivity for cauda equina syndrome.

                                                          A key distinction between the two is that cauda equaina syndrome in general has an asymmetric weakness with primarily LMN signs. These patient are going to have urinary retention that presents later from the onset of injury.

                                                          OK, to summarize, Conus medullaris syndrome you damage spinal cord, think early onset issues of bowel and bladder with UMN vs CE syndrome you have more damage of peripheral nerve roots and you in general will have a progressive inconitence with UMN signs.

                                                          RAHUL, I have also heard of this acronym, SCIWORA. What is this clinical entity?

                                                          SCIWORA stands for Spinal Cord Injury WithOut Radiographic Abnormality (SCIWORA)

                                                          In the pediatric population this differential is greater concern in pediatric population due to laxity of ligaments and weaker muscles

                                                          In this disorder, there is No discernible fracture on conventional films or computed tomography scans however patients may have spinal cord injury or on exam neurological deficits. The Mechanism is transient subluxation, stretching, or vascular compromise.

                                                          Finally, let's contrast neurogenic shock with spinal shock — this is a subtle distinction clinically but has been described in the literature Rahul can you shed some light on that?

                                                          • Spinal Shock Syndrome with a temporary loss of neurologic function and tone below a level of an acute lesion
                                                          • Presents as flaccid paralysis, loss of sensation, loss of deep tendon reflexes, and urinary bladder incontinence
                                                          • Spinal reflexes often return in a predictive manner with the reflexes in the genital region among the first to reappear
                                                          • Spinal shock, when accompanied by hemodynamic compromise with loss of vasomotor tone, is generally going to be known as neurogenic shock. Neurogenic shock typically occurs in patients with a T5 injury and above however can be seen in any lesion throughout the spinal cord.
                                                          
                                                          

                                                          If our history, physical, and diagnostic investigation led us to neurogenic shock related to acute traumatic spinal cord injury as our diagnosis, what would be your general management of framework?

                                                          • We have made a key theme today regarding the interruption of autonomic pathways in the spinal cord causing decreased vascular resistance and bradycardia. As such, your management should be focused on resuscitation and re-initiation of sympathetic tone in the form of vasopressors.
                                                          • Remember that Patients with traumatic spinal cord injury may also suffer from hemodynamic shock related to blood loss and other complications.
                                                          • An adequate blood pressure is believed to be critical in maintaining adequate perfusion to the injured spinal cord and thereby limiting secondary ischemic injury.
                                                          • Bradycardia caused by cervical spinal cord or high thoracic spinal cord disruption may require external pacing or administration of atropine. However in studies atropine has not been shown to completely reverse neurogenic shock.
                                                          
                                                          

                                                          What about steroid use in spinal cord injuries?

                                                          • Methylprednisolone is the only treatment that has been suggested in clinical trials to improve neurologic outcomes in patients with acute, nonpenetrating TSCI. However, the evidence is limited, and its use is debated.
                                                          • In animal experiments, administration of glucocorticoids after a spinal cord injury reduces edema, prevents intracellular potassium depletion, and improves neurologic recovery - this is especially true within the first eight hours after injury.
                                                          • In 2013, based upon the available evidence, the American Association of Neurological Surgeons and Congress of Neurological Surgeons stated that the use of glucocorticoids in acute spinal cord injury is not recommended. Use of glucocorticoids in this setting appears to be declining.
                                                          • Let's focus our management on the vasopressor use — as mentioned prior, vasopressors should be considered in cases of neurogenic shock esp if there is failure to respond to crystalloid, and no alternative diagnosis for hypotension.
                                                          • Your go to agents are going to be those that have a-lpha 1 activity to reestabllish vasomotor tone:
                                                          • Norepinephrine or Phenylephrine are your medications of choice in this setting
                                                          • Note phenylephrine may cause reflex bradycardia as this is a pure alpha one agonist.
                                                          
                                                          

                                                          In terms of prognosis:

                                                          • Adult studies have cited: 10%-20% of patients with spinal cord injuries do not survive to hospitalization.
                                                          • Most recovery starts within the first few weeks and plateaus in the first 3-6 months
                                                          • Better prognosis for ambulation include
                                                          • Younger age, decreased severity of impairment, incomplete injury, and lower level of injury
                                                          
                                                          

                                                          This is a great time for us to highlight the multi-disciplinary effort that goes into caring for these children. It is important in the acute setting to work closely with neurosurgery, ortho, neurology, and the critical care team and further in the subacute setting involving the rehabilitation team.

                                                          • Leading causes of death in children with spinal cord injury are respiratory conditions and pnuemonia so working closely with speech therapy for oromotor function is imperative in management.
                                                          • I would advise trainees and anyone interested to consider reading chapter 34 entitled shock states in Fuhrman & Zimmerman - Textbook of Pediatric Critical Care to review the hemodynamic patterns seen in our discussion of neurogenic shock.
                                                          
                                                          

                                                          This concludes our episode on Neurogenic shock. We hope you found value in our short, case-based podcast. We welcome you to share your feedback, subscribe & place a review on our podcast! Please visit our website picudoconcall.org which showcases our episodes as well as our Doc on Call management cards. PICU Doc on Call is hosted by myself Pradip Kamat and my cohost Dr. Rahul Damania. Stay tuned for our next episode! Thank you!

                                                          References:

                                                          Powell A, Davidson L. Pediatric spinal cord injury: a review by organ system. Phys Med Rehabil Clin N Am. 2015 Feb;26(1):109-32. doi: 10.1016/j.pmr.2014.09.002. PMID: 25479784.

                                                          Farrell CA, Hannon M, Lee LK. Pediatric spinal cord injury without radiographic abnormality in the era of advanced imaging. Curr Opin Pediatr. 2017 Jun;29(3):286-290. doi: 10.1097/MOP.0000000000000481. PMID: 28306628.

                                                          Yue JK, Tsolinas RE, Burke JF, Deng H, Upadhyayula PS, Robinson CK, Lee YM, Chan AK, Winkler EA, Dhall SS. Vasopressor support in managing acute spinal cord injury: current knowledge. J Neurosurg Sci. 2019 Jun;63(3):308-317. doi: 10.23736/S0390-5616.17.04003-6. Epub 2017 Mar 1. PMID: 28252264.

                                                          ]]>16946572-237d-4b46-8a05-0c85302be221Sun, 26 Sep 2021 03:00:00 -040019:45falsefull3030Macrophage Activation SyndromeWelcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.

                                                          I'm Pradip Kamat and I'm Rahul Damania. We are coming to you from Children's Healthcare of Atlanta - Emory University School of Medicine.

                                                          Welcome to our Episode of 17-year old with h/o of SLE and now acute liver failure.

                                                          Here's the case presented by Rahul:

                                                          A 17-year old teenage female year old presents to the PICU with acute liver failure. Important past h/o includes a diagnosis of SLE on therapy with prednisone, mycophenolate (cellcept), and plaquenil.

                                                          4 days prior to this admission, patient presented to an OSH with RUQ pain, vomiting (non bloody & no bilious), fever & malaise. Initially due to concern for "lupus Flare" patient was given steroids at the OSH.

                                                          At the OSH notable initial labs included a mild transaminitis and an INR of 1.5. She suddenly at the OSH developed fluid refractory hypotension and was started on a pressor. Due to continued worsening of her transaminitis well as a rising INR on her repeat labs she was referred to our tertiary PICU for further management.

                                                          Pertinent history also includes a negative urine pregnancy test. No recreational drug use, and only as needed use of Tylenol.

                                                          She now is in the PICU. She generally appears tired and ill. She is tachypneic on 4 LPM of nasal canulla and her oxygen saturation is 98%. She has a non-focal lung exam.

                                                          Her cardiac exam is notable for tachycardia, and pertinently no gallop, rub or murmur.

                                                          Her abdominal exam is non-focal except for mild discomfort on palpation of the RUQ with a palpable liver edge. Her extremities are cool with 3-4 capillary refill time. She is able to answer questions but intermittently doses off. No rash is noted.

                                                          To summarize key elements from this case, this patient has:

                                                          • H/o of lupus and is on immunosuppressive medications
                                                          • New onset fever/malaise
                                                          • This sounds like a LUPUS flare as she has a clinical picture of generalized inflammation.
                                                          
                                                          

                                                          Rahul: Lets pause right here and take a look at key history and physical exam components in a patient who has a chronic auto-immune condition:

                                                          • Fever, malaise and feeling tired all signs of constitutional symptoms.
                                                          • She has abdominal pain and vomiting that could again be related to systemic inflammation but also an intra-hepatic lesion.
                                                          
                                                          

                                                          Are there some red-flag symptoms or physical exam components which you could highlight?

                                                          • This patient has signs of shock!
                                                          • Tachycardia with delayed cap refill and cool extremities
                                                          • Tachypnea
                                                          • & hepatomegaly which could indicate increased central venous pressures.
                                                          • Initially her outside presentation of fluid refractory shock is of utmost concern!
                                                          • Fluid refractory shock with multi organ presentation involving liver, kidney and the blood/coagulation systems
                                                          • All of these elements bring up a concern for some acute life threatening process such as sepsis, or even immune dys-regulation due to her h/o of Lupus
                                                          • To continue with our case, the patients labs were consistent with:Acute liver dysfunction (Elevated AST and ALT in the thousands, Total bilirubin 1.6, GGT 56) although the total bilirubin is not elevated to a degree I would expect.
                                                          • AKI (creatinine 2.18)
                                                          • An uptrending Coagulopathy with elevated PT and INR: PT 120 and a peak INR of 16
                                                          • Thrombocytopenia: Platelets < 50K
                                                          • She had a peak lactate 9.2
                                                          • and concurrent Metabolic acidemia: serum HCO3 7, and pH 7.18.
                                                          • A Pertinent negative: Normal serum ammonia <38 micromol/L (nl < 50)
                                                          • Finally, she had an elevated WBC 20.5K/ Hgb 9.7, Platelet 42. CRP 4.2/ESR 5
                                                          
                                                          

                                                          OK to summarize, we have: a 17 yr old female with SLE on mycophenolate (cellcept) who presents with fever, hypotension, AKI and liver dysfunction with severe coagulopathy, although we do not have other labs- This brings up the concern for acute macrophage activation syndrome (MAS) the topic of our discussion today.

                                                          • Let's start with a short multiple choice question:
                                                          • 12 year old male with h/o systemic onset juvenile idiopathic arthritis (JIA) presents with fever, rash, hypotension, acute respiratory distress with hypoxia. Mental status is normal. He also has acute kidney injury, transaminitis, coagulopathy, metabolic acidemia as well as anemia and thrombocytopenia. His liver and spleen are enlarged and he has scattered lymphadenopathy. The laboratory findings most suggestive of acute macrophage activation syndrome in this patient is:
                                                          • Erythrocyte Sedimentation Rate > 100
                                                          • ADAMS13 activity < 10%
                                                          • Serum Ferritin > 20, 000ng/mL
                                                          • Fibrinogen (> 500mg/dL)
                                                          • The correct answer is serum ferritin > 20,000ng/mL. Any patient with systemic JIA who presents with high fever, heptao-splenomegaly with evidence of multi-organ dysfunction should be considered to have the potentially life threatening complication of systemic inflammatory disorders: acute macrophage activation syndrome (MAS) unless proven otherwise. The 2016 Classification criteria for MAS was published (Ravelli A. et al. Ann Rheum Dis 2016; 75:481-489) requires a Ferritin > 684ng/mL and any two of the following:
                                                          • A platelet count < 181 X 109/L (181K)
                                                          • AST > 48units
                                                          • Triglycerides > 156 mg/dL
                                                          • Fibrinogen ≤ 360mg/dL
                                                          
                                                          

                                                          OK lets summarize, platelets less than 180K, fibronogen <360, transaminitis >AST 48 and hypertriglcyeridemia! Remember many of these values are acute phase reactants

                                                          Correct Rahul, also the above Laboratory abnormalities should not be otherwise explained by another patient condition, such as concomitant immune-mediated thrombocytopenia, infectious hepatitis, visceral leishmaniasis or familial hyperlipidemia.

                                                          Are there any other inflammatory mediators or subtleties you would like to highlight with this disease?

                                                          • A falling ESR, especially with a high CRP, is concerning for MAS and is secondary to low fibrinogen in the setting of consumptive coagulopathy.
                                                          • In the question, patient's ESR is elevated. Low or absent ADAMS T-13 activity is more suggestive of thrombocytopenic purpura (TTP), which is not the case here as mental status is preserved indicating no CNS involvement. In MAS there is typically consumption of fibrinogen not its elevation. The elevated ferritin (> 10,000ng/mL) along with other systemic findings in the patient in the question is highly suggestive of MAS. Additional labs that would suggest MAS include demonstration of hemophagocytosis in bone marrow or other tissue, elevated D-dimers, lactic acid dehydrogenase (LDH), triglycerides, low natural killer (NK) cell function, and elevated soluble IL-2 receptor levels.
                                                          
                                                          

                                                          Great highlight of the incorrect answers the pathophysiology of increased immune activation is key along with dysfibrinogenemia — this is likely due to microangiopathic consumption

                                                          Rahul can you briefly tell us a bit about macrophage activation syndrome?

                                                          • MAS is classified among the group of hemophagocytic lymphohistiocytosis (HLH), so HLH is the umbrella term.
                                                          • HLH includes familial HLH and secondary HLH. Secondary HLH is triggered by several causes, including infection, drugs, malignancy, and rheumatic disorder. Remember in our case the patient had Lupus
                                                          • In MAS A common hypothesis in MAS is that there is a defect in lymphocyte cytolytic activity, which means that lymphocytes are not able to kill cells appropriately.
                                                          
                                                          

                                                          Let's break down the pathophysiology a bit further.

                                                          1. There is a genetic predisposition, and that is to having increased macrophage responsiveness
                                                          2. There is some form of background inflammatory activity. What cytokines are elevated?
                                                          3. IL-6
                                                          4. IL-1
                                                          5. IL-18
                                                          6. What does IL-6 do?
                                                          7. Decreases NK cell function
                                                          8. So now you have bad T cell cytolytic function and decreased NK cell cytolytic function. What does this lead to?
                                                          9. Prolonged cell to cell interactions and amplification of a pro0inflammatory cascade.
                                                          10. So now we have genetic predisposition some background cytokine inflammatory activity with cytokine production and now we layer in the third element of the pathophysiology — A trigger!
                                                          11. What are triggers: acute on chronic inflammation & especially infection!
                                                          12. This trigger will be important to capture in our understand as management will be geared towards reversing this trigger. So where does the hemophagocytosis come about in the term hemophagocytic lymphohistiocytosis? Well, the cytokine storm results in activation of macrophages which are known as hemophagocytes. There's a particular cytokine IFN gamma that make macrophages angry and it is this response that can lead to multi-organ dysfunction.
                                                          
                                                          

                                                          Pradip, now with this summary let's dive into MAS and how it relates to HLH?

                                                          • MAS is a life threatening illness is a form of secondary hemophagocytic lymphohistiocytosis (HLH) and a common complication of rheumatologic conditions, such as systemic JIA. The occurence of MAS has been well reported in other autoimmune or auto-inflammatory conditions, such as, adult-onset and childhood-onset systemic lupus erythematosus, Kawasaki disease, and periodic fever syndromes.
                                                          • Characteristic clinical]]>Welcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.

                                                            I'm Pradip Kamat and I'm Rahul Damania. We are coming to you from Children's Healthcare of Atlanta - Emory University School of Medicine.

                                                            Welcome to our Episode of 17-year old with h/o of SLE and now acute liver failure.

                                                            Here's the case presented by Rahul:

                                                            A 17-year old teenage female year old presents to the PICU with acute liver failure. Important past h/o includes a diagnosis of SLE on therapy with prednisone, mycophenolate (cellcept), and plaquenil.

                                                            4 days prior to this admission, patient presented to an OSH with RUQ pain, vomiting (non bloody & no bilious), fever & malaise. Initially due to concern for "lupus Flare" patient was given steroids at the OSH.

                                                            At the OSH notable initial labs included a mild transaminitis and an INR of 1.5. She suddenly at the OSH developed fluid refractory hypotension and was started on a pressor. Due to continued worsening of her transaminitis well as a rising INR on her repeat labs she was referred to our tertiary PICU for further management.

                                                            Pertinent history also includes a negative urine pregnancy test. No recreational drug use, and only as needed use of Tylenol.

                                                            She now is in the PICU. She generally appears tired and ill. She is tachypneic on 4 LPM of nasal canulla and her oxygen saturation is 98%. She has a non-focal lung exam.

                                                            Her cardiac exam is notable for tachycardia, and pertinently no gallop, rub or murmur.

                                                            Her abdominal exam is non-focal except for mild discomfort on palpation of the RUQ with a palpable liver edge. Her extremities are cool with 3-4 capillary refill time. She is able to answer questions but intermittently doses off. No rash is noted.

                                                            To summarize key elements from this case, this patient has:

                                                            • H/o of lupus and is on immunosuppressive medications
                                                            • New onset fever/malaise
                                                            • This sounds like a LUPUS flare as she has a clinical picture of generalized inflammation.
                                                            
                                                            

                                                            Rahul: Lets pause right here and take a look at key history and physical exam components in a patient who has a chronic auto-immune condition:

                                                            • Fever, malaise and feeling tired all signs of constitutional symptoms.
                                                            • She has abdominal pain and vomiting that could again be related to systemic inflammation but also an intra-hepatic lesion.
                                                            
                                                            

                                                            Are there some red-flag symptoms or physical exam components which you could highlight?

                                                            • This patient has signs of shock!
                                                            • Tachycardia with delayed cap refill and cool extremities
                                                            • Tachypnea
                                                            • & hepatomegaly which could indicate increased central venous pressures.
                                                            • Initially her outside presentation of fluid refractory shock is of utmost concern!
                                                            • Fluid refractory shock with multi organ presentation involving liver, kidney and the blood/coagulation systems
                                                            • All of these elements bring up a concern for some acute life threatening process such as sepsis, or even immune dys-regulation due to her h/o of Lupus
                                                            • To continue with our case, the patients labs were consistent with:Acute liver dysfunction (Elevated AST and ALT in the thousands, Total bilirubin 1.6, GGT 56) although the total bilirubin is not elevated to a degree I would expect.
                                                            • AKI (creatinine 2.18)
                                                            • An uptrending Coagulopathy with elevated PT and INR: PT 120 and a peak INR of 16
                                                            • Thrombocytopenia: Platelets < 50K
                                                            • She had a peak lactate 9.2
                                                            • and concurrent Metabolic acidemia: serum HCO3 7, and pH 7.18.
                                                            • A Pertinent negative: Normal serum ammonia <38 micromol/L (nl < 50)
                                                            • Finally, she had an elevated WBC 20.5K/ Hgb 9.7, Platelet 42. CRP 4.2/ESR 5
                                                            
                                                            

                                                            OK to summarize, we have: a 17 yr old female with SLE on mycophenolate (cellcept) who presents with fever, hypotension, AKI and liver dysfunction with severe coagulopathy, although we do not have other labs- This brings up the concern for acute macrophage activation syndrome (MAS) the topic of our discussion today.

                                                            • Let's start with a short multiple choice question:
                                                            • 12 year old male with h/o systemic onset juvenile idiopathic arthritis (JIA) presents with fever, rash, hypotension, acute respiratory distress with hypoxia. Mental status is normal. He also has acute kidney injury, transaminitis, coagulopathy, metabolic acidemia as well as anemia and thrombocytopenia. His liver and spleen are enlarged and he has scattered lymphadenopathy. The laboratory findings most suggestive of acute macrophage activation syndrome in this patient is:
                                                            • Erythrocyte Sedimentation Rate > 100
                                                            • ADAMS13 activity < 10%
                                                            • Serum Ferritin > 20, 000ng/mL
                                                            • Fibrinogen (> 500mg/dL)
                                                            • The correct answer is serum ferritin > 20,000ng/mL. Any patient with systemic JIA who presents with high fever, heptao-splenomegaly with evidence of multi-organ dysfunction should be considered to have the potentially life threatening complication of systemic inflammatory disorders: acute macrophage activation syndrome (MAS) unless proven otherwise. The 2016 Classification criteria for MAS was published (Ravelli A. et al. Ann Rheum Dis 2016; 75:481-489) requires a Ferritin > 684ng/mL and any two of the following:
                                                            • A platelet count < 181 X 109/L (181K)
                                                            • AST > 48units
                                                            • Triglycerides > 156 mg/dL
                                                            • Fibrinogen ≤ 360mg/dL
                                                            
                                                            

                                                            OK lets summarize, platelets less than 180K, fibronogen <360, transaminitis >AST 48 and hypertriglcyeridemia! Remember many of these values are acute phase reactants

                                                            Correct Rahul, also the above Laboratory abnormalities should not be otherwise explained by another patient condition, such as concomitant immune-mediated thrombocytopenia, infectious hepatitis, visceral leishmaniasis or familial hyperlipidemia.

                                                            Are there any other inflammatory mediators or subtleties you would like to highlight with this disease?

                                                            • A falling ESR, especially with a high CRP, is concerning for MAS and is secondary to low fibrinogen in the setting of consumptive coagulopathy.
                                                            • In the question, patient's ESR is elevated. Low or absent ADAMS T-13 activity is more suggestive of thrombocytopenic purpura (TTP), which is not the case here as mental status is preserved indicating no CNS involvement. In MAS there is typically consumption of fibrinogen not its elevation. The elevated ferritin (> 10,000ng/mL) along with other systemic findings in the patient in the question is highly suggestive of MAS. Additional labs that would suggest MAS include demonstration of hemophagocytosis in bone marrow or other tissue, elevated D-dimers, lactic acid dehydrogenase (LDH), triglycerides, low natural killer (NK) cell function, and elevated soluble IL-2 receptor levels.
                                                            
                                                            

                                                            Great highlight of the incorrect answers the pathophysiology of increased immune activation is key along with dysfibrinogenemia — this is likely due to microangiopathic consumption

                                                            Rahul can you briefly tell us a bit about macrophage activation syndrome?

                                                            • MAS is classified among the group of hemophagocytic lymphohistiocytosis (HLH), so HLH is the umbrella term.
                                                            • HLH includes familial HLH and secondary HLH. Secondary HLH is triggered by several causes, including infection, drugs, malignancy, and rheumatic disorder. Remember in our case the patient had Lupus
                                                            • In MAS A common hypothesis in MAS is that there is a defect in lymphocyte cytolytic activity, which means that lymphocytes are not able to kill cells appropriately.
                                                            
                                                            

                                                            Let's break down the pathophysiology a bit further.

                                                            1. There is a genetic predisposition, and that is to having increased macrophage responsiveness
                                                            2. There is some form of background inflammatory activity. What cytokines are elevated?
                                                            3. IL-6
                                                            4. IL-1
                                                            5. IL-18
                                                            6. What does IL-6 do?
                                                            7. Decreases NK cell function
                                                            8. So now you have bad T cell cytolytic function and decreased NK cell cytolytic function. What does this lead to?
                                                            9. Prolonged cell to cell interactions and amplification of a pro0inflammatory cascade.
                                                            10. So now we have genetic predisposition some background cytokine inflammatory activity with cytokine production and now we layer in the third element of the pathophysiology — A trigger!
                                                            11. What are triggers: acute on chronic inflammation & especially infection!
                                                            12. This trigger will be important to capture in our understand as management will be geared towards reversing this trigger. So where does the hemophagocytosis come about in the term hemophagocytic lymphohistiocytosis? Well, the cytokine storm results in activation of macrophages which are known as hemophagocytes. There's a particular cytokine IFN gamma that make macrophages angry and it is this response that can lead to multi-organ dysfunction.
                                                            
                                                            

                                                            Pradip, now with this summary let's dive into MAS and how it relates to HLH?

                                                            • MAS is a life threatening illness is a form of secondary hemophagocytic lymphohistiocytosis (HLH) and a common complication of rheumatologic conditions, such as systemic JIA. The occurence of MAS has been well reported in other autoimmune or auto-inflammatory conditions, such as, adult-onset and childhood-onset systemic lupus erythematosus, Kawasaki disease, and periodic fever syndromes.
                                                            • Characteristic clinical features of MAS are high, non-remitting fever, hepatosplenomegaly, generalized lymphadenopathy, central nervous system dysfunction and hemorrhagic manifestations.
                                                            • Typical laboratory abnormalities include pancytopenia, increased levels of ferritin, liver enzymes, lactate dehydrogenase, triglycerides, D-dimers and soluble interleukin 2 (IL-2) receptor α (also known as soluble CD25 (sCD25)), and decreased fibrinogen levels.
                                                            • A typical histopathological feature of MAS is the accumulation of well differentiated macrophages exhibiting hemophagocytic activity in bone marrow biopsy specimens or aspirates. Although the prevalence of MAS among patients with systemic JIA has been estimated to be ∼10%, recent reports suggest that subclinical MAS may occur in as many as 30–40% of patients with systemic JIA.
                                                            • MAS can result in progressive multiorgan failure and eventually a fatal outcome if unrecognized. Recent studies indicate a mortality rate of 8%. Early recognition of MAS is often challenging, given the lack of a single pathognomonic clinical or laboratory feature. Furthermore, histopathological features of hemophagocytosis may not be present in the initial stages and lack specificity for hemophagocytic syndromes. In addition, features of MAS may be difficult to distinguish from other conditions that may present with overlapping manifestations, such as flares of systemic JIA, lupus or systemic infections.
                                                            • MAS associated with SLE is rare and the incidence is about 0.9–4.6% but survival from MAS in febrile SLE patients who are admitted to the hospital ranges is 64% vs 97%.(p<0.001) in those without MAS. The odds of in-hospital mortality was 64.5, 95% CI: 7.6-544; p<0.001).
                                                            
                                                            

                                                            OK so HLH is the umbrella term and if a patient has signs and symptoms of acute inflammation + end organ dysfunction with a chronic rheumatological disease, you defintiely want to consider MAS. MAS in febrile SLE patients has a poor outcome.

                                                            As you think about our case, what would be your differential?

                                                            • Sepsis with DIC or liver dysfunction
                                                            • Flare of systemic JIA, lupus or primary rheumatologic disease
                                                            • Remember cytokine release syndrome in patients who get CAR-T therapy is a form of MAS.
                                                            
                                                            

                                                            Pradip: If you had to work up this patient with MAS what would be your diagnostic approach?

                                                            Initial labs include: CBC with diff, DIC panel, CMP, Ferritin, Soluble IL-2R. Blood/urine analysis/cultures. Patient in MOF, I would also trend lactates, blood gas, CMP and DIC panel at least every Q12 and as needed. Consult with rheumatology, infectious disease experts for their help with diagnosis and management. Given difficulty with distinguishing acute liver failure with DIC from MAS, factor V, VII and VIII levels (decreased in sepsis but not in liver disease) may be helpful. Additionally, PICU docs must be vigilant for neutropenic sepsis and opportunistic fungal infections, correct electrolyte imbalances, and use blood products to correct anemia, thrombocytopenia and coagulopathy.

                                                            • Alternative biomarkers for MAS—such as soluble IL-2 receptor, CD163, and IL-18—have shown promise. However, these tests are not universally available and generally have long turnaround times.
                                                            • It is important to r/o infection early but that may be difficult to do. I would send a viral panel which includes SARS COV-2 PCR
                                                            • Imaging: CXR, abdominal ultrasound, and echocardiography
                                                            
                                                            

                                                            Ferritin > 10K with evidence of hemophagocytosis in the bone marrow is most suggestive of MAS in a patient who has a presentation suggestive of MAS.

                                                            Pradip: If our history, physical, and diagnostic investigation led us to Macrophage activation syndrome (MAS) as our diagnosis what would be your general management of framework?

                                                            • Good basic PICU care with close attention to airway, breathing and hemodynamics. As modern medicine is a team sport consult with ID, rheumatology, hepatology etc. These patients typically need mechanical ventilation (On CMV use a high PEEP, low FIO2, low TV lung protective strategies). Patients may need HFOV for pulmonary hemorrhage. CVL, arterial lines should be placed. Avoid benzodiazepines for sedation, and prevent secondary kidney or liver toxicity (avoid nephrotoxic medications, dose antibiotics based on levels, avoid acetaminophen). As MAS is not readily distinguishable from sepsis-initial broad-spectrum antibiotics should be initiated.
                                                            • Although previously steroids/cyclosporine were the first line therapy: More recently, cytokine specific therapy with agents like anakinra an IL-1 receptor antagonist (2-4mg/kg s.c. every 6-24 hours) is rapidly effective. Anakinra blocks the biologic activity of both IL-1α and IL-1β by competitively inhibiting their binding to IL-1R. IV anakinra may be indicated if platelets < 20, neurologic symptoms and subcutaneous skin edema. A distinct advantage of anakinra is that the drug is less hepatotoxic, less immunosuppressive and has shorter half-life compared to etoposide or tocilizumab. Anakinra may help avoid steroids especially if diagnosis is not clear and there is a danger of masking lymphoma due to the steroids.
                                                            • Rahul its important to note that 2 other drugs (IL-1 beta receptor antagonist canakinumab and IL-6 inhibitor tocilizumab) while decreasing some of the clinical findings of MAS- such that patients may present with less fevers and hepatomegaly, as well as change lab features and the patient can thus have lower ferritin, lower fibrinogen, and lower CRP. Moreover, the excellent response of sJIA features to canakinumab and tocilizumab with simultaneous development of MAS features in some patients also suggests that the role of IL-1beta and IL-6 in MAS development might be limited
                                                            • In addition, plasma exchange and high-flow continuous veno-venous hemofiltration have shown promise. The use of extracorporeal cytokine removal therapies (CytoSorb) may show some selective efficacy in such patients with MAS.
                                                            
                                                            

                                                            That was a great summary, I would also advocate for treating the underlying cause!

                                                            This concludes our episode on acute macrophage activating syndrome We hope you found value in our short, case-based podcast. We welcome you to share your feedback, subscribe & place a review on our podcast! Please visit our website picudoconcall.org which showcases our episodes as well as our Doc on Call management cards. PICU Doc on Call is co-hosted by myself Dr. Pradip Kamat and Dr. Rahul Damania. Stay tuned for our next episode! Thank you!

                                                            ]]>ca42abaa-f087-4f74-a490-157ff8d399feSun, 19 Sep 2021 03:00:00 -040023:30falsefull2929Teenager with SLE, Hypotension, and Liver DysfunctionWelcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.

                                                            I'm Pradip Kamat and I'm Rahul Damania. We are coming to you from Children's Healthcare of Atlanta - Emory University School of Medicine.

                                                            Welcome to our Episode of 17-year old with h/o of SLE and now acute liver failure.

                                                            Here's the case presented by Rahul:

                                                            A 17-year old teenage female year old presents to the PICU with acute liver failure. Important past h/o includes a diagnosis of SLE on therapy with prednisone, mycophenolate (cellcept), and plaquenil.

                                                            4 days prior to this admission, patient presented to an OSH with RUQ pain, vomiting (non bloody & no bilious), fever & malaise. Initially due to concern for "lupus Flare" patient was given steroids at the OSH.

                                                            At the OSH notable initial labs included a mild transaminitis and an INR of 1.5. She suddenly at the OSH developed fluid refractory hypotension and was started on a pressor. Due to continued worsening of her transaminitis well as a rising INR on her repeat labs she was referred to our tertiary PICU for further management.

                                                            Pertinent history also includes a negative urine pregnancy test. No recreational drug use, and only as needed use of Tylenol.

                                                            She now is in the PICU. She generally appears tired and ill. She is tachypneic on 4 LPM of nasal canulla and her oxygen saturation is 98%. She has a non-focal lung exam.

                                                            Her cardiac exam is notable for tachycardia, and pertinently no gallop, rub or murmur.

                                                            Her abdominal exam is non-focal except for mild discomfort on palpation of the RUQ with a palpable liver edge. Her extremities are cool with 3-4 capillary refill time. She is able to answer questions but intermittently doses off. No rash is noted.

                                                            To summarize key elements from this case, this patient has:

                                                            • H/o of lupus and is on immunosuppressive medications
                                                            • New onset fever/malaise
                                                            • This sounds like a LUPUS flare as she has a clinical picture of generalized inflammation.
                                                            
                                                            

                                                            Rahul: Lets pause right here and take a look at key history and physical exam components in a patient who has a chronic auto-immune condition:

                                                            • Fever, malaise and feeling tired all signs of constitutional symptoms.
                                                            • She has abdominal pain and vomiting that could again be related to systemic inflammation but also an intro-hepatic lesion.
                                                            
                                                            

                                                            Are there some red-flag symptoms or physical exam components which you could highlight?

                                                            • This patient has signs of shock!
                                                            • Tachycardia with delayed cap refill and cool extremities
                                                            • Tachypnea
                                                            • & hepatomegaly which could indicate increased central venous pressures.
                                                            • Initially her outside presentation of fluid refractory shock is of utmost concern!
                                                            • Fluid refractory shock with multi organ presentation involving liver, kidney and the blood/coagulation systems
                                                            • All of these elements bring up a concern for some acute life threatening process such as sepsis, or even immune dys-regulation due to her h/o of Lupu
                                                            
                                                            

                                                            To continue with our case, the patients labs were consistent with:

                                                            • Acute liver dysfunction (Elevated AST and ALT in the thousands, Total bilirubin 1.6, GGT 56) although the total bilirubin is not elevated to a degree I would expect.
                                                            • AKI (creatinine 2.18)
                                                            • An uptrending Coagulopathy with elevated PT and INR: PT 120 and a peak INR of 16
                                                            • Thrombocytopenia: Platelets < 50K
                                                            • She had a peak lactate 9.2
                                                            • and concurrent Metabolic acidemia: serum HCO3 7, and pH 7.18.
                                                            • A Pertinent negative: Normal serum ammonia <38 micromol/L (nl < 50)
                                                            • Finally, she had an elevated WBC 20.5K/ Hgb 9.7, Platelet 42. CRP 4.2/ESR 5
                                                            
                                                            

                                                            OK to summarize, we have: a 17 yr old female with SLE on mycophenolate (cellcept)

                                                            • Who presents with fever, hypotension, AKI and liver dysfunction with severe coagulopathy. Although we do not have other labs- This brings up the concern for acute macrophage activation syndrome (MAS) the topic of our discussion today.
                                                            • Let's start with a short multiple choice question:
                                                            • 12 year old male with h/o systemic onset juvenile idiopathic arthritis (JIA) presents with fever, rash, hypotension, acute respiratory distress with hypoxia. Mental status is normal. He also has acute kidney injury, transaminitis, coagulopathy, metabolic acidemia as well as anemia and thrombocytopenia. His liver and spleen are enlarged and he has scattered lymphadenopathy. The laboratory findings most suggestive of acute macrophage activation syndrome in this patient is:
                                                            • Erythrocyte Sedimentation Rate > 100
                                                            • ADAMS13 activity < 10%
                                                            • Serum Ferritin > 20, 000ng/mL
                                                            • Fibrinogen (> 500mg/dL)
                                                            • The correct answer is serum ferritin > 20,000ng/mL. Any patient with systemic JIA who presents with high fever, heptao-splenomegaly with evidence of multi-organ dysfunction should be considered to have the potentially life threatening complication of systemic inflammatory disorders: acute macrophage activation syndrome (MAS) unless proven otherwise. The 2016 Classification criteria for MAS was published (Ravelli A. et al. Ann Rheum Dis 2016; 75:481-489) requires a Ferritin > 684ng/mL and any two of the following:
                                                            • A platelet count < 181 X 109/L (181K)
                                                            • AST > 48units
                                                            • Triglycerides > 156 mg/dL
                                                            • Fibrinogen ≤ 360mg/dL
                                                            
                                                            

                                                            Ok, let's summarize: platelets less than 180K, fibronogen <360, transaminitis >AST 48 and hypertriglcyeridemia! Remember many of these values are acute phase reactants

                                                            • Correct, Rahul, also the above Laboratory abnormalities should not be otherwise explained by another patient condition, such as concomitant immune-mediated thrombocytopenia, infectious hepatitis, visceral leishmaniasis or familial hyperlipidemia.
                                                            • Are there any other inflammatory mediators or subtleties you would like to highlight with this disease?
                                                            • A falling ESR, especially with a high CRP, is concerning for MAS and is secondary to low fibrinogen in the setting of consumptive coagulopathy.
                                                            • In the question patients ESR is elevated. Low or absent ADAMS T-13 activity is more suggestive of thrombocytopenic purpura (TTP), which is not the case here as mental status is preserved indicating no CNS involvement. In MAS there is typically consumption of fibrinogen not its elevation. The elevated ferritin (> 10,000ng/mL) along with other systemic findings in the patient in the question is highly suggestive of MAS. Additional labs that would suggest MAS include demonstration of hemophagocytosis in bone marrow or other tissue, elevated D-dimers, lactic acid dehydrogenase (LDH), triglycerides, low natural killer (NK) cell function, and elevated soluble IL-2 receptor levels.
                                                            
                                                            

                                                            Great highlight of the incorrect answers the pathophysiology of increased immune activation is key along with dysfibrinogenemia — this is likely due to microangiopathic consumption

                                                            • Rahul can you briefly tell us a bit about macrophage activation...]]>Welcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.

                                                              I'm Pradip Kamat and I'm Rahul Damania. We are coming to you from Children's Healthcare of Atlanta - Emory University School of Medicine.

                                                              Welcome to our Episode of 17-year old with h/o of SLE and now acute liver failure.

                                                              Here's the case presented by Rahul:

                                                              A 17-year old teenage female year old presents to the PICU with acute liver failure. Important past h/o includes a diagnosis of SLE on therapy with prednisone, mycophenolate (cellcept), and plaquenil.

                                                              4 days prior to this admission, patient presented to an OSH with RUQ pain, vomiting (non bloody & no bilious), fever & malaise. Initially due to concern for "lupus Flare" patient was given steroids at the OSH.

                                                              At the OSH notable initial labs included a mild transaminitis and an INR of 1.5. She suddenly at the OSH developed fluid refractory hypotension and was started on a pressor. Due to continued worsening of her transaminitis well as a rising INR on her repeat labs she was referred to our tertiary PICU for further management.

                                                              Pertinent history also includes a negative urine pregnancy test. No recreational drug use, and only as needed use of Tylenol.

                                                              She now is in the PICU. She generally appears tired and ill. She is tachypneic on 4 LPM of nasal canulla and her oxygen saturation is 98%. She has a non-focal lung exam.

                                                              Her cardiac exam is notable for tachycardia, and pertinently no gallop, rub or murmur.

                                                              Her abdominal exam is non-focal except for mild discomfort on palpation of the RUQ with a palpable liver edge. Her extremities are cool with 3-4 capillary refill time. She is able to answer questions but intermittently doses off. No rash is noted.

                                                              To summarize key elements from this case, this patient has:

                                                              • H/o of lupus and is on immunosuppressive medications
                                                              • New onset fever/malaise
                                                              • This sounds like a LUPUS flare as she has a clinical picture of generalized inflammation.
                                                              
                                                              

                                                              Rahul: Lets pause right here and take a look at key history and physical exam components in a patient who has a chronic auto-immune condition:

                                                              • Fever, malaise and feeling tired all signs of constitutional symptoms.
                                                              • She has abdominal pain and vomiting that could again be related to systemic inflammation but also an intro-hepatic lesion.
                                                              
                                                              

                                                              Are there some red-flag symptoms or physical exam components which you could highlight?

                                                              • This patient has signs of shock!
                                                              • Tachycardia with delayed cap refill and cool extremities
                                                              • Tachypnea
                                                              • & hepatomegaly which could indicate increased central venous pressures.
                                                              • Initially her outside presentation of fluid refractory shock is of utmost concern!
                                                              • Fluid refractory shock with multi organ presentation involving liver, kidney and the blood/coagulation systems
                                                              • All of these elements bring up a concern for some acute life threatening process such as sepsis, or even immune dys-regulation due to her h/o of Lupu
                                                              
                                                              

                                                              To continue with our case, the patients labs were consistent with:

                                                              • Acute liver dysfunction (Elevated AST and ALT in the thousands, Total bilirubin 1.6, GGT 56) although the total bilirubin is not elevated to a degree I would expect.
                                                              • AKI (creatinine 2.18)
                                                              • An uptrending Coagulopathy with elevated PT and INR: PT 120 and a peak INR of 16
                                                              • Thrombocytopenia: Platelets < 50K
                                                              • She had a peak lactate 9.2
                                                              • and concurrent Metabolic acidemia: serum HCO3 7, and pH 7.18.
                                                              • A Pertinent negative: Normal serum ammonia <38 micromol/L (nl < 50)
                                                              • Finally, she had an elevated WBC 20.5K/ Hgb 9.7, Platelet 42. CRP 4.2/ESR 5
                                                              
                                                              

                                                              OK to summarize, we have: a 17 yr old female with SLE on mycophenolate (cellcept)

                                                              • Who presents with fever, hypotension, AKI and liver dysfunction with severe coagulopathy. Although we do not have other labs- This brings up the concern for acute macrophage activation syndrome (MAS) the topic of our discussion today.
                                                              • Let's start with a short multiple choice question:
                                                              • 12 year old male with h/o systemic onset juvenile idiopathic arthritis (JIA) presents with fever, rash, hypotension, acute respiratory distress with hypoxia. Mental status is normal. He also has acute kidney injury, transaminitis, coagulopathy, metabolic acidemia as well as anemia and thrombocytopenia. His liver and spleen are enlarged and he has scattered lymphadenopathy. The laboratory findings most suggestive of acute macrophage activation syndrome in this patient is:
                                                              • Erythrocyte Sedimentation Rate > 100
                                                              • ADAMS13 activity < 10%
                                                              • Serum Ferritin > 20, 000ng/mL
                                                              • Fibrinogen (> 500mg/dL)
                                                              • The correct answer is serum ferritin > 20,000ng/mL. Any patient with systemic JIA who presents with high fever, heptao-splenomegaly with evidence of multi-organ dysfunction should be considered to have the potentially life threatening complication of systemic inflammatory disorders: acute macrophage activation syndrome (MAS) unless proven otherwise. The 2016 Classification criteria for MAS was published (Ravelli A. et al. Ann Rheum Dis 2016; 75:481-489) requires a Ferritin > 684ng/mL and any two of the following:
                                                              • A platelet count < 181 X 109/L (181K)
                                                              • AST > 48units
                                                              • Triglycerides > 156 mg/dL
                                                              • Fibrinogen ≤ 360mg/dL
                                                              
                                                              

                                                              Ok, let's summarize: platelets less than 180K, fibronogen <360, transaminitis >AST 48 and hypertriglcyeridemia! Remember many of these values are acute phase reactants

                                                              • Correct, Rahul, also the above Laboratory abnormalities should not be otherwise explained by another patient condition, such as concomitant immune-mediated thrombocytopenia, infectious hepatitis, visceral leishmaniasis or familial hyperlipidemia.
                                                              • Are there any other inflammatory mediators or subtleties you would like to highlight with this disease?
                                                              • A falling ESR, especially with a high CRP, is concerning for MAS and is secondary to low fibrinogen in the setting of consumptive coagulopathy.
                                                              • In the question patients ESR is elevated. Low or absent ADAMS T-13 activity is more suggestive of thrombocytopenic purpura (TTP), which is not the case here as mental status is preserved indicating no CNS involvement. In MAS there is typically consumption of fibrinogen not its elevation. The elevated ferritin (> 10,000ng/mL) along with other systemic findings in the patient in the question is highly suggestive of MAS. Additional labs that would suggest MAS include demonstration of hemophagocytosis in bone marrow or other tissue, elevated D-dimers, lactic acid dehydrogenase (LDH), triglycerides, low natural killer (NK) cell function, and elevated soluble IL-2 receptor levels.
                                                              
                                                              

                                                              Great highlight of the incorrect answers the pathophysiology of increased immune activation is key along with dysfibrinogenemia — this is likely due to microangiopathic consumption

                                                              • Rahul can you briefly tell us a bit about macrophage activation syndrome?
                                                              • MAS is classified among the group of hemophagocytic lymphohistiocytosis (HLH), so HLH is the umbrella term.
                                                              • HLH includes familial HLH and secondary HLH. Secondary HLH is triggered by several causes, including infection, drugs, malignancy, and rheumatic disorder. Remember in our case the patient had Lupus
                                                              • In MAS A common hypothesis in MAS is that there is a defect in lymphocyte cytolytic activity, which means that lymphocytes are not able to kill cells appropriately.
                                                              • Lets break down the pathophysiology a bit further.
                                                              
                                                              
                                                              1. There is a genetic predisposition, and that is to having increased macrophage responsiveness
                                                              2. There is some form of background inflammatory activity. What cytokines are elevated?
                                                              3. IL-6
                                                              4. IL-1
                                                              5. IL-18
                                                              6. What does IL-6 do?
                                                              7. Decreases NK cell function
                                                              8. So now you have bad T cell cytolytic function and decreased NK cell cytolytic function. What does this lead to?
                                                              9. Prolonged cell to cell interactions and amplification of a pro0inflammatory cascade.
                                                              10. So now we have genetic predisposition some background cytokine inflammatory activity with cytokine production and now we layer in the third element of the pathophysiology — A trigger!
                                                              11. What are triggers: acute on chronic inflammation & especially infection!
                                                              12. This trigger will be important to capture in our understand as management will be geared towards reversing this trigger. So where does the hemophagocytosis come about in the term hemophagocytic lymphohistiocytosis? Well, the cytokine storm results in activation of macrophages which are known as hemophagocytes. There's a particular cytokine IFN gamma that make macrophages angry and it is this response that can lead to multi-organ dysfunction.
                                                              
                                                              

                                                              Pradip, now with this summary let's dive into MAS and how it relates to HLH?

                                                              • MAS is a life threatening illness is a form of secondary hemophagocytic lymphohistiocytosis (HLH) and a common complication of rheumatologic conditions, such as systemic JIA. The occurence of MAS has been well reported in other autoimmune or auto-inflammatory conditions, such as, adult-onset and childhood-onset systemic lupus erythematosus, Kawasaki disease, and periodic fever syndromes.
                                                              • Characteristic clinical features of MAS are high, non-remitting fever, hepatosplenomegaly, generalized lymphadenopathy, central nervous system dysfunction and hemorrhagic manifestations.
                                                              • Typical laboratory abnormalities include pancytopenia, increased levels of ferritin, liver enzymes, lactate dehydrogenase, triglycerides, D-dimers and soluble interleukin 2 (IL-2) receptor α (also known as soluble CD25 (sCD25)), and decreased fibrinogen levels.
                                                              • A typical histopathological feature of MAS is the accumulation of well differentiated macrophages exhibiting hemophagocytic activity in bone marrow biopsy specimens or aspirates. Although the prevalence of MAS among patients with systemic JIA has been estimated to be ∼10%, recent reports suggest that subclinical MAS may occur in as many as 30–40% of patients with systemic JIA.
                                                              • MAS can result in progressive multiorgan failure and eventually a fatal outcome if unrecognized. Recent studies indicate a mortality rate of 8%. Early recognition of MAS is often challenging, given the lack of a single pathognomonic clinical or laboratory feature. Furthermore, histopathological features of hemophagocytosis may not be present in the initial stages and lack specificity for hemophagocytic syndromes. In addition, features of MAS may be difficult to distinguish from other conditions that may present with overlapping manifestations, such as flares of systemic JIA, lupus or systemic infections.
                                                              • MAS associated with SLE is rare and the incidence is about 0.9–4.6% but survival from MAS in febrile SLE patients who are admitted to the hospital ranges is 64% vs 97%.(p<0.001) in those without MAS. The odds of in-hospital mortality was 64.5, 95% CI: 7.6-544; p<0.001).
                                                              
                                                              

                                                              OK, so HLH is the umbrella term and if a patient has signs and symptoms of acute inflammation + end organ dysfunction with a chronic rheumatological disease, you defintiely want to consider MAS. MAS in febrile SLE patients has a poor outcome.

                                                              As you think about our case, what would be your differential?

                                                              • Sepsis with DIC or liver dysfunction
                                                              • Flare of systemic JIA, lupus or primary rheumatologic disease
                                                              • Remember cytokine release syndrome in patients who get CAR-T therapy is a form of MAS.
                                                              • Pradip: If you had to work up this patient with MAS what would be your diagnostic approach?
                                                              • Initial labs include: CBC with diff, DIC panel, CMP, Ferritin, Soluble IL-2R. Blood/urine analysis/cultures. Patient in MOF, I would also trend lactates, blood gas, CMP and DIC panel at least every Q12 and as needed. Consult with rheumatology, infectious disease experts for their help with diagnosis and management. Given difficulty with distinguishing acute liver failure with DIC from MAS, factor V, VII and VIII levels (decreased in sepsis but not in liver disease) may be helpful. Additionally, PICU docs must be vigilant for neutropenic sepsis and opportunistic fungal infections, correct electrolyte imbalances, and use blood products to correct anemia, thrombocytopenia and coagulopathy.
                                                              • Alternative biomarkers for MAS—such as soluble IL-2 receptor, CD163, and IL-18—have shown promise. However, these tests are not universally available and generally have long turnaround times.
                                                              • It is important to r/o infection early but that may be difficult to do. I would send a viral panel which includes SARS COV-2 PCR
                                                              • Imaging: CXR, abdominal ultrasound, and echocardiography
                                                              
                                                              

                                                              Ferritin > 10K with evidence of hemophagocytosis in the bone marrow is most suggestive of MAS in a patient who has a presentation suggestive of MAS.

                                                              • Pradip: If our history, physical, and diagnostic investigation led us to Macrophage activation syndrome (MAS) as our diagnosis what would be your general management of framework?
                                                              • Good basic PICU care with close attention to airway, breathing and hemodynamics. As modern medicine is a team sport consult with ID, rheumatology, hepatology etc. These patients typically need mechanical ventilation (On CMV use a high PEEP, low FIO2, low TV lung protective strategies). Patients may need HFOV for pulmonary hemorrhage. CVL, arterial lines should be placed. Avoid benzodiazepines for sedation, and prevent secondary kidney or liver toxicity (avoid nephrotoxic medications, dose antibiotics based on levels, avoid acetaminophen). As MAS is not readily distinguishable from sepsis-initial broad-spectrum antibiotics should be initiated.
                                                              • Although previously steroids/cyclosporine were the first line therapy: More recently, cytokine specific therapy with agents like anakinra an IL-1 receptor antagonist (2-4mg/kg s.c. every 6-24 hours) is rapidly effective. Anakinra blocks the biologic activity of both IL-1α and IL-1β by competitively inhibiting their binding to IL-1R. IV anakinra may be indicated if platelets < 20, neurologic symptoms and subcutaneous skin edema. A distinct advantage of anakinra is that the drug is less hepatotoxic, less immunosuppressive and has shorter half-life compared to etoposide or tocilizumab. Anakinra may help avoid steroids especially if diagnosis is not clear and there is a danger of masking lymphoma due to the steroids.
                                                              • Rahul its important to note that 2 other drugs (IL-1 beta receptor antagonist canakinumab and IL-6 inhibitor tocilizumab) while decreasing some of the clinical findings of MAS- such that patients may present with less fevers and hepatomegaly, as well as change lab features and the patient can thus have lower ferritin, lower fibrinogen, and lower CRP. Moreover, the excellent response of sJIA features to canakinumab and tocilizumab with simultaneous development of MAS features in some patients also suggests that the role of IL-1beta...]]>75ba6ed8-13a4-4509-b5e6-79f88e34b352Sun, 05 Sep 2021 03:00:00 -040023:30falsefull2828A Child with Severe Wrist FlexionWelcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.

                                                                I'm Pradip Kamat and I'm Rahul Damania and we are coming to you from Children's Healthcare of Atlanta - Emory University School of Medicine in Atlanta, GA.Today we are going to present a case of a 3 year old presenting with bilateral hyper-flexed wrists.

                                                                Here is Rahul with our case:

                                                                A 3 yo previously healthy M presents to the emergency department after his mother noted his wrists becoming completely stiff and flexed. Despite several attempts to stretch out his wrist, his mother was unable to place them back into position. She brought him to the ED for further evaluation. Importantly, mother denies any trauma or injury. Mom notes that this happened once before one month ago. The episode lasted 10 min and self-resolved. She did not seek medical attention at that time. Patient has no history of bleeding, bruising or chronic medical conditions. His immunizations are UTD. Family hx was relatively unremarkable however the mother states that she gets admitted to the hospital for Kidney Stones 4-5 times per year. She usually follows with a urologist. Though she is on diuretic therapy for recurrent renal stones, she denies that her son has any access to these medications & also denies any ingestion. She does state that patient is a picky eater and does not drink milk but will eat cheese often with 4-5 cups of juice. Mother denies any recent upper respiratory tract symptoms, vomiting, constipation, urinary abnormalities or changes in gait.

                                                                Upon presentation to the ED, his vital signs were stable. His physical exam is normal except for Bilateral hands in flexion with digits on flexion as well. After some resistance the examiner was able to extend hands. There were no abrasions or signs of cutaneous injury in his bilateral hands. Full range of motion of elbow and shoulder as well as full range of motion of ankle and knee as well as hip. Prior to drawing blood for a diagnostic work-up the patient undergoes an EKG which shows some artifact but is notable for a prolonged QTc interval of 560.

                                                                To summarize key elements from this case so far, we have a toddler with

                                                                • Bilateral hyper-flexion of the wrists which seem to be in a tonic state and is recurrent
                                                                • A family history of renal metabolic disease.
                                                                • and finally, an EKG abnormality.
                                                                • Rahul one key pertinent negative at this stage is that there is no trauma & patient has full range of motion at other large joints
                                                                • Rahul, let's transition to key history and physical elements when you think about bilateral wrist flexion.
                                                                
                                                                
                                                                1. This is an interesting chief complaint, however I would tailor my history to assess for trauma as this seems to be a primary MSK issue.
                                                                
                                                                
                                                                • The key feature here is that the patient has bilateral wrist involvement which brings up the concern for an underlying systemic cause such as an electrolyte abnormality, connective tissue disorder, or muscular abnormality. The family history of recurrent kidney stones points more towards a familial renal or electrolyte problem.
                                                                • I would ask about any trauma related to skin wounds. As this patient is in a tonic state, I would worry about tetanus.
                                                                • I would also get a good dietary history as excessive juice consumption may have limited nutritional value.
                                                                
                                                                
                                                                1. On physical exam, I would look for any other MSK abnormalities with this bilateral wrist flexion. Especially if we are heading down the route of nutritional abnormality, electrolyte disturbance or renal anomaly, I would like to assess for any bowing of the legs, joint flaring, any metacarpal shortening, or rib abnormality.
                                                                
                                                                

                                                                Pradip, I would love to hear more about the emergency room diagnostic work-up in this patient...

                                                                • To continue with our case, the patients labs were consistent with:
                                                                • A very low ionized calcium of 2.2 (normal 4.4-5.4mg/dl). Also, his total serum Ca was low — < 5mg/dL (Nl range 8.9-10.4mg/dl) with a relatively normal albumin.
                                                                • His CMP was notable for an elevated Alkaline Phosphatase at 963 with normal liver function and bilirubin.
                                                                • The rest of his electrolytes, renal function, and CBC were normal. As the primary concern was regarding calcium homeostasis, a PTH was sent and revealed a markedly elevated value of 823 pg/mL and his 25 Vitamin D level was low at 3.6 ng
                                                                • A urine Ca:Creatine ratio was elevated and finally a radiological joint survey of wrists showed osteopenia, physeal widening consistent with the final impression bringing up concern for rickets.
                                                                • The patient was given 60mg/kg of calcium gluconate and was transferred to the PICU for closer diagnostics & monitoring in the setting of severe hypoCa.
                                                                
                                                                

                                                                OK to summarize, we have:

                                                                • A 3 year-old M with bilateral hyper-flexed wrists due to severe hypocalcemia in the setting of hypovitaminosis D.
                                                                • Rahul Let's start with a short multiple choice question very relevant to PICU:
                                                                • A 5 year boy is admitted PICU with acute respiratory failure secondary to poly-trauma sustained after being involved in a motor vehicle collision in which the boy was an unrestrained passenger. After initial resuscitation with normal saline, the patient received rapid infusion of 4 units of packed red cells for hemorrhagic shock and a Hgb of 3gm% over a very short period of time. The patient is started on phenytoin for seizure prophylaxis due to traumatic brain injury. After initial resuscitation and stabilization, the patient develops an abnormal rhythm on the monitor and is now hypotensive. His blood gas drawn post transfusion is notable for a metabolic alkalosis and an ionized ca of 2. The hypotension and abnormal rhythm improves with IV repletion of calcium gluconate.
                                                                • The most likely explanation for the patients hypocalcemia is
                                                                • A. Pancreatic injury
                                                                • B. Citrate chelation of Ca
                                                                • C. Sepsis
                                                                • D. Phenytoin
                                                                • The correct answer to this question is (B) Citrate Chelation of Serum CaCitrate intoxication is a frequent complication after massive blood transfusions and often presents itself as metabolic alkalosis. The reason this term comes about is due to the conversion of citrate, which is applied as an anticoagulant in blood bags, to bicarbonate, and this conversion happens, predominantly in the liver. So, Stored blood is anti-coagulated using citrate (3 g/unit of RBC), which chelates calcium.
                                                                • Typically a healthy adult, the liver metabolizes 3 g of citrate in 5 min. Infusion rates greater than 1 unit of RBC over 5 min, or liver dysfunction, increase citrate concentration and lowers plasma ionized calcium.
                                                                • To highlight our other answer choices, we do not have enough evidence to suggest that there is injury to the pancreas at this stage and acute pancreatitis does not cause hypocalcemia this quickly. Although in a relatively subacute setting, acute pancreatitis can lead to hypocalcemia. This is primarily due to auto-digestion of mesenteric fat by activated pancreatic enzymes resulting in release of free fatty acids which form calcium salts, transient hypoparathyroidism and hypomagnesemia.
                                                                • While hypocalcemia can be seen in sepsis and critical illness in general and the etiology is usually multifactorial. In sepsis, the effect of the bacteremic state and the inflammatory mediators on PTH secretion and function can result in hypocalcemia.
                                                                • Phenytoin is known to cause hypocalcemia by altering the bone and mineral metabolism. It increases impairs normal Vitamin D metabolism, which in turn lowers the calcium absorption from gut and causes hypocalcemia. This effect is unlikely to be seen with use of phenytoin in a patient with normal renal function.
                                                                
                                                                

                                                                Before we go into diagnostic management, I want to particularly highlight some physiologic aspects of Ca homeostasis:

                                                                Only 1% of totally body Ca is in the extracellular volume. 99% of the body's calcium is in the bone. the ECF ca exists as protein bound (mostly albumin) (~40%), 10% as chelated and 50% as ionized. Ionized Ca is the active form of Ca.

                                                                Serum Ca is tightly regulated by PTH, vitamin D, and calcitonin by their action on the gut, kidneys and bone.

                                                                Actions of PTH: In the kidney PTH inhibits phosphate reabsorption (remembered as Phosphate Trashing Hormone) and promotes phosphaturia. This loss of phosphate shifts flow of Ca from bone to the ECF.

                                                                PTH also facilitates distal tubular reabsorption of filtered Ca. PTH also production of 1,25-dihydroxy Vitamin D to facilitate intestinal absorption of calcium and phosphate. Thus PTH helps increase serum ca and decrease serum phosphate.

                                                                Calcitonin: secreted in response to increased serum ca, helps divert Ca to the bones (remembered by "tones the bones"). It promotes calciuria and phosphaturia.

                                                                An increase in serum pH of 0.1 unit can cause ionized Ca++ to fall by 0.16mg/dl. The total ca will drop 0.8mg/dL fro every 1gm/dL decreases in serum albumin. The change in total Ca and ionized ca are independent of each other.

                                                                • As we have talked about a few presentations of hypocalcemia thus far as well as calcium homeostasis — but I do want to highlight some subtle but...]]>Welcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.

                                                                  I'm Pradip Kamat and I'm Rahul Damania and we are coming to you from Children's Healthcare of Atlanta - Emory University School of Medicine in Atlanta, GA.Today we are going to present a case of a 3 year old presenting with bilateral hyper-flexed wrists.

                                                                  Here is Rahul with our case:

                                                                  A 3 yo previously healthy M presents to the emergency department after his mother noted his wrists becoming completely stiff and flexed. Despite several attempts to stretch out his wrist, his mother was unable to place them back into position. She brought him to the ED for further evaluation. Importantly, mother denies any trauma or injury. Mom notes that this happened once before one month ago. The episode lasted 10 min and self-resolved. She did not seek medical attention at that time. Patient has no history of bleeding, bruising or chronic medical conditions. His immunizations are UTD. Family hx was relatively unremarkable however the mother states that she gets admitted to the hospital for Kidney Stones 4-5 times per year. She usually follows with a urologist. Though she is on diuretic therapy for recurrent renal stones, she denies that her son has any access to these medications & also denies any ingestion. She does state that patient is a picky eater and does not drink milk but will eat cheese often with 4-5 cups of juice. Mother denies any recent upper respiratory tract symptoms, vomiting, constipation, urinary abnormalities or changes in gait.

                                                                  Upon presentation to the ED, his vital signs were stable. His physical exam is normal except for Bilateral hands in flexion with digits on flexion as well. After some resistance the examiner was able to extend hands. There were no abrasions or signs of cutaneous injury in his bilateral hands. Full range of motion of elbow and shoulder as well as full range of motion of ankle and knee as well as hip. Prior to drawing blood for a diagnostic work-up the patient undergoes an EKG which shows some artifact but is notable for a prolonged QTc interval of 560.

                                                                  To summarize key elements from this case so far, we have a toddler with

                                                                  • Bilateral hyper-flexion of the wrists which seem to be in a tonic state and is recurrent
                                                                  • A family history of renal metabolic disease.
                                                                  • and finally, an EKG abnormality.
                                                                  • Rahul one key pertinent negative at this stage is that there is no trauma & patient has full range of motion at other large joints
                                                                  • Rahul, let's transition to key history and physical elements when you think about bilateral wrist flexion.
                                                                  
                                                                  
                                                                  1. This is an interesting chief complaint, however I would tailor my history to assess for trauma as this seems to be a primary MSK issue.
                                                                  
                                                                  
                                                                  • The key feature here is that the patient has bilateral wrist involvement which brings up the concern for an underlying systemic cause such as an electrolyte abnormality, connective tissue disorder, or muscular abnormality. The family history of recurrent kidney stones points more towards a familial renal or electrolyte problem.
                                                                  • I would ask about any trauma related to skin wounds. As this patient is in a tonic state, I would worry about tetanus.
                                                                  • I would also get a good dietary history as excessive juice consumption may have limited nutritional value.
                                                                  
                                                                  
                                                                  1. On physical exam, I would look for any other MSK abnormalities with this bilateral wrist flexion. Especially if we are heading down the route of nutritional abnormality, electrolyte disturbance or renal anomaly, I would like to assess for any bowing of the legs, joint flaring, any metacarpal shortening, or rib abnormality.
                                                                  
                                                                  

                                                                  Pradip, I would love to hear more about the emergency room diagnostic work-up in this patient...

                                                                  • To continue with our case, the patients labs were consistent with:
                                                                  • A very low ionized calcium of 2.2 (normal 4.4-5.4mg/dl). Also, his total serum Ca was low — < 5mg/dL (Nl range 8.9-10.4mg/dl) with a relatively normal albumin.
                                                                  • His CMP was notable for an elevated Alkaline Phosphatase at 963 with normal liver function and bilirubin.
                                                                  • The rest of his electrolytes, renal function, and CBC were normal. As the primary concern was regarding calcium homeostasis, a PTH was sent and revealed a markedly elevated value of 823 pg/mL and his 25 Vitamin D level was low at 3.6 ng
                                                                  • A urine Ca:Creatine ratio was elevated and finally a radiological joint survey of wrists showed osteopenia, physeal widening consistent with the final impression bringing up concern for rickets.
                                                                  • The patient was given 60mg/kg of calcium gluconate and was transferred to the PICU for closer diagnostics & monitoring in the setting of severe hypoCa.
                                                                  
                                                                  

                                                                  OK to summarize, we have:

                                                                  • A 3 year-old M with bilateral hyper-flexed wrists due to severe hypocalcemia in the setting of hypovitaminosis D.
                                                                  • Rahul Let's start with a short multiple choice question very relevant to PICU:
                                                                  • A 5 year boy is admitted PICU with acute respiratory failure secondary to poly-trauma sustained after being involved in a motor vehicle collision in which the boy was an unrestrained passenger. After initial resuscitation with normal saline, the patient received rapid infusion of 4 units of packed red cells for hemorrhagic shock and a Hgb of 3gm% over a very short period of time. The patient is started on phenytoin for seizure prophylaxis due to traumatic brain injury. After initial resuscitation and stabilization, the patient develops an abnormal rhythm on the monitor and is now hypotensive. His blood gas drawn post transfusion is notable for a metabolic alkalosis and an ionized ca of 2. The hypotension and abnormal rhythm improves with IV repletion of calcium gluconate.
                                                                  • The most likely explanation for the patients hypocalcemia is
                                                                  • A. Pancreatic injury
                                                                  • B. Citrate chelation of Ca
                                                                  • C. Sepsis
                                                                  • D. Phenytoin
                                                                  • The correct answer to this question is (B) Citrate Chelation of Serum CaCitrate intoxication is a frequent complication after massive blood transfusions and often presents itself as metabolic alkalosis. The reason this term comes about is due to the conversion of citrate, which is applied as an anticoagulant in blood bags, to bicarbonate, and this conversion happens, predominantly in the liver. So, Stored blood is anti-coagulated using citrate (3 g/unit of RBC), which chelates calcium.
                                                                  • Typically a healthy adult, the liver metabolizes 3 g of citrate in 5 min. Infusion rates greater than 1 unit of RBC over 5 min, or liver dysfunction, increase citrate concentration and lowers plasma ionized calcium.
                                                                  • To highlight our other answer choices, we do not have enough evidence to suggest that there is injury to the pancreas at this stage and acute pancreatitis does not cause hypocalcemia this quickly. Although in a relatively subacute setting, acute pancreatitis can lead to hypocalcemia. This is primarily due to auto-digestion of mesenteric fat by activated pancreatic enzymes resulting in release of free fatty acids which form calcium salts, transient hypoparathyroidism and hypomagnesemia.
                                                                  • While hypocalcemia can be seen in sepsis and critical illness in general and the etiology is usually multifactorial. In sepsis, the effect of the bacteremic state and the inflammatory mediators on PTH secretion and function can result in hypocalcemia.
                                                                  • Phenytoin is known to cause hypocalcemia by altering the bone and mineral metabolism. It increases impairs normal Vitamin D metabolism, which in turn lowers the calcium absorption from gut and causes hypocalcemia. This effect is unlikely to be seen with use of phenytoin in a patient with normal renal function.
                                                                  
                                                                  

                                                                  Before we go into diagnostic management, I want to particularly highlight some physiologic aspects of Ca homeostasis:

                                                                  Only 1% of totally body Ca is in the extracellular volume. 99% of the body's calcium is in the bone. the ECF ca exists as protein bound (mostly albumin) (~40%), 10% as chelated and 50% as ionized. Ionized Ca is the active form of Ca.

                                                                  Serum Ca is tightly regulated by PTH, vitamin D, and calcitonin by their action on the gut, kidneys and bone.

                                                                  Actions of PTH: In the kidney PTH inhibits phosphate reabsorption (remembered as Phosphate Trashing Hormone) and promotes phosphaturia. This loss of phosphate shifts flow of Ca from bone to the ECF.

                                                                  PTH also facilitates distal tubular reabsorption of filtered Ca. PTH also production of 1,25-dihydroxy Vitamin D to facilitate intestinal absorption of calcium and phosphate. Thus PTH helps increase serum ca and decrease serum phosphate.

                                                                  Calcitonin: secreted in response to increased serum ca, helps divert Ca to the bones (remembered by "tones the bones"). It promotes calciuria and phosphaturia.

                                                                  An increase in serum pH of 0.1 unit can cause ionized Ca++ to fall by 0.16mg/dl. The total ca will drop 0.8mg/dL fro every 1gm/dL decreases in serum albumin. The change in total Ca and ionized ca are independent of each other.

                                                                  • As we have talked about a few presentations of hypocalcemia thus far as well as calcium homeostasis — but I do want to highlight some subtle but clinically relevant findings in hypocalcemia, namely petechiae - this is because Ca is integral in platelet metabolism and when you have low ica, platelets will have decreased activation and thus you will have physical exam findings related to primary hemostasis. Second, remember that hypocalcemia in neonates may present as stridor.
                                                                  • 'LETS CONCLUDE OUR PODCAST WITH DIAGNOSTIC WORK-UP & MANAGEMENT FRAMEWORKS. If you had to work up our patient with hypocalcemia, what would be your diagnostic approach?
                                                                  • Rahul one way to approach any patient with hypocalcemia is to measure serum PTH level. You can then divide causes associated with elevated PTH level & causes associated with low PTH levels.
                                                                  • In general when serum Ca is low, PTH level should go up by triggering release of Ca and phosphate from the bones as well as absorbing Ca from the kidneys. PTH also will trigger formation of 1,25 dihydroxyvitamin D formation which increases intestinal absorption of Ca and phosphate.
                                                                  • So if you have have Hypocalcemia and a high PTH level: think of PTH resistance, calcium loss or calcium intake/absorption problems. PTH resistance (endorgan resistance, missense mutations in PTH or hypomagnesemia). Pseudohypoparathyroidism (X-linked dominant) can present with physical findings that variably include short bones, short stature, a stocky build, early-onset obesity and ectopic ossifications, as well as endocrine defects that often include resistance to parathyroid hormone (PTH) and TSH. Patients with PTH resistance usually have high serum phosphate levels.
                                                                  • Ca loss can be acute (sepsis, acute pancreatitis, TLS and even respiratory alkalosis) OR Chronic causes include renal disease, hyperPhosphatemia and metastases.
                                                                  • A common cause of poor calcium uptake and poor management of calcium homeostasis is deficiency of or resistance to vitamin D.
                                                                  • Hypocalcemia and Low PTH level: Can be congenital as in DiGeorge syndrome or acquired causes such as HIV infection, autoimmune, destruction of PTH glands after surgery or radiation. Infiltration of gland with cancer, sarcoidosis, or iron or copper deposition.
                                                                  • Alright listeners, this can be very confusing with arrows etc. so lets summarize with a conceptual framework. Remember PTH physiologically increases Ca concentration and decreases Phosphate concentration. So if you have hypoparathyroidism, which means that your PTH levels are low, you will have hypoCa & hyperPhosphatemia. With calcium homeostasis disorders take it back to the normal parathryoid axis and then branch out from there
                                                                  • Exactly Rahul, so how does Vitamin D get integrated into this pathophysiologic or diagnostic framework?
                                                                  • Vitamin D Deficiency: Could be genetic or acquired: Enzyme deficiencies or Vitamin D receptor problems.
                                                                  • Common causes include: obesity, malabsorption, and poor exposure to sunlight and problems with nutritional intake which also could be important given "picky eating" behavior in our patient. A toddler typically doesn't consume non dairy sources of calcium (beans/green leafy vegetables)-thus exacerbating poor calcium absorption caused by Vitamin D deficiency. Babies who breast feed and are not supplemented with Vitamin D, those who are premature or if mother had Vitamin D deficiency- can also have Vitamin D deficiency.
                                                                  • I do want to call out Vitamin D deficiency 2/2 malabsorption as this is frequently tested on boards in the context of cystic fibrosis and the exocrine insufficiency which can occur along with Celiac disease where you get VIt D insufficiency due to intestinal failure.
                                                                  • Exactly Rahul, whether you're talking about PTH or Vitamin D, to be comprehensive, A good approach for labs would be to send some basic labs such as CBC, CMP, Urine analysis, blood gas, ionized calcium. Labs such as ionized Ca, serum calcium, magnesium, potassium etc help to fix abnormal values quickly which should be the # 1 priority while a search for diagnosis is being made.
                                                                  • A consult with endocrine as well as nephrology services may help with other labs that need to be sent. The help of our friendly PICU nutritionist is invaluable to get detailed dietary history as well as to make dietary suggestions.
                                                                  • Let's go into the clinical relevance of these labs which you will get...
                                                                  • Labs to determine underlying cause include:
                                                                  • PTH: Key value to investigating cause of hypocalcemia as we have described above.
                                                                  • Serum phosphate: High level indicates end organ resistance or renal disease. Low value with high PTH suggests secondary hypoparathyroidism such as Vit D deficincy.
                                                                  • Alkaline phosphatase- a bone turnover marker (elevation in patient with hypocalcemia suggests vitamin D deficiency),
                                                                  • 25-hydroxyvitamin D (major circulating form of vitamin D and best marker of vitamin D status).
                                                                  • The blood 25-hydroxyvitamin D level corresponds with vitamin D intake and activity; the half-life of 25-hydroxyvitamin D is 2 to 3 weeks, as compared with a half-life of 4 to 6 hours for 1,25-dihydroxyvitamin D. (hence 25-hydroxy Vit D is measured).
                                                                  • amylase, lipase(for suspected pancreatitis), CPK (if suspect muscle breakdown), urine ca:creatinine ration (to determine abnormal renal calcium excretion and renal tubular reabsorption)
                                                                  • Adrenocorticotropin, cortisol, and thyroid-stimulating hormone, for suspected polyendocrine failure
                                                                  • Rahul we mentioned in our case the imaging and EKG as part of the presentation, what are salient points with regards to these diagnostic tests?
                                                                  • Imaging studies: x-ray of metaphysis of a long bone (such as wrist or knee). Hand images may show shortened fourth and fifth metacarpals and suggest pseudohypoparathyroidism type 1a. In hypoparathyroidism, skull x-ray may show intracerebral calcifications (such as basal ganglia calcifications). Chest radiograph to evaluate for rachitic rosary.
                                                                  • EKG: Prolonged QT interval on electrocardiogram as a result of ST-segment lengthening.
                                                                  • Consult with genetics if there is suspicion for a genetic cause.
                                                                  • In our patient: The total as well as serum ionized ca are low. there is appropriately elevated PTH as well as alkaline phosphatase, normal serum phosphate level, low 25 hydroxy vitamin D points to severe Vitamin D deficiency due to poor nutritional intake. (Nutritional Rickets)
                                                                  • If our history, physical, and diagnostic investigation led us to hypocalcemia due to Vitamin D deficiency what would be the management frame work?
                                                                  • Initial focus should be on providing good basic PICU care. Attention to airway, breathing and hemodynamics should be a priority in such patients.
                                                                  • Before diving into diagnostics, every attempt to correct abnormal values must be made and the levels frequently reassessed.
                                                                  • Calcium: If symptomatic or severe, EKG changes: can use 10% calcium gluconate or calcium chloride as boluses followed by calcium gluconate infusion, which should be titrated to maintain normal serum ionized ca levels.
                                                                  • Remember listeners that ca is a divalent cation so which other divalent cation would you want to also make sure is within reference range in your hypocalcemia management? You got it, magnesium. If patient has hypomagnesemia -correct magnesium concurrently, since hypocalcemia is refractory until magnesium deficiency is corrected.
                                                                  • You got it! So shifting back to our ca replacement management approach once patient can tolerate PO, they should be given calcium carbonate.
                                                                  • For patient with vitamin D deficiency or hypoparathyroidism: Supplementation with Vitamin D analogues: 1,25-dihydroxycholecalciferol (calcitriol), or Vitamin D3.
                                                                  • One thing to watch for as this childs calcium normalizes is the "hungry bone syndrome" a condition in which there is paradoxical worsening of hypocalcemia after initiation of vitamin D therapy. This condition is thought to be due to rapid bone-mineral uptake by the demineralized skeleton, and management may require very high doses of calcium, as well as occasional therapeutic doses of calcitriol (1,25-dihydroxyvitamin D), the active form of vitamin D.
                                                                  • How do we follow up on such patients and monitor their response to therapy: Follow blood levels of calcium, phosphate, 25-hydroxyvitamin D, PTH, and alkaline phosphatase and the urinary calcium:creatinine ratio approximately 4 weeks after the initiation of treatment and at monthly intervals until resolution of laboratory abnormalities. Most children will show improvement in about 3 months of their radiological abnormalities.
                                                                  • Pradip where can our listeners read more information about hypocalcemia ?
                                                                  • Rahul I would highly recommend that our listeners read the Case by Virkud Y et al published in NEJM 2020 (N Engl J Med 2020;383:2462-70. DOI: 10.1056/NEJMcpc2027078)
                                                                  • Also chapter 71 page 126-pages 877-878 of the latest edition of Furhmanns and Zimmerman's textbook of Pediatric Critical care has information on hypocalcemia.
                                                                  • Chapter 30, pages 930-933 Lucking et al. Pediatric Critical care Text and Study Guide Second edition volume 1.
                                                                  • These references will be in the show notes
                                                                  
                                                                  

                                                                  Alright to summarize today's take home points — remember that when you have hypocalcemia you care going to be twitchy. Remember the mnenonic CATS go NUMB which reviews the...]]>25de857b-4cbc-4924-b776-cc6af5a68217Sun, 29 Aug 2021 03:00:00 -040028:20falsefull2727Toxic Shock SyndromeWelcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.

                                                                  I'm Pradip Kamat and I'm Rahul Damania and we are coming to you from Children's Healthcare of Atlanta - Emory University School of Medicine.

                                                                  Welcome to our Episode of a 16 year old with fever and a rash.

                                                                  Here's the case:

                                                                  A 16 year old F presents to the PICU with generalized weakness, fever and a diffuse rash**.** Three days prior to admission she stated that she was feeling lightheaded and the day after she started having frequent non-bloody diarrhea. She states that she has otherwise been healthy, no sick contacts or travel, and the only change in her life was her menstrual cycle which ended a few days before her symptoms started. She says that about two weeks ago, she went to her primary care physician to get an in-grown toe nail drained, but was able to recover after some analgesia and antibiotics for a week. On day of admission her mother brings her into the ED as she says her rash continues to progress. Her mother states that the rash looks like a sunburn. Mother noticed on day of admission that her daughter now had red injected eyes bilaterally without discharge, and was becoming increasingly confused with her fevers. Of note, the patient has also has had decreased oral intake as she says her mouth quote hurts when she swallows. She has had no sore throat, congestion, dysuria, or headache. She presents to the ED febrile to 39 C and tachycardic to 130 bpm. She is ill appearing and has orthostatic vital signs. Her exam is notable for palpable diffuse myalgia, oropharyngeal hyperemia, diffuse erythroderma, and conjunctival injection. She is noted to have a hyperdynamic precordium and faint crackles bilaterally. Her L toe is mildly erythematous with no discharge, necrosis or pain to palpation. Acute resuscitation and diagnostics are begun and patient is transferred to the pediatric intensive care unit.

                                                                  To summarize key elements from this case, this patient has:

                                                                  • Hx of a fever and multisystem involvement including GI manifestations, myalgias, confusion, mucositis, and rash
                                                                  • This is in the setting of a local drainage procedure and course of antibiotics.
                                                                  • In addition, she presents now with fever, hypotension, and tachycardia.
                                                                  • These elements so far bring up a broad differential but for now we can agree that it seems that she has signs of acute inflammation or infection throughout her body.
                                                                  
                                                                  

                                                                  nsition into some history and physical exam components of this case.

                                                                  1. If we take a step back, what are key history features in a child who presents with fever & rash?
                                                                  
                                                                  
                                                                  • Understanding the characteristics of the rash, the evolution, and progression of the rash is important.
                                                                  • In the setting of myalgias, fever, headache, and rash you should think of assessing for any recent travel as tick-borne illnesses commonly present with this symptomatology.
                                                                  • You also want to assess for recent antibiotic exposures, sexual history, and surgical history - in our case, our patient had a recent procedure on her toe
                                                                  
                                                                  
                                                                  1. Are there some red-flag symptoms or physical exam components which you could highlight?
                                                                  
                                                                  
                                                                  • Absolutely, when a child presents with fever and a rash, it is important to stratify two major elements:
                                                                  
                                                                  
                                                                  1. You want to assess the degree of toxicity in relation to the symptomatology:
                                                                  2. Lethargy, irritatbility, altered sensorium, poor perfusion, pallor or cyanosis may indicate serious illness.
                                                                  3. Understanding the duration of fever in the setting of suspected total body inflammation is important, however the importance of the heigh of fever in predicting the risk of serious illness is unclear.
                                                                  4. We will visit a differential a bit later in this podcast, however I do want to highlight that the presence of tachycardia and tachypnea in any patient with fever and rash suggests the possibility of sepsis.
                                                                  5. When you notice these red-flag symptoms it is important to focus on resuscitation and treatment rather than pursuing diagnostics.
                                                                  
                                                                  
                                                                  • To continue with our case, our patients labs were consistent with:
                                                                  • An AKI - with her creatinine being three times the upper limit of normal.
                                                                  • A transaminitis and indirect hyperbilirubinemia.
                                                                  • Thrombocytopenia
                                                                  • Pyuria on UA with negative LE or nitrites.
                                                                  • And finally, an elevated CPK at 2000 units/L.
                                                                  • Looking ahead in this case, our patient had negative serologies for RMSF, leptospirosis, measles.
                                                                  
                                                                  

                                                                  Ok, to summarize, we have:

                                                                  • 16 yo F who presents with fever, diffuse erythroderma, signs of systemic inflammation, and multi-organ dysfunction all of which bring up concern for Toxic Shock Syndrome, the topic of our discussion today.
                                                                  • Let's start with a short multiple choice question:
                                                                  • A patient presents with fever and rash and concern for Staphylococcal Toxic Shock Syndrome. Which of the following describes the mechanism of pathogenesis behind this diagnosis?
                                                                  • A. Increased TLR-4 binding with LPS.
                                                                  • B. Endotoxin production.
                                                                  • C. Increased MHC II binding with T-cell receptor.
                                                                  • D. Cytokine release of TGF-beta and IL-10.
                                                                  • The answer is C. Increased MHC II binding with T-cell receptor. Staphylococcal Toxic Shock Syndrome characteristically has a TSST-1 exotoxin which is present in all of menstrual cases toxic shock syndrome and about half the non-menstrual cases of toxic shock syndrome. The interaction and stabilization between the antigen presenting cells and T-cell receptors cause a massive cytokine storm and thus this superAg can be one of the major virulence factors behind the multi-system involvement we see in toxic-shock-syndrome. Interestingly, one of the cytokines which is released in this syndrome is TNF and this inhibits neutrophil function. Data suggests that TSST-1 in addition to TNF do not engender Staph to have a purulent response and this may be due to lack of PMN recruitment.
                                                                  • As you think about our case, what would be your differential?
                                                                  • This is an interesting differential however given her symptomatology and disease progression I would focus my differential to infectious entities first. These include but are not limited to:
                                                                  • Disseminated Meningococcemia ( type of rash, lack of meningismus)
                                                                  • Rocky Mountain Spotted Fever (type of rash, exposure/travel history)
                                                                  • Leptospirosis (type of rash/ exposure to rodents feces and urine)
                                                                  • Dengue fever (bleeding besides arthralgias and rash)
                                                                  • Typhoid fever
                                                                  • Now Staph Scalded skin syndrome may have similar nomenclature and pathogenesis as TSS however they are slightly different. A review article published in Clinical Infectious Diseases in 2006, highlighted key differences between SSS and TSS. These included:
                                                                  • Age — as patients with TSS are older with a median age of 12...]]>Welcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.

                                                                    I'm Pradip Kamat and I'm Rahul Damania and we are coming to you from Children's Healthcare of Atlanta - Emory University School of Medicine.

                                                                    Welcome to our Episode of a 16 year old with fever and a rash.

                                                                    Here's the case:

                                                                    A 16 year old F presents to the PICU with generalized weakness, fever and a diffuse rash**.** Three days prior to admission she stated that she was feeling lightheaded and the day after she started having frequent non-bloody diarrhea. She states that she has otherwise been healthy, no sick contacts or travel, and the only change in her life was her menstrual cycle which ended a few days before her symptoms started. She says that about two weeks ago, she went to her primary care physician to get an in-grown toe nail drained, but was able to recover after some analgesia and antibiotics for a week. On day of admission her mother brings her into the ED as she says her rash continues to progress. Her mother states that the rash looks like a sunburn. Mother noticed on day of admission that her daughter now had red injected eyes bilaterally without discharge, and was becoming increasingly confused with her fevers. Of note, the patient has also has had decreased oral intake as she says her mouth quote hurts when she swallows. She has had no sore throat, congestion, dysuria, or headache. She presents to the ED febrile to 39 C and tachycardic to 130 bpm. She is ill appearing and has orthostatic vital signs. Her exam is notable for palpable diffuse myalgia, oropharyngeal hyperemia, diffuse erythroderma, and conjunctival injection. She is noted to have a hyperdynamic precordium and faint crackles bilaterally. Her L toe is mildly erythematous with no discharge, necrosis or pain to palpation. Acute resuscitation and diagnostics are begun and patient is transferred to the pediatric intensive care unit.

                                                                    To summarize key elements from this case, this patient has:

                                                                    • Hx of a fever and multisystem involvement including GI manifestations, myalgias, confusion, mucositis, and rash
                                                                    • This is in the setting of a local drainage procedure and course of antibiotics.
                                                                    • In addition, she presents now with fever, hypotension, and tachycardia.
                                                                    • These elements so far bring up a broad differential but for now we can agree that it seems that she has signs of acute inflammation or infection throughout her body.
                                                                    
                                                                    

                                                                    nsition into some history and physical exam components of this case.

                                                                    1. If we take a step back, what are key history features in a child who presents with fever & rash?
                                                                    
                                                                    
                                                                    • Understanding the characteristics of the rash, the evolution, and progression of the rash is important.
                                                                    • In the setting of myalgias, fever, headache, and rash you should think of assessing for any recent travel as tick-borne illnesses commonly present with this symptomatology.
                                                                    • You also want to assess for recent antibiotic exposures, sexual history, and surgical history - in our case, our patient had a recent procedure on her toe
                                                                    
                                                                    
                                                                    1. Are there some red-flag symptoms or physical exam components which you could highlight?
                                                                    
                                                                    
                                                                    • Absolutely, when a child presents with fever and a rash, it is important to stratify two major elements:
                                                                    
                                                                    
                                                                    1. You want to assess the degree of toxicity in relation to the symptomatology:
                                                                    2. Lethargy, irritatbility, altered sensorium, poor perfusion, pallor or cyanosis may indicate serious illness.
                                                                    3. Understanding the duration of fever in the setting of suspected total body inflammation is important, however the importance of the heigh of fever in predicting the risk of serious illness is unclear.
                                                                    4. We will visit a differential a bit later in this podcast, however I do want to highlight that the presence of tachycardia and tachypnea in any patient with fever and rash suggests the possibility of sepsis.
                                                                    5. When you notice these red-flag symptoms it is important to focus on resuscitation and treatment rather than pursuing diagnostics.
                                                                    
                                                                    
                                                                    • To continue with our case, our patients labs were consistent with:
                                                                    • An AKI - with her creatinine being three times the upper limit of normal.
                                                                    • A transaminitis and indirect hyperbilirubinemia.
                                                                    • Thrombocytopenia
                                                                    • Pyuria on UA with negative LE or nitrites.
                                                                    • And finally, an elevated CPK at 2000 units/L.
                                                                    • Looking ahead in this case, our patient had negative serologies for RMSF, leptospirosis, measles.
                                                                    
                                                                    

                                                                    Ok, to summarize, we have:

                                                                    • 16 yo F who presents with fever, diffuse erythroderma, signs of systemic inflammation, and multi-organ dysfunction all of which bring up concern for Toxic Shock Syndrome, the topic of our discussion today.
                                                                    • Let's start with a short multiple choice question:
                                                                    • A patient presents with fever and rash and concern for Staphylococcal Toxic Shock Syndrome. Which of the following describes the mechanism of pathogenesis behind this diagnosis?
                                                                    • A. Increased TLR-4 binding with LPS.
                                                                    • B. Endotoxin production.
                                                                    • C. Increased MHC II binding with T-cell receptor.
                                                                    • D. Cytokine release of TGF-beta and IL-10.
                                                                    • The answer is C. Increased MHC II binding with T-cell receptor. Staphylococcal Toxic Shock Syndrome characteristically has a TSST-1 exotoxin which is present in all of menstrual cases toxic shock syndrome and about half the non-menstrual cases of toxic shock syndrome. The interaction and stabilization between the antigen presenting cells and T-cell receptors cause a massive cytokine storm and thus this superAg can be one of the major virulence factors behind the multi-system involvement we see in toxic-shock-syndrome. Interestingly, one of the cytokines which is released in this syndrome is TNF and this inhibits neutrophil function. Data suggests that TSST-1 in addition to TNF do not engender Staph to have a purulent response and this may be due to lack of PMN recruitment.
                                                                    • As you think about our case, what would be your differential?
                                                                    • This is an interesting differential however given her symptomatology and disease progression I would focus my differential to infectious entities first. These include but are not limited to:
                                                                    • Disseminated Meningococcemia ( type of rash, lack of meningismus)
                                                                    • Rocky Mountain Spotted Fever (type of rash, exposure/travel history)
                                                                    • Leptospirosis (type of rash/ exposure to rodents feces and urine)
                                                                    • Dengue fever (bleeding besides arthralgias and rash)
                                                                    • Typhoid fever
                                                                    • Now Staph Scalded skin syndrome may have similar nomenclature and pathogenesis as TSS however they are slightly different. A review article published in Clinical Infectious Diseases in 2006, highlighted key differences between SSS and TSS. These included:
                                                                    • Age — as patients with TSS are older with a median age of 12 years compared to 4 years with SSS.
                                                                    • Presence of bullae that rupture with light pressure (i.e. are nikolsky sign +) due to SSS's exofoliative toxin.
                                                                    • And lack of mucous membrane involvement which can stratify this from TSS and other severe exfoliative skin conditions.
                                                                    • Sepsis or septic shock due to other pathogens is important to have at the top of your differential. Gram negative, fungal pathogens, or culture negative sepsis may clasicilly not be associated with rash but making the empiric diagnosis at the bedside upon presentation is key.
                                                                    • Ok so we covered differentials related to fever and rash that are infectious in nature. Are there other broad categories to consider?
                                                                    • Yes, inflammatory causes are important to also pursue:
                                                                    • Drug reactions may have fever, systemic symptoms, and dermatological involvement. These include Steven Johnsons syndrome (SJS), Toxic epidermal necrolysis (TEN), or DRESS syndrome.
                                                                    • I would also add COVID-19 related multi inflammatory syndrome to our differential and its close mimicker Kawasaki disease.
                                                                    • Especially when a child presents with a prodrome of fever for 5 days and systemic signs of inflammation, you should think about Kawasaki disease and also its severe manifestations, namely myocarditis.
                                                                    • That was a great differential. Before we continue, we want to revisit some key points from our case that narrowed our differential to Staphylococcal Toxic shock syndrome and cover some brief points regarding this condition:
                                                                    • Firstly, we classically are tested in board exams of the retained tampon leading to TSS however in actuality menstrual cases of TSS are on the decline. This decrease may be explained by the withdrawal of highlight absorbent tampons and the absence of polyacrylate rayon-containing products from the market. Nonetheless, doing a pelvic exam is important to assess for retained tampons.
                                                                    • At least half of reported Staphylococcal TSS cases are not related to menstruation and thus a variety of clinical circumstances can be associated. In our case, post procedure or surgical wound infections can be a trigger but the literature also cites burns and even respiratory infections such as the flu. In a report of 5300 TSS cases over a decade, the proportion of TSS cases following surgical procedures increased from 15 percent to about 27 percent. The case-fatality rate for non menstrual TSS was 5%.
                                                                    • Secondly I want to highlight Streptococcal TSS. Surgical triggers may be common in history but in diving into the literature it seems that Streptococcal TSS has more of a virulent nature. These patients present with:
                                                                    • Myonecrosis and a necrotizing fasciitis picture often with no visible break in the skin.
                                                                    • They can have coagulopathy liver dysfunction and ARDS
                                                                    • Typically you will isolate GAS from a normally sterile site but I wanted to highlight this phenomena as these patients can present with vascular collapse!
                                                                    
                                                                    

                                                                    Let’s conclude by going through a diagnostic and management framework for TSS:

                                                                    • If you had to work up this patient with TSS, what would be your diagnostic approach?
                                                                    • Routine blood tests:
                                                                    • CBC'd
                                                                    • CMP
                                                                    • Lactate
                                                                    • Blood gas
                                                                    • & coagulation studies is where I would start
                                                                    • In our case with myositis getting a CK is reasonable
                                                                    • Microbiological testing including 2 sets of blood cultures, UA, urine cultures, and as mentioned blood cultures will be important.
                                                                    • I would also consider getting a wound culture if there is a surgical site abnormality along with inflammatory markers.
                                                                    • Key point It is important to do a pelvic exam and nasopharyngeal exam to isolate any foreign or retained bodies as you want to really establish source control
                                                                    • Of note, blood and sterile site cultures are positive for S. aureus in <5% of toxic shock cases, and testing for TSST is typically an academic exercise.
                                                                    • If our history, physical, and diagnostic investigation led us to Toxic Shock Syndrome as our diagnosis what would be your general management of framework?
                                                                    • Great question, I first off want to say that there have been none to very few randomized trials or evidence-based guidelines defining treatment regimens.
                                                                    • You will not go wrong in the early stages to parallel the management of septic shock. This includes:
                                                                    • Aggressive fluid resuscitation use of vasopressors or inotropes
                                                                    • Initiation of broad spectrum antibiotics
                                                                    • Supportive measures such as mechanical ventilation or renal replacement therapy when indicated. In a paper published in Annals of IM in 2005, renal dysfunction and central nervous system involvement are common and may occur more often in non menstrual TSS
                                                                    • I think a key element here is to support end organ dysfunction and also treat the underlying cause - in this case it is the source control.
                                                                    • What antibiotic regimen would you recommend:
                                                                    • Clindamycin with Vancomycin can be an initial therapy.
                                                                    • Studies have cited that the addition of clindamycin as a protein synthesis inhibitor can have the potential to suppress toxin production. Clindamycin is often added for its in vitro ability to suppress toxin production as well as evidence that clindamycin may reduce mortality in patients with streptococcal toxic shock syndrome. This was well defined in an older study published in 1997 which showed toxic shock syndrome toxin-1 (TSST-1) production is completely inhibited by clindamycin in logarithmic and stationary phase growth.
                                                                    • Excellent review on this, I would also encourage clinicians to consult Pediatric Infectious Disease as their invaluable expertise & following of culture data is crucial.
                                                                    • Once you get culture data, you can narrow to more MSSA tailored antibiotics like:
                                                                    • Nafcillin or oxacillin
                                                                    • Is there a role for IVIg?
                                                                    • No trials evaluating use in staphylococcal toxic shock syndrome have been identified. However there have been case reports showing efficacy in streptococcal toxic shock syndrome. In vitro data shows that Staph aureus superantigens are less effectively inhibited by IVIG than streptococcal Ag. The Red Book suggests that there could be a potential role for IV Ig in patient with fluid refractory TSS as IVIg may play a role in neutralizing toxin. You should consider this in patients who are critically ill, unresponsive to fluid resuscitation, an undrainable infection, pulmonary edema, and oliguria.
                                                                    • And finally to add, Use of corticosteroids therapy is controversial. There seems to be a potential survival benefit in animal models.
                                                                    • Invitro studies show that dexamethasone suppresses TSST-1-induced cytokine production. In a study published in 1984 in JAMA, early adjunctive treatment with corticosteroids may be associated with reduced severity and duration of toxic shock syndrome symptoms but not decreased mortality. The current AAP Red Book does not mention a role for steroids.
                                                                    
                                                                    ]]>42c43836-2721-401a-b5e5-bba6949c6848Sun, 22 Aug 2021 03:00:00 -040019:52falsefull2626Shock in the Setting of Recent TravelWelcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.

                                                                    I'm Pradip Kamat and I'm Rahul Damania and we are coming to you from Children's Healthcare of Atlanta - Emory University School of Medicine.

                                                                    Welcome to our PICU Doc On Call Mini-Case series. In this episode, we present a 15 year old girl who is admitted for shock after returning from her recent travel to NIgeria.

                                                                    Here's the case:

                                                                    13y F with no significant past medical history presents with 4 days of fever, headache, watery, non-bloody diarrhea, non-bloody, non-bilious emesis, decreased PO intake with worsening myalgias, fatigue, and weakness. She had traveled with her mother to Nigeria earlier this month and returned a week ago. Over the weekend mom consulted her pediatrician who prescribed an antiemetic without significant improvement of her symptoms. Once patient progressed to becoming light headed and weak, the mom decided to bring her to ED where she was found to be have tachycardia and hypotension. She required 3 L of crystalloid resuscitation was started an epinephrine continuous infusion and transferred to the PICU. Patient was found to have acute kidney injury with an elevated Cr, as well as a primarily direct hyperbilirubinemia and associated anemia and thrombocytopenia.

                                                                    Her other history elements were notable for fever and difficulty breathing. Prior to traveling to Nigeria she did receive travel vaccinations and took mefloquine prophylaxis. She also had a negative COVID screen. While in Nigeria she denies exposure to animals, raw food intake, and only recalls that she may have had a few mosquito bites but this was well after returning from Nigeria until 7 days prior to presentation to the ED.

                                                                    She presents to the PICU with hypotension, tachycardia at 160 bpm, tachypnea, and normal saturations. Her physical exam is notable for cool peripheral extremities, RUQ tenderness, and bilateral crackles.

                                                                    She had no murmurs or gallops on her initial exam. Pertinently, she had no rash, lymphadenopathy or scleral icterus.

                                                                    • This is a teenage girl who has fever and constitutional symptoms after returning from travel abroad
                                                                    • She now presents with fluid refractory shock, tachycardia that is out of proportion to dehydration and signs of end-organ failure.
                                                                    • Notable negatives include: No LNadenopathy, hepatosplenomegaly, or a rash
                                                                    • Synthesizing these symptoms together → we are thinking that this picture may be related to a contracted infection or inflammatory condition related to her travel.
                                                                    • Let's transition into some history and physical exam components of this case.
                                                                    
                                                                    
                                                                    1. What are key history features in this child who presents with fever and shock after a recent travel outside the US (Nigeria-West Africa)
                                                                    
                                                                    
                                                                    • Diarrhea and emesis days before presentation
                                                                    • High Fever with no rash
                                                                    • Mental status is maintained although she did have an headache
                                                                    • Light headed and weakness are symptoms suggestive of dehydration and even shock
                                                                    • Physical exam findings of importance here include- patient presenting with tachycardia, signs of poor perfusion such as delayed cap refill, cool extremities, hypotension. It is unique that even though she has RUQ pain there is no jaundice.
                                                                    
                                                                    

                                                                    2. Are there some red-flag symptoms or physical exam components which you could highlight in a

                                                                    patient with the above history and recent travel.

                                                                    • Weakness, light-headedness, shock, tachycardia, poor perfusion, fever and evidence of multi-organ dysfunction are suggestive of an acute and possibly life threatening infection acquired during travel. Given her travel to West Africa: I would be worried about falciparum malaria, dengue fever, typhoid fever, and cholera. Other diseases to be concerned about especially given her travel h/o include leptospirosis, chickungunya, Crimean-Congo hemorrhagic fever, African tick bite fever etc. I would be also concerned about bacterial sepsis with a source such as the kidney, bowel, or intrapelvic organs.
                                                                    • To continue with our case, the patients labs were consistent with:
                                                                    • Anemia 11/33, thrombocytopenia 12, and leukopenia WBC 4.55 with 92% segs. On her smear her RBC morphology was described as normal.
                                                                    • Elevated BUN and creatinine with no acidemia
                                                                    • Elevated liver enzymes (AST/ALT and Tbilirubin). Although her synthetic liver function was preserved
                                                                    • Elevated lactate, a BNP of 309 and troponin of 11.5.
                                                                    • Given her fever and travel history the ED team also sent a blood culture (large volume) and a thick and thin smears for malaria. In the PICU after consulting with ID service , we sent GI PCR, Dengue serology IgM and IgG) and NS-1 antigen.
                                                                    • We also did an EKG, ECHO (given her tachycardia and shock).
                                                                    • The lab personnel called to report that a malarial parasite was seen at 0.8% on the smear. The ID attending who examined the smear confirmed multiple ring forms in cells which goes along with Plasmodium falciparum, but unable to exclude different types of Malaria. A PCR for speciation of type of malaria was also sent.
                                                                    
                                                                    

                                                                    OK to summarize, we have a:

                                                                    • 13 yo female who presented with, fever, shock, and multi-organ dysfunction with a h/o recent travel. Given the findings of falciparum malaria on her blood smears, we confirm a diagnosis of falciparum malaria in this patients. Although her parasitemia level is < 5%, her clinical presentation of shock, AKI suggests she has severe malaria.
                                                                    • Let's start with a short multiple choice question:
                                                                    • A patient with severe Falciparum malaria who presents in shock, AKI and a parasite level of 10%, and inability to keep PO medications due to emesis, which of the following in the initial drug of choice?
                                                                    • A. Quinidine
                                                                    • B. Artemesin
                                                                    • C. Artensunate
                                                                    • D. Doxycycline
                                                                    • Correct answer is C. Artensunate given IV. As recommended by the CDC as well as the American Academy of Pediatrics' Red book. IV Quinidine is no longer available in the US.
                                                                    • Artemesin can be used if patient can tolerate PO while awaiting IV Artensunate. Drugs like doxycycline are slow acting antimalarials that would not take effect until well after 24 hours and are not effective in severe malaria. Other PO medications which can be used include artemether-lumefantrine (Coartem™) because of its fast onset of action as well as atovaquone-proguanil (Malarone), quinine, and mefloquine. As for any malaria treatment, the interim regimen should not include the medication used for chemoprophylaxis if possible.
                                                                    • As you think about our case, what would be your differential?
                                                                    • Broadly speaking you want to think about other causes of fever, and shock with multiorgan dysfunction in a traveler returning to the US, I would think of
                                                                    • Sepsis (pyelonephritis, pneumonia, ruptured appendicitis, ovarian abscess etc.): Negative blood culture
                                                                    • Leptospirosis (no exposure to rodent or food contaminated with rodents urine or feces. No conjunctivitis, rash or jaundice)
                                                                    • Typhoid fever (GI PCR would confirm)
                                                                    • Dengue (no rash or muscle/joint or eye pain
                                                                    • Chickungunya (no joint pain or rash, argues against this)
                                                                    • Ebola (lack of conjunctivitis, DIC/hemorrhage)
                                                                    • Food poisoning and hypovolemic shock (fever would be unlikely)
                                                                    • Always think of SARS-COV-2 especially in this child who is not vaccinated. Her presentation with fever, GI symptoms and shock could be a manifestation of MIS-C. (SARS CoV-2 Ab negative)
                                                                    • Rahul if a patient develops a fever or symptoms 21 days after travel to a foreign country certain disease such as dengue, rickettsial infections, Zika virus infection, and viral hemorrhagic fevers are unlikely, regardless of the traveler’s exposure history.
                                                                    • Infectious causes may be further narrowed by pretravel vaccinations and chemoprophylaxis, although neither approach is 100% effective like our patient who did not take her mefloquine correctly. The incubation period (time to onset of malaria symptoms) in most cases ranges from as soon as 7 days after being bitten by an infected mosquito to about 30 days and is shortest for P falciparum and longest for P malariae
                                                                    • If you had to work up this patient with severe malaria what would be some of the lab investigations you would send:
                                                                    • Fever in a returning traveler requires a good history and a physical examination. Besides a complete blood count with differential, comprehensive metabolic panel, CRP, Procal, blood Cx (large volume), UA/UCx and in a patient with shock and poor perfusion- I would send a lactate, get a chest radiograph, EKG and an echocardiograph.
                                                                    • After consulting with infectious diseases: I would send thick and thin (to speciate type of parasite) blood films to test for malaria parasite. The thick film allows for concentration of the blood to find parasites that may be present at low density, whereas the thin film is most useful for species identification and determination of the density of red blood cells infected with parasites. If initial blood smears test negative for Plasmodium species but malaria remains a possibility, the smear should be repeated every 12 to 24 hours during a...]]>Welcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.

                                                                      I'm Pradip Kamat and I'm Rahul Damania and we are coming to you from Children's Healthcare of Atlanta - Emory University School of Medicine.

                                                                      Welcome to our PICU Doc On Call Mini-Case series. In this episode, we present a 15 year old girl who is admitted for shock after returning from her recent travel to NIgeria.

                                                                      Here's the case:

                                                                      13y F with no significant past medical history presents with 4 days of fever, headache, watery, non-bloody diarrhea, non-bloody, non-bilious emesis, decreased PO intake with worsening myalgias, fatigue, and weakness. She had traveled with her mother to Nigeria earlier this month and returned a week ago. Over the weekend mom consulted her pediatrician who prescribed an antiemetic without significant improvement of her symptoms. Once patient progressed to becoming light headed and weak, the mom decided to bring her to ED where she was found to be have tachycardia and hypotension. She required 3 L of crystalloid resuscitation was started an epinephrine continuous infusion and transferred to the PICU. Patient was found to have acute kidney injury with an elevated Cr, as well as a primarily direct hyperbilirubinemia and associated anemia and thrombocytopenia.

                                                                      Her other history elements were notable for fever and difficulty breathing. Prior to traveling to Nigeria she did receive travel vaccinations and took mefloquine prophylaxis. She also had a negative COVID screen. While in Nigeria she denies exposure to animals, raw food intake, and only recalls that she may have had a few mosquito bites but this was well after returning from Nigeria until 7 days prior to presentation to the ED.

                                                                      She presents to the PICU with hypotension, tachycardia at 160 bpm, tachypnea, and normal saturations. Her physical exam is notable for cool peripheral extremities, RUQ tenderness, and bilateral crackles.

                                                                      She had no murmurs or gallops on her initial exam. Pertinently, she had no rash, lymphadenopathy or scleral icterus.

                                                                      • This is a teenage girl who has fever and constitutional symptoms after returning from travel abroad
                                                                      • She now presents with fluid refractory shock, tachycardia that is out of proportion to dehydration and signs of end-organ failure.
                                                                      • Notable negatives include: No LNadenopathy, hepatosplenomegaly, or a rash
                                                                      • Synthesizing these symptoms together → we are thinking that this picture may be related to a contracted infection or inflammatory condition related to her travel.
                                                                      • Let's transition into some history and physical exam components of this case.
                                                                      
                                                                      
                                                                      1. What are key history features in this child who presents with fever and shock after a recent travel outside the US (Nigeria-West Africa)
                                                                      
                                                                      
                                                                      • Diarrhea and emesis days before presentation
                                                                      • High Fever with no rash
                                                                      • Mental status is maintained although she did have an headache
                                                                      • Light headed and weakness are symptoms suggestive of dehydration and even shock
                                                                      • Physical exam findings of importance here include- patient presenting with tachycardia, signs of poor perfusion such as delayed cap refill, cool extremities, hypotension. It is unique that even though she has RUQ pain there is no jaundice.
                                                                      
                                                                      

                                                                      2. Are there some red-flag symptoms or physical exam components which you could highlight in a

                                                                      patient with the above history and recent travel.

                                                                      • Weakness, light-headedness, shock, tachycardia, poor perfusion, fever and evidence of multi-organ dysfunction are suggestive of an acute and possibly life threatening infection acquired during travel. Given her travel to West Africa: I would be worried about falciparum malaria, dengue fever, typhoid fever, and cholera. Other diseases to be concerned about especially given her travel h/o include leptospirosis, chickungunya, Crimean-Congo hemorrhagic fever, African tick bite fever etc. I would be also concerned about bacterial sepsis with a source such as the kidney, bowel, or intrapelvic organs.
                                                                      • To continue with our case, the patients labs were consistent with:
                                                                      • Anemia 11/33, thrombocytopenia 12, and leukopenia WBC 4.55 with 92% segs. On her smear her RBC morphology was described as normal.
                                                                      • Elevated BUN and creatinine with no acidemia
                                                                      • Elevated liver enzymes (AST/ALT and Tbilirubin). Although her synthetic liver function was preserved
                                                                      • Elevated lactate, a BNP of 309 and troponin of 11.5.
                                                                      • Given her fever and travel history the ED team also sent a blood culture (large volume) and a thick and thin smears for malaria. In the PICU after consulting with ID service , we sent GI PCR, Dengue serology IgM and IgG) and NS-1 antigen.
                                                                      • We also did an EKG, ECHO (given her tachycardia and shock).
                                                                      • The lab personnel called to report that a malarial parasite was seen at 0.8% on the smear. The ID attending who examined the smear confirmed multiple ring forms in cells which goes along with Plasmodium falciparum, but unable to exclude different types of Malaria. A PCR for speciation of type of malaria was also sent.
                                                                      
                                                                      

                                                                      OK to summarize, we have a:

                                                                      • 13 yo female who presented with, fever, shock, and multi-organ dysfunction with a h/o recent travel. Given the findings of falciparum malaria on her blood smears, we confirm a diagnosis of falciparum malaria in this patients. Although her parasitemia level is < 5%, her clinical presentation of shock, AKI suggests she has severe malaria.
                                                                      • Let's start with a short multiple choice question:
                                                                      • A patient with severe Falciparum malaria who presents in shock, AKI and a parasite level of 10%, and inability to keep PO medications due to emesis, which of the following in the initial drug of choice?
                                                                      • A. Quinidine
                                                                      • B. Artemesin
                                                                      • C. Artensunate
                                                                      • D. Doxycycline
                                                                      • Correct answer is C. Artensunate given IV. As recommended by the CDC as well as the American Academy of Pediatrics' Red book. IV Quinidine is no longer available in the US.
                                                                      • Artemesin can be used if patient can tolerate PO while awaiting IV Artensunate. Drugs like doxycycline are slow acting antimalarials that would not take effect until well after 24 hours and are not effective in severe malaria. Other PO medications which can be used include artemether-lumefantrine (Coartem™) because of its fast onset of action as well as atovaquone-proguanil (Malarone), quinine, and mefloquine. As for any malaria treatment, the interim regimen should not include the medication used for chemoprophylaxis if possible.
                                                                      • As you think about our case, what would be your differential?
                                                                      • Broadly speaking you want to think about other causes of fever, and shock with multiorgan dysfunction in a traveler returning to the US, I would think of
                                                                      • Sepsis (pyelonephritis, pneumonia, ruptured appendicitis, ovarian abscess etc.): Negative blood culture
                                                                      • Leptospirosis (no exposure to rodent or food contaminated with rodents urine or feces. No conjunctivitis, rash or jaundice)
                                                                      • Typhoid fever (GI PCR would confirm)
                                                                      • Dengue (no rash or muscle/joint or eye pain
                                                                      • Chickungunya (no joint pain or rash, argues against this)
                                                                      • Ebola (lack of conjunctivitis, DIC/hemorrhage)
                                                                      • Food poisoning and hypovolemic shock (fever would be unlikely)
                                                                      • Always think of SARS-COV-2 especially in this child who is not vaccinated. Her presentation with fever, GI symptoms and shock could be a manifestation of MIS-C. (SARS CoV-2 Ab negative)
                                                                      • Rahul if a patient develops a fever or symptoms 21 days after travel to a foreign country certain disease such as dengue, rickettsial infections, Zika virus infection, and viral hemorrhagic fevers are unlikely, regardless of the traveler’s exposure history.
                                                                      • Infectious causes may be further narrowed by pretravel vaccinations and chemoprophylaxis, although neither approach is 100% effective like our patient who did not take her mefloquine correctly. The incubation period (time to onset of malaria symptoms) in most cases ranges from as soon as 7 days after being bitten by an infected mosquito to about 30 days and is shortest for P falciparum and longest for P malariae
                                                                      • If you had to work up this patient with severe malaria what would be some of the lab investigations you would send:
                                                                      • Fever in a returning traveler requires a good history and a physical examination. Besides a complete blood count with differential, comprehensive metabolic panel, CRP, Procal, blood Cx (large volume), UA/UCx and in a patient with shock and poor perfusion- I would send a lactate, get a chest radiograph, EKG and an echocardiograph.
                                                                      • After consulting with infectious diseases: I would send thick and thin (to speciate type of parasite) blood films to test for malaria parasite. The thick film allows for concentration of the blood to find parasites that may be present at low density, whereas the thin film is most useful for species identification and determination of the density of red blood cells infected with parasites. If initial blood smears test negative for Plasmodium species but malaria remains a possibility, the smear should be repeated every 12 to 24 hours during a 72-hour period, ideally with at least 3 smears. Serologic testing (rapid diagnostic test or RDT) generally is not helpful. PCR is most useful to confirm species of malaria. If there is diarrhea and vomiting then a GI PCR and testing for SARS-COV-2 maybe useful. If there are respiratory symptoms respiratory viral panel which includes SARS-COV-2 must be performed. Serologic testing for dengue, chikungunya, leptospirosis and rickettsioses may be required. If there is fever with abdominal pain or tenderness- suspect acute cholangitis (stones, liver flukes), liver abscess (pyogenic or amoebic)-may need ultrasound, blood cultures or stool examination. Practitioners to keep in mind that the returning traveler may present with ruptured appendicitis, UTI/pyelonephritis, pancreatitis etc). These conditions need to be sought with appropriate lab and imaging.
                                                                      
                                                                      

                                                                      To summarize - thick smears finds the parasites whereas thin is for species identification

                                                                      • If our history, physical, and diagnostic investigation led us to severe malaria as our diagnosis what would be your general management of framework?
                                                                      • Let me reiterate that a patient is said to have severe malaria if the patient's parasite load is ≥ 5% or the patient has any of the following:
                                                                      • Impaired consciousness, Seizures, Circulatory collapse/shock, Pulmonary edema or acute respiratory distress syndrome (ARDS), Acidosis, Acute kidney injury, Abnormal bleeding or disseminated intravascular coagulation (DIC), Jaundice (must be accompanied by at least one other sign) and Severe anemia (Hb <7 g/dL).
                                                                      • Cerebral malaria, characterized by altered mental status and manifesting with a range of neurologic signs and symptoms, including generalized seizures, signs of increased intracranial pressure (confusion and progression to stupor or coma), and death
                                                                      • Any patient with severe malaria requires admission to the PICU as there can be rapid decline in the patients clinical status. Initial management of airway, breathing followed by resuscitation with balanced intravenous fluids should be started. Frequent checks as well as correction of glucose and electrolyte imbalances is recommended as well as close monitoring of urine output.
                                                                      • Rahul our patient had mild cardiomegaly on CXR, mildly depressed cardiac function (LV and RV) on echo and mild elevation of her BNP and troponin. Can you shed some light on myocardial depression in patients with severe malaria?
                                                                      • Pradip-initially our patient presented in shock so a quick echo done at bedside revealed some mild-moderate cardiac dysfunction with no pericardial effusion. An EKG revealed diffuse ST segment elevation. Patient was on epinephrine and MIlrinone for her cardiac dysfunction. Her echo+ekg findings along with elevated biomarkers were strongly suggestive of malarial myocarditis. Mainstay of treatment consists of hemodynamic cardiac support and treatment of the underlying malarial infection. We saw gradual improvement of her cardiac function with malaria therapy. In fact a cardiac MRI done prior to discharge was completely normal.
                                                                      
                                                                      

                                                                      A recent paper by Kotlyar et al in PCCM journal (2018; 19:179–185) reported on myocardial function and Injury by echocardiography and cardiac biomarkers in African Children with severe plasmodium falciparum malaria. The authors reported from their echocardiographic data that most children (96.2%) with severe P. falciparum malaria have normal EF despite some elevation of the cardiac biomarkers. Although there was evidence for myocardial injury (elevated cardiac troponin I), this did not correlate with cardiac dysfunction.

                                                                      • Pradip Let's go into specific elements of management, how would you treat severe malaria
                                                                      • CDC malaria clinicians are on call 24/7 to provide advice to healthcare providers on the diagnosis and treatment of malaria and can be reached through the CDC Malaria Hotline
                                                                      • For severe malaria: IV artensunate is the drug of choice . If patient is able to take PO, the patient should be treated with artemether-lumefantrine (Coartem™) because of its fast onset of action, or atovaquone-proguanil (Malarone). When IV artesunate arrives, immediately discontinue the oral medication and start parenteral treatment. Each dose of IV artesunate is 2.4 mg/kg. A dose of IV artesunate should be given at 0, 12, and 24 hours. Patients on treatment for severe malaria should have one set of blood smears (thick and thin smear) performed every 12–24 hours until a negative result (no Plasmodium parasites are detected) is reported. If, after the 3rd IV artesunate dose, the patient’s parasite density is >1%, IV artesunate treatment should be continued with the recommended dose once a day for a maximum of 7 days until parasite density is ≤1%. Doses given at 0, 12, and 24 hours count as 1 day, which means up to 6 additional days. Clinicians should proceed with full course of oral follow-on treatment as above as soon as parasite density ≤1% and the patient is able to tolerate oral medications.
                                                                      • Intravenous artesunate is safe in infants, children, and pregnant women in the second and third trimesters. The only formal contraindication to IV artesunate treatment is known allergy to IV artemisinins.
                                                                      • All persons treated for severe malaria with IV artesunate should be monitored weekly for up to four weeks after treatment initiation for evidence of hemolytic anemia.
                                                                      • As for any malaria treatment, the regimen selection should not include the medication used for chemoprophylaxis.
                                                                      • Previously, CDC recommended exchange transfusion be considered for certain severely ill persons. However, exchange transfusion has not been proven beneficial in an adequately powered randomized controlled trial. In 2013, CDC conducted an analysis of cases of severe malaria treated with exchange transfusion and was unable to demonstrate a survival benefit of the procedure. Considering this evidence, CDC no longer recommends the use of exchange transfusion as an adjunct procedure for the treatment of severe malaria.
                                                                      
                                                                      

                                                                      This concludes our PICU Mini case Series Episode on Fever and shock in the PICU patient after recent travel . We hope you found value in our short, case-based podcast. We welcome you to share your feedback, subscribe & place a review on our podcast! Please visit our website picudoconcall.org which showcases our episodes as well as our Doc on Call management cards. PICU Doc on Call is hosted by myself Pradip Kamat and Dr. Rahul Damania. Stay tuned for our next episode! Thank you!

                                                                      • More information can be found
                                                                      • Thwaites G and Day Nicholas PJ. Approach to fever in the returning traveler. N Engl J Med 2017; 376:548-560
                                                                      • AAP Red Book 2021. Page 493-503
                                                                      • Gupta et al, "Malaria and the Heart: JACC State-Of-The-Art Review." J Am Coll Cardiol. 2021 Mar, 77 (8) 1110–1121,
                                                                      • Kotlyar S, Olupot-Olupot P, Nteziyaremye J, et al.Assessment of Myocardial Function and Injury by Echocardiography and Cardiac Biomarkers in African Children With Severe Plasmodium falciparum Malaria. Pediatric Critical Care Medicine 2018; 19:179–185
                                                                      
                                                                      ]]>efa363d6-8a95-426e-86bf-069bc1c776a2Sun, 15 Aug 2021 03:00:00 -040024:07falsefull2525Hypernatremia in the PICUWelcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.

                                                                      I'm Pradip Kamat and I'm Rahul Damania and we are coming to you from Children's Healthcare of Atlanta - Emory University School of Medicine.

                                                                      Welcome to our Episode of a 9 year old girl with worsening seizures in the setting of an electrolyte abnormality.

                                                                      Here's the case:

                                                                      A 9 year old girl presents to the ED with increased frequency of seizures, dehydration and listlessness. She has h/o of global developmental delay, congenital hydrocephalous (with VP shunt in place with her last revision 3 years prior, and seizure d/o treated with Leviteracetam. She usually has one or two focal seizures per day but on day of admission she had multiple prolonged seizures which were also generalized tonic clonic in semiology. Per her caregiver, the patient usually eats by mouth and mother typically gives her 3 cups of water daily. There is no history of diarrhea but patient has had 2-3 bouts of non-bloody non-bilous emesis on day of presentation. Looking at her growth chart, the patient has also lost ~ 2KG of her weight in the last 3 months and has had poor follow up with her PCP. In the ED she has a hypovolemic shock picture as she is hypothermic, tachycardic, tachpneic, and hypotensive with appropriate saturations. Blood gas is notable for a mild metabolic acidosis. Patient receives abortive seizure rescue. A head CT showed no increased in hydrocephalus, no mass or hemorrhage and a shunt series confirms patency of her VP shunt. Most pertinently to this case, her serum sodium on her RFP was undetectable at a value of = >200mEQ/dL; this was confirmed by a repeat lab draw and POC value. Other notable findings included an elevated Cr for age, an elevated BUN and a microcytic anemia. Patient was given a NS bolus, had cultures drawn, was started on broad spectrum abx therapy, stabilized and sent to the PICU.

                                                                      To summarize key elements from this case, this patient has:

                                                                      • A history of GDD with epilepsy and shunted hydrocephalus.
                                                                      • A stigmata of cachexia.
                                                                      • And a presentation of hypovolemic shock secondary to decreased intake, increased loss, and potential underlying concern for sepsis.
                                                                      • The most important element of this case is her extreme hypernatremia
                                                                      • All of these factors in this case point to our topic of discussion today → the approach to hypovloemic hypernatremia 2/2 to dehydration.
                                                                      • Let's transition into some history and physical exam components of hypovolemic hypernatremia?
                                                                      
                                                                      
                                                                      1. Key history features in patients who present with Hypovolemic HyperNa include:
                                                                      
                                                                      
                                                                      • Increased losses such as emesis
                                                                      • Decreased intake, and in this setting potentially lack of access to free water
                                                                      • Listlessness which could be related to cerebral hypoperfusion
                                                                      • Increase in seizure frequency due to increased rapid depolarization of Na channels in the brain and fluid shifts
                                                                      • And weight loss → all of these factors were seen in our case.
                                                                      • Of note if this patient was a neonate considering a high-pitched cry in the setting of hyperNa & dehydration could be a subtle history finding.
                                                                      
                                                                      
                                                                      1. Are there some red-flag symptoms or physical exam components which you could highlight?
                                                                      
                                                                      
                                                                      • Our patient is Non verbal and has global delay secondary to a remote neurological insult
                                                                      • She may not have intact ability to communicate or vocalize thirst.
                                                                      • Apart from her mucous membranes, dry cracked lips, decreased skin turgor that can be described as doughy, and prolonged capillary refill, I think it is important to highlight her hypotension - as BP is one of the last vital signs in pediatrics to be abnormal in intravascular volume depletion. To me, this really stratifies this patient into severe dehydration and potentially septic shock.
                                                                      
                                                                      

                                                                      This is a great point — understanding % volume loss and its correlation to vital sign and PE anomalies is key. Remember a sensitive marker for dehydration in pediatrics is tachycardia and a late finding if you are primarily dealing with dehydration is hypotension. This indicates that counter-regulatory responses are unable to maintain adequate systemic vascular resistance (SVR) and that there is a significant loss of intravascular volume. In our patient, we also noticed her weight loss on presentation which not only brings up the concern for malnutrition but it also serves as an adjunct measure of dehydration. In fact, in a 2009 paper assessing dehydration in pediatrics it was noted that the gold standard for confirming the diagnosis of hypovolemia in children is comparison of body weight before and after rehydration.

                                                                      • To continue with our case, the patients labs were consistent with:
                                                                      • Severe Hypernatremia
                                                                      • Elevated BUN and Cr which point to an AKI
                                                                      • And interestingly mild anemia → this could be a nutritional aberrancy such as iron deficiency anemia or anemia of chronic disease in the setting of her complex underlying condition but it also brings up the concern for hypovolemic shock secondary to bleeding. Pertinently she had no signs of external or internal bleeding, but it is important to stratify this element as your resuscitation efforts — i.e. whether you would give crystalloid or colloid can be guided by this subtlety.
                                                                      
                                                                      

                                                                      Correct, it is important to highlight that in the setting of dehydration Hct values would be increased. In a 2006 Study in Transfusion, Valeri and colleagues concluded that the Hct values in hypovolemic anemic patients are elevated because the plasma volume does not increase to achieve the normovolemic anemic state.

                                                                      OK to summarize, we have:

                                                                      • 9 year old with global developmental delay who has emesis, dehydration and a serum Na of 200 mEq/L. This brings to the topic of our discussion today namely hypernatremia in the PICU.
                                                                      • Let's start with a short multiple choice question: 15 year old with h/o diabetes insipidus presents with a serum Na of 175mEq/L. 4 months ago his serum Na was 140mEq/L. Currently patient is obtunded with decreased skin turgor, fever and a blood pressure of 140/80 mmHg. Patient has been stressed due to school work and been non compliant with his DDAVP resulting in polyuria for almost 5 days.
                                                                      • Treatment goal for this patient is
                                                                      
                                                                      

                                                                      a. Reduce serum sodium concentration to normal in first 12 hours

                                                                      b. Reduce serum sodium concentration to normal in 24 hours

                                                                      c. Reduce serum sodium concentration to 150 mEq/L in 24 hours

                                                                      d. Reduce serum sodium concentration by 10 mEq/L in 24 hours

                                                                      The correct answer is d. Reduce serum concentration by 10-12 mEq/L in first 24 hours; you can also think of this as not correcting the sodium more than 0.5 meQ/L per hour → thus in 24 hrs you should not lower the sodium by more than 12. I think listeners should remember that it is important to gradually lower the sodium in patients who have developed hypernatremia slowly over a period of days especially when Na is > 165mEq/L. Pradip, why is this?

                                                                      • Patients with hypernatremia develop idiogenic osmoles to protect the brain from dehydration within hours. Numerous fatal cases of cerebral edema and herniation have occurred with rapid correction over a 24-hour period, leading to recommendations for correction over no less than 48 hours. General trend is for slow correction over 48 hours.
                                                                      
                                                                      

                                                                      A mnemonic that can be useful is high to low the brain will blow; i.e. if a patient has chronic hypernatremia that is corrected too acutely,...]]>Welcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.

                                                                      I'm Pradip Kamat and I'm Rahul Damania and we are coming to you from Children's Healthcare of Atlanta - Emory University School of Medicine.

                                                                      Welcome to our Episode of a 9 year old girl with worsening seizures in the setting of an electrolyte abnormality.

                                                                      Here's the case:

                                                                      A 9 year old girl presents to the ED with increased frequency of seizures, dehydration and listlessness. She has h/o of global developmental delay, congenital hydrocephalous (with VP shunt in place with her last revision 3 years prior, and seizure d/o treated with Leviteracetam. She usually has one or two focal seizures per day but on day of admission she had multiple prolonged seizures which were also generalized tonic clonic in semiology. Per her caregiver, the patient usually eats by mouth and mother typically gives her 3 cups of water daily. There is no history of diarrhea but patient has had 2-3 bouts of non-bloody non-bilous emesis on day of presentation. Looking at her growth chart, the patient has also lost ~ 2KG of her weight in the last 3 months and has had poor follow up with her PCP. In the ED she has a hypovolemic shock picture as she is hypothermic, tachycardic, tachpneic, and hypotensive with appropriate saturations. Blood gas is notable for a mild metabolic acidosis. Patient receives abortive seizure rescue. A head CT showed no increased in hydrocephalus, no mass or hemorrhage and a shunt series confirms patency of her VP shunt. Most pertinently to this case, her serum sodium on her RFP was undetectable at a value of = >200mEQ/dL; this was confirmed by a repeat lab draw and POC value. Other notable findings included an elevated Cr for age, an elevated BUN and a microcytic anemia. Patient was given a NS bolus, had cultures drawn, was started on broad spectrum abx therapy, stabilized and sent to the PICU.

                                                                      To summarize key elements from this case, this patient has:

                                                                      • A history of GDD with epilepsy and shunted hydrocephalus.
                                                                      • A stigmata of cachexia.
                                                                      • And a presentation of hypovolemic shock secondary to decreased intake, increased loss, and potential underlying concern for sepsis.
                                                                      • The most important element of this case is her extreme hypernatremia
                                                                      • All of these factors in this case point to our topic of discussion today → the approach to hypovloemic hypernatremia 2/2 to dehydration.
                                                                      • Let's transition into some history and physical exam components of hypovolemic hypernatremia?
                                                                      
                                                                      
                                                                      1. Key history features in patients who present with Hypovolemic HyperNa include:
                                                                      
                                                                      
                                                                      • Increased losses such as emesis
                                                                      • Decreased intake, and in this setting potentially lack of access to free water
                                                                      • Listlessness which could be related to cerebral hypoperfusion
                                                                      • Increase in seizure frequency due to increased rapid depolarization of Na channels in the brain and fluid shifts
                                                                      • And weight loss → all of these factors were seen in our case.
                                                                      • Of note if this patient was a neonate considering a high-pitched cry in the setting of hyperNa & dehydration could be a subtle history finding.
                                                                      
                                                                      
                                                                      1. Are there some red-flag symptoms or physical exam components which you could highlight?
                                                                      
                                                                      
                                                                      • Our patient is Non verbal and has global delay secondary to a remote neurological insult
                                                                      • She may not have intact ability to communicate or vocalize thirst.
                                                                      • Apart from her mucous membranes, dry cracked lips, decreased skin turgor that can be described as doughy, and prolonged capillary refill, I think it is important to highlight her hypotension - as BP is one of the last vital signs in pediatrics to be abnormal in intravascular volume depletion. To me, this really stratifies this patient into severe dehydration and potentially septic shock.
                                                                      
                                                                      

                                                                      This is a great point — understanding % volume loss and its correlation to vital sign and PE anomalies is key. Remember a sensitive marker for dehydration in pediatrics is tachycardia and a late finding if you are primarily dealing with dehydration is hypotension. This indicates that counter-regulatory responses are unable to maintain adequate systemic vascular resistance (SVR) and that there is a significant loss of intravascular volume. In our patient, we also noticed her weight loss on presentation which not only brings up the concern for malnutrition but it also serves as an adjunct measure of dehydration. In fact, in a 2009 paper assessing dehydration in pediatrics it was noted that the gold standard for confirming the diagnosis of hypovolemia in children is comparison of body weight before and after rehydration.

                                                                      • To continue with our case, the patients labs were consistent with:
                                                                      • Severe Hypernatremia
                                                                      • Elevated BUN and Cr which point to an AKI
                                                                      • And interestingly mild anemia → this could be a nutritional aberrancy such as iron deficiency anemia or anemia of chronic disease in the setting of her complex underlying condition but it also brings up the concern for hypovolemic shock secondary to bleeding. Pertinently she had no signs of external or internal bleeding, but it is important to stratify this element as your resuscitation efforts — i.e. whether you would give crystalloid or colloid can be guided by this subtlety.
                                                                      
                                                                      

                                                                      Correct, it is important to highlight that in the setting of dehydration Hct values would be increased. In a 2006 Study in Transfusion, Valeri and colleagues concluded that the Hct values in hypovolemic anemic patients are elevated because the plasma volume does not increase to achieve the normovolemic anemic state.

                                                                      OK to summarize, we have:

                                                                      • 9 year old with global developmental delay who has emesis, dehydration and a serum Na of 200 mEq/L. This brings to the topic of our discussion today namely hypernatremia in the PICU.
                                                                      • Let's start with a short multiple choice question: 15 year old with h/o diabetes insipidus presents with a serum Na of 175mEq/L. 4 months ago his serum Na was 140mEq/L. Currently patient is obtunded with decreased skin turgor, fever and a blood pressure of 140/80 mmHg. Patient has been stressed due to school work and been non compliant with his DDAVP resulting in polyuria for almost 5 days.
                                                                      • Treatment goal for this patient is
                                                                      
                                                                      

                                                                      a. Reduce serum sodium concentration to normal in first 12 hours

                                                                      b. Reduce serum sodium concentration to normal in 24 hours

                                                                      c. Reduce serum sodium concentration to 150 mEq/L in 24 hours

                                                                      d. Reduce serum sodium concentration by 10 mEq/L in 24 hours

                                                                      The correct answer is d. Reduce serum concentration by 10-12 mEq/L in first 24 hours; you can also think of this as not correcting the sodium more than 0.5 meQ/L per hour → thus in 24 hrs you should not lower the sodium by more than 12. I think listeners should remember that it is important to gradually lower the sodium in patients who have developed hypernatremia slowly over a period of days especially when Na is > 165mEq/L. Pradip, why is this?

                                                                      • Patients with hypernatremia develop idiogenic osmoles to protect the brain from dehydration within hours. Numerous fatal cases of cerebral edema and herniation have occurred with rapid correction over a 24-hour period, leading to recommendations for correction over no less than 48 hours. General trend is for slow correction over 48 hours.
                                                                      
                                                                      

                                                                      A mnemonic that can be useful is high to low the brain will blow; i.e. if a patient has chronic hypernatremia that is corrected too acutely, you have the potential to develop cerebral edema. In a landmark study published in NEJM in 2015, the authors concluded that rapid correction of hypernatremia can lead to cerebral edema to the relative inability of the brain to extrude idiogenic osmoles. Furthermore a study published in pediatric emergency care in 2013 showed that serum sodium correction rate > 0.5 mEq/L/hour was associated with increased risk of mortality and convulsion in neonates with hypernatremia dehydration admitted to neonatal intensive care unit.

                                                                      Rahul: what would be some of the anatomic changes seen in the brain due to the resultant hyperosmolarity from hypernatremia?

                                                                      • Anatomic changes seen with the hyperosmolar state include loss of volume of brain cells with resultant tearing of cerebral vessels due to local ECM shear stress forces. As you have an imbalance in frank starling capillary mechanics and subsequent flow through your cerebral vasculature, you may also see capillary and venous congestion, subcortical or subarachnoid bleeding, and interestingly, venous sinus thrombosis.
                                                                      
                                                                      

                                                                      I'd like to make a big point about the phenomena of sinus venous thrombosis as this has been well described in Pediatric Review articles. Taking it back to the basics, Virchow's triad gives us a framework on how to think about mechanisms of thrombosis. During hypernatremic dehydration at a micro-level there is endothelial stress and subsequent injury which can subsequently lead to venous sinus thrombosis. These patients can present with altered mental status, severe headache, and seizures.

                                                                      Rahul, that was a great framework → as we conclude our podcast, Iets hone in on three areas: a schema in understanding hypernatremia, a diagnostic approach, and finally a management framework.

                                                                      In general, how do you think about hypernatremia?

                                                                      • I think Pradip one easy way to approach hypernatremia is to think of it as a water loss problem or a salt gain problem. Hypernatremia can exist as any of the following 3 scenarios, and these are all correlated to total body water.
                                                                      • First, low total body water: Patients with a low total body water and hypernatremia have a loss of water in relative excess of sodium losses. This can occur from vomiting and diarrhea or renal losses from osmotic diuresis.
                                                                      • Second Normal Total body Water: Loss of water occurs without excessive sodium losses in some conditions → these patients are going to be relatively euvolemic. Extrarenal losses result from increased respiratory losses as may occur with tachypnea, hyperventilation, or mechanical ventilation with inadequate humidification are examples of this phenomena.
                                                                      • We also think about further insensible loss scenarios such as transcutaneous losses associated with fever, burns, extreme prematurity, or use of phototherapy or radiant warmers in the neonate without adequate water replacement. In general, another well-described cause of euvolemic hypernatremia is DI which can be a podcast in and of itself!
                                                                      • Finally we think about increase in total body sodium and subsequent total body water: Usually from iatrogenic causes such as administration of Na HCO3, hypertonic saline or improperly concentrated infant formula.
                                                                      • In a 2017 systematic review the authors looked at acute sodium toxicity due to dietary intake. They cited factors such as social media challenges and even charities that advocated eating small amount of salt to empathize with Syrian refugees. They concluded that a lethal dose of <5 teaspoons of salt ingested acutely can lead to pediatric fatality.
                                                                      • If you had to work up this patient with hypernatremia what would be your diagnostic approach?
                                                                      • I would highly suggest getting a nephrology consult in this patient.
                                                                      • A comprehensive metabolic panel, Urine analysis
                                                                      • Urine analysis especially of the first urine specimen preferably prior to rehydration to determine specific gravity
                                                                      • If you are suspecting DI, getting urine Na and electrolytes may be indicated
                                                                      • In this our patient case, she presented with increased seizures and altered sensorium, thus A CT scan of the head is recommended to evaluate for hemorrhage and shunt malfunction.
                                                                      • Due to hypothermia a blood culture, urine CX, a CBC with diff, CRP and procal would be useful. As this child has concern for increased catabolism in the setting of failure to thrive and lack of access getting a CPK to rule out rhabdomyolysis as a cause of intrinsic AKI would be useful.
                                                                      • Finally a renal US may be necessary based on laboratory and urinary findings.
                                                                      
                                                                      

                                                                      I like this list Pradip, totally agree that a coordinated effort with nephrology can help in this setting as these patients may have renal dysfunction and there can be a collaborative effort in tracking electrolytes after we choose the appropriate rehydration fluid management. I would also recommend tracking weights as a part of your initial diagnostic plan!

                                                                      • Our history physical and investigational undertaking has led us to severe hypernatremia as our diagnosis what would be your general management of framework?
                                                                      • Patient needs to be adequately resuscitated to correct hypotension, protection of airway, and if necessary AEDs to control of seizures. Continuous EEG monitoring must be considered especially if patient is intubated. Most importantly, correction of underlying disease process giving rise to hypernatremia should be the goal. In our case it was dehydration due to lack of access to free water.
                                                                      • Gradual correction of serum hypernatremia ~ 12-15 mEq/L/day. Frequent monitoring of serum Na(Q2 hr initially), as well as close eye on UOP
                                                                      • As hypernatremia is toxic to the beta islet cells, their dysfunction can lead to associated hyperglycemia.
                                                                      • Estimated deficits, ongoing maintenance requirements, and additional excessive losses must be accounted for in calculations of the amount of fluid replacement required. In general 2-2.5 times maintenance IVF fluids usually with NACl is necessary especially with severe dehydration.
                                                                      • In a precise academic approach calculating the free water deficit may be helpful:
                                                                      • The equation is:
                                                                      • 0.6 x wt (kg) x [(current Na+/140) – 1] = this gives you liters of fluids:
                                                                      • In acute dehydration you can take this fluid deficit and resusicate 50% of the volume you calculate over the first 12 hrs, and the remaining in the next 24 hrs could be a potential management strategy.
                                                                      • If patient has central DI: Vasopressin, DDAVP along with replacement of UOP may be needed.
                                                                      • In hypernatremic dehydration, the intracellular fluid moves into the extravascular space due to hypernatremia hence the patients dehydration may be underestimated.
                                                                      • If patient has renal failure dialysis may be necessary
                                                                      
                                                                      ]]>0468dda7-9563-4518-b75e-d2fd7fbfff95Sun, 08 Aug 2021 03:00:00 -040021:01falsefull2424PICU Bugs and Drugs: Rational Use of Antibiotics In The PICUWelcome to PICU Doc On Call, a podcast dedicated to current and aspiring intensivists. My name is Pradip Kamat

                                                                      and my name is Rahul Damania and we come to you from Children's Healthcare of Atlanta Emory University School of Medicine. Today's episode is dedicated to the rational use of antibiotics in the PICU

                                                                      We are delighted to be joined by two brilliant Pediatric clinical pharmacists Ms Whitney Moore and Ms. Stephanie Yasechko from Children's Healthcare of Atlanta.

                                                                      I will turn it over to Rahul to start with our patient case...

                                                                      • Case
                                                                      
                                                                      

                                                                      An 8-year-old female (24 kg, 130 cm) with PMH significant for severe persistent asthma and history of multiple PICU admissions presents to the ED with swelling, redness and inability to bear weight in her (L) lower leg.

                                                                      Patient had just finished soccer practice the evening prior to her ED visit when she first noticed swelling and redness of her left lower leg. She also had a fever as well as some non-bloody, non-bilious emesis. Her past h/o is significant for poorly controlled asthma with multiple admissions to the PICU.

                                                                      Upon arrival to the ED, patient's BP was hypotensive, tachycardic, and tachypneic. She was given two 20 mL/kg NS boluses, and blood cultures were drawn in addition to a CBC, BMP, and UA.

                                                                      Labs were notable for an elevated white count, lactate, and serum Cr. Patient was given a dose of antibiotic, and transported to the PICU for further workup and management.

                                                                      Whitney and Stephanie welcome to PICU Doc on call.

                                                                      Thanks Rahul and Pradip for having us. Neither one of us have any financial disclosures or conflicts of interest.

                                                                      We want to divide today's discussion into 3 segments- antibiotic selection, transition into dosing and end with therapeutic monitoring

                                                                      Whitney, what are some of the factors to consider prior to choosing an antibiotic regimen in our patient case with a preliminary diagnosis of cellulitis of the left lower extremity with possible sepsis?

                                                                      • Whitney: First and foremost you want to consider your host so really diving deep into the patient’s past medical history and secondly we should consider the likely pathogens that are causing the patient’s infection. In this case given the invasive nature of her infection and recent hospital admissions I would start Vancomycin and Cefepime. Once blood cultures results are back, we can then tailor or narrow her antibiotics based on susceptibilities.
                                                                      
                                                                      

                                                                      Stephanie what are some of the other factors to consider prior to starting antibiotics in this patient?

                                                                      • Other things to consider include her multiple previous hospitalizations, significant exposure to broad-spectrum antibiotics, whether or not she is immunocompromised, the presence of chronic conditions like lung disease, ventilator/trach dependency, and if patient was a resident of a long term care facility. Additionally any history of organ or bone marrow transplant or malignancy with use of chemotherapy/radiation, and/or a history of growth of multiple drug resistant organisms.
                                                                      
                                                                      

                                                                      This is an important point - infectious disease is not just about the relevant pathogen or "bug" but it is also about understanding the host status!

                                                                      Stephanie -why vancomycin and cefepime in this case?

                                                                      • In this patient the major pathogens to consider include: P. aeruginosa (give her multiple previous PICU admissions).
                                                                      • Also she has extensive cellulitis which necessitates antibiotic coverage against Methicillin resistant staph aureus (MRSA) and Streptococcus pyogenes . So our options in this case include vancomycin for broad-spectrum gram positive coverage, and generally either piperacillin/tazobactam or cefepime for broad-spectrum gram negative and pseudomonal coverage.
                                                                      • As you can see by patient’s Scr, it appears that she is presenting in AKI since we have no history of her having any type of renal impairment at baseline; therefore, to minimize additional AKI risk, cefepime would be our most appropriate choice for the time being. There is literature that shows us that the combination of vancomycin and piperacillin/tazobactam specifically has a much higher risk of AKI than other nephrotoxic combinations and should be avoided if possible.
                                                                      
                                                                      

                                                                      Whitney lets now transition from abx selection to dosing — how would you dose vancomycin and cefepime in our patient case?

                                                                      • An appropriate dose of vancomycin to start out here would be 15 mg/kg, with a maximum of 1000 mg. However, instead of scheduling a defined frequency, pharmacy would recommend a x1 dose, and check a level in a couple of hours in patients who present with any type of unstable renal function. However, traditional vancomycin dosing in patients with normal renal function is either 20 mg/kg/dose IV every 8 hours or 15 mg/kg/dose IV every 6 hours with a max of 1000 mg/dose.
                                                                      • Cefepime is traditionally dosed at 50 mg/kg/dose IV every 8 hours; however, since our patient has AKI, we should calculate her CrCl or estimated GFR to renally adjust the dose. As you all know there are a couple of equations we could use to calculate her clearance. But the modified Bedside Schwartz equation is the gold standard for pediatric patients. Once the GFR or CrCl is calculated we can then adjust the dose for her AKI.
                                                                      
                                                                      

                                                                      I think this is a great time to start to highlight the importance of collaboration between the intensivists, nursing & the pharmacy team. These children already are tenuous and as we treat with broad spectrum abx it is important to also consider the side effects such as nephrotoxicity of broad spectrum antibiotics.

                                                                      As we discussed specifics of dosing of Vanc and Cefepime, Stephanie, if we take a step back what are some of the other factors to consider prior to antibiotic dosing?

                                                                      • In terms of selecting the most appropriate dose, we always want to consider factors like age, weight, renal/hepatic function, as well as the area in the body we wish to penetrate (CNS, bone, blood, etc.).
                                                                      • Additionally, it is very important to identify whether or not the patient is currently receiving continuous renal replacement therapy(CRRT), plasma exchange, ECMO, or fluids and/or diuretics, because all of these can affect drugs quite significantly from a pharmacokinetic standpoint.
                                                                      • Lexicomp (available either as a paper-back or online) is the gold standard for pediatric dosing. And of course your clinical pharmacist specialist is always available to help with dosing references, and can provide recommendations on how to most appropriately dose your specific patient
                                                                      
                                                                      

                                                                      Whitney how would you monitor the patient given evidence of AKI and the need for a nephrotoxic antibiotic such as vancomycin?

                                                                      • Depending on the severity of the renal dysfunction, the vancomycin level can be checked anywhere from 8-24 hours post administration
                                                                      • A therapeutic steady-state drug concentration is generally reached after the administration of about 3-4 doses (or 4 to 5 half-lives). The therapeutic goal trough level is 10-15 mcg/mL for all infections, except for those harder to penetrate areas like the CNS or the heart. In these cases the target trough is higher at 15-20 mcg/mL.
                                                                      
                                                                      

                                                                      To summarize, those "hard to reach areas" such as the blood brain barrier or the heart — we should ensure a higher trough in order for us to reach therapeutic effect.

                                                                      Stephanie, what are important points regarding trough monitoring for vancomycin?

                                                                      • Trough monitoring represents a therapeutic controversy within the pharmacy community, as recent vancomycin dosing guidelines have changed to now recommend area under the curve (AUC) guided monitoring as the most efficacious and safe way to monitor the drug given its narrow therapeutic range and increased nephrotoxic risk with trough monitoring.
                                                                      • Here at our institution, we have not yet fully incorporated this new monitoring technique. We are reserving AUC monitoring for patients with MRSA bacteremia or unable to achieve therapeutic troughs with traditional dosing.
                                                                      
                                                                      

                                                                      This is a great practical example, as the bedside staff it is important to optimize communication as antibiotic troughs are time sensitive.

                                                                      Now that we have discussed vancomycin, Stephanie what about dosing and monitoring of cefepime in our patient?

                                                                      • Cefepime, does not require therapeutic drug monitoring, so determination of an appropriate dose is dependent on CrCL, and it is important to recognize that continuous adjustments may need to be made as renal function improves or declines.
                                                                      • Refer to Lexicomp for all renal dose adjustments. Rule of thumb, if CrCL > 50, a patient can be dosed normally. Anything less should be evaluated.
                                                                      
                                                                      

                                                                      Let's wrap up this section by summarizing some important dosing points for Vancomycin and Cefepime. Whitney, as your patient improves how would you approach de-escalation of abx?

                                                                      • There are two important points I want you to remember when dosing vancomycin and cefepime. First, is knowing the maximum dose of each medication. Cefepime we max the dose at 2000 mg per dose, and our initial starting dose maximum for vancomycin is 1000 mg, as mentioned. We can go up to 1250 but only after we have drawn levels and need to. But knowing the maximum dose is an important point to consider when dosing a large patient because you don’t want to exceed an adult dose. The second important point I want you to remember is calculating the patient’s clearance and adjusting the dose and/or...]]>Welcome to PICU Doc On Call, a podcast dedicated to current and aspiring intensivists. My name is Pradip Kamat

                                                                        and my name is Rahul Damania and we come to you from Children's Healthcare of Atlanta Emory University School of Medicine. Today's episode is dedicated to the rational use of antibiotics in the PICU

                                                                        We are delighted to be joined by two brilliant Pediatric clinical pharmacists Ms Whitney Moore and Ms. Stephanie Yasechko from Children's Healthcare of Atlanta.

                                                                        I will turn it over to Rahul to start with our patient case...

                                                                        • Case
                                                                        
                                                                        

                                                                        An 8-year-old female (24 kg, 130 cm) with PMH significant for severe persistent asthma and history of multiple PICU admissions presents to the ED with swelling, redness and inability to bear weight in her (L) lower leg.

                                                                        Patient had just finished soccer practice the evening prior to her ED visit when she first noticed swelling and redness of her left lower leg. She also had a fever as well as some non-bloody, non-bilious emesis. Her past h/o is significant for poorly controlled asthma with multiple admissions to the PICU.

                                                                        Upon arrival to the ED, patient's BP was hypotensive, tachycardic, and tachypneic. She was given two 20 mL/kg NS boluses, and blood cultures were drawn in addition to a CBC, BMP, and UA.

                                                                        Labs were notable for an elevated white count, lactate, and serum Cr. Patient was given a dose of antibiotic, and transported to the PICU for further workup and management.

                                                                        Whitney and Stephanie welcome to PICU Doc on call.

                                                                        Thanks Rahul and Pradip for having us. Neither one of us have any financial disclosures or conflicts of interest.

                                                                        We want to divide today's discussion into 3 segments- antibiotic selection, transition into dosing and end with therapeutic monitoring

                                                                        Whitney, what are some of the factors to consider prior to choosing an antibiotic regimen in our patient case with a preliminary diagnosis of cellulitis of the left lower extremity with possible sepsis?

                                                                        • Whitney: First and foremost you want to consider your host so really diving deep into the patient’s past medical history and secondly we should consider the likely pathogens that are causing the patient’s infection. In this case given the invasive nature of her infection and recent hospital admissions I would start Vancomycin and Cefepime. Once blood cultures results are back, we can then tailor or narrow her antibiotics based on susceptibilities.
                                                                        
                                                                        

                                                                        Stephanie what are some of the other factors to consider prior to starting antibiotics in this patient?

                                                                        • Other things to consider include her multiple previous hospitalizations, significant exposure to broad-spectrum antibiotics, whether or not she is immunocompromised, the presence of chronic conditions like lung disease, ventilator/trach dependency, and if patient was a resident of a long term care facility. Additionally any history of organ or bone marrow transplant or malignancy with use of chemotherapy/radiation, and/or a history of growth of multiple drug resistant organisms.
                                                                        
                                                                        

                                                                        This is an important point - infectious disease is not just about the relevant pathogen or "bug" but it is also about understanding the host status!

                                                                        Stephanie -why vancomycin and cefepime in this case?

                                                                        • In this patient the major pathogens to consider include: P. aeruginosa (give her multiple previous PICU admissions).
                                                                        • Also she has extensive cellulitis which necessitates antibiotic coverage against Methicillin resistant staph aureus (MRSA) and Streptococcus pyogenes . So our options in this case include vancomycin for broad-spectrum gram positive coverage, and generally either piperacillin/tazobactam or cefepime for broad-spectrum gram negative and pseudomonal coverage.
                                                                        • As you can see by patient’s Scr, it appears that she is presenting in AKI since we have no history of her having any type of renal impairment at baseline; therefore, to minimize additional AKI risk, cefepime would be our most appropriate choice for the time being. There is literature that shows us that the combination of vancomycin and piperacillin/tazobactam specifically has a much higher risk of AKI than other nephrotoxic combinations and should be avoided if possible.
                                                                        
                                                                        

                                                                        Whitney lets now transition from abx selection to dosing — how would you dose vancomycin and cefepime in our patient case?

                                                                        • An appropriate dose of vancomycin to start out here would be 15 mg/kg, with a maximum of 1000 mg. However, instead of scheduling a defined frequency, pharmacy would recommend a x1 dose, and check a level in a couple of hours in patients who present with any type of unstable renal function. However, traditional vancomycin dosing in patients with normal renal function is either 20 mg/kg/dose IV every 8 hours or 15 mg/kg/dose IV every 6 hours with a max of 1000 mg/dose.
                                                                        • Cefepime is traditionally dosed at 50 mg/kg/dose IV every 8 hours; however, since our patient has AKI, we should calculate her CrCl or estimated GFR to renally adjust the dose. As you all know there are a couple of equations we could use to calculate her clearance. But the modified Bedside Schwartz equation is the gold standard for pediatric patients. Once the GFR or CrCl is calculated we can then adjust the dose for her AKI.
                                                                        
                                                                        

                                                                        I think this is a great time to start to highlight the importance of collaboration between the intensivists, nursing & the pharmacy team. These children already are tenuous and as we treat with broad spectrum abx it is important to also consider the side effects such as nephrotoxicity of broad spectrum antibiotics.

                                                                        As we discussed specifics of dosing of Vanc and Cefepime, Stephanie, if we take a step back what are some of the other factors to consider prior to antibiotic dosing?

                                                                        • In terms of selecting the most appropriate dose, we always want to consider factors like age, weight, renal/hepatic function, as well as the area in the body we wish to penetrate (CNS, bone, blood, etc.).
                                                                        • Additionally, it is very important to identify whether or not the patient is currently receiving continuous renal replacement therapy(CRRT), plasma exchange, ECMO, or fluids and/or diuretics, because all of these can affect drugs quite significantly from a pharmacokinetic standpoint.
                                                                        • Lexicomp (available either as a paper-back or online) is the gold standard for pediatric dosing. And of course your clinical pharmacist specialist is always available to help with dosing references, and can provide recommendations on how to most appropriately dose your specific patient
                                                                        
                                                                        

                                                                        Whitney how would you monitor the patient given evidence of AKI and the need for a nephrotoxic antibiotic such as vancomycin?

                                                                        • Depending on the severity of the renal dysfunction, the vancomycin level can be checked anywhere from 8-24 hours post administration
                                                                        • A therapeutic steady-state drug concentration is generally reached after the administration of about 3-4 doses (or 4 to 5 half-lives). The therapeutic goal trough level is 10-15 mcg/mL for all infections, except for those harder to penetrate areas like the CNS or the heart. In these cases the target trough is higher at 15-20 mcg/mL.
                                                                        
                                                                        

                                                                        To summarize, those "hard to reach areas" such as the blood brain barrier or the heart — we should ensure a higher trough in order for us to reach therapeutic effect.

                                                                        Stephanie, what are important points regarding trough monitoring for vancomycin?

                                                                        • Trough monitoring represents a therapeutic controversy within the pharmacy community, as recent vancomycin dosing guidelines have changed to now recommend area under the curve (AUC) guided monitoring as the most efficacious and safe way to monitor the drug given its narrow therapeutic range and increased nephrotoxic risk with trough monitoring.
                                                                        • Here at our institution, we have not yet fully incorporated this new monitoring technique. We are reserving AUC monitoring for patients with MRSA bacteremia or unable to achieve therapeutic troughs with traditional dosing.
                                                                        
                                                                        

                                                                        This is a great practical example, as the bedside staff it is important to optimize communication as antibiotic troughs are time sensitive.

                                                                        Now that we have discussed vancomycin, Stephanie what about dosing and monitoring of cefepime in our patient?

                                                                        • Cefepime, does not require therapeutic drug monitoring, so determination of an appropriate dose is dependent on CrCL, and it is important to recognize that continuous adjustments may need to be made as renal function improves or declines.
                                                                        • Refer to Lexicomp for all renal dose adjustments. Rule of thumb, if CrCL > 50, a patient can be dosed normally. Anything less should be evaluated.
                                                                        
                                                                        

                                                                        Let's wrap up this section by summarizing some important dosing points for Vancomycin and Cefepime. Whitney, as your patient improves how would you approach de-escalation of abx?

                                                                        • There are two important points I want you to remember when dosing vancomycin and cefepime. First, is knowing the maximum dose of each medication. Cefepime we max the dose at 2000 mg per dose, and our initial starting dose maximum for vancomycin is 1000 mg, as mentioned. We can go up to 1250 but only after we have drawn levels and need to. But knowing the maximum dose is an important point to consider when dosing a large patient because you don’t want to exceed an adult dose. The second important point I want you to remember is calculating the patient’s clearance and adjusting the dose and/or frequency based on the patients renal function if needed.
                                                                        • Now, in regards to de-escalation of antibiotics, once the patient is no longer septic, with a resolved AKI, and cultures and susceptibilities have resulted, the team will determine if a full treatment course is warranted or not. If it is, then broad-spectrum antibiotics can be discontinued, and we can narrow to an antibiotic that the patient's pathogen is susceptible to.
                                                                        
                                                                        

                                                                        This is an important point — narrowing broad spectrum antimicrobials optimizes antibiotic stewardship.

                                                                        As we build on our case, Stephanie, if the blood culture grew Methicillin sensitive staph Aureus (MSSA) what antibiotic would be used and how will it be dosed?

                                                                        • When a patient's blood culture is positive for MSSA, it is considered an invasive infection. Most common sources of bacteremia include endocarditis, skin and soft tissue infections, intravascular catheter infections, bone and joint infections, pneumonia, etc. and in 25% there is no source.
                                                                        • MSSA can give rise to sepsis syndrome and septic shock with a mortality of 10-20%.
                                                                        • We typically use nafcillin or oxacillin 2 gm IV Q4 hours or even an infusion. One retrospective study reported that continuous oxacillin was an effective alternative to intermittent oxacillin for the treatment of infective endocarditis caused by MSSA and may improve microbiological cure.
                                                                        • Cefazolin can also be used. Patients who cannot be treated with beta-lactams, should be administered vancomycin or daptomycin. For uncomplicated bacteremia, a two week regimen is used. For complicated infection we typically do a 4-6 week course.
                                                                        • Finally, understanding that patients who have toxic shock syndrome from staphylococcal species, Clindamycin has been shown to have bacteriostatic effects and reduce production of bacterial toxins!
                                                                        
                                                                        

                                                                        Key points: MSSA likes to form a biofilm especially on internal hardware, and continuous oxacillin may be an effective option for treatment prior to consider removing the hardware for source control.

                                                                        Our final portion of this podcast relates to specific clinical scenarios. We will be covering broad spectrum therapy for specific patient populations. We will cover anti-microbial coverage for patients who have:

                                                                        1. Hematologic malignancies
                                                                        2. Solid organ transplant on immunosuppression
                                                                        3. Neontal sepsis
                                                                        4. Sickle cell
                                                                        
                                                                        

                                                                        and ...Children with:

                                                                        1. VP shunts
                                                                        2. Perforated appendicitis
                                                                        3. Lemierre's disease
                                                                        4. ...and finally the undifferentiated, critically ill, child.
                                                                        
                                                                        

                                                                        Whitney lets start with patients who have an underlying hematologic malignancies. What would be an initial empiric anti-microbial regimen for these patients?

                                                                        • We typically use Cefepime, or zosyn, for gram negative coverage to cover bugs like pseudomonas & enterobacteriaceae. And for enhanced Gram positive coverage for your staph and strep we add vancomycin especially if there is presence of a central line associated bloodstream infection (BSI), or if the patient has severe mucositis, a skin and soft tissue infection, pneumonia or is hemodynamically unstable).
                                                                        • If the patients fever continues with no source identification by about day 5 (4 to 7 window), consider adding an antifungal agent like micafungin or caspofungin. And if patient happens to already be on an antifungal for prophylaxis, consider adding voriconazole.
                                                                        
                                                                        

                                                                        And what about the the patient who has a solid organ transplant on immunosuppression who presents with septic shock?

                                                                        • In transplant patients or those on immunosuppression we should first consider the fact that some immunosuppressive medications are known to be nephrotoxic and interact with other medications. Second thing we should consider like I mentioned before is our host. If they are immune compromised they will need broader coverage. Therefore, the most appropriate choices would be vancomycin and cefepime. If the patient continues to clinically decompensated, then it would be appropriate to add on that antifungal coverage with micafungin.
                                                                        
                                                                        

                                                                        This is an important point - immuno-suppresants may compound end organ dysfunction and further, may have key drug interactions, such as CYP enzymes, which may alter your antimicrobial or antifungal kinetics.

                                                                        Stephanie, let's continue with our specific patient populations which antibiotics would we consider in neonatal sepsis?

                                                                        • Ampicillin +Cefotaxime OR Ampicillin +gentamicin but given shortage of cefotaxime we should consider ampicillin with ceftazidime.
                                                                        • We want to cover Group B streptococci, E Coli and other gram negatives along with listeria species.
                                                                        • Discontinue antibiotics if cultures are negative after 48 hours and suspicion for infection is low based on inflammatory markers.
                                                                        
                                                                        

                                                                        (Stephanie) What about the patient with fever, headache, altered sensorium concerning for bacterial meningitis, can you also comment on the patient with ventriculoperitoneal shunt infection and brain abscess?

                                                                        • So in this scenario, it is essential to select antimicrobials that penetrate the CNS. Therefore, generally speaking, an appropriate selection would be vancomycin and ceftriaxone. The more inflamed the meninges are, the greater CNS penetration you are going to get with vancomycin. We would also add metronidazole for brain abscess to vancomycin and ceftriaxone to cover for anaerobic organisms.
                                                                        
                                                                        

                                                                        The addition of Vancomycin combined with Ceftriaxone especially in patients who have meningitis and no hardware is important in overcoming resistant S. Pneumo strains.

                                                                        Whitney, what is our coverage for perforated appendicitis with sepsis?

                                                                        • For a perforated appendicitis with sepsis, piperacillin/tazobactam (Zosyn) is our preferred agent. Also the combination of Ampicillin +gentamicin + metronidazole can be used. When thinking of appendicitis you want to cover for your GI bugs like klebsiella, proteus, bacteroides and other anaerobes.
                                                                        • One thing to note when thinking about gut coverage is clindamycin's resistance to B. fragilis is increasing and is up to 60% worldwide, therefore, it’s no longer recommended for intra-abdominal infections.
                                                                        
                                                                        

                                                                        Stephanie, What about neck abscesses and septic thrombophlebitis (such as Lemierre syndrome)

                                                                        • A beta-lactamase resistant beta-lactam antibiotic (ampicillin/sulbactam) is recommended as an empiric therapy due to case reports of treatment failures with penicillin secondary to beta-lactamase producing F. necrophorum.
                                                                        • Antibiotics should of course be tailored to the culture results and susceptibility data when available.
                                                                        • Alternative options include clindamycin or metronidazole for patients with significant clinical allergy to beta-lactams. Clindamycin is preferred (for head, neck and lung anaerobic infections) as it has activity against metronidazole-resistant organisms such as actinomycetes and peptostreptococci.
                                                                        
                                                                        

                                                                        (Allen BW, Anjum F, Bentley TP. Lemierre Syndrome. [Updated 2020 Dec 4]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK499846.)

                                                                        It is important for us to highlight that the likely microbe associated with Lemierre's is Fusobacterium necrophorum!

                                                                        Whitney, lets conclude with our final patient population. What is your typical coverage in patient with Sickle cell disease who presents with sepsis, or acute chest syndrome?

                                                                        • Levofloxacin is our agent of choice in this scenario to provide routine bacterial coverage as well as atypical coverage. Traditionally we would have done a 3rd generation cephalosporin, but we try to avoid the empiric use of ceftriaxone due to the association with life threatening hemolysis after administration.
                                                                        
                                                                        

                                                                        Though this incidence is rare, it is important to understand that CTX can cause intravascular hemolysis in these patients who already have compromised Oxygen delivery due to their anemia.

                                                                        Alright Stephanie, we have reached the end of our episode today... but I have one more question, as a fellow, when I am on call and we have a previously healthy child who presents to the PICU who is critically ill and hemodynamically unstable, what antibiotics should we consider ?

                                                                        • Once again, the concept of where exactly we think the source of the infection is will drive antibiotic selection with the goal of providing the best empiric therapy for the most likely pathogen(s). In a previously healthy patient who has really had no recent hospitalizations or antibiotic exposure, we could start with ceftriaxone. If the patient, however, has MRSA of PSE risk factors, at that point we would then need to broaden to vancomycin and either cefepime/ceftazidime/or piperacillin/tazobactam.
                                                                        
                                                                        

                                                                        To take this episode home, remember to consider host status, source of infection, and likely microbes prior to initiation of broad spectrum therapy!

                                                                        Whitney and Stephanie thank you so much for your expertise on common bugs and drugs — this was a great discussion, and we value your expertise. What are your take home clinical pearls for anti-microbials in the PICU..

                                                                        Stephanie: Your clinical pharmacist can always help with choice of antibiotics as well as dosing and monitoring, especially in critically-ill children with AKI or hepatic dysfunction.

                                                                        Whitney: The...]]>8a51498e-7d22-431a-be49-3968bb5a802bSun, 01 Aug 2021 03:00:00 -040022:15falsefull2323How to Read And Critically Review a Manuscript
                                                                        

                                                                        Welcome to PICU Doc On Call, a podcast dedicated to current and aspiring intensivists. My name is Pradip Kamat

                                                                        My name is Rahul Damania, a current 2nd year pediatric critical care fellow. We come to you from Children's Healthcare of Atlanta and the Emory University School of Medicine Atlanta, GA

                                                                        Today's episode is dedicated to How to Read And Critically Review a Paper not only for the Journal club presentation at the fellows conferences but also for use in your clinical practice as a pediatric intensivist.

                                                                        We are delighted to be joined by Jocelyn Grunwell, MD, PhD. Dr. Grunwell is an Assistant Professor of Pediatrics-Pediatric Critical Critical Care at Emory University School of Medicine in Atlanta, GA. She is a K-scholar with research interests in mitochondrial dysfunction in critical illness, the airway immune response in pediatric acute respiratory distress syndrome, and near-fatal asthma. She is on twitter @GrunwellJocelyn.

                                                                        Rahul: Dr Grunwell welcome to picu doc on call. We are delighted to have you on our podcast today to discuss how to read & critically review a manuscript.

                                                                        Grunwell: Thank you Rahul and Pradip for having me on PICU DOC on Call. I have no conflicts of interest or financial disclosures.

                                                                        Q1. Rahul: Dr Grunwell: Why should a pediatric intensivist (whether in training or as a faculty) read journal articles?

                                                                        Grunwell: There are several reasons you might want to read journal articles, and your reading should be tailored to your goals. For example, first, you may want to learn more about a clinical topic to understand how to diagnose, treat or manage a disease. 2nd you may want to find the best evidence for how to treat a patient. 3rd, you may want to learn about the basic biology or mechanisms of a disease. Finally, you may want to identify gaps in a particular field of research to develop a research plan and write a proposal to explore a new research area.

                                                                        Q2: Dr Grunwell: Where do you find manuscripts relevant to intensivists?

                                                                        First, I would like to suggest that the learners and faculty in pediatric critical care make a habit of reading at the very least the abstracts in various pediatric journals even if they don't have the time to read an entire article. I generally go to Pediatric Critical Care Medicine, Critical Care Medicine, Critical Care Explorations, Pediatrics, Journal of Pediatrics, NEJM, JAMA Pediatrics, and the family of American Thoracic Society journals on a weekly basis. You can set-up your account so that the table of contents of these journals will be emailed to you. There are apps available, such as ReadQxMD, where you can be alerted to new content of interest to you. You can sign up and follow the accounts of several journals of interest to you on Twitter. There is also a useful, free website sponsored by Dr. Hari Krishnan called picujournalwatch.com in which Dr Krishnan has journal articles well-organized. The website is constantly updated to show the latest manuscripts relevant to our field. You can keep your articles organized by topic in software such as EndNote. Also doing a search on PubMed, OVID etc. can also be helpful to find latest information on a topic. Talking to a medical library scientists is very useful to structure a systematic search for articles or to get a article from a journal that is not available at your institution.

                                                                        Q3: Dr Grunwell can you define the term level of evidence?

                                                                        Grunwell: the term level of evidence - or traditional hierarchy of evidence - refers to what degree that information can be trusted based on the study design.

                                                                        The most common question is related to therapy or an intervention. Levels of therapy are typically represented as a pyramid with systematic reviews or meta-analyses positioned at the top of the pyramid followed by well-designed randomized control trials, and then observational studies. Observational studies include cohort studies or case-control studies. Case studies, laboratory-based studies with animal or in vitro models (aka: preclinical studies), and consensus or expert opinion lie at the bottom of the pyramid hierarchy. Based on this pyramid structure of evidence, the message is clear: Not all evidence and information is equivalent.

                                                                        Q3. Pradip: Dr. Grunwell what is a critical appraisal of a manuscript and how does it help us?

                                                                        Grunwell: Critical appraisal is the systematic evaluation of clinical research papers and it is used to judge the article's trustworthiness, its value and relevance in a particular context. Critical appraisal helps you to systematically evaluate whether:

                                                                        • The study addresses a CLEARLY FOCUSED QUESTION
                                                                        • The study uses VALID METHODS to address this question
                                                                        • The valid results of the study are IMPORTANT
                                                                        • The VALID, IMPORTANT results are APPLICABLE to your patients or population
                                                                        
                                                                        

                                                                        So the goal of learning critical appraisal helps you:

                                                                        • identify the most relevant papers
                                                                        • distinguish evidence from opinion, assumptions, misreporting, and beliefsP
                                                                        • assess the validity of the study
                                                                        • assess the usefulness and clinical applicability of the study
                                                                        • recognize any potential for bias.
                                                                        
                                                                        

                                                                        Q4. Dr Grunwell what are some of the key components of the appraisal process of a manuscript?

                                                                        I generally ask 3 preliminary questions when I look at a paper:

                                                                        1. What was the research question and why was the study needed? ( After a brief background about the topic under study, the paper's introduction should clearly state the research question and the hypothesis.)
                                                                        2. What was the research design? (For example, is this a primary or secondary study; If primary, then was it a laboratory experiment, clinical trial, survey, observational, or a case series study? If secondary, then was it a review or a clinical guideline, decision analyses, or economic analyses)?
                                                                        3. Was the research design appropriate to the question? It can be helpful to categorize the study into a therapeutic, diagnostic, prognostic, randomized control trial, qualitative, an epidemiologic/descriptive study, or a meta-analysis. There are evidence-based medicine worksheets that can help you structure a formal review and make sure you consider all aspects of the study. These worksheets can be found in many different languages at the Centre for Evidence-Based Medicine at The University of Oxford in the United Kingdom under Critical Appraisal Tools. The web address will be in the show notes (https://www.cebm.ox.ac.uk/resources/ebm-tools/critical-appraisal-tools) The Evidence-Based Medicine Toolbox from Toronto, Canada also have critical appraisal worksheets and resources to learn evidence-based medicine. This link will also be available in the show notes? https://ebm-tools.knowledgetranslation.net/.
                                                                        
                                                                        

                                                                        OK to summarize, understand the question and the study design and then assess whether the appropriate design was used to answer a central question!

                                                                        Q5. Dr Grunwell what is a general framework of how we should approach a manuscript?

                                                                        Dr Grunwell: In order to explain the structure of a scientific paper, I use the analogy of a story. Think about your favorite fairy tale: there is a beginning - where the scene is set and the characters are introduced; there is a middle - where the action happens, and there is an ending - where there is a lesson learned or a moral of the story. By analogy, every scientific paper has an introduction - where you set the background and importance of the question and introduce the subject matter - the who, the what, and the why of the study). The middle of the article is where the action happens - you explain how you did the study in the methods section and what happened (what you found) in the results section. Finally, the article has an ending where you discuss the results within a larger context of other studies by comparing and contrasting, noting similarities and explaining discrepancies to other work, and acknowledging limitations. Finally you make a conclusion based on your results - can you recommend this therapy or diagnostic study for your patients?.

                                                                        I really like the story analogy as this really frames our next segment of how to systematically read a scientific paper.

                                                                        Q6. Dr Grunwell: What is the first step in the critical appraisal of the scientific paper?

                                                                        A good first step would be just to skim through an article (start with the abstract) to understand the aims, key data and conclusions. Early considerations as you are skimming through the manuscript)-

                                                                        • Main question - Relevant? Interesting?
                                                                        • Original topic - Address a gap? Clear & easy to read?
                                                                        • Conclusions consistent with the evidence presented?
                                                                        • Do the experiments/data address the main question?
                                                                        • Is there a disagreement with current consensus & is this disagreement justified by the data gathered?
                                                                        • Do the Tables & Figures tell the story/add to the paper?
                                                                        
                                                                        

                                                                        This is a bird's eye view to get yourself oriented.

                                                                        Dr. Grunwell, in general, how does the introduction help you as you critically appraise a manuscript?

                                                                        Grunwell: When we look at the introduction we can formulate the problem

                                                                        Define who the question is about? (how would I describe a group of patients similar to this one)

                                                                        Define which maneuver you are considering in this patient or population and if necessary, a comparison maneuver: (drug treatment vs. standard therapy or placebo)

                                                                        Define the outcome:...]]>
                                                                        

                                                                        Welcome to PICU Doc On Call, a podcast dedicated to current and aspiring intensivists. My name is Pradip Kamat

                                                                        My name is Rahul Damania, a current 2nd year pediatric critical care fellow. We come to you from Children's Healthcare of Atlanta and the Emory University School of Medicine Atlanta, GA

                                                                        Today's episode is dedicated to How to Read And Critically Review a Paper not only for the Journal club presentation at the fellows conferences but also for use in your clinical practice as a pediatric intensivist.

                                                                        We are delighted to be joined by Jocelyn Grunwell, MD, PhD. Dr. Grunwell is an Assistant Professor of Pediatrics-Pediatric Critical Critical Care at Emory University School of Medicine in Atlanta, GA. She is a K-scholar with research interests in mitochondrial dysfunction in critical illness, the airway immune response in pediatric acute respiratory distress syndrome, and near-fatal asthma. She is on twitter @GrunwellJocelyn.

                                                                        Rahul: Dr Grunwell welcome to picu doc on call. We are delighted to have you on our podcast today to discuss how to read & critically review a manuscript.

                                                                        Grunwell: Thank you Rahul and Pradip for having me on PICU DOC on Call. I have no conflicts of interest or financial disclosures.

                                                                        Q1. Rahul: Dr Grunwell: Why should a pediatric intensivist (whether in training or as a faculty) read journal articles?

                                                                        Grunwell: There are several reasons you might want to read journal articles, and your reading should be tailored to your goals. For example, first, you may want to learn more about a clinical topic to understand how to diagnose, treat or manage a disease. 2nd you may want to find the best evidence for how to treat a patient. 3rd, you may want to learn about the basic biology or mechanisms of a disease. Finally, you may want to identify gaps in a particular field of research to develop a research plan and write a proposal to explore a new research area.

                                                                        Q2: Dr Grunwell: Where do you find manuscripts relevant to intensivists?

                                                                        First, I would like to suggest that the learners and faculty in pediatric critical care make a habit of reading at the very least the abstracts in various pediatric journals even if they don't have the time to read an entire article. I generally go to Pediatric Critical Care Medicine, Critical Care Medicine, Critical Care Explorations, Pediatrics, Journal of Pediatrics, NEJM, JAMA Pediatrics, and the family of American Thoracic Society journals on a weekly basis. You can set-up your account so that the table of contents of these journals will be emailed to you. There are apps available, such as ReadQxMD, where you can be alerted to new content of interest to you. You can sign up and follow the accounts of several journals of interest to you on Twitter. There is also a useful, free website sponsored by Dr. Hari Krishnan called picujournalwatch.com in which Dr Krishnan has journal articles well-organized. The website is constantly updated to show the latest manuscripts relevant to our field. You can keep your articles organized by topic in software such as EndNote. Also doing a search on PubMed, OVID etc. can also be helpful to find latest information on a topic. Talking to a medical library scientists is very useful to structure a systematic search for articles or to get a article from a journal that is not available at your institution.

                                                                        Q3: Dr Grunwell can you define the term level of evidence?

                                                                        Grunwell: the term level of evidence - or traditional hierarchy of evidence - refers to what degree that information can be trusted based on the study design.

                                                                        The most common question is related to therapy or an intervention. Levels of therapy are typically represented as a pyramid with systematic reviews or meta-analyses positioned at the top of the pyramid followed by well-designed randomized control trials, and then observational studies. Observational studies include cohort studies or case-control studies. Case studies, laboratory-based studies with animal or in vitro models (aka: preclinical studies), and consensus or expert opinion lie at the bottom of the pyramid hierarchy. Based on this pyramid structure of evidence, the message is clear: Not all evidence and information is equivalent.

                                                                        Q3. Pradip: Dr. Grunwell what is a critical appraisal of a manuscript and how does it help us?

                                                                        Grunwell: Critical appraisal is the systematic evaluation of clinical research papers and it is used to judge the article's trustworthiness, its value and relevance in a particular context. Critical appraisal helps you to systematically evaluate whether:

                                                                        • The study addresses a CLEARLY FOCUSED QUESTION
                                                                        • The study uses VALID METHODS to address this question
                                                                        • The valid results of the study are IMPORTANT
                                                                        • The VALID, IMPORTANT results are APPLICABLE to your patients or population
                                                                        
                                                                        

                                                                        So the goal of learning critical appraisal helps you:

                                                                        • identify the most relevant papers
                                                                        • distinguish evidence from opinion, assumptions, misreporting, and beliefsP
                                                                        • assess the validity of the study
                                                                        • assess the usefulness and clinical applicability of the study
                                                                        • recognize any potential for bias.
                                                                        
                                                                        

                                                                        Q4. Dr Grunwell what are some of the key components of the appraisal process of a manuscript?

                                                                        I generally ask 3 preliminary questions when I look at a paper:

                                                                        1. What was the research question and why was the study needed? ( After a brief background about the topic under study, the paper's introduction should clearly state the research question and the hypothesis.)
                                                                        2. What was the research design? (For example, is this a primary or secondary study; If primary, then was it a laboratory experiment, clinical trial, survey, observational, or a case series study? If secondary, then was it a review or a clinical guideline, decision analyses, or economic analyses)?
                                                                        3. Was the research design appropriate to the question? It can be helpful to categorize the study into a therapeutic, diagnostic, prognostic, randomized control trial, qualitative, an epidemiologic/descriptive study, or a meta-analysis. There are evidence-based medicine worksheets that can help you structure a formal review and make sure you consider all aspects of the study. These worksheets can be found in many different languages at the Centre for Evidence-Based Medicine at The University of Oxford in the United Kingdom under Critical Appraisal Tools. The web address will be in the show notes (https://www.cebm.ox.ac.uk/resources/ebm-tools/critical-appraisal-tools) The Evidence-Based Medicine Toolbox from Toronto, Canada also have critical appraisal worksheets and resources to learn evidence-based medicine. This link will also be available in the show notes? https://ebm-tools.knowledgetranslation.net/.
                                                                        
                                                                        

                                                                        OK to summarize, understand the question and the study design and then assess whether the appropriate design was used to answer a central question!

                                                                        Q5. Dr Grunwell what is a general framework of how we should approach a manuscript?

                                                                        Dr Grunwell: In order to explain the structure of a scientific paper, I use the analogy of a story. Think about your favorite fairy tale: there is a beginning - where the scene is set and the characters are introduced; there is a middle - where the action happens, and there is an ending - where there is a lesson learned or a moral of the story. By analogy, every scientific paper has an introduction - where you set the background and importance of the question and introduce the subject matter - the who, the what, and the why of the study). The middle of the article is where the action happens - you explain how you did the study in the methods section and what happened (what you found) in the results section. Finally, the article has an ending where you discuss the results within a larger context of other studies by comparing and contrasting, noting similarities and explaining discrepancies to other work, and acknowledging limitations. Finally you make a conclusion based on your results - can you recommend this therapy or diagnostic study for your patients?.

                                                                        I really like the story analogy as this really frames our next segment of how to systematically read a scientific paper.

                                                                        Q6. Dr Grunwell: What is the first step in the critical appraisal of the scientific paper?

                                                                        A good first step would be just to skim through an article (start with the abstract) to understand the aims, key data and conclusions. Early considerations as you are skimming through the manuscript)-

                                                                        • Main question - Relevant? Interesting?
                                                                        • Original topic - Address a gap? Clear & easy to read?
                                                                        • Conclusions consistent with the evidence presented?
                                                                        • Do the experiments/data address the main question?
                                                                        • Is there a disagreement with current consensus & is this disagreement justified by the data gathered?
                                                                        • Do the Tables & Figures tell the story/add to the paper?
                                                                        
                                                                        

                                                                        This is a bird's eye view to get yourself oriented.

                                                                        Dr. Grunwell, in general, how does the introduction help you as you critically appraise a manuscript?

                                                                        Grunwell: When we look at the introduction we can formulate the problem

                                                                        Define who the question is about? (how would I describe a group of patients similar to this one)

                                                                        Define which maneuver you are considering in this patient or population and if necessary, a comparison maneuver: (drug treatment vs. standard therapy or placebo)

                                                                        Define the outcome: Reduced mortality, length of stay, better quality of life cost savings, etc.

                                                                        Q7 Pradip: As you read further after your broad overview how do you identify areas for improvement or major flaws in study design?

                                                                        Dr Grunwell: I would encourage listeners to closely look at Tables, figures and images— What story are these data telling you? Can you recreate the story from the data presented WITHOUT reading a single word of the text? You should be able to follow the experimental argument and draw conclusions based solely on the evidence presented in the tables and figures.

                                                                        Some things to watch for:

                                                                        Are the authors drawing a conclusion that is contradicted by the author’s own statistical or qualitative evidence.

                                                                        Are they using a discredited or flawed method?

                                                                        • how are they sampling a population, do they have appropriate controls, how precise are their measurements, was the analysis conducted in a systematic manner?
                                                                        • Are they asking a valid question?
                                                                        
                                                                        

                                                                        -Are the authors ignoring a process that is known to have a strong influence on the area under study?

                                                                        Asking questions which correlate to the author's point of view is essential.

                                                                        Correct, using this process it is important to summarize the research question by:

                                                                        • Stating the main question addressed
                                                                        • and Summarizing the goals or objectives.
                                                                        • This helps to conceptualize the research, and allows focus on the successful aspects of the paper.
                                                                        
                                                                        

                                                                        Transitioning to the methods section of a paper, Do Grunwell how do we assess the quality of the methods used in a study?

                                                                        I guess the real question is whether the study in question is original and what does the new research add to the scientific literature? For example, is this a continuation of a large study or field of research.Does it address previous methodological shortcomings? Will numerical results add significantly to a meta-analysis?

                                                                        Is the study population different?

                                                                        Is the clinical issue important enough, or does there exist sufficient doubt in key-decision makers, to make new evidence ‘politically’ desirable?

                                                                        Dr Grunwell as we assess the methods section how do we narrow in on the population of interest and specifically relate the methodology and paper to our patient cohort whom we serve clinically?

                                                                        This is a great question. I would think about whether the patients

                                                                        1. Are the subjects more, or less, ill than who you see?
                                                                        2. Are the subjects of a different ethnicity, live a different lifestyle, from your own patients?
                                                                        3. Did the subjects receive more, or different, attention during the study that you can give your patients?
                                                                        4. Unlike most patients you care for, did the subjects have nothing wrong with them apart from the condition being studied?
                                                                        5. Did the subjects have potentially confounding exposures similar to your patients?
                                                                        
                                                                        

                                                                        To summarize a central theme of our episode thus far is to read a paper with a perspective on how this applies to your setting - in our case it is critically ill children

                                                                        Lets transition and talk about the layers of bias which may be present in the results or even discussion portion of the manuscript, Dr Grunwell can you highlight the sources of bias in a study?

                                                                        Bias occurs when there is a systematic difference between the results from a study and the true state of affairs. Bias is often introduced when a study is being designed, but can be introduced at any stage. Appropriate statistical methods can reduce the effect of bias, but may not eliminate it. Increasing the sample size does not reduce bias.

                                                                        We need to look at the treatment group and control group very closely to make sure both are treated equally.

                                                                        Selection bias: can result from incomplete randomization. So patients included in the study are not representative of the population which you intended to analyze.

                                                                        Performance bias can result from systematic differences in care received by the intervention and control groups because either the participant or the researcher know what group they were assigned - so there are differences in care received other than the intervention being compared

                                                                        Exclusion bias refers to systematic differences in withdrawal or participants from a study arm. For example, there may be more withdrawals from the intervention compared to the placebo arm of a trial due to side effects; alternatively, there may be more withdrawals from the placebo arm of the trial compared to the intervention arm due to lack of improvement in clinical condition.

                                                                        Detection bias is the systematic differences in outcome assessment between groups. Blinding (or masking) of outcome assessors may reduce the risk that knowledge of which intervention was received, rather than the intervention itself, affects outcome measurement.

                                                                        Alright listeners lets summarize the various types of bias — selection is due to incomplete randomization, performance bias involves a lack of blinding, exclusion bias refers to the element of attrition, and detection bias refers to the impact the intervention has with respects to the control.

                                                                        Dr Grunwell what are the preliminary statistical questions which need to be addressed in a manuscript?

                                                                        Grunwell: Three statistical questions should be addressed:

                                                                        First, there should be a sample size calculation to determine the power to detect a true difference between groups

                                                                        –To calculate a sample size, there needs to be a defined amount of difference between 2 groups that is a clinically significant effect

                                                                        –You will need to know the Mean and Standard deviation (or variance) of the principal outcome variable

                                                                        Second, the study must be continued for long enough for the effect to be reflected in the primary outcome.

                                                                        Third, the completeness of follow-up should be high. For example, < 70% follow-up may be sub-optimal. You can make an assessment of completeness by looking at the rate of withdrawal from the study (some reasons for low completeness include suspected adverse reaction, loss of motivation, loss to follow-up (moving from study area), or death).

                                                                        Dr Grunwell lets conclude our podcast by going into how do you evaluate the Results and Discussion section of a manuscript?

                                                                        The results should tell us what was discovered or confirmed. I make sure to see if it tells a coherent story. The authors should describe in simple terms what the data show and refer to statistical analyses such as significance and goodness of fit. Its should evaluate observed trends.

                                                                        Explains significance of results to a wider understanding. Outcome should be a critical analysis of the data collected.

                                                                        How do you look at the conclusion of a study?

                                                                        The conclusion should basically reflect upon whether or not the aims are achieved. Conclusion should not have surprises in them and should be evidence-based. It typically is short and relates directly to the question and outcome.

                                                                        Dr Grunwell this was a wonderful summary and discussion today — what our resources our listeners can utilize to improve their understanding about research methodology:

                                                                        How to read a paper by Trisha Greenhalgh

                                                                        Users' Guide to medical literature by Gordon Guyatt

                                                                        I also would recommend writing science by Joshua Schimel.

                                                                        I always give my fellows a paper by my undergraduate research mentor, Professor George M. Whitesides titled the "Whitesides' Group: Writing a Paper" in the journal Advanced Materials.

                                                                        I recommend that PCCM fellows keep reading papers in PCCM and CCM journal - at the very least peruse through the abstracts especially when they are busy on-service, etc. Structured and interactive journal clubs can help practice critical appraisal skills.

                                                                        A community approach is definitely essential in staying current on new research?

                                                                        Dr. Grunwell we appreciate your insights on today's podcast, as we wrap up, would you mind highlighting your personal pearls with respect to critical appraisal of manuscript ?

                                                                        1. To develop a new habit, such as skimming abstracts and journal articles, its best to start small. For example, choose 1-2 journals to peruse and get the table of contents emailed to you.
                                                                        2. Be curious and start a journal club and try using the critical appraisal templates or worksheets when assessing the article. Make the journal club a fun and social experience.
                                                                        3. Learning new skills takes practice, and any investment you make in learning critical appraisal skills will help you become a better writer, researcher and clinician.
                                                                        4. Tables and figures should stand alone and tell the story. Invest time in trying to understand what the evidence supports in the article by interpreting the information in the tables and figures yourself before reading the text of the paper in its entirety.
                                                                        
                                                                        

                                                                        We went through a systematic process on how to collect, organize, synthesize & apply journal articles from manuscript to bedside! Having close collaboration with your medical librarian is essential along with a curiosity to learn is essential to optimize your evidence based knowledge and stay up to date on the literature

                                                                        This concludes our episode today on how to read a paper. We thank Dr Jocelyn Grunwell for her expertise on this topic. We hope you found value in this short podcast. We welcome you to share your feedback & place a review on our podcast. PICU Doc on Call is co-hosted by me Pradip Kamat and myself Dr. Rahul Damania.

                                                                        Stay tuned for our next episode! Thank you

                                                                        References:

                                                                        How to read a Paper 5th Edition by Trisha Greenhalgh. Wiley Blackwell publishers

                                                                        White J....]]>04661d9b-11b7-46a3-8a4b-39686abce615Sun, 25 Jul 2021 03:00:00 -040024:22falsefull2222Thyroid Storm in the PICUWelcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.

                                                                        I'm Pradip Kamat

                                                                        and I'm Rahul Damania and we are coming to you from Children's Healthcare of Atlanta - Emory University School of Medicine.

                                                                        Welcome to our PICU Mini-Series Episode a 10 month old who is intubated for acute respiratory failure secondary to RSV bronchiolitis.

                                                                        Here's the case:

                                                                        A 10-month-old full-term infant girl old is intubated for acute respiratory failure secondary to RSV bronchiolitis. Patient was brought to the ED by parents on day 3 of her illness with h/o cough, congestion and worsening respiratory distress. She has had increasing WOB and grunting. After assessment in the ED where the patient had a brief trial of HFNC, she was intubated with a 4.0 ETT due to persistent hypoxemia. Pertinently, her viral panel was positive for RSV, and the patient was transferred to the PICU. In the PICU, patient was ventilated using PRVC: Set TV of 90cc (patient is 11KG), PEEP 6, PS 10, and FIO2 40%. Throughout her course, she was mechanically ventilated and sedated for about a week. She required a continuous infusion of rocuronium due to decreased lung compliance and high peak pressures. Patient weaned on her ventilator settings by ICU day 7 and the decision to move towards extubation was made.

                                                                        To summarize key elements from this case, this patient has:

                                                                        • 10 month old with acute respiratory failure secondary to RSV infection and with a secondary bacterial infection due to H.Influenza.
                                                                        • Had about a six day course on the ventilator requiring sedation and NMB
                                                                        • and now we are at the discussion of extubation readiness.Rahul, do you mind summarizing the patient's peri-extubation course?
                                                                        
                                                                        

                                                                        Sure Pradip, so on day 6 of hospitalization our patient was weaned to low mechanical ventilator settings. The chest radiograph, which initially showed evidence of interstitial pneumonitis and atelectasis now improved and the patient had improved secretion burden. The patient was on ceftriaxone throughout the hospital course as her ETT cx with which grew Hemophilus Influenzae.

                                                                        • What about the patient's neurological status?
                                                                        • The patient was initially on fentanyl, dexmedetomidine and a rocuronium infusion — a day prior to considering extubation, the patient was off of the continuous rocuronium infusion oxygenating and ventilating well. The patient prior to extubation was wide awake and appropriate during the morning sedation holiday.
                                                                        • Any other important clinical markers?
                                                                        • Yes, the patient's clinical exam including lung exam was reassuring. The patient underwent a pressure support trial PEEP 5, CPAP 10 and had a normal respiratory effort with exhaled of about 5 mL/kg. The RT, however mentioned that the patient did not have a "leak" when performing the leak test. The finally the patient was given a few doses of furosemide for diuresis prior to extubation.
                                                                        • Awesome, today's episode we really want to focus on extubation readiness however prior to this discussion, can we take a step back and talk about some red-flag symptoms which led to intubation for this patient?
                                                                        • This patient had severe respiratory distress which progressed to failure.
                                                                        • The tachypnea, decreased mentation, and grunting were key signs that the patient was progressing to endotracheal intubation.
                                                                        • Grunting is important to highlight as this refers to the child generating auto-PEEP to combat the atelectasis present in bronchiolitis.
                                                                        • Remember that a child's chest wall has a high compliance and a decreased propensity for outward elastic recoil — this in essence reduces FRC and thus there is a more balance towards the inward recoil of the long (closing capacity). The highly compliant chest wall and the natural inward recoil of the infant lung creates a propensity towards atelectasis and subsequent impairments in breathing. Low FRC can also create increase PVR which can thus imbalance optimal cardiopulmonary interactions.
                                                                        
                                                                        

                                                                        OK let's transition to our topic of discussion by a quick summary:

                                                                        • A 10 month old after 6 days of MV is now ready for extubation.
                                                                        • Let's start with a short multiple choice question:
                                                                        • In children deemed ready for extubation by clinicians, which of the following is most likely to be associated with reintubation?
                                                                        • A) High breath by breath variability
                                                                        • B) Failed Pressure Support trial
                                                                        • C) Duration of mechanical ventilation
                                                                        • D) No leak around the ETT prior to extubation
                                                                        • Correct answer is A. Pediatric extubation failure rate ranges from 2-20%. Although extubation failure is usually multifactorial, High respiratory variability during spontaneous breathing trials is independently associated with extubation failure in children.
                                                                        • A recent paper by Kelby et al in CCM 2020-found that after controlling for confounding variables such as age and neurologic diagnosis, reported that both coefficient of variation of respiratory rate and decreased maximal change in airway pressure generated during airway occlusion had almost 3-fold higher risk of extubation failure. When this subset of children developed post-extubation upper airway obstruction, reintubation rates were greater than 30%.
                                                                        • What about the other factors we had in our answer choices like the Pressure Support Trial?
                                                                        • Children fail PS trial for variety of reasons including ETT size, sedation, to name a few. Khemani and colleagues (Intensive Care Med. 2016 Aug; 42(8):1214-22)reported that regardless of endotracheal tube size, pressure support during extubation readiness tests significantly underestimates post-extubation effort of breathing.
                                                                        • Further, A 2009 paper by Newth et al (Pediatr Crit Care Med. 2009 Jan;10(1):1-11.) reported in systematic review of weaning and extubation for pediatric patients on mechanical ventilation, that extubation failure bore little relationship to the duration of MV.
                                                                        • I think it is important to highlight that though we frequently perform PS trials, we should assess other factors such as primary reason for extubation being reversed, secretions, and even neuromuscular components - extubation does not just refer to lungs being ready to have less support!
                                                                        • Yes Rahul, absolutely agree — I do want to mention A controversial topic has always been the utility of measuring a leak pressure around the ETT to predict upper airway obstruction. A study by Khemani et al (Am J Respir Crit care 2016 Jan 15;193(2):198-209) reported the risk factors independently associated with subglottic UAO, included low cuff leak volume or high preextubation leak pressure, poor sedation, and preexisting UAO (P < 0.04) for cuffed ETTs; and age (range, 1 mo to 5 yr) for uncuffed ETTs (P < 0.04). For uncuffed ETTs, the presence or absence of preextubation leak was not associated with subglottic UAO.
                                                                        • Lets summarize - upper airway obstruction involves checking if there is flow (in the form of pressure) surrounding the ETT — key point younger patients (1 mo to 5 yr old) with uncuffed tubes have risk to develop UAO peri-extubation.
                                                                        • An older study by Wratney et al (Pediatr Crit Care Med. 2008 Sep;9(5):490-6) had previously reported that an endotracheal tube air leak pressure >/=30 cm H2O measured in the non-nparalyzed patient before extubation or for the duration of mechanical ventilation was common and did not predict an increased risk for extubation failure. The authors in that study concluded that- Pediatric patients who are clinically identified as candidates for an extubation trial but do not have an endotracheal tube air leak may successfully tolerate removal of the endotracheal tube.
                                                                        • This suggests that having a leak may not be necessary for a patient to successfully extubate.
                                                                        • So Rahul for our listeners What are factors associated with extubation failure?
                                                                        • Thats an excellent question. Factors correlated with an increased risk of extubation failure include a longer duration of sedative use, younger age, higher complexity of medical conditions, and diaphragmatic dysfunction. The most common reported cause of extubation failure in pediatric patients is upper-airway obstruction, with other causes that include respiratory insufficiency, muscular weakness, cardiac dysfunction, and neurologic impairment. Duration of MV, PRISM III score did not predict extubation in a multivariable analysis reported by Krasinkiewicz et al (Respiratory Care April 2021 Vol 66 No 4).
                                                                        
                                                                        

                                                                        Pradip, What are the main barriers to extubation in pediatrics?

                                                                        Thats an excellent question Rahul. One study published in Respiratory Care in` 2021 Vol 66 No 4) reported that in patients who had their passed the extubation readiness test, most common reason for holding off extubation was a planned procedure, neurologic diagnosis/status of the patient, and no leak around the ETT, other factors included high ventilator rates and over sedation, hemodynamic instability, fluid status etc.

                                                                        I think it is important for us to truly consider procedures or imaging which are planned to play a factor in our timeline for extubation readiness - this mitigates the risk for re-intubation - which is especially important in children with difficult airways!

                                                                        Rahul: how do majority of children's hospitals perform extubation readiness test prior to extubation?

                                                                        • I think Pradip there is considerable variation in the methodology of ERT. Some common practices which I have noted as a fellow include: A daily spontaneous breathing trial performed probably early in the am (~4am) by the RTs. As long as patient didn't require any procedure (imaging or surgery), hemodynamically stable, patient spontaneously breathing, FIO2 < 50% (some use 40%),...]]>Welcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.

                                                                          I'm Pradip Kamat

                                                                          and I'm Rahul Damania and we are coming to you from Children's Healthcare of Atlanta - Emory University School of Medicine.

                                                                          Welcome to our PICU Mini-Series Episode a 10 month old who is intubated for acute respiratory failure secondary to RSV bronchiolitis.

                                                                          Here's the case:

                                                                          A 10-month-old full-term infant girl old is intubated for acute respiratory failure secondary to RSV bronchiolitis. Patient was brought to the ED by parents on day 3 of her illness with h/o cough, congestion and worsening respiratory distress. She has had increasing WOB and grunting. After assessment in the ED where the patient had a brief trial of HFNC, she was intubated with a 4.0 ETT due to persistent hypoxemia. Pertinently, her viral panel was positive for RSV, and the patient was transferred to the PICU. In the PICU, patient was ventilated using PRVC: Set TV of 90cc (patient is 11KG), PEEP 6, PS 10, and FIO2 40%. Throughout her course, she was mechanically ventilated and sedated for about a week. She required a continuous infusion of rocuronium due to decreased lung compliance and high peak pressures. Patient weaned on her ventilator settings by ICU day 7 and the decision to move towards extubation was made.

                                                                          To summarize key elements from this case, this patient has:

                                                                          • 10 month old with acute respiratory failure secondary to RSV infection and with a secondary bacterial infection due to H.Influenza.
                                                                          • Had about a six day course on the ventilator requiring sedation and NMB
                                                                          • and now we are at the discussion of extubation readiness.Rahul, do you mind summarizing the patient's peri-extubation course?
                                                                          
                                                                          

                                                                          Sure Pradip, so on day 6 of hospitalization our patient was weaned to low mechanical ventilator settings. The chest radiograph, which initially showed evidence of interstitial pneumonitis and atelectasis now improved and the patient had improved secretion burden. The patient was on ceftriaxone throughout the hospital course as her ETT cx with which grew Hemophilus Influenzae.

                                                                          • What about the patient's neurological status?
                                                                          • The patient was initially on fentanyl, dexmedetomidine and a rocuronium infusion — a day prior to considering extubation, the patient was off of the continuous rocuronium infusion oxygenating and ventilating well. The patient prior to extubation was wide awake and appropriate during the morning sedation holiday.
                                                                          • Any other important clinical markers?
                                                                          • Yes, the patient's clinical exam including lung exam was reassuring. The patient underwent a pressure support trial PEEP 5, CPAP 10 and had a normal respiratory effort with exhaled of about 5 mL/kg. The RT, however mentioned that the patient did not have a "leak" when performing the leak test. The finally the patient was given a few doses of furosemide for diuresis prior to extubation.
                                                                          • Awesome, today's episode we really want to focus on extubation readiness however prior to this discussion, can we take a step back and talk about some red-flag symptoms which led to intubation for this patient?
                                                                          • This patient had severe respiratory distress which progressed to failure.
                                                                          • The tachypnea, decreased mentation, and grunting were key signs that the patient was progressing to endotracheal intubation.
                                                                          • Grunting is important to highlight as this refers to the child generating auto-PEEP to combat the atelectasis present in bronchiolitis.
                                                                          • Remember that a child's chest wall has a high compliance and a decreased propensity for outward elastic recoil — this in essence reduces FRC and thus there is a more balance towards the inward recoil of the long (closing capacity). The highly compliant chest wall and the natural inward recoil of the infant lung creates a propensity towards atelectasis and subsequent impairments in breathing. Low FRC can also create increase PVR which can thus imbalance optimal cardiopulmonary interactions.
                                                                          
                                                                          

                                                                          OK let's transition to our topic of discussion by a quick summary:

                                                                          • A 10 month old after 6 days of MV is now ready for extubation.
                                                                          • Let's start with a short multiple choice question:
                                                                          • In children deemed ready for extubation by clinicians, which of the following is most likely to be associated with reintubation?
                                                                          • A) High breath by breath variability
                                                                          • B) Failed Pressure Support trial
                                                                          • C) Duration of mechanical ventilation
                                                                          • D) No leak around the ETT prior to extubation
                                                                          • Correct answer is A. Pediatric extubation failure rate ranges from 2-20%. Although extubation failure is usually multifactorial, High respiratory variability during spontaneous breathing trials is independently associated with extubation failure in children.
                                                                          • A recent paper by Kelby et al in CCM 2020-found that after controlling for confounding variables such as age and neurologic diagnosis, reported that both coefficient of variation of respiratory rate and decreased maximal change in airway pressure generated during airway occlusion had almost 3-fold higher risk of extubation failure. When this subset of children developed post-extubation upper airway obstruction, reintubation rates were greater than 30%.
                                                                          • What about the other factors we had in our answer choices like the Pressure Support Trial?
                                                                          • Children fail PS trial for variety of reasons including ETT size, sedation, to name a few. Khemani and colleagues (Intensive Care Med. 2016 Aug; 42(8):1214-22)reported that regardless of endotracheal tube size, pressure support during extubation readiness tests significantly underestimates post-extubation effort of breathing.
                                                                          • Further, A 2009 paper by Newth et al (Pediatr Crit Care Med. 2009 Jan;10(1):1-11.) reported in systematic review of weaning and extubation for pediatric patients on mechanical ventilation, that extubation failure bore little relationship to the duration of MV.
                                                                          • I think it is important to highlight that though we frequently perform PS trials, we should assess other factors such as primary reason for extubation being reversed, secretions, and even neuromuscular components - extubation does not just refer to lungs being ready to have less support!
                                                                          • Yes Rahul, absolutely agree — I do want to mention A controversial topic has always been the utility of measuring a leak pressure around the ETT to predict upper airway obstruction. A study by Khemani et al (Am J Respir Crit care 2016 Jan 15;193(2):198-209) reported the risk factors independently associated with subglottic UAO, included low cuff leak volume or high preextubation leak pressure, poor sedation, and preexisting UAO (P < 0.04) for cuffed ETTs; and age (range, 1 mo to 5 yr) for uncuffed ETTs (P < 0.04). For uncuffed ETTs, the presence or absence of preextubation leak was not associated with subglottic UAO.
                                                                          • Lets summarize - upper airway obstruction involves checking if there is flow (in the form of pressure) surrounding the ETT — key point younger patients (1 mo to 5 yr old) with uncuffed tubes have risk to develop UAO peri-extubation.
                                                                          • An older study by Wratney et al (Pediatr Crit Care Med. 2008 Sep;9(5):490-6) had previously reported that an endotracheal tube air leak pressure >/=30 cm H2O measured in the non-nparalyzed patient before extubation or for the duration of mechanical ventilation was common and did not predict an increased risk for extubation failure. The authors in that study concluded that- Pediatric patients who are clinically identified as candidates for an extubation trial but do not have an endotracheal tube air leak may successfully tolerate removal of the endotracheal tube.
                                                                          • This suggests that having a leak may not be necessary for a patient to successfully extubate.
                                                                          • So Rahul for our listeners What are factors associated with extubation failure?
                                                                          • Thats an excellent question. Factors correlated with an increased risk of extubation failure include a longer duration of sedative use, younger age, higher complexity of medical conditions, and diaphragmatic dysfunction. The most common reported cause of extubation failure in pediatric patients is upper-airway obstruction, with other causes that include respiratory insufficiency, muscular weakness, cardiac dysfunction, and neurologic impairment. Duration of MV, PRISM III score did not predict extubation in a multivariable analysis reported by Krasinkiewicz et al (Respiratory Care April 2021 Vol 66 No 4).
                                                                          
                                                                          

                                                                          Pradip, What are the main barriers to extubation in pediatrics?

                                                                          Thats an excellent question Rahul. One study published in Respiratory Care in` 2021 Vol 66 No 4) reported that in patients who had their passed the extubation readiness test, most common reason for holding off extubation was a planned procedure, neurologic diagnosis/status of the patient, and no leak around the ETT, other factors included high ventilator rates and over sedation, hemodynamic instability, fluid status etc.

                                                                          I think it is important for us to truly consider procedures or imaging which are planned to play a factor in our timeline for extubation readiness - this mitigates the risk for re-intubation - which is especially important in children with difficult airways!

                                                                          Rahul: how do majority of children's hospitals perform extubation readiness test prior to extubation?

                                                                          • I think Pradip there is considerable variation in the methodology of ERT. Some common practices which I have noted as a fellow include: A daily spontaneous breathing trial performed probably early in the am (~4am) by the RTs. As long as patient didn't require any procedure (imaging or surgery), hemodynamically stable, patient spontaneously breathing, FIO2 < 50% (some use 40%), PEEP ≤ 6cm H2O, SPO2 > 92% and TV exhaled ~ 6-8cc/kg on PIP ≤25 cm H2O. These are the patients who we deem on minimal vent settings. The sedation is decreased or a propofol bridge is added followed by a switch to PS CPAP trial (PS 8-10cm H2O and CPAP of 5cm H2O) for at least 2 hours. It is also important to correlate PO status with timing of extubation especially if the patient does well with the SBT.
                                                                          • After switching to PS/CPAP If patient has no hemodynamic issues, hypoxia, increased WOB and a normal blood gas, the patient's secretions are manageable, upper air reflexes are intact and neuromuscular function is sufficiently good to achieve an adequate vital capacity and maximum inspiratory pressure, GCS > 8—patient is considered a likely candidate for extubation. Most institutions will also check a leak around the ETT the night before. Some may decide to use a dose of decadron prior to extubation (although this is not supported by pediatric studies). Some extubate patient directly to room air, whereas others may use NIPPV such as CPAP or HFNC.
                                                                          • Pradip, what are the signs of failure of ERT and what should be done in patients who fail their spontaneous breathing trial?
                                                                          • Rahul, Signs of failure during ERT: include apnea, Exhaled TV < 5ml/kg, tachypnea for age, increased respiratory effort, desaturation below target SpO2 and unstable hemodynamics. Patients SBT can be repeated later in the day, sedation, fluid balance etc may require modification of optimization. The concept of sprinting -where the patient is subjected to SBT and allowed to remain on PS/CPAP for few hours everyday and which is subsequently increased is useful in those who are slow to wean off their ventilatory support.
                                                                          
                                                                          

                                                                          In essence this may optimize their neuromuscular strength.

                                                                          • Can you comment on any objective indices used in pediatrics as predictors of successful extubation?
                                                                          • Rahul two indices used to objectively predict success of extubation were the rapid shallow breathing index (RSBI) and the compliance, resistance, oxygenation, and pressure index (CROP index).
                                                                          • A paper by Thiagarajan et al (Am J Respir Crit Care Med. 1999 Nov; 160(5 Pt 1):1562-6.) reported on 227 mechanically ventilated children.
                                                                          • Extubation failures had higher RSBIs and lower CROP index values. A RSBI value of </= 8 breaths/ml/kg had a sensitivity of 74% and specificity of 74%, whereas a CROP value of >/= 0.15 ml/kg/breaths/min had a sensitivity of 83% and specificity of 53% for extubation success. IN contrast adult studies have shown that a CROP ≥ 13.5 ml/breat/min had a specificity of 91.9% and sensitivity of 87.9% in predicting extubation success.
                                                                          • OK to summarize - high rapid shallow breathing index and poor compliance, resistance, oxygenation indices indicate negative predictors for successful extubation
                                                                          
                                                                          

                                                                          Thats correct — for more detail, The RSBI is a ratio of spontaneous TV to RR (adjusted for age). the CROP index is the compliance, respiratory rate, oxygenation and pressure index. The CROP index (ml/ kg/breaths/min) was calculated using the formula: Cdyn × NIF × (PaO2 /PAO2 )/RR.

                                                                          • Let's break this down:
                                                                          • Cdyn - is a function of plateau - peep / TV.
                                                                          • NIF measures conducting zone resistance
                                                                          • and the OI index involves patient gas as well as alveolar gas which brings into the FiO2 the patient is receiving.
                                                                          
                                                                          

                                                                          Rahul what is the role of respiratory muscle weakness in extubation outcomes?

                                                                          • Khemani et al (Crit Care Med. 2017 Aug; 45(8):e798-e805.) used respiratory measurements using esophageal manometry and respiratory inductance plethysmography to assess respiratory muscle strength and predict respiratory extubation failure.
                                                                          • The authors reported in their study that 35% of children had diminished respiratory muscle strength (aPiMax ≤ 30 cm H2O) at the time of extubation, and were nearly three times more likely to be reintubated than those with preserved strength (aPiMax > 30 cm H2O; 14% vs 5.5%; p = 0.006). aPiMax = maximum airway pressure during airway occlusion (aPiMax). the authors concluded that Neuromuscular weakness at the time of extubation was common in children and was independently associated with reintubation, particularly when post-extubation effort was high.
                                                                          
                                                                          

                                                                          To summarize Neuromuscular status is essential to assess peri extubation - this is especially true in patients with myopathies either stress, paralytic or steroid related or primary muscular dystrophies.

                                                                          Correct, also, More recently Glau et al (Pediatr Crit Care Med. 2020 Sep;21(9):e672-e678) reported Diaphragm atrophy is associated with prolonged post extubation noninvasive positive pressure ventilation in children with acute respiratory failure.Serial bedside diaphragm ultrasound may identify children at risk for prolonged noninvasive positive pressure ventilation use after extubation. However There was no difference in diaphragmatic parameters (atrophy rate, and peri-extubation diaphragmatic thickness in expiration and inspiration) in extubation success versus failure (Mistri S. et al. Pediatr Pulmonol. 2020 Dec;55(12):3457-3464).

                                                                          So Rahul to look at our case again, what about her metabolic alkalosis prior to extubation ?

                                                                          • I generally correct metabolic alkalosis (when Sr HCO3 ≥30) using acetazolamide or chloride in form of K chloride. I also optimize Mag, Phos and Ca in any patient prior to extubation. I also optimize the nurtitional status with help of our PICU dietician as soon as a patient is intubated.
                                                                          • To wrap up, Rahul, why should we extubate patients early?
                                                                          
                                                                          

                                                                          Great question: There is increased morbidity from prolonged mechanical ventilation: To name a few— VAP, pneumothorax, muscle weakness, atrophy of diaphragm, pressure sores, subglottic stenosis (can happen in less than a week of MV), unplanned extubation with cardiac arrest, and prolonged ICU length of stay. Additionally delirium and need for abstinence medications and rehabilitation.

                                                                          The SCCM's ICU liberation ABCDEF bundle recommends use of spontaneous breathing trials and spontaneous awakening trials to improve patients outcomes. PCCM providers should strive for early mobility, minimal sedation, focus on analgesia as well as push to liberate patient from MV as soon as safely possible.

                                                                          To highlight a key concept from today - extubation readiness is a coordinated effort in the PICU - it involves asessments from RTs nurses and as well as physicians and advanced care providers. Understand the primary etiology why the patient was intubated and whether or not that cause was reversed. Plan to complete imaging Or procedures within reason prior to activating the patient. Understand components such as sedation, neuromuscular weakness, and secretions to provide a holistic assessment on extubation readiness!

                                                                          • Pradip - Are there any recent publications related to extubation success?
                                                                          • Furhman and Zimmermans latest edition of the textbook of Pediatric Critical Care chapter 54 page 642
                                                                          • A recent article by Krasinkiewicz et al in respiratory Care April 2021 Vol 66 no 4 has done a great job on extubation readiness practices and barriers to extubation in pediatric patients.
                                                                          
                                                                          

                                                                          This concludes our episode on Extubation Readiness We hope you found value in our short, case-based podcast. We welcome you to share your feedback, subscribe & place a review on our podcast! Please visit our website picudoconcall.org which showcases our episodes as well as our Doc on Call management cards. PICU Doc on Call is co-hosted by myself Dr. Rahul Damania and my cohost Dr Pradip Kamat. Stay tuned for our next episode! Thank you!

                                                                          ]]>c9a5f309-8b14-4fef-a3ae-e9b0ead4fd9eSun, 18 Jul 2021 03:00:00 -040013:12falsefull2121Value of the Librarian in PedsICU EducationWelcome to PICU Doc On Call, a podcast dedicated to current and aspiring intensivists. My name is Pradip Kamat

                                                                          and my name is Rahul Damania and we come to you from Children's Healthcare of Atlanta Emory University School of Medicine. Today's episode is dedicated to optimizing your Pediatric Critical Care Knowledge and study skills by utilizing your medical librarian.

                                                                          We are delighted to be joined by Ms. Carrie Price a health Professions librarian. Carrie was formerly at the Welch Medical Library, serving the faculty, students and staff of Johns Hopkins Medical Institutions. Ms Price is currently at the Albert S. Cook Library of Towson University in Towson, Maryland.

                                                                          Ms Price is an expert searcher with a strong interest in user-centered and instructional design, evidence-based medicine, and inter-professional education.

                                                                          Ms Price also maintains and updates a YouTube Channel with videos about citation management, searching, and evidence-based medicine. Carrie is on twitter @carrieprice78

                                                                          Q1. Carrie welcome to PICU DOC on Call Podcast. Our topic today— Value of the librarian in PedsICU education and it is one of the first in our series of how learners can organize their study habits while rotating in the PEDS ICU.

                                                                          Carrie: Thanks Rahul and Pradip for having me on PICU DOC on Call podcast. I have no conflicts of interest or financial disclosures.

                                                                          Q2. Carrie tell us your story and how you came to be an expert medical librarian ?

                                                                          Carrie: I came into librarianship as a second career, after a first career in nonprofit development. I was fortunate to start my work in libraries at Johns Hopkins University, where I worked as a library assistant in access services while getting my masters degree in library science. During this time my mom was diagnosed with appendix cancer, a rare cancer, (she's okay now), and through the time we spent together in the hospital, I noticed there was a medical library in the building. I had this epiphany that librarians weren't limited by traditional career paths. From then I started focusing on health and consumer health classes. Later, at a work all-staff meeting, I literally bumped into the former director of the Welch Medical Library, and the rest is history! I applied for an open position, was hired, and started working at the Welch Medical Library in 2012. It has been an incredible experience. I am fortunate to work extensively with a number of departments and divisions at Johns Hopkins and now at Towson University, so my experiences have been really multidisciplinary. In the past I worked as a physical therapy technician, which was awesome and helped inform the knowledge I brought to the profession. I've taken a lot of professional development in the field. I just never stop learning, and I love sharing information on Twitter, YouTube, and on my website, which is carrieprice78.github.io.

                                                                          This is such an amazing story!

                                                                          Q3: Carrie the practice of critical care medicine requires that learners in the Peds ICU remain current in their knowledge of the literature. Given an overwhelming amount of information out there how should these learners drink from that fire hydrant without being blown away?

                                                                          Carrie: I think that's an excellent question. Prior to the arrival of internet, most additional knowledge was acquired from physically going to a library and perusing through peer reviewed journals and textbooks. Now, things are digital and even "born-digital" — and there is so much information available online and on your phone.... I understand that given how much information is out there, a learner can feel overwhelmed and have difficulty trusting the information they see. That's why critical appraisal is a key part of evidence-based practice. Studies have shown the value of readily-available information in patient care and have highlighted the role of the library and librarian in support of clinical practice.

                                                                          In 1996 Sackett et al (BMJ 1996). defined evidence based medicine (EBM) as “the conscientious, explicit and judicious use of current best evidence in making decisions about the care of the individual patient." It's come to be seen as a combination of sound research evidence, clinical expertise, and patient preference. While the Accreditation Council for Graduate Medical Education (ACGME) requires peds residents to have formal training in EBM, there is considerable variation in what constitutes EBM training. This is where learners can pull from the expertise of medical librarians, who are experts in searching and evaluating literature. I suggest reaching out to your medical librarian right away. They can help you set up search alerts for topics of interest and journal tables of contents from PubMed and other resources. There are also apps, there is an app called QxMD that can help you be more aware of current literature in fields you follow. There's another app called Browzine, which you may have access to through your institution, where you can subscribe to journal table of contents. You can also find clinical, evidence-based, frequently-updated summaries with tools like UpToDate and DynaMed, depending on what you have through your institution.

                                                                          Having comprehensive resources such as UpToDate and Dynamed can help you curtail individual studies into a concise review!

                                                                          Q4. Carrie: now that you brought out the concept of Evidence-Based Medicine, what are some of the appropriate venues for teaching evidence based prospects in the Peds ICU environment?

                                                                          Almost all pediatric critical care medicine fellowships have a fellow conferences where learners have "protected time" for their education. Fellows conferences can have journal clubs, lectures, chapter reviews and case reports. Fellows conference could be one of the best venues for teaching EBM, where faculty and learners can interact. I think EBM practices should be a part of the peer-peer sign out after a call or service, or morning report. Programs can invite librarians to attend meetings, or seek help of a librarian while preparing for presentations. I also want to emphasize that with daily patient care rounds in the PICU — most fellows should question practices on rounds, which are handed down from previous trainees but don't always have sound evidence behind the practice, or some new research may have changed practice or knowledge. You can reach out to your librarian with these kinds of queries. Librarians can also help with PICO question formulation, searching for and appraising the evidence, and translating evidence into practice—all critical aspects of EBM.

                                                                          As trainees we are always wanting to optimize our clinical skills and understanding by asking the Why, the How, and the Why Not behind certain clinical scenarios in children! Asking these PICO questions, which stands for isolating the Population, Intervention, Comparison, and Outcome can help us ascertain key clinical questions which come up in our training!

                                                                          Q5. Carrie: How are librarians utilized by the pediatric residency programs ?

                                                                          There is an excellent study by Boykan and Jacobson (2017) which evaluated this exact question by surveying ~ 91 Program Directors of Pediatric Residency Programs in the US.

                                                                          In their study, Boykan and Jacobson reported that 80% of programs utilized medical librarians. Most of these librarians assisted with scholarly or research projects (74%), addressed clinical questions (62%), and taught on any topic — not necessarily EBM (58%) — it might be something like citation management or workflow tools. Only 17% of program directors stated that librarians were involved in teaching EBM on a regular basis. Size of the program mattered the most when it came to the use of librarians. Smaller programs (≤29 residents) were more likely to utilize librarians (100%) than were medium (30-59 residents) (71%) or large programs (>60 residents) (75%). The authors concluded that while most pediatric residency programs have an EBM curriculum and engage medical librarians in various ways, librarians’ expertise in teaching EBM is underutilized. It is important to stress that regardless of the program size, the cost of utilizing librarians did not appear to be a barrier.

                                                                          Q6. Carrie: How can librarians help the Peds ICU fellow and other learners in the PICU with respect to clinical practice?

                                                                          In the clinical practice arena with the PICU: As librarians, understand the Peds ICU fellow and other learners, especially in their first year of training, will be very busy from the get go. The peds ICU fellow and other learners, such as the advance practice nurses, serve the role of team leaders within the picu: managing residents, medical students, and the clinical care team, and report to their PICU attending. Some programs are very busy and leave very little time to adequately prepare for gathering the evidence necessary for making informed clinical decisions. Research has shown that when clinical librarians are involved in providing information in the patient care setting, answers to clinical questions can be obtained more quickly and efficiently. (McGowan et al Plos One 2008; Oliver et al. J Med Libr Ass 2011). The Value Study by Marshall et al. noted that clinicians who had used their librarian had changed patient care based on the information they received. This was spread across patient education, diagnosis and differential diagnosis, choice of medication, and... overall they felt that they had made more informed clinical decisions because they were able to receive timely, high-quality information. Your librarian can efficiently and effectively search for evidence, which can be quickly appraised and put to use by busy Peds ICU fellows or others. Librarians can provide information for fellows/faculty during morning reports, grand rounds, committees, morbidity and mortality conferences,...]]>Welcome to PICU Doc On Call, a podcast dedicated to current and aspiring intensivists. My name is Pradip Kamat

                                                                          and my name is Rahul Damania and we come to you from Children's Healthcare of Atlanta Emory University School of Medicine. Today's episode is dedicated to optimizing your Pediatric Critical Care Knowledge and study skills by utilizing your medical librarian.

                                                                          We are delighted to be joined by Ms. Carrie Price a health Professions librarian. Carrie was formerly at the Welch Medical Library, serving the faculty, students and staff of Johns Hopkins Medical Institutions. Ms Price is currently at the Albert S. Cook Library of Towson University in Towson, Maryland.

                                                                          Ms Price is an expert searcher with a strong interest in user-centered and instructional design, evidence-based medicine, and inter-professional education.

                                                                          Ms Price also maintains and updates a YouTube Channel with videos about citation management, searching, and evidence-based medicine. Carrie is on twitter @carrieprice78

                                                                          Q1. Carrie welcome to PICU DOC on Call Podcast. Our topic today— Value of the librarian in PedsICU education and it is one of the first in our series of how learners can organize their study habits while rotating in the PEDS ICU.

                                                                          Carrie: Thanks Rahul and Pradip for having me on PICU DOC on Call podcast. I have no conflicts of interest or financial disclosures.

                                                                          Q2. Carrie tell us your story and how you came to be an expert medical librarian ?

                                                                          Carrie: I came into librarianship as a second career, after a first career in nonprofit development. I was fortunate to start my work in libraries at Johns Hopkins University, where I worked as a library assistant in access services while getting my masters degree in library science. During this time my mom was diagnosed with appendix cancer, a rare cancer, (she's okay now), and through the time we spent together in the hospital, I noticed there was a medical library in the building. I had this epiphany that librarians weren't limited by traditional career paths. From then I started focusing on health and consumer health classes. Later, at a work all-staff meeting, I literally bumped into the former director of the Welch Medical Library, and the rest is history! I applied for an open position, was hired, and started working at the Welch Medical Library in 2012. It has been an incredible experience. I am fortunate to work extensively with a number of departments and divisions at Johns Hopkins and now at Towson University, so my experiences have been really multidisciplinary. In the past I worked as a physical therapy technician, which was awesome and helped inform the knowledge I brought to the profession. I've taken a lot of professional development in the field. I just never stop learning, and I love sharing information on Twitter, YouTube, and on my website, which is carrieprice78.github.io.

                                                                          This is such an amazing story!

                                                                          Q3: Carrie the practice of critical care medicine requires that learners in the Peds ICU remain current in their knowledge of the literature. Given an overwhelming amount of information out there how should these learners drink from that fire hydrant without being blown away?

                                                                          Carrie: I think that's an excellent question. Prior to the arrival of internet, most additional knowledge was acquired from physically going to a library and perusing through peer reviewed journals and textbooks. Now, things are digital and even "born-digital" — and there is so much information available online and on your phone.... I understand that given how much information is out there, a learner can feel overwhelmed and have difficulty trusting the information they see. That's why critical appraisal is a key part of evidence-based practice. Studies have shown the value of readily-available information in patient care and have highlighted the role of the library and librarian in support of clinical practice.

                                                                          In 1996 Sackett et al (BMJ 1996). defined evidence based medicine (EBM) as “the conscientious, explicit and judicious use of current best evidence in making decisions about the care of the individual patient." It's come to be seen as a combination of sound research evidence, clinical expertise, and patient preference. While the Accreditation Council for Graduate Medical Education (ACGME) requires peds residents to have formal training in EBM, there is considerable variation in what constitutes EBM training. This is where learners can pull from the expertise of medical librarians, who are experts in searching and evaluating literature. I suggest reaching out to your medical librarian right away. They can help you set up search alerts for topics of interest and journal tables of contents from PubMed and other resources. There are also apps, there is an app called QxMD that can help you be more aware of current literature in fields you follow. There's another app called Browzine, which you may have access to through your institution, where you can subscribe to journal table of contents. You can also find clinical, evidence-based, frequently-updated summaries with tools like UpToDate and DynaMed, depending on what you have through your institution.

                                                                          Having comprehensive resources such as UpToDate and Dynamed can help you curtail individual studies into a concise review!

                                                                          Q4. Carrie: now that you brought out the concept of Evidence-Based Medicine, what are some of the appropriate venues for teaching evidence based prospects in the Peds ICU environment?

                                                                          Almost all pediatric critical care medicine fellowships have a fellow conferences where learners have "protected time" for their education. Fellows conferences can have journal clubs, lectures, chapter reviews and case reports. Fellows conference could be one of the best venues for teaching EBM, where faculty and learners can interact. I think EBM practices should be a part of the peer-peer sign out after a call or service, or morning report. Programs can invite librarians to attend meetings, or seek help of a librarian while preparing for presentations. I also want to emphasize that with daily patient care rounds in the PICU — most fellows should question practices on rounds, which are handed down from previous trainees but don't always have sound evidence behind the practice, or some new research may have changed practice or knowledge. You can reach out to your librarian with these kinds of queries. Librarians can also help with PICO question formulation, searching for and appraising the evidence, and translating evidence into practice—all critical aspects of EBM.

                                                                          As trainees we are always wanting to optimize our clinical skills and understanding by asking the Why, the How, and the Why Not behind certain clinical scenarios in children! Asking these PICO questions, which stands for isolating the Population, Intervention, Comparison, and Outcome can help us ascertain key clinical questions which come up in our training!

                                                                          Q5. Carrie: How are librarians utilized by the pediatric residency programs ?

                                                                          There is an excellent study by Boykan and Jacobson (2017) which evaluated this exact question by surveying ~ 91 Program Directors of Pediatric Residency Programs in the US.

                                                                          In their study, Boykan and Jacobson reported that 80% of programs utilized medical librarians. Most of these librarians assisted with scholarly or research projects (74%), addressed clinical questions (62%), and taught on any topic — not necessarily EBM (58%) — it might be something like citation management or workflow tools. Only 17% of program directors stated that librarians were involved in teaching EBM on a regular basis. Size of the program mattered the most when it came to the use of librarians. Smaller programs (≤29 residents) were more likely to utilize librarians (100%) than were medium (30-59 residents) (71%) or large programs (>60 residents) (75%). The authors concluded that while most pediatric residency programs have an EBM curriculum and engage medical librarians in various ways, librarians’ expertise in teaching EBM is underutilized. It is important to stress that regardless of the program size, the cost of utilizing librarians did not appear to be a barrier.

                                                                          Q6. Carrie: How can librarians help the Peds ICU fellow and other learners in the PICU with respect to clinical practice?

                                                                          In the clinical practice arena with the PICU: As librarians, understand the Peds ICU fellow and other learners, especially in their first year of training, will be very busy from the get go. The peds ICU fellow and other learners, such as the advance practice nurses, serve the role of team leaders within the picu: managing residents, medical students, and the clinical care team, and report to their PICU attending. Some programs are very busy and leave very little time to adequately prepare for gathering the evidence necessary for making informed clinical decisions. Research has shown that when clinical librarians are involved in providing information in the patient care setting, answers to clinical questions can be obtained more quickly and efficiently. (McGowan et al Plos One 2008; Oliver et al. J Med Libr Ass 2011). The Value Study by Marshall et al. noted that clinicians who had used their librarian had changed patient care based on the information they received. This was spread across patient education, diagnosis and differential diagnosis, choice of medication, and... overall they felt that they had made more informed clinical decisions because they were able to receive timely, high-quality information. Your librarian can efficiently and effectively search for evidence, which can be quickly appraised and put to use by busy Peds ICU fellows or others. Librarians can provide information for fellows/faculty during morning reports, grand rounds, committees, morbidity and mortality conferences, and more. One case controlled study has (Banks DE, Shi R, Timm DF, et al. J Med Libr Assoc. 2007;95(4):381-387) demonstrated that librarian support was associated with saved resources and reduced costs beyond a health practitioner’s time savings; a librarian’s presence at morning report correlated positively with shorter length of stays and lower hospital charges in 55 cases with 136 matched comparisons.

                                                                          This is such a key point, leveraging your instutitions libarian can serve to be a bimodal learning process! As both trainee and librarian collaborate learning can be optimized and this can ultimately affect patient outcome!

                                                                          Q7. Carrie: How can librarians help the Peds ICU fellow and other learners in the PICU with respect to research and their scholarly activities?

                                                                          At most institutions, Librarians and library professionals choose what resources and databases to buy: they negotiate prices; ensure that electronic resource vendors have the information they need to provide access; ensure remote access through proxy servers; organize the information on digital portals and guides; build interfaces and education to facilitate searching; and collect and analyze usage data to validate use of institutional resources.

                                                                          Most PedsICU fellows require some scholarly activity (research/publication) during their fellowship. Besides talking early on with the statistician, Peds ICU fellows and learners could really benefit talking to a librarian about their research question prior to initiation of the research project. Medical librarians are your research partner! A 2015 publication by Rethlefsen et al. showed that librarian involvement on systematic reviews in general internal medicine correlated with higher quality reported searches. Additionally,y our librarian can update you with new references from your literature search, and over time, help you understand your research impact. And like I said, they can help you set up alerts and understand what's out there and how the literature is trending in your areas of interest. The librarians can help with organizing references needed for the project. If a full text article is not available, the librarians can help you obtain it through inter-library loan. Librarians are invaluable to decreasing the stress of fellow/learner embarding on a research project.

                                                                          Q8. Carrie: Do you see a role for the healthcare librarian in patient safety and quality initiatives?

                                                                          Yes! Many institutions will also have fellows on a committee or two within the PICU based on their interests such as the airway safety committee, vascular access committee etc. Librarians have an increasing role in providing patient- and family-centered information and can help the fellows acquire the latest information and evidence, which may be necessary to update protocol or guidelines commonly used in the PICU. Fellows and learners should approach librarians when faced with the task of updating a previous protocol, guidelines, standard of care, algorithm or best practice documents used in their PICUs to get the best and the latest available evidence.

                                                                          Q9 Ms Price: whats your advice to the fellows with respect to online databases use to access medical information:

                                                                          I think fellowship programs should invite their librarian to speak to the fellows and the PICU team to inform the learners of what resources their institutional library provides. Most libraries, especially in the healthcare setting, have a number of resources free and easily accessible, with access to content that you wouldn't have otherwise. The most commonly utilized is the free resource PubMed, from the U.S. National Library of Medicine. It's considered one of the premier databases for health and biomedical literature, containing over 32 million records. It does not include full text journal articles; however, links to the full text are often present when available from other sources, either through your university or institution, or through the publisher's website or PubMed Central. Your institutional library will have its own collections of journals and databases provided to you free of charge. Even Google Scholar can be helpful for finding hard-to-locate articles and interfacing with citation management tools. I should also mention that good collection of the latest articles from the Peds ICU literature is provided by Dr. Hari Krishnan at picujournalwatch.com.

                                                                          Q10. Carrie what are some good resources to store articles, citations for future use? (Carrie please add/delete stuff as you want)..

                                                                          There are a lot of good resources for storing references collectively called reference or citation management software: there are Zotero, Mendeley, EndNote, and actually a lot more. They all kind of compete with each other so they're all pretty good, and the ones I just mentioned are either completely free or have free versions. Most reference management software programs have the same functions: importing references, organizing, storing, and creating citations and bibliographies in a manuscript. These can be a huge time saver for the busy pedsICU fellow — and your librarian can help you get set up and get started with the tool you select. Personal preferences, type of operating software used, and pricing may factor in choice of reference management software. I cant stress enough to save your work, hopefully to the cloud, for ready access anywhere, but also in case there is a malfunction or loss of your device. Another great tool — not a citation management tool, but one that everyone who has published or hopes to publish should sign up for is ORCID. ORCID is open researcher and contributor ID. It's a free researcher profile system that is increasingly being used and even required for grant applications and article submissions. This researcher profile system can help you save all your research products in one place, update your CV, speed up the process of creating your Biosketch or applying for grants, and help disambiguate you from other researchers. You can check it out at orcid.org.

                                                                          OK to summarize, have a reference manager which can quickly capture and organize key articles — as you delve into your research project utilize this reference manager and their respective integrations to streamline your manuscript process!

                                                                          Q11 Carrie we appreciate your insights on today's podcasts, as we wrap up, would you mind highlighting your personal clinical pearls?

                                                                          I think I would say that the medical librarian is your friend. Set up a meeting with them early on in your fellowship. Make use of this invaluable resource for not only to improve on your clinical work, patient outcomes, and decreasing costs but also for research, systematic and scoping reviews, quality and safety initiatives within the PICU. We can save you time doing literature searches, getting you the latest and best evidence, helping you organize citations, requesting the reference/article you need for that case report or lecture presentation, even finding Creative Commons medical images for use in posters and presentations. We can be there at the point of need, at morning report, journal clubs, department meetings, and we can help faculty with creation of medical education and EBM instructional materials. Librarians should be included in development of educational curriculums, written into grants, considered co-authors as a part of an author research team, and included in-class teaching for PICU fellow conferences. Faculty can and should coordinate with medical librarians for optimal training of the peds ICU fellows and other learners.

                                                                          To summarize today's episode...

                                                                          We learnt today the immense value, which the medical librarians bring to the learning environment of the Peds ICU. Medical librarian Carrie Prices would like to see more involvement of medical librarians in the development and maintenance of PedsICU learning curriculum. A collaborative approach between the librarians, faculty, fellows and other allied health personnel my be a win win for all including the patients and their families.

                                                                          This concludes our episode today on Value of the Librarian in PedsICU Education. We hope you found value in this short podcast. We welcome you to share your feedback & place a review on our podcast. PICU Doc on Call is co-hosted by me Pradip Kamat and my cohost Dr. Rahul Damania. Please visit our website picudoconcall.org

                                                                          Stay tuned for our next episode! Thank you

                                                                          References:

                                                                          Quesenberry, A. C., Oelschlegel, S., Earl, M., Leonard, K., & Vaughn, C. J. (2016). The impact of library resources and services on the scholarly activity of medical faculty and residents. Medical Reference Services Quarterly, 35(3), 259-265.

                                                                          Rethlefsen, M. L., Farrell, A. M., Osterhaus Trzasko, L. C., & Brigham, T. J. (2015). Librarian co-authors correlated with higher quality reported search strategies in general internal medicine systematic reviews. Journal of clinical epidemiology, 68(6), 617–626. https://doi.org/10.1016/j.jclinepi.2014.11.025

                                                                          Sollenberger, J. F., & Holloway, R. G. (2013). The evolving role and value of libraries and librarians in health care. JAMA, 310(12), 1231-1232.

                                                                          Boykan, R., & Jacobson, R. M. (2017). The role of librarians in teaching evidence-based medicine to pediatric residents: a survey of pediatric residency program directors. Journal of the Medical Library Association : JMLA, 105(4), 355–360. https://doi.org/10.5195/jmla.2017.178

                                                                          Ullah, M., & Ameen, K. (2019). Teaching information literacy skills to medical...]]>59c57657-07c5-4f36-bb17-330812076a42Sun, 04 Jul 2021 03:00:00 -040020:01falsefull2020Acute Salicylate ToxicityToday’s episode focuses on salicylate toxicity, specifically in the case of a teenager with abdominal pain and emesis. Join us in this discussion of symptoms, patient history, diagnosis, management, and treatment. 

                                                                          Show Highlights:

                                                                          • Our case: A 15-year-old female is admitted to the PICU for intentionally ingesting a large amount of aspirin tablets. She had epigastric abdominal pain with some non-biliary, non-bloody emesis when she presented to the outside emergency department twelve hours post-ingestion. She denies any neurological symptoms, including tinnitus but appears anxious and tachypneic. In the emergency department, her salicylate level was 45 mg/dL after her ingestion of about 250 aspirin tablets of 325 mg each. The patient is previously healthy, denies the use of illicit drugs and alcohol, is not sexually active, and has no allergies. 
                                                                          • To summarize the key elements of this case and patient history, she has ingested potentially toxic amounts of aspirin and has suicidal ideation but has no tinnitus or other neurological symptoms. 
                                                                          • Physical examination results show stable vital signs except for a temp of 38.8C; she has persistent tachypnea and mild epigastric tenderness but no rashes or previous cutting scars.
                                                                          • Patient labs were consistent with a 12-hour salicylate level of 45 mg/dL, liver function, Bun/Creatinine, and coagulation profile are all normal. Her anion gap is slightly elevated, urine pH is 6, specific gravity is normal, and urine pregnancy test is negative. 
                                                                          • Based on patient history, physical exam, and labs, it appears that the patient has GI symptoms of early salicylate toxicity. Ingesting potentially toxic amounts of aspirin brings concern for life-threatening injuries to organs and possible loss of life. Let’s quiz ourselves with a short multiple-choice question:
                                                                          • A teenager with a previous history of suicidal attempt now presents with confusion, increased respiratory rate, fever, and diaphoresis. Her physical exam including the pupillary exam is normal. Her labs are remarkable for a pH of 7.45, CO2 of 19, HCO3 of 11, serum anion gap of 20meQ/L, serum K of 2.9, and serum glucose of 180 mg/dL. There are weakly positive ketones in the urine. The next step in management of this patient is:
                                                                          • A) NaHCO3 infusion
                                                                          • B) Insulin infusion
                                                                          • C) Oral activated charcoal
                                                                          • D) Hemodialysis dialysis
                                                                          • The correct answer to this question is A) Sodium bicarbonate infusion.
                                                                          • Insulin therapy is not the answer because serum glucose is low, and a patient with a pH>7.25 is unlikely to have DKA.
                                                                          • While activated charcoal can be used, especially followed by sorbitol given with the first dose, we need to be cautious about its use with an altered mental status as in the patient above.
                                                                          • Since we do not have a salicylate level at this stage, offering hemodialysis should not be the first step, although it can be considered later given the neurological symptoms. 
                                                                          • Remember: Any patient with a previous history of suicidal ideation who presents with confusion, fever, and diaphoresis with the above labs is suggestive of mixed respiratory alkalosis with high anion gap metabolic acidosis is highly suggestive of aspirin poisoning. Always examine the pupils in any case of poisoning, as that may point one towards a possible toxidrome. 
                                                                          • Let’s highlight how basic science correlates with ASA poisoning:
                                                                          • Remember the mechanism of action. Aspirin is a cyclo-oxygenase inhibitor which blocks prostaglandin production and has an antithrombotic effect by inhibiting platelet generation of thromboxane A2.
                                                                          • Salicylates are weak acids which interfere with the Krebs cycle and specifically uncouple oxidative phosphorylation. This leads to acidosis, heat production, and hypoglycemia.
                                                                          • Although not common, neuromuscular irritability manifested as paratonia (inability to relax muscles) and extreme muscle rigidity can develop, further contributing to hyperthermia and increasing the risk of rhabdomyolysis.
                                                                          • Salicylates induce fatty acid metabolism resulting in ketone production which can further compound the anion gap metabolic acidosis.
                                                                          • Disruption of the electron transport chain causes a dissociative shock picture in which there is adequate oxygen delivery, however, the tissues are unable to uptake the oxygen.
                                                                          • Considerations in the diagnostic approach to our patient with salicylate poisoning:
                                                                          • Salicylate poisoning can happen acutely (usually in young adults with suicidal ideation) or chronically, which often happens in the elderly who are taking aspirin therapeutically but have an inadvertent overdose. Because the pathways for salicylate elimination are fully saturated in those taking the drug chronically, a higher toxicity can occur at even a lower dose. 
                                                                          • The plasma level of salicylate required to elicit symptoms tends to be lower in chronic than in acute salicylate poisoning. In cases of acute salicylate toxicity, rising plasma levels are roughly correlated with the development of expected clinical manifestations, but such correlations are notoriously absent with chronic toxicity. 
                                                                          • Salicylate poisoning should be suspected in any patient with the following:
                                                                          • Possible ingestion of known or unknown drug
                                                                          • Tinnitus, nausea, vomiting, tachypnea, and altered mental status
                                                                          • Elevated anion gap metabolic acidosis; remember that the patient can present with a mixed respiratory alkalosis and an anion gap metabolic acidosis
                                                                          • Any elderly patient on chronic aspirin therapy who presents with agitation, confusion, hallucinations, slurred speech, seizures, and coma; “salicylate jag” refers to restlessness and mental aberrations that resemble alcohol intoxication
                                                                          • Your diagnosis will likely be confirmed by elevated serum salicylate concentration!
                                                                          • It is important to check salicylate levels with serial measurements every three hours because toxicity can be delayed. Once you get the level, you can stratify the level of toxicity:
                                                                          • Generally, a level of 15-30 mg/dL is considered therapeutic for inflammatory conditions, but levels can exceed 40-50 within 1-2 hours of a single ingestion.
                                                                          • Significant toxicity begins to manifest at a level >45 with tinnitus, vertigo, nausea, vomiting, and hyperventilation.
                                                                          • A level of 50-70 indicates severe intoxication; the patient can have fever, sweating, listlessness, and incoordination.
                                                                          • At levels exceeding 75, patients are at risk for hallucinations, seizures, cerebral edema, coma, noncardiogenic pulmonary edema, and cardiovascular collapse. 
                                                                          • Other major testing to consider include acetaminophen level, acid-base status with electrolytes, blood gas, urine pH, and pregnancy test, renal and liver function tests, and possible head CT if there are signs of cerebral edema or persistent altered mental status. 
                                                                          • If the history, physical exam, and diagnostic investigation lead us to a salicylate poisoning diagnosis, the general management framework would be as follows:
                                                                          • Management is based on supportive care and elimination of salicylate, including gastric decontamination with activated charcoal and possibly polyethylene glycol via a nasogastric tube.
                                                                          • The airway should be protected with intubation for respiratory failure, in the obtunded or delirious patient, or for a procedure such as dialysis access catheter placement. Avoid a low respiratory rate because any decrease in pH from a rising PCO2 can enhance movement of salicylate into tissues, and the patient can worsen.
                                                                          • In fluid management, use Lactated Ringer’s solution since normal saline can cause normal anion gap acidosis and lower pH. A hallmark of therapy for salicylate ingestion is the alkalinization of the patient’s urine until the serum salicylate level is <40 mg/dL, metabolic acidosis is resolved, and the patient is asymptomatic with a normal respiratory rate. It is recommended to give one meQ/Kg initial bolus of NaHCO3 followed by three ampules of NaHCO3 added to one liter of D5W, with the goal of keeping the urine pH above 7.5. Add some KCL to this as hypokalemia can occur. Check serial blood gases, along with ionized calcium and magnesium, and avoid a serum pH above 7.5. 
                                                                          • Hemodialysis should be considered for the patient because the water solubility, small size, low volume of distribution, and absence of tissue binding make salicylate an ideal substance to dialyze. 
                                                                          • Urinary alkalinization is NOT a substitute for dialysis and can be stopped once dialysis is initiated. 
                                                                          • Hemodialysis should be considered for any patient with severe signs or symptoms, including severe fluid and electrolyte disturbances, altered mental status, cerebral edema, acute respiratory distress syndrome, and acute kidney injury. 
                                                                          • Hemodialysis is recommended if the plasma salicylate level is greater than 90 mg/dL or greater than 80 if kidney function is impaired. 
                                                                          • Conventional hemodialysis is preferred, but hemoperfusion or CVVH is acceptable if hemodialysis is not available or the patient is unstable.
                                                                          Today’s episode focuses on salicylate toxicity, specifically in the case of a teenager with abdominal pain and emesis. Join us in this discussion of symptoms, patient history, diagnosis, management, and treatment. 

                                                                          Show Highlights:

                                                                          • Our case: A 15-year-old female is admitted to the PICU for intentionally ingesting a large amount of aspirin tablets. She had epigastric abdominal pain with some non-biliary, non-bloody emesis when she presented to the outside emergency department twelve hours post-ingestion. She denies any neurological symptoms, including tinnitus but appears anxious and tachypneic. In the emergency department, her salicylate level was 45 mg/dL after her ingestion of about 250 aspirin tablets of 325 mg each. The patient is previously healthy, denies the use of illicit drugs and alcohol, is not sexually active, and has no allergies. 
                                                                          • To summarize the key elements of this case and patient history, she has ingested potentially toxic amounts of aspirin and has suicidal ideation but has no tinnitus or other neurological symptoms. 
                                                                          • Physical examination results show stable vital signs except for a temp of 38.8C; she has persistent tachypnea and mild epigastric tenderness but no rashes or previous cutting scars.
                                                                          • Patient labs were consistent with a 12-hour salicylate level of 45 mg/dL, liver function, Bun/Creatinine, and coagulation profile are all normal. Her anion gap is slightly elevated, urine pH is 6, specific gravity is normal, and urine pregnancy test is negative. 
                                                                          • Based on patient history, physical exam, and labs, it appears that the patient has GI symptoms of early salicylate toxicity. Ingesting potentially toxic amounts of aspirin brings concern for life-threatening injuries to organs and possible loss of life. Let’s quiz ourselves with a short multiple-choice question:
                                                                          • A teenager with a previous history of suicidal attempt now presents with confusion, increased respiratory rate, fever, and diaphoresis. Her physical exam including the pupillary exam is normal. Her labs are remarkable for a pH of 7.45, CO2 of 19, HCO3 of 11, serum anion gap of 20meQ/L, serum K of 2.9, and serum glucose of 180 mg/dL. There are weakly positive ketones in the urine. The next step in management of this patient is:
                                                                          • A) NaHCO3 infusion
                                                                          • B) Insulin infusion
                                                                          • C) Oral activated charcoal
                                                                          • D) Hemodialysis dialysis
                                                                          • The correct answer to this question is A) Sodium bicarbonate infusion.
                                                                          • Insulin therapy is not the answer because serum glucose is low, and a patient with a pH>7.25 is unlikely to have DKA.
                                                                          • While activated charcoal can be used, especially followed by sorbitol given with the first dose, we need to be cautious about its use with an altered mental status as in the patient above.
                                                                          • Since we do not have a salicylate level at this stage, offering hemodialysis should not be the first step, although it can be considered later given the neurological symptoms. 
                                                                          • Remember: Any patient with a previous history of suicidal ideation who presents with confusion, fever, and diaphoresis with the above labs is suggestive of mixed respiratory alkalosis with high anion gap metabolic acidosis is highly suggestive of aspirin poisoning. Always examine the pupils in any case of poisoning, as that may point one towards a possible toxidrome. 
                                                                          • Let’s highlight how basic science correlates with ASA poisoning:
                                                                          • Remember the mechanism of action. Aspirin is a cyclo-oxygenase inhibitor which blocks prostaglandin production and has an antithrombotic effect by inhibiting platelet generation of thromboxane A2.
                                                                          • Salicylates are weak acids which interfere with the Krebs cycle and specifically uncouple oxidative phosphorylation. This leads to acidosis, heat production, and hypoglycemia.
                                                                          • Although not common, neuromuscular irritability manifested as paratonia (inability to relax muscles) and extreme muscle rigidity can develop, further contributing to hyperthermia and increasing the risk of rhabdomyolysis.
                                                                          • Salicylates induce fatty acid metabolism resulting in ketone production which can further compound the anion gap metabolic acidosis.
                                                                          • Disruption of the electron transport chain causes a dissociative shock picture in which there is adequate oxygen delivery, however, the tissues are unable to uptake the oxygen.
                                                                          • Considerations in the diagnostic approach to our patient with salicylate poisoning:
                                                                          • Salicylate poisoning can happen acutely (usually in young adults with suicidal ideation) or chronically, which often happens in the elderly who are taking aspirin therapeutically but have an inadvertent overdose. Because the pathways for salicylate elimination are fully saturated in those taking the drug chronically, a higher toxicity can occur at even a lower dose. 
                                                                          • The plasma level of salicylate required to elicit symptoms tends to be lower in chronic than in acute salicylate poisoning. In cases of acute salicylate toxicity, rising plasma levels are roughly correlated with the development of expected clinical manifestations, but such correlations are notoriously absent with chronic toxicity. 
                                                                          • Salicylate poisoning should be suspected in any patient with the following:
                                                                          • Possible ingestion of known or unknown drug
                                                                          • Tinnitus, nausea, vomiting, tachypnea, and altered mental status
                                                                          • Elevated anion gap metabolic acidosis; remember that the patient can present with a mixed respiratory alkalosis and an anion gap metabolic acidosis
                                                                          • Any elderly patient on chronic aspirin therapy who presents with agitation, confusion, hallucinations, slurred speech, seizures, and coma; “salicylate jag” refers to restlessness and mental aberrations that resemble alcohol intoxication
                                                                          • Your diagnosis will likely be confirmed by elevated serum salicylate concentration!
                                                                          • It is important to check salicylate levels with serial measurements every three hours because toxicity can be delayed. Once you get the level, you can stratify the level of toxicity:
                                                                          • Generally, a level of 15-30 mg/dL is considered therapeutic for inflammatory conditions, but levels can exceed 40-50 within 1-2 hours of a single ingestion.
                                                                          • Significant toxicity begins to manifest at a level >45 with tinnitus, vertigo, nausea, vomiting, and hyperventilation.
                                                                          • A level of 50-70 indicates severe intoxication; the patient can have fever, sweating, listlessness, and incoordination.
                                                                          • At levels exceeding 75, patients are at risk for hallucinations, seizures, cerebral edema, coma, noncardiogenic pulmonary edema, and cardiovascular collapse. 
                                                                          • Other major testing to consider include acetaminophen level, acid-base status with electrolytes, blood gas, urine pH, and pregnancy test, renal and liver function tests, and possible head CT if there are signs of cerebral edema or persistent altered mental status. 
                                                                          • If the history, physical exam, and diagnostic investigation lead us to a salicylate poisoning diagnosis, the general management framework would be as follows:
                                                                          • Management is based on supportive care and elimination of salicylate, including gastric decontamination with activated charcoal and possibly polyethylene glycol via a nasogastric tube.
                                                                          • The airway should be protected with intubation for respiratory failure, in the obtunded or delirious patient, or for a procedure such as dialysis access catheter placement. Avoid a low respiratory rate because any decrease in pH from a rising PCO2 can enhance movement of salicylate into tissues, and the patient can worsen.
                                                                          • In fluid management, use Lactated Ringer’s solution since normal saline can cause normal anion gap acidosis and lower pH. A hallmark of therapy for salicylate ingestion is the alkalinization of the patient’s urine until the serum salicylate level is <40 mg/dL, metabolic acidosis is resolved, and the patient is asymptomatic with a normal respiratory rate. It is recommended to give one meQ/Kg initial bolus of NaHCO3 followed by three ampules of NaHCO3 added to one liter of D5W, with the goal of keeping the urine pH above 7.5. Add some KCL to this as hypokalemia can occur. Check serial blood gases, along with ionized calcium and magnesium, and avoid a serum pH above 7.5. 
                                                                          • Hemodialysis should be considered for the patient because the water solubility, small size, low volume of distribution, and absence of tissue binding make salicylate an ideal substance to dialyze. 
                                                                          • Urinary alkalinization is NOT a substitute for dialysis and can be stopped once dialysis is initiated. 
                                                                          • Hemodialysis should be considered for any patient with severe signs or symptoms, including severe fluid and electrolyte disturbances, altered mental status, cerebral edema, acute respiratory distress syndrome, and acute kidney injury. 
                                                                          • Hemodialysis is recommended if the plasma salicylate level is greater than 90 mg/dL or greater than 80 if kidney function is impaired. 
                                                                          • Conventional hemodialysis is preferred, but hemoperfusion or CVVH is acceptable if hemodialysis is not available or the patient is unstable.
                                                                          • Keep close communication with poison control and the clinical toxicologist because of the life-threatening complications that can occur.
                                                                          • Repeat the salicylate level at least every three hours until the level is down-trending. 
                                                                          • Learn more about salicylate toxicity from these sources:
                                                                          • The review of salicylate toxicity by Palmer and Clegg from the New England Journal of Medicine, June 2020
                                                                          • Chapter 126, p. 1503 of the latest edition of Fuhrmanns and Zimmerman’s textbook of Pediatric Critical Care
                                                                          • Clinical pearls:
                                                                          • A salicylate level of 300 mg/kg can result in severe toxicity and even death. Salicylate toxicity must be suspected in any patient presenting with fever, diaphoresis, mixed respiratory alkalosis, and metabolic acidosis.
                                                                          • Urinary alkalinization using NaHCO3 in IV fluids is the hallmark of therapy to prevent systemic absorption of the drug. Serial measurements of serum K, Magnesium, and a blood gas are required during the process of alkalinization, and urinary pH should be maintained at 7.5 or greater.
                                                                          • Despite normal serum glucose, the CSF glucose can be low. Dextrose can be used for acute delirium. 
                                                                          • Indications for dialysis include plasma salicylate level >90 mg/dL or >80 mg/dL if kidney function is impaired. Any severe signs or symptoms, including severe fluid and electrolyte disturbances, cerebral edema, acute respiratory distress syndrome, and acute kidney injury are indications for dialysis. 
                                                                          
                                                                          ]]>c9a1fcbd-2a32-49a0-870c-237ad480fb51Sun, 27 Jun 2021 03:00:00 -040018:12falsefull1919PICU Approach to Thyroid StormToday’s episode is dedicated to the approach to thyroid storm. It’s the first in our Mini-Case series.

                                                                          Show Highlights:

                                                                          Our case, symptoms, and diagnosis: A 12-year-old female presents to the PICU with chest discomfort. She was noted to be anxious by her parents over the past few days. They felt she was a bit "off," as she would constantly drop items and have a tremor. A few weeks prior to these symptoms, she was noted to have rhinorrhea, congestion, and progressive neck swelling. Her parents became increasingly concerned this morning as her temperature was 104F. Per her parents, she was agitated throughout the night and became increasingly somnolent in the early morning. 

                                                                          To summarize key elements from this case, this patient has:

                                                                          • Chest pain likely due to a cardiac etiology or musculoskeletal cause.
                                                                          • Tremor likely due to a primary neurologic cause or increased metabolic drive.
                                                                          • Neck swelling with fever after a prodrome of URI symptoms which could be concerning for lymphadenitis or thyroid goiter.
                                                                          • Synthesizing these symptoms together, this patient likely has a systemic etiology such as hyperthyroidism, with the most severe manifestation being thyroid storm, a toxidrome, or a pheochromocytoma. Given the fever and altered mental status, considering sepsis is key.
                                                                          
                                                                          

                                                                          Key history features in this child with tachycardia and signs of hyperthyroidism:

                                                                          • High fevers up to 104F
                                                                          • Altered mental status
                                                                          • Neck swelling 
                                                                          
                                                                          

                                                                          Red flag symptoms and physical exam components in a patient with severe hyperthyroidism include:

                                                                          • Airway
                                                                          • Check for dyspnea or stridor when the patient is supine.
                                                                          • Do a Mallampati assessment.
                                                                          • Auscultate for a bruit in the neck. 
                                                                          • Cardiovascular system
                                                                          • Concerns include congestive heart failure and cardiac dysrhythmias.
                                                                          • Widened pulse pressure is common 
                                                                          
                                                                          

                                                                          The American Thyroid Association has advocated for the Burch-Wartofsky Point Scale (BWPS) for severe thyrotoxicosis. A score of 45 or higher indicates thyroid storm. A case-control study published in 2015 in the Journal of Endocrinology noted that the BWPS may overdiagnose up to 20% of patients. Clinical criteria on the BWPS include the following:

                                                                          • Thermoregulatory dysfunction
                                                                          • Central nervous system effects
                                                                          • Gastrointestinal-hepatic dysfunction
                                                                          • Cardiovascular dysfunction
                                                                          • Congestive heart failure
                                                                          • Presence or absence of a precipitant history of URI or underlying thyroid condition
                                                                          
                                                                          

                                                                          Back to our specific case, the patient's labs are consistent with low TSH and elevated free T4, indicating primary hyperthyroidism, positive for TSH-receptor antibodies, and the diagnosis of thyroid storm was confirmed.

                                                                          • Other lab findings included elevated WBC, high ALT and AST, elevated glucose, and elevated cortisol. Her cardiac evaluation was notable for sinus tachycardia with occasional PACs.
                                                                          • Other important labs include a coagulation panel, BNP and lactate, CRP, procalcitonin, blood cultures, and basic blood chemistries.
                                                                          
                                                                          

                                                                          Let’s quiz ourselves with a multiple choice question:

                                                                          • A patient with thyroid storm is admitted to the PICU. He is started on thyroid modulating therapy. Which of the following mechanisms of action does this medication likely work by?
                                                                          •  A. Activate Thyroid Peroxidase
                                                                          •  B. Inhibit Thyroid Peroxidase
                                                                          •  C. Inhibit Iodine Uptake within the Thyroid
                                                                          •  D. Increase conversion from T4 to T3
                                                                          
                                                                          

                                                                             The correct answer is B. The most likely medication which is used in thyroid storm is methimazole or propylthiouracil. Both of these medications block thyroid peroxidase.

                                                                           In terms of differential in our case, you want to think about other causes of fever, tachycardia, and CNS dysfunction, including, but not limited to sepsis, serotonin syndrome, neuroleptic malignant syndrome, heatstroke, and drug intoxication. 

                                                                          The diagnostic approach for our patient should focus on her history and physical examination. Be sure to include thyroid function tests, cardiac evaluation via EKG or Echo, chest x-ray, blood culture, urine analysis, and lateral neck radiographs to assess airway compression. 

                                                                          The general management framework for the diagnosis of thyroid storm should include a multimodal approach to block thyroid hormone production and action quickly, reverse systemic decompensation, and identify and treat any underlying causes and precipitants of thyroid storm. The key components are:

                                                                          • Optimal communication between the pediatric endocrinology team and ICU staff
                                                                          • Acute resuscitative measures in the PICU, such as aggressive cooling measures, IV fluids, and stress-dose steroids
                                                                          • Management of thyroid storm is characterized by the “Five Bs”:
                                                                          • Block synthesis of new thyroid hormone with antithyroid medications like PTU or methimazole
                                                                          • Block release of thyroid hormone with inorganic iodine
                                                                          • Block conversion of T4 into T3
                                                                          • Block peripheral effects of thyroid hormone with beta-blockers like atenolol and [propranolol
                                                                          • Block iodine uptake with the use of cholestyramine
                                                                          
                                                                          ]]>Today’s episode is dedicated to the approach to thyroid storm. It’s the first in our Mini-Case series.

                                                                          Show Highlights:

                                                                          Our case, symptoms, and diagnosis: A 12-year-old female presents to the PICU with chest discomfort. She was noted to be anxious by her parents over the past few days. They felt she was a bit "off," as she would constantly drop items and have a tremor. A few weeks prior to these symptoms, she was noted to have rhinorrhea, congestion, and progressive neck swelling. Her parents became increasingly concerned this morning as her temperature was 104F. Per her parents, she was agitated throughout the night and became increasingly somnolent in the early morning. 

                                                                          To summarize key elements from this case, this patient has:

                                                                          • Chest pain likely due to a cardiac etiology or musculoskeletal cause.
                                                                          • Tremor likely due to a primary neurologic cause or increased metabolic drive.
                                                                          • Neck swelling with fever after a prodrome of URI symptoms which could be concerning for lymphadenitis or thyroid goiter.
                                                                          • Synthesizing these symptoms together, this patient likely has a systemic etiology such as hyperthyroidism, with the most severe manifestation being thyroid storm, a toxidrome, or a pheochromocytoma. Given the fever and altered mental status, considering sepsis is key.
                                                                          
                                                                          

                                                                          Key history features in this child with tachycardia and signs of hyperthyroidism:

                                                                          • High fevers up to 104F
                                                                          • Altered mental status
                                                                          • Neck swelling 
                                                                          
                                                                          

                                                                          Red flag symptoms and physical exam components in a patient with severe hyperthyroidism include:

                                                                          • Airway
                                                                          • Check for dyspnea or stridor when the patient is supine.
                                                                          • Do a Mallampati assessment.
                                                                          • Auscultate for a bruit in the neck. 
                                                                          • Cardiovascular system
                                                                          • Concerns include congestive heart failure and cardiac dysrhythmias.
                                                                          • Widened pulse pressure is common 
                                                                          
                                                                          

                                                                          The American Thyroid Association has advocated for the Burch-Wartofsky Point Scale (BWPS) for severe thyrotoxicosis. A score of 45 or higher indicates thyroid storm. A case-control study published in 2015 in the Journal of Endocrinology noted that the BWPS may overdiagnose up to 20% of patients. Clinical criteria on the BWPS include the following:

                                                                          • Thermoregulatory dysfunction
                                                                          • Central nervous system effects
                                                                          • Gastrointestinal-hepatic dysfunction
                                                                          • Cardiovascular dysfunction
                                                                          • Congestive heart failure
                                                                          • Presence or absence of a precipitant history of URI or underlying thyroid condition
                                                                          
                                                                          

                                                                          Back to our specific case, the patient's labs are consistent with low TSH and elevated free T4, indicating primary hyperthyroidism, positive for TSH-receptor antibodies, and the diagnosis of thyroid storm was confirmed.

                                                                          • Other lab findings included elevated WBC, high ALT and AST, elevated glucose, and elevated cortisol. Her cardiac evaluation was notable for sinus tachycardia with occasional PACs.
                                                                          • Other important labs include a coagulation panel, BNP and lactate, CRP, procalcitonin, blood cultures, and basic blood chemistries.
                                                                          
                                                                          

                                                                          Let’s quiz ourselves with a multiple choice question:

                                                                          • A patient with thyroid storm is admitted to the PICU. He is started on thyroid modulating therapy. Which of the following mechanisms of action does this medication likely work by?
                                                                          •  A. Activate Thyroid Peroxidase
                                                                          •  B. Inhibit Thyroid Peroxidase
                                                                          •  C. Inhibit Iodine Uptake within the Thyroid
                                                                          •  D. Increase conversion from T4 to T3
                                                                          
                                                                          

                                                                             The correct answer is B. The most likely medication which is used in thyroid storm is methimazole or propylthiouracil. Both of these medications block thyroid peroxidase.

                                                                           In terms of differential in our case, you want to think about other causes of fever, tachycardia, and CNS dysfunction, including, but not limited to sepsis, serotonin syndrome, neuroleptic malignant syndrome, heatstroke, and drug intoxication. 

                                                                          The diagnostic approach for our patient should focus on her history and physical examination. Be sure to include thyroid function tests, cardiac evaluation via EKG or Echo, chest x-ray, blood culture, urine analysis, and lateral neck radiographs to assess airway compression. 

                                                                          The general management framework for the diagnosis of thyroid storm should include a multimodal approach to block thyroid hormone production and action quickly, reverse systemic decompensation, and identify and treat any underlying causes and precipitants of thyroid storm. The key components are:

                                                                          • Optimal communication between the pediatric endocrinology team and ICU staff
                                                                          • Acute resuscitative measures in the PICU, such as aggressive cooling measures, IV fluids, and stress-dose steroids
                                                                          • Management of thyroid storm is characterized by the “Five Bs”:
                                                                          • Block synthesis of new thyroid hormone with antithyroid medications like PTU or methimazole
                                                                          • Block release of thyroid hormone with inorganic iodine
                                                                          • Block conversion of T4 into T3
                                                                          • Block peripheral effects of thyroid hormone with beta-blockers like atenolol and [propranolol
                                                                          • Block iodine uptake with the use of cholestyramine
                                                                          
                                                                          ]]>5c84bc38-856f-47a9-8253-9ec0e3348f9eSun, 20 Jun 2021 03:00:00 -040013:09falsefull1818Introducing PICU Doc On Call Mini Case SeriesWe've got an exciting new series for the show and we can't wait to share with you our PICU Doc On Call Mini Case Series. Coming this weekend!
                                                                          ]]>We've got an exciting new series for the show and we can't wait to share with you our PICU Doc On Call Mini Case Series. Coming this weekend!
                                                                          ]]>d7daf6a3-aa07-4d06-962f-527262a2a533Thu, 17 Jun 2021 03:00:00 -040002:05falsefullPediatric Bone Marrow Transplant Dr. Muna QayedToday's episode is dedicated to Critical Illness In Children With Hematopoietic Stem Cell Transplants.

                                                                          We are delighted to be joined by Dr. Muna Qayed, Associate Professor of Pediatrics Emory University School of Medicine , Atlanta, GA. She is also the Director of the Blood and Marrow Transplant Program at the Aflac Cancer and Blood Disorders Center at Children's Healthcare of Atlanta.

                                                                          Our Case: A 10 year old female with refractory high-risk ALL s/p mismatched unrelated donor transplantation T+13 days presents as a transfer to the PICU with abdominal distention, worsening jaundice, and escalating nasal cannula requirements. The patient's post-transplant course was complicated by gram-negative bacteremia requiring fluid resuscitation. A CXR upon transfer to the PICU is notable for bilateral airspace disease, a right sided pleural effusion, and hypoexpanded lung fields. The patient is promptly intubated, sedated and started on renal replacement therapy. Echo labs, and further imaging are pending.

                                                                          What are the classic pediatric indications for BMT?

                                                                          • Autologous BMT (where donor cells are from the patient/recipient) is used as consolidation in some solid tumors such as High risk neuroblastoma, brain tumors like medulloblastoma, and germ cell tumors, and are a standard treatment approach in relapsed Hodgkin lymphoma
                                                                          • Allogeneic BMT-where in the donor cells are derived from another individual are typically used for hematologic malignancies. ALL and AML are most common pediatric indications.
                                                                          • Also allogeneic BMT are used for wide spectrum of nonmalignant hematology conditions such as hemoglobinopathies ( Sickle cell disease, Thalassemia), and severe aplastic anemia, and inherited bone marrow failure syndromes, as well as some metabolic disorders and immune-deficiency disorders such as SCID, HLH and other primary immune regulatory disorders.
                                                                          
                                                                          

                                                                          The sources of graft in BMT?

                                                                          • Stem cells (which give rise to different types of blood cells - red cells, white cells and platelets are derived from the bone marrow. Thus the overall process is known as Bone Marrow Transplantation.
                                                                          • Stem cells can be also derived from peripheral blood - when the donor is treated with granulocyte colony stimulating factor or G-CSF.
                                                                          • There are some key advantages here, which include the ability to collect a much higher stem cell dose, with faster hematopoietic recovery.
                                                                          • However the downside is a higher T cell content of the graft with subsequent increased risk of graft versus host disease.
                                                                          • Umbilical cord blood is also used as a source of stem cells.
                                                                          • Mega doses of stem cells are used to overcome histocompatibility barriers of mismatched transplantation. Majority of T cells have to be removed from donor pool to prevent severe GVHD., Increase risk of infection and relapse of patients original disease.
                                                                          
                                                                          

                                                                          Explain the human leucocyte antigen (HLA) and its role in BMT?

                                                                          • The Major Histocompatibility complex (MHC) system known as the human leukocyte antigen (HLA) in humans is located on the short arm of chromosome 6 and contains the most polymorphic gene cluster of the entire human genome.
                                                                          • The HLA consists of regions designated as "classes". Class I and class II are relevant to stem cell transplant.
                                                                          • The main function of HLA class I gene products (HLA-A, -B, and -C) is to present endogenous peptides to responding CD8+ T Cells, HLA class I antigens are expressed on all nucleated cells and platelets.
                                                                          • While the class II coded molecules HLA-DR, -DP, and –DQ have restricted expression and process exogenous peptides for presentation to CD4+ helper T Cells, and are expressed on antigen presenting cells. HLA-A, HLA-B, HLA-C and HLA-DR are traditionally the loci critical for matching for stem cell donor.
                                                                          • In addition to deciding on the source of the graft, we have to make decisions on who the donor will be. If a matched sibling donor is not available (or in some inherited conditions that may not be an option as a donor), then matched unrelated donors or matched cord blood units of appropriate size can provide a good option to proceed.
                                                                          • Then come considerations of mismatched unrelated donors, and haplo-identical related donors.
                                                                          • The type of donor and degree of match dictates the type of GVHD prophylaxis we will use and further immunosuppression.
                                                                          
                                                                          ]]>Today's episode is dedicated to Critical Illness In Children With Hematopoietic Stem Cell Transplants.

                                                                          We are delighted to be joined by Dr. Muna Qayed, Associate Professor of Pediatrics Emory University School of Medicine , Atlanta, GA. She is also the Director of the Blood and Marrow Transplant Program at the Aflac Cancer and Blood Disorders Center at Children's Healthcare of Atlanta.

                                                                          Our Case: A 10 year old female with refractory high-risk ALL s/p mismatched unrelated donor transplantation T+13 days presents as a transfer to the PICU with abdominal distention, worsening jaundice, and escalating nasal cannula requirements. The patient's post-transplant course was complicated by gram-negative bacteremia requiring fluid resuscitation. A CXR upon transfer to the PICU is notable for bilateral airspace disease, a right sided pleural effusion, and hypoexpanded lung fields. The patient is promptly intubated, sedated and started on renal replacement therapy. Echo labs, and further imaging are pending.

                                                                          What are the classic pediatric indications for BMT?

                                                                          • Autologous BMT (where donor cells are from the patient/recipient) is used as consolidation in some solid tumors such as High risk neuroblastoma, brain tumors like medulloblastoma, and germ cell tumors, and are a standard treatment approach in relapsed Hodgkin lymphoma
                                                                          • Allogeneic BMT-where in the donor cells are derived from another individual are typically used for hematologic malignancies. ALL and AML are most common pediatric indications.
                                                                          • Also allogeneic BMT are used for wide spectrum of nonmalignant hematology conditions such as hemoglobinopathies ( Sickle cell disease, Thalassemia), and severe aplastic anemia, and inherited bone marrow failure syndromes, as well as some metabolic disorders and immune-deficiency disorders such as SCID, HLH and other primary immune regulatory disorders.
                                                                          
                                                                          

                                                                          The sources of graft in BMT?

                                                                          • Stem cells (which give rise to different types of blood cells - red cells, white cells and platelets are derived from the bone marrow. Thus the overall process is known as Bone Marrow Transplantation.
                                                                          • Stem cells can be also derived from peripheral blood - when the donor is treated with granulocyte colony stimulating factor or G-CSF.
                                                                          • There are some key advantages here, which include the ability to collect a much higher stem cell dose, with faster hematopoietic recovery.
                                                                          • However the downside is a higher T cell content of the graft with subsequent increased risk of graft versus host disease.
                                                                          • Umbilical cord blood is also used as a source of stem cells.
                                                                          • Mega doses of stem cells are used to overcome histocompatibility barriers of mismatched transplantation. Majority of T cells have to be removed from donor pool to prevent severe GVHD., Increase risk of infection and relapse of patients original disease.
                                                                          
                                                                          

                                                                          Explain the human leucocyte antigen (HLA) and its role in BMT?

                                                                          • The Major Histocompatibility complex (MHC) system known as the human leukocyte antigen (HLA) in humans is located on the short arm of chromosome 6 and contains the most polymorphic gene cluster of the entire human genome.
                                                                          • The HLA consists of regions designated as "classes". Class I and class II are relevant to stem cell transplant.
                                                                          • The main function of HLA class I gene products (HLA-A, -B, and -C) is to present endogenous peptides to responding CD8+ T Cells, HLA class I antigens are expressed on all nucleated cells and platelets.
                                                                          • While the class II coded molecules HLA-DR, -DP, and –DQ have restricted expression and process exogenous peptides for presentation to CD4+ helper T Cells, and are expressed on antigen presenting cells. HLA-A, HLA-B, HLA-C and HLA-DR are traditionally the loci critical for matching for stem cell donor.
                                                                          • In addition to deciding on the source of the graft, we have to make decisions on who the donor will be. If a matched sibling donor is not available (or in some inherited conditions that may not be an option as a donor), then matched unrelated donors or matched cord blood units of appropriate size can provide a good option to proceed.
                                                                          • Then come considerations of mismatched unrelated donors, and haplo-identical related donors.
                                                                          • The type of donor and degree of match dictates the type of GVHD prophylaxis we will use and further immunosuppression.
                                                                          
                                                                          ]]>e17a4527-6f11-463b-b979-336efe813b80Sun, 13 Jun 2021 03:00:00 -040033:18falsefull171716: Undifferentiated Neonate in the PICU Today's episode is dedicated to the approach to the unstable neonate. Join us as we discuss the anatomic and physiological considerations for the neonate, initial investigations, and management framework on stabilizing a child. 

                                                                          We are delighted to be joined by Dr. Michael Wolf, Associate Professor of Pediatrics at Emory University School of Medicine, and Associate Medical Director of the Cardiac Intensive Care Unit at Children's Healthcare of Atlanta. The CICU at Children’s is one of the highest volume pediatric heart centers in the nation. Dr. Wolf is also Chair of the "You Matter Program" at Children's Healthcare of Atlanta, which addresses physician resilience and second victim syndrome in providers.

                                                                          Show Highlights:

                                                                          •  Our case, symptoms, and diagnosis: A 4-day-old former full-term neonate delivered via C-section for non-reassuring fetal heart tones is to be discharged from the well-child nursery. On the day of discharge, the child is noted to have progressive tachypnea, tachycardia, and progressive acrocyanosis. The extremities are cool, and the child has delayed capillary refill. Pulse-oximetry is notable for a discordance between upper and lower extremity saturations. Femoral pulses are poorly palpable. Blood gas is significant for metabolic acidosis. The patient is rushed to the NICU, and the process to transfer the baby to a pediatric cardiac intensive care facility is initiated.
                                                                          • Important considerations to keep in mind for the neonatal or infant population are according to the traditional Airway-Breathing-Circulation model:
                                                                          • Airway--The infant airway is prone to dynamic obstruction due to a larger tongue and epiglottis, compliant soft tissues, and their obligatory nose breathing.
                                                                          • Breathing--Differences in chest wall dynamics, oxygen metabolism, and respiratory musculature place the small infant at greater risk for respiratory failure than the older child.
                                                                          • Cardiac--Considerations focus on key events in the transition from fetal to neonatal circulation, and include the initiation of prostaglandins and calcium administration to drive contractility..
                                                                          • Shock categories to consider for the neonate include hypovolemic shock from hemorrhage, obstructive entities like severe pulmonary hypertension, and septic shock. 
                                                                          • Initial stabilization of the neonate includes the following lab testing and imaging: blood gas and glucose determination, basic electrolytes, vital signs and clinical exam data, and prostaglandin infusions to reestablish blood flow. The loop of intervention and reassessment is imperative as you acutely stabilize a child with neonatal shock!
                                                                          • Other key diagnostics include four extremity blood pressure and low extremity pulses, pre- and post-ductal saturations, bedside echocardiography, and delving into the history with prenatal screening. 
                                                                          • The management framework focuses on prostaglandins and dosage protocols, the availability of intubation equipment, and the risk of necrotizing enterocolitis (NEC).
                                                                          • Besides congenital heart defects, other considerations for the unstable neonate are sepsis, infusions of ionotropes, cardiac catheterizations, and possible balloon valvuloplasty. 
                                                                          • Takeaway clinical pearls regarding the unstable neonate:
                                                                          • Always think about prostaglandins when approaching the neonate with shock.
                                                                          • Use a physical exam to check pulses and blood pressure.
                                                                          • Remember that a focused, rapid, bedside echocardiogram can help diagnose shock. 
                                                                          • We hope you learned something from today’s discussion of the importance of a broad differential, key presentation features of congenital heart disease, and the importance of early PG initiation in the management of an unstable neonate. 
                                                                          
                                                                          ]]> Today's episode is dedicated to the approach to the unstable neonate. Join us as we discuss the anatomic and physiological considerations for the neonate, initial investigations, and management framework on stabilizing a child. 

                                                                          We are delighted to be joined by Dr. Michael Wolf, Associate Professor of Pediatrics at Emory University School of Medicine, and Associate Medical Director of the Cardiac Intensive Care Unit at Children's Healthcare of Atlanta. The CICU at Children’s is one of the highest volume pediatric heart centers in the nation. Dr. Wolf is also Chair of the "You Matter Program" at Children's Healthcare of Atlanta, which addresses physician resilience and second victim syndrome in providers.

                                                                          Show Highlights:

                                                                          •  Our case, symptoms, and diagnosis: A 4-day-old former full-term neonate delivered via C-section for non-reassuring fetal heart tones is to be discharged from the well-child nursery. On the day of discharge, the child is noted to have progressive tachypnea, tachycardia, and progressive acrocyanosis. The extremities are cool, and the child has delayed capillary refill. Pulse-oximetry is notable for a discordance between upper and lower extremity saturations. Femoral pulses are poorly palpable. Blood gas is significant for metabolic acidosis. The patient is rushed to the NICU, and the process to transfer the baby to a pediatric cardiac intensive care facility is initiated.
                                                                          • Important considerations to keep in mind for the neonatal or infant population are according to the traditional Airway-Breathing-Circulation model:
                                                                          • Airway--The infant airway is prone to dynamic obstruction due to a larger tongue and epiglottis, compliant soft tissues, and their obligatory nose breathing.
                                                                          • Breathing--Differences in chest wall dynamics, oxygen metabolism, and respiratory musculature place the small infant at greater risk for respiratory failure than the older child.
                                                                          • Cardiac--Considerations focus on key events in the transition from fetal to neonatal circulation, and include the initiation of prostaglandins and calcium administration to drive contractility..
                                                                          • Shock categories to consider for the neonate include hypovolemic shock from hemorrhage, obstructive entities like severe pulmonary hypertension, and septic shock. 
                                                                          • Initial stabilization of the neonate includes the following lab testing and imaging: blood gas and glucose determination, basic electrolytes, vital signs and clinical exam data, and prostaglandin infusions to reestablish blood flow. The loop of intervention and reassessment is imperative as you acutely stabilize a child with neonatal shock!
                                                                          • Other key diagnostics include four extremity blood pressure and low extremity pulses, pre- and post-ductal saturations, bedside echocardiography, and delving into the history with prenatal screening. 
                                                                          • The management framework focuses on prostaglandins and dosage protocols, the availability of intubation equipment, and the risk of necrotizing enterocolitis (NEC).
                                                                          • Besides congenital heart defects, other considerations for the unstable neonate are sepsis, infusions of ionotropes, cardiac catheterizations, and possible balloon valvuloplasty. 
                                                                          • Takeaway clinical pearls regarding the unstable neonate:
                                                                          • Always think about prostaglandins when approaching the neonate with shock.
                                                                          • Use a physical exam to check pulses and blood pressure.
                                                                          • Remember that a focused, rapid, bedside echocardiogram can help diagnose shock. 
                                                                          • We hope you learned something from today’s discussion of the importance of a broad differential, key presentation features of congenital heart disease, and the importance of early PG initiation in the management of an unstable neonate. 
                                                                          
                                                                          ]]>3c398357-e0f8-41ab-a9b6-197f9a5b29b8Sun, 06 Jun 2021 03:00:00 -040016:04falsefull1616Catheter Directed Thrombolysis in the PICUToday’s episode is dedicated to venous/arterial thrombi, also known as catheter directed thrombolysis.

                                                                          We are delighted to be joined by Dr. Anne E. Gill, Assistant Professor of Radiology and Imaging Sciences at Emory University School of Medicine. She is a pediatric interventional radiologist at Children’s Healthcare of Atlanta. Her areas of expertise include pediatric thromboembolic disease, vascular malformations, enteric feeding tube access, and interventional oncology. Dr. Gill is on Twitter @AnneGillMD. 

                                                                          Show Highlights:

                                                                          • Our case, symptoms, and diagnosis: A 17-year old girl with antithrombin III deficiency presented with bilateral leg pain to an outside ED. Duplex ultrasound of the bilateral lower extremities revealed extensive acute bilateral deep vein thrombosis. A CT scan of the abdomen and pelvis showed an extensive occlusive clot in the inferior vena cava involving the infrarenal and suprarenal IVC. She was transferred to our hospital and admitted to the ICU for thrombolysis and initiation of catheter-directed TPA infusion. In interventional radiology, an IVC filter was placed in the suprarenal IVC; additionally, the venogram in IR showed complete thrombosis of the right upper femoral, external iliac, common iliac, and IVC, with collateral veins in the right lower extremity draining into the thrombosed upper femoral vein. Interventional radiology performed pharmacomechanical thrombolysis and balloon angioplasty of right external iliac, common iliac, and IVC and placed infusion catheter to drip tPA from right femoral vein to the IVC filter. The patient was also placed on continuous heparin drip for systemic anticoagulation management. Morphine and Dexmedetomidine were used for pain management.
                                                                          • The overall prevalence of systemic venous occlusion in children is difficult to ascertain due to their asymptomatic quality.
                                                                          • Congenital SVOs in children can be due to developmental hypoplasia or agenesis of major conducting veins; they can happen in utero or manifest as neonatal thrombosis. 
                                                                          • Acquired causes of SVOs can include catheter acquired obstruction, hypercoagulability/thrombophilia, mechanical obstruction, and trauma.
                                                                          • A careful history is necessary to determine whether the occlusion was a congenital or acquired SVO.
                                                                          • This is challenging because symptoms of venous obstruction in children may not present until later in life.
                                                                          • This distinction is important as it affects the procedures that can be done.
                                                                          • Better outcomes are possible if a native pathway is present, even if it’s diminished from chronic obstruction and scarring. 
                                                                          • Clinical presentations of systemic venous occlusions in children include head and neck swelling coupled with shortness of breath. In patients with acute DVT, venous congestion can manifest as prolonged capillary refill, coolness of extremities, and bluish discoloration to frank venous ischemia with loss of pulses. 
                                                                          • Chronic DVT in extremities can present with a sense of heaviness, aching pain, and fatigue with activity; these symptoms are collectively described as post-thrombotic syndrome.
                                                                          • Remember that obstruction to flow can compromise oxygen delivery!
                                                                          • Common causes of venous occlusions are mal-positioned or wrongly sized central venous catheters, May-Turner syndrome, and long-standing central venous access lines in dialysis patients. 
                                                                          • CDT is not recommended for DVTs below the inguinal ligament, based on the ATTRACT trial in 2017 that showed that CDT is most beneficial in veins above the inguinal ligament.
                                                                          • Contraindications for CDT in children include allergy to tPA, active bleeding, surgery within the last 14 days, any invasive procedures in the last three days, recent seizures, recent trauma, or coagulopathy which can’t be easily corrected. Caution is needed with premature infants and those with HTN or other risk factors for bleeding. 
                                                                          • Diagnostics needed prior to consulting on a patient with venous occlusion include Doppler US, CT or MRI to visualize central vessels, cone-beam CT (CBCT), and hematology consult.
                                                                          • General principles of venous recanalization for acute venous occlusion:
                                                                          • Acute venous occlusions are typically related to acute thromboembolism.
                                                                          • Intravascular ultrasound (IVUS) is a valuable tool.
                                                                          • CDT with a catheter dripping tPA overnight.
                                                                          • Balloon angioplasty followed by systemic anticoagulation.
                                                                          • Treatment options for chronic venous occlusions range from endovascular angioplasty and stenting to surgical bypass grafts or prosthetic graft reconstruction. Endovascular techniques are more widely accepted in pediatrics.
                                                                          • Post-procedure patients in the PICU should have neurological monitoring and pain management, along with careful monitoring of the heparin infusion and tPA management. Worsening conditions may point to surgical interventions. 
                                                                          • Dr. Gill explains the protocol developed for heparin and tPA dosage and monitoring.
                                                                          • Precautions needed by the PICU doctor for patients getting tPA and heparin include no arterial sticks, intramuscular injections, rectal temperatures, catheters, NSAIDs, or other platelet drugs. The key is a collaborative approach between interventional radiology, anesthesia, and hematology.
                                                                          • Once the IR physician is satisfied with clot removal and blood flow in the previously occluded vessel, a decision is made to stop the tPA infusion.
                                                                          • IR also provides other services like chest tube, PICC line, and GT placements, lumbar punctures, biopsies of liver/kidneys, and thermal ablation of solid tumors or painful bony metastases.
                                                                          • Takeaway clinical pearls include the collaborative team of anesthesia, hematology, PICU, and IR for optimal outcomes. IR should be called early and often. Labs should be followed closely, especially Fibrinogen, platelets, and hemoglobin/hematocrit. 
                                                                          
                                                                          ]]>Today’s episode is dedicated to venous/arterial thrombi, also known as catheter directed thrombolysis.

                                                                          We are delighted to be joined by Dr. Anne E. Gill, Assistant Professor of Radiology and Imaging Sciences at Emory University School of Medicine. She is a pediatric interventional radiologist at Children’s Healthcare of Atlanta. Her areas of expertise include pediatric thromboembolic disease, vascular malformations, enteric feeding tube access, and interventional oncology. Dr. Gill is on Twitter @AnneGillMD. 

                                                                          Show Highlights:

                                                                          • Our case, symptoms, and diagnosis: A 17-year old girl with antithrombin III deficiency presented with bilateral leg pain to an outside ED. Duplex ultrasound of the bilateral lower extremities revealed extensive acute bilateral deep vein thrombosis. A CT scan of the abdomen and pelvis showed an extensive occlusive clot in the inferior vena cava involving the infrarenal and suprarenal IVC. She was transferred to our hospital and admitted to the ICU for thrombolysis and initiation of catheter-directed TPA infusion. In interventional radiology, an IVC filter was placed in the suprarenal IVC; additionally, the venogram in IR showed complete thrombosis of the right upper femoral, external iliac, common iliac, and IVC, with collateral veins in the right lower extremity draining into the thrombosed upper femoral vein. Interventional radiology performed pharmacomechanical thrombolysis and balloon angioplasty of right external iliac, common iliac, and IVC and placed infusion catheter to drip tPA from right femoral vein to the IVC filter. The patient was also placed on continuous heparin drip for systemic anticoagulation management. Morphine and Dexmedetomidine were used for pain management.
                                                                          • The overall prevalence of systemic venous occlusion in children is difficult to ascertain due to their asymptomatic quality.
                                                                          • Congenital SVOs in children can be due to developmental hypoplasia or agenesis of major conducting veins; they can happen in utero or manifest as neonatal thrombosis. 
                                                                          • Acquired causes of SVOs can include catheter acquired obstruction, hypercoagulability/thrombophilia, mechanical obstruction, and trauma.
                                                                          • A careful history is necessary to determine whether the occlusion was a congenital or acquired SVO.
                                                                          • This is challenging because symptoms of venous obstruction in children may not present until later in life.
                                                                          • This distinction is important as it affects the procedures that can be done.
                                                                          • Better outcomes are possible if a native pathway is present, even if it’s diminished from chronic obstruction and scarring. 
                                                                          • Clinical presentations of systemic venous occlusions in children include head and neck swelling coupled with shortness of breath. In patients with acute DVT, venous congestion can manifest as prolonged capillary refill, coolness of extremities, and bluish discoloration to frank venous ischemia with loss of pulses. 
                                                                          • Chronic DVT in extremities can present with a sense of heaviness, aching pain, and fatigue with activity; these symptoms are collectively described as post-thrombotic syndrome.
                                                                          • Remember that obstruction to flow can compromise oxygen delivery!
                                                                          • Common causes of venous occlusions are mal-positioned or wrongly sized central venous catheters, May-Turner syndrome, and long-standing central venous access lines in dialysis patients. 
                                                                          • CDT is not recommended for DVTs below the inguinal ligament, based on the ATTRACT trial in 2017 that showed that CDT is most beneficial in veins above the inguinal ligament.
                                                                          • Contraindications for CDT in children include allergy to tPA, active bleeding, surgery within the last 14 days, any invasive procedures in the last three days, recent seizures, recent trauma, or coagulopathy which can’t be easily corrected. Caution is needed with premature infants and those with HTN or other risk factors for bleeding. 
                                                                          • Diagnostics needed prior to consulting on a patient with venous occlusion include Doppler US, CT or MRI to visualize central vessels, cone-beam CT (CBCT), and hematology consult.
                                                                          • General principles of venous recanalization for acute venous occlusion:
                                                                          • Acute venous occlusions are typically related to acute thromboembolism.
                                                                          • Intravascular ultrasound (IVUS) is a valuable tool.
                                                                          • CDT with a catheter dripping tPA overnight.
                                                                          • Balloon angioplasty followed by systemic anticoagulation.
                                                                          • Treatment options for chronic venous occlusions range from endovascular angioplasty and stenting to surgical bypass grafts or prosthetic graft reconstruction. Endovascular techniques are more widely accepted in pediatrics.
                                                                          • Post-procedure patients in the PICU should have neurological monitoring and pain management, along with careful monitoring of the heparin infusion and tPA management. Worsening conditions may point to surgical interventions. 
                                                                          • Dr. Gill explains the protocol developed for heparin and tPA dosage and monitoring.
                                                                          • Precautions needed by the PICU doctor for patients getting tPA and heparin include no arterial sticks, intramuscular injections, rectal temperatures, catheters, NSAIDs, or other platelet drugs. The key is a collaborative approach between interventional radiology, anesthesia, and hematology.
                                                                          • Once the IR physician is satisfied with clot removal and blood flow in the previously occluded vessel, a decision is made to stop the tPA infusion.
                                                                          • IR also provides other services like chest tube, PICC line, and GT placements, lumbar punctures, biopsies of liver/kidneys, and thermal ablation of solid tumors or painful bony metastases.
                                                                          • Takeaway clinical pearls include the collaborative team of anesthesia, hematology, PICU, and IR for optimal outcomes. IR should be called early and often. Labs should be followed closely, especially Fibrinogen, platelets, and hemoglobin/hematocrit. 
                                                                          
                                                                          ]]>e4ae88f4-89b0-469b-887a-63956b05dad4Sun, 30 May 2021 03:00:00 -040031:15falsefull1515Differentiation and Management of Diabetic Ketoacidosis (DKA) and Hyperosmolar Hyperglycemic State (HHS)Today’s episode is dedicated to the differentiation and management of diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS)

                                                                          We are delighted to be joined by Dr. Eric Felner. Dr. Felner is a Professor of Pediatrics/Pediatric Endocrinology at the Emory University School of Medicine and is an Adjunct Professor of Chemical and Biomedical Engineering at Georgia Tech.

                                                                          Show Highlights:

                                                                          • Our case, symptoms, and diagnosis: A 15-year-old male presents with a one-week history of increased urination. He is otherwise healthy except for a viral URI last week. He is found to be disoriented and tachycardic, with an exam notable for delayed peripheral capillary refill and cool extremities. The patient has deep, labored respirations upon examination, and labs confirm hyperglycemia with a serum glucose of 850, mild acidosis, and 2+ ketones. His CPK level is elevated, and a crystalloid fluid bolus is started. 
                                                                          • Hyperosmolar hyperglycemic state is defined as a serum glucose greater than 600 mg/dL, serum osmolality of 330 mOsm/kg, and the absence of ketosis and acidosis.
                                                                          • The key difference between HHS and DKA is that DKA is characterized by the presence of ketones in the blood and acidosis, but HHS means these are completely absent.
                                                                          • Even though DKA and HHS are similar, their management strategies have their own nuances.
                                                                          • In DKA, the lack of insulin leads to management strategies, while HHS is marked by complete dehydration and excessive urination. 
                                                                          • Factors that point to HHS will be a very overweight child, family history, and ethnicity; Type-2 diabetes is much more common in African-American, Latin-American, and Native-American children, while Type-1 is more common in Caucasians. 
                                                                          • Specific labs for patients with suspected DKA or HHS include a comprehensive metabolic panel (CMP), blood gas, and CPK for HHS.
                                                                          • For both conditions, management strategies focus on insulin and fluid administration, but there are key differentiations:
                                                                          • DKA is managed using the triple bag therapy that was pioneered by Dr. Felner.
                                                                          • There is a risk for cerebral edema with administering fluid.
                                                                          • The most important data relating to fluid administration with regard to neurological outcomes is what we have learned in calculating fluids with the “2x maintenance formula” to guard against mistakes that could result in cerebral edema.
                                                                          • Key considerations regarding low-dose vs. standard-dose insulin therapy revolve around the weight and age of the pediatric patient.
                                                                          • For HHS, the key is to manage fluids and give insulin; for Type-1 diabetics, the key is to eliminate acidosis.
                                                                          • Key PICU management pearls in minimizing cerebral edema risks are to determine the level of sickness by the PCO2 level, high BUN, and by not giving bicarbonate. Remember that children under age 5 have a higher risk for cerebral edema.
                                                                          • In the management of both DKA and HHS, remember that it comes down to how sick a patient is and not necessarily following the numbers. 
                                                                          • In general pediatrics, managing a sick DKA patient means giving an IV, administer fluids, and call a specialist management team right away.
                                                                          • Dr. Felner discusses the association between COVID-19 and Type 1 diabetes based on his experience. 
                                                                          • As intensivists and endocrinology teams work together to transition patients to an intermittent insulin regimen, it’s important to remember how to convert from IV insulin to subQ insulin. 
                                                                          • Takeaway clinical pearls include the key diagnostic elements between DKA and HHS. In HHS, patients will have higher glucose levels, milder acidosis, mild ketosis, and increased dehydration. Both conditions will have insulin and fluid management, and HHS patients may require increased fluid resuscitation. 
                                                                          
                                                                          

                                                                           

                                                                          ]]>Today’s episode is dedicated to the differentiation and management of diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS)

                                                                          We are delighted to be joined by Dr. Eric Felner. Dr. Felner is a Professor of Pediatrics/Pediatric Endocrinology at the Emory University School of Medicine and is an Adjunct Professor of Chemical and Biomedical Engineering at Georgia Tech.

                                                                          Show Highlights:

                                                                          • Our case, symptoms, and diagnosis: A 15-year-old male presents with a one-week history of increased urination. He is otherwise healthy except for a viral URI last week. He is found to be disoriented and tachycardic, with an exam notable for delayed peripheral capillary refill and cool extremities. The patient has deep, labored respirations upon examination, and labs confirm hyperglycemia with a serum glucose of 850, mild acidosis, and 2+ ketones. His CPK level is elevated, and a crystalloid fluid bolus is started. 
                                                                          • Hyperosmolar hyperglycemic state is defined as a serum glucose greater than 600 mg/dL, serum osmolality of 330 mOsm/kg, and the absence of ketosis and acidosis.
                                                                          • The key difference between HHS and DKA is that DKA is characterized by the presence of ketones in the blood and acidosis, but HHS means these are completely absent.
                                                                          • Even though DKA and HHS are similar, their management strategies have their own nuances.
                                                                          • In DKA, the lack of insulin leads to management strategies, while HHS is marked by complete dehydration and excessive urination. 
                                                                          • Factors that point to HHS will be a very overweight child, family history, and ethnicity; Type-2 diabetes is much more common in African-American, Latin-American, and Native-American children, while Type-1 is more common in Caucasians. 
                                                                          • Specific labs for patients with suspected DKA or HHS include a comprehensive metabolic panel (CMP), blood gas, and CPK for HHS.
                                                                          • For both conditions, management strategies focus on insulin and fluid administration, but there are key differentiations:
                                                                          • DKA is managed using the triple bag therapy that was pioneered by Dr. Felner.
                                                                          • There is a risk for cerebral edema with administering fluid.
                                                                          • The most important data relating to fluid administration with regard to neurological outcomes is what we have learned in calculating fluids with the “2x maintenance formula” to guard against mistakes that could result in cerebral edema.
                                                                          • Key considerations regarding low-dose vs. standard-dose insulin therapy revolve around the weight and age of the pediatric patient.
                                                                          • For HHS, the key is to manage fluids and give insulin; for Type-1 diabetics, the key is to eliminate acidosis.
                                                                          • Key PICU management pearls in minimizing cerebral edema risks are to determine the level of sickness by the PCO2 level, high BUN, and by not giving bicarbonate. Remember that children under age 5 have a higher risk for cerebral edema.
                                                                          • In the management of both DKA and HHS, remember that it comes down to how sick a patient is and not necessarily following the numbers. 
                                                                          • In general pediatrics, managing a sick DKA patient means giving an IV, administer fluids, and call a specialist management team right away.
                                                                          • Dr. Felner discusses the association between COVID-19 and Type 1 diabetes based on his experience. 
                                                                          • As intensivists and endocrinology teams work together to transition patients to an intermittent insulin regimen, it’s important to remember how to convert from IV insulin to subQ insulin. 
                                                                          • Takeaway clinical pearls include the key diagnostic elements between DKA and HHS. In HHS, patients will have higher glucose levels, milder acidosis, mild ketosis, and increased dehydration. Both conditions will have insulin and fluid management, and HHS patients may require increased fluid resuscitation. 
                                                                          
                                                                          

                                                                           

                                                                          ]]>54739fc9-e564-4368-b14a-92e8ae8f0ba9Sun, 23 May 2021 03:00:00 -040040:38falsefull1414Acute Severe HypertensionToday, we welcome Dr. Stella Shin, Assistant Professor of Pediatrics-Pediatric Nephrology at The Emory University School of Medicine. Dr Shin is also the Director of General Pediatric Nephrology and the Director of Acute Kidney Replacement Therapy at The Children's Healthcare of Atlanta in Atlanta, GA. Her interests include nephrotoxic medication stewardship, health informatics and healthcare quality improvement. She is on twitter @BabyBeanDoc

                                                                          A 17 year old previously healthy thinly built male teenager is brought to the emergency department for sudden development of blurred vision. Patient has a h/o headaches for the last few months accompanied by abdominal pain and relieved by vomiting. He has also felt his heart racing during such episodes and accompanied by profuse sweating. Patient had tried various over the counter pain medications without much improvement in his headaches or abdominal pain. An initial CT scan of the head reveled no intracranial pathology. ED physician noted a a blood pressure of 200/120 mm HG and a pulse of 132beats/minute. He is started on nicardipine in the ICU.

                                                                          • Definitions for normal and high blood pressure come from the AAP clinical practice guidelines for screening and management of high blood pressure. According to these guidelines:
                                                                          • Normal BP is a blood pressure reading that is < 90%ile for children 1-12 yrs of age: A normal BP for teenagers 13 years and older = <120/<80.
                                                                          • High blood pressure is divided into three categories: Elevated BP, Stage 1 HTN, and Stage 2 HTN. This is further delineated into categories for children 1-12 yo and 13 or older.
                                                                          • For children 1-12 yo:
                                                                          • Elevated BP is a BP that is >/= 90%ile but <95%ile, or a BP of 120/80 up to <95%ile, whichever is lower.
                                                                          • Stage 1 HTN is a BP that is ≥95%ile to <95%ile+12 mmHg, or a BP of 130/80 to 139/89, whichever is lower.
                                                                          • Stage 2 HTN is a BP that is ≥95%ile+12 mmHg, or a BP that is ≥140/90, whichever is lower.
                                                                          • It's much more simple for children 13 and older:
                                                                          • Elevated BP is 120/<80 to 129/<80
                                                                          • Stage 1 HTN is 130/80 to 139/89
                                                                          • Stage 2 HTN is >/= 140/90
                                                                          • That's a lot of numbers and cut offs to remember. To make it easy, in general, hypertension in children and adolescents is defined as a sustained systolic and/or diastolic blood pressure elevation ≥ 95%ile for age, gender, and height. And adult BP cut offs are used for teenagers 13 years or older.
                                                                          
                                                                          

                                                                          Acute severe hypertension is defined as significant blood pressure elevation with or without of acute target-organ damage from the hypertension.

                                                                          This is further classified based on target organ involvement into hypertensive urgency and hypertensive emergency. The key difference between the two is whether target organ injury is present.

                                                                          Hypertensive Urgency is acute severe hypertension WITHOUT acute target-organ damage. Hypertensive urgency is not associated with adverse short-term outcomes and can be managed in the ambulatory setting.

                                                                          Hypertensive Emergency is acute severe hypertension that is accompanied by acute target-organ injury. It is a medical emergency with substantial morbidity and mortality requiring immediate treatment in an ICU.

                                                                          It is important to note for our listeners that acute sever hypertension is on a spectrum with hypertensive urgency and emergency, and these diagnoses exist on a spectrum!

                                                                          Our discussion focused on acute severe hypertension, which is a medical emergency especially when there is target organ injury. A titratable infusion of an antihypertensive such as nicardipine should be the first line to lower the BP by 25% in first 8 hours as precipitous drop may cause cerebral ischemia. While there are multiple IV antihypertensives, the pediatric critical care team should be should be aware of the pharmacology and relevant side effects of these agents in efforts to choose the best drug for the patients condition. Early consultation with nephrology is warranted in these patients along with monitoring of end organ function.

                                                                          ]]>Today, we welcome Dr. Stella Shin, Assistant Professor of Pediatrics-Pediatric Nephrology at The Emory University School of Medicine. Dr Shin is also the Director of General Pediatric Nephrology and the Director of Acute Kidney Replacement Therapy at The Children's Healthcare of Atlanta in Atlanta, GA. Her interests include nephrotoxic medication stewardship, health informatics and healthcare quality improvement. She is on twitter @BabyBeanDoc

                                                                          A 17 year old previously healthy thinly built male teenager is brought to the emergency department for sudden development of blurred vision. Patient has a h/o headaches for the last few months accompanied by abdominal pain and relieved by vomiting. He has also felt his heart racing during such episodes and accompanied by profuse sweating. Patient had tried various over the counter pain medications without much improvement in his headaches or abdominal pain. An initial CT scan of the head reveled no intracranial pathology. ED physician noted a a blood pressure of 200/120 mm HG and a pulse of 132beats/minute. He is started on nicardipine in the ICU.

                                                                          • Definitions for normal and high blood pressure come from the AAP clinical practice guidelines for screening and management of high blood pressure. According to these guidelines:
                                                                          • Normal BP is a blood pressure reading that is < 90%ile for children 1-12 yrs of age: A normal BP for teenagers 13 years and older = <120/<80.
                                                                          • High blood pressure is divided into three categories: Elevated BP, Stage 1 HTN, and Stage 2 HTN. This is further delineated into categories for children 1-12 yo and 13 or older.
                                                                          • For children 1-12 yo:
                                                                          • Elevated BP is a BP that is >/= 90%ile but <95%ile, or a BP of 120/80 up to <95%ile, whichever is lower.
                                                                          • Stage 1 HTN is a BP that is ≥95%ile to <95%ile+12 mmHg, or a BP of 130/80 to 139/89, whichever is lower.
                                                                          • Stage 2 HTN is a BP that is ≥95%ile+12 mmHg, or a BP that is ≥140/90, whichever is lower.
                                                                          • It's much more simple for children 13 and older:
                                                                          • Elevated BP is 120/<80 to 129/<80
                                                                          • Stage 1 HTN is 130/80 to 139/89
                                                                          • Stage 2 HTN is >/= 140/90
                                                                          • That's a lot of numbers and cut offs to remember. To make it easy, in general, hypertension in children and adolescents is defined as a sustained systolic and/or diastolic blood pressure elevation ≥ 95%ile for age, gender, and height. And adult BP cut offs are used for teenagers 13 years or older.
                                                                          
                                                                          

                                                                          Acute severe hypertension is defined as significant blood pressure elevation with or without of acute target-organ damage from the hypertension.

                                                                          This is further classified based on target organ involvement into hypertensive urgency and hypertensive emergency. The key difference between the two is whether target organ injury is present.

                                                                          Hypertensive Urgency is acute severe hypertension WITHOUT acute target-organ damage. Hypertensive urgency is not associated with adverse short-term outcomes and can be managed in the ambulatory setting.

                                                                          Hypertensive Emergency is acute severe hypertension that is accompanied by acute target-organ injury. It is a medical emergency with substantial morbidity and mortality requiring immediate treatment in an ICU.

                                                                          It is important to note for our listeners that acute sever hypertension is on a spectrum with hypertensive urgency and emergency, and these diagnoses exist on a spectrum!

                                                                          Our discussion focused on acute severe hypertension, which is a medical emergency especially when there is target organ injury. A titratable infusion of an antihypertensive such as nicardipine should be the first line to lower the BP by 25% in first 8 hours as precipitous drop may cause cerebral ischemia. While there are multiple IV antihypertensives, the pediatric critical care team should be should be aware of the pharmacology and relevant side effects of these agents in efforts to choose the best drug for the patients condition. Early consultation with nephrology is warranted in these patients along with monitoring of end organ function.

                                                                          ]]>3124a0a0-5ed4-4379-afc0-ae0fff8a8a51Sun, 16 May 2021 03:00:00 -040020:13falsefull1313Acute Management of HyperkalemiaToday’s episode is dedicated to acute management of hyperkalemia in the PICU. Join us as we discuss the patient case, symptoms, and treatment. 

                                                                          We are delighted to be joined by Dr. Roshan George, Associate Professor of Pediatrics, a practicing Pediatric Nephrologist at Children’s Healthcare of Atlanta, and the Program Director of Pediatric Nephrology Fellowship at Emory University School of Medicine. 

                                                                          Show Highlights:

                                                                          • Our case, symptoms, and diagnosis: A two-year-old male with a history of focal segmental glomerulosclerosis controlled on chronic prednisone therapy presents to the PICU for respiratory failure. The patient is noted to be hypotensive and tachycardic. Potassium is elevated at 6.4 with no hemolysis noted. The EKG is notable for peak T waves, and the patient is also noted to be anuric. 
                                                                          • Definition of hyperkalemia: a potassium serum level higher than 5.5 (Be sure to correlate your lab sample with clinical and telemetry changes to rule out pseudohyperkalemia)
                                                                          • Common causes of hyperkalemia:
                                                                          • Increased intake of potassium
                                                                          • Transcellular shift
                                                                          • Decreased renal excretion
                                                                          • Inborn error of metabolism, especially adrenal problems
                                                                          • Why it’s important to be vigilant about hyperkalemia in patients with chronic kidney disease, end-stage renal disease, acute kidney injury, and those with a transplanted kidney
                                                                          • Clinical manifestations of hyperkalemia:
                                                                          • The risk is for cardiac conduction abnormalities and muscle weakness/paralysis.
                                                                          • Adverse events can occur with levels > 5.5mEq/L, and the risk increases as levels rise.
                                                                          • Any serum K level > 6mEq/L is significant, regardless of EKG changes.
                                                                          • Two hallmarks that can drive effective management of hyperkalemia are EKG findings and laboratory confirmation of elevated serum potassium.
                                                                          • Other important labs for patients with hyperkalemia include a basic electrolyte panel to assess kidney function, CBC, and serum blood gas to assess acid/base balance. (A medication check for K supplements or ACE inhibitors should also be done.)
                                                                          • Steps in the management of hyperkalemia:
                                                                          • First, caution should be exercised that any K level > 5.5 is a medical emergency and should be addressed immediately without finding the etiology. 
                                                                          • Stabilize the cardiac membrane.
                                                                          • Shift potassium with insulin and glucose, bicarbonate, and B2 adrenergic agents.
                                                                          • The long-term goal should be to improve excretion with Kayexalate or Furosemide (Remember the mnemonic: “Loops lose K.”)
                                                                          • General considerations about dialysis are:
                                                                          • CVVH vs. HD
                                                                          • Severe hyperkalemia is a key indication for RRT in acutely ill patients.
                                                                          • Hemodialysis can be used in an emergency.
                                                                          • Takeaway clinical pearls regarding hyperkalemia: 
                                                                          • Make sure the potassium level is accurate.
                                                                          • Consider the next steps in potassium removal.
                                                                          • Remember that etiology is the last step.
                                                                          
                                                                          ]]>Today’s episode is dedicated to acute management of hyperkalemia in the PICU. Join us as we discuss the patient case, symptoms, and treatment. 

                                                                          We are delighted to be joined by Dr. Roshan George, Associate Professor of Pediatrics, a practicing Pediatric Nephrologist at Children’s Healthcare of Atlanta, and the Program Director of Pediatric Nephrology Fellowship at Emory University School of Medicine. 

                                                                          Show Highlights:

                                                                          • Our case, symptoms, and diagnosis: A two-year-old male with a history of focal segmental glomerulosclerosis controlled on chronic prednisone therapy presents to the PICU for respiratory failure. The patient is noted to be hypotensive and tachycardic. Potassium is elevated at 6.4 with no hemolysis noted. The EKG is notable for peak T waves, and the patient is also noted to be anuric. 
                                                                          • Definition of hyperkalemia: a potassium serum level higher than 5.5 (Be sure to correlate your lab sample with clinical and telemetry changes to rule out pseudohyperkalemia)
                                                                          • Common causes of hyperkalemia:
                                                                          • Increased intake of potassium
                                                                          • Transcellular shift
                                                                          • Decreased renal excretion
                                                                          • Inborn error of metabolism, especially adrenal problems
                                                                          • Why it’s important to be vigilant about hyperkalemia in patients with chronic kidney disease, end-stage renal disease, acute kidney injury, and those with a transplanted kidney
                                                                          • Clinical manifestations of hyperkalemia:
                                                                          • The risk is for cardiac conduction abnormalities and muscle weakness/paralysis.
                                                                          • Adverse events can occur with levels > 5.5mEq/L, and the risk increases as levels rise.
                                                                          • Any serum K level > 6mEq/L is significant, regardless of EKG changes.
                                                                          • Two hallmarks that can drive effective management of hyperkalemia are EKG findings and laboratory confirmation of elevated serum potassium.
                                                                          • Other important labs for patients with hyperkalemia include a basic electrolyte panel to assess kidney function, CBC, and serum blood gas to assess acid/base balance. (A medication check for K supplements or ACE inhibitors should also be done.)
                                                                          • Steps in the management of hyperkalemia:
                                                                          • First, caution should be exercised that any K level > 5.5 is a medical emergency and should be addressed immediately without finding the etiology. 
                                                                          • Stabilize the cardiac membrane.
                                                                          • Shift potassium with insulin and glucose, bicarbonate, and B2 adrenergic agents.
                                                                          • The long-term goal should be to improve excretion with Kayexalate or Furosemide (Remember the mnemonic: “Loops lose K.”)
                                                                          • General considerations about dialysis are:
                                                                          • CVVH vs. HD
                                                                          • Severe hyperkalemia is a key indication for RRT in acutely ill patients.
                                                                          • Hemodialysis can be used in an emergency.
                                                                          • Takeaway clinical pearls regarding hyperkalemia: 
                                                                          • Make sure the potassium level is accurate.
                                                                          • Consider the next steps in potassium removal.
                                                                          • Remember that etiology is the last step.
                                                                          
                                                                          ]]>28817482-a5ec-4d92-ab85-fca20f697fa9Sun, 09 May 2021 03:00:00 -040015:15falsefull1212Management of High Risk Intubations in the PICUToday’s episode is dedicated to the intubation of the critically ill pediatric patient. Join us as we discuss the patient case, symptoms, and treatment.

                                                                          We are delighted to be joined by Dr. Heather Viamonte. Dr. Viamonte is an Assistant Professor of Pediatrics at Emory University School of Medicine. She is a Pediatric Cardiac Intensivist at the Children’s Heart Center and the Director of Cardiac ECMO. The Children’s Heart Center is a 30-bed, dedicated cardiac intensive care unit at the Children’s Healthcare of Atlanta at Egleston. She is a newly published author whose book, Wilde Type, has already been released, and a second novel is on its way to publication. Dr. Viamonte is on Twitter as @hk_jacobs. 

                                                                          Show Highlights:

                                                                          • Our case, symptoms, and diagnosis: A four-month-old patient is admitted to the PICU from the emergency department for acute respiratory failure on high-flow nasal cannula. The child’s condition has slowly deteriorated over the last few hours and now requires intubation. An echo is performed pre-intubation due to enlarged cardiac silhouette on chest radiograph demonstrating left ventricular dysfunction with ejection fraction in the low 40s. The patient’s saturations are dipping to the mid-80s despite being on maximal HFNC support. 
                                                                          • Common indications for intubation in the PICU or CICU include acute respiratory failure, upper airway obstruction, hemodynamic instability, management of increased ICP, mediastinal masses, protection of the airway, as well as for procedures and safe transport.
                                                                          • Patient conditions with a high risk prior to endotracheal intubation include congenital or acquired heart disease, an infant or child with hemodynamic instability, pulmonary hypertension, upper airway obstruction, increased ICP, and mediastinal masses.
                                                                          • Factors in infants and children with congenital heart disease that make them high risk for intubation include anatomical or physiologic issues that could lead to cardiac arrests, such as systemic ventricular dysfunction, single ventricle physiology, arrhythmias, pulmonary hypertension, and coronary artery anomalies.
                                                                          • Why an understanding of the patient’s past medical history and overall physiology are important for risk stratification
                                                                          • Anatomical concerns that should be assessed in infants and children prior to intubation include genetic syndrome heart defects that could interfere with bag-mask ventilation, airway visualization, or laryngoscopy. These could include morbid obesity and abnormalities of the face, mouth, and teeth. 
                                                                          • In conceptualizing congenital heart defects prior to intubation, the overriding concern is blood flow to the heart and lungs. Three factors to consider are volume overload, pressure overload, and systemic hypoxemia.
                                                                          • Patients can have anatomical and physiological difficulties with regards to airway management, especially in those who are critically ill and those with cardiac disease.
                                                                          • Four important clinical scenarios for physiologic derangements are hypoxemia, hypotension, metabolic acidosis, and congenital heart lesion pathophysiology.
                                                                          • Remember that infants and children have a higher fragility factor and are at a higher risk for rapid desaturation, hypoxic brain injury, and cardiac arrest. 
                                                                          • Key factors for the intensivist are fine attention to detail, optimizing your monitoring equipment, and anticipating risk factors for peri-intubation cardiac arrest. 
                                                                          • Special considerations with intubation for the patient with severe metabolic acidosis are necessary to prevent cardiovascular collapse and pulmonary hypertension.
                                                                          • How systolic dysfunction from either ventricle plays into the process of intubation
                                                                          • Factors to consider to mitigate risk in intubation include preparation, a multidisciplinary approach, intubation equipment nearby, and management of the post-intubation period.
                                                                          • Dr. Viamonte shares her perspectives on sedation and other medications to consider with intubation.
                                                                          • Takeaway clinical pearls regarding intubation of the critically-ill, high-risk patient include maintaining the patient’s cardiopulmonary reserve, leveraging team potential and resources, and mitigating chaos. “Advance preparation is the key to success.”
                                                                          
                                                                          
                                                                          ]]>Today’s episode is dedicated to the intubation of the critically ill pediatric patient. Join us as we discuss the patient case, symptoms, and treatment.

                                                                          We are delighted to be joined by Dr. Heather Viamonte. Dr. Viamonte is an Assistant Professor of Pediatrics at Emory University School of Medicine. She is a Pediatric Cardiac Intensivist at the Children’s Heart Center and the Director of Cardiac ECMO. The Children’s Heart Center is a 30-bed, dedicated cardiac intensive care unit at the Children’s Healthcare of Atlanta at Egleston. She is a newly published author whose book, Wilde Type, has already been released, and a second novel is on its way to publication. Dr. Viamonte is on Twitter as @hk_jacobs. 

                                                                          Show Highlights:

                                                                          • Our case, symptoms, and diagnosis: A four-month-old patient is admitted to the PICU from the emergency department for acute respiratory failure on high-flow nasal cannula. The child’s condition has slowly deteriorated over the last few hours and now requires intubation. An echo is performed pre-intubation due to enlarged cardiac silhouette on chest radiograph demonstrating left ventricular dysfunction with ejection fraction in the low 40s. The patient’s saturations are dipping to the mid-80s despite being on maximal HFNC support. 
                                                                          • Common indications for intubation in the PICU or CICU include acute respiratory failure, upper airway obstruction, hemodynamic instability, management of increased ICP, mediastinal masses, protection of the airway, as well as for procedures and safe transport.
                                                                          • Patient conditions with a high risk prior to endotracheal intubation include congenital or acquired heart disease, an infant or child with hemodynamic instability, pulmonary hypertension, upper airway obstruction, increased ICP, and mediastinal masses.
                                                                          • Factors in infants and children with congenital heart disease that make them high risk for intubation include anatomical or physiologic issues that could lead to cardiac arrests, such as systemic ventricular dysfunction, single ventricle physiology, arrhythmias, pulmonary hypertension, and coronary artery anomalies.
                                                                          • Why an understanding of the patient’s past medical history and overall physiology are important for risk stratification
                                                                          • Anatomical concerns that should be assessed in infants and children prior to intubation include genetic syndrome heart defects that could interfere with bag-mask ventilation, airway visualization, or laryngoscopy. These could include morbid obesity and abnormalities of the face, mouth, and teeth. 
                                                                          • In conceptualizing congenital heart defects prior to intubation, the overriding concern is blood flow to the heart and lungs. Three factors to consider are volume overload, pressure overload, and systemic hypoxemia.
                                                                          • Patients can have anatomical and physiological difficulties with regards to airway management, especially in those who are critically ill and those with cardiac disease.
                                                                          • Four important clinical scenarios for physiologic derangements are hypoxemia, hypotension, metabolic acidosis, and congenital heart lesion pathophysiology.
                                                                          • Remember that infants and children have a higher fragility factor and are at a higher risk for rapid desaturation, hypoxic brain injury, and cardiac arrest. 
                                                                          • Key factors for the intensivist are fine attention to detail, optimizing your monitoring equipment, and anticipating risk factors for peri-intubation cardiac arrest. 
                                                                          • Special considerations with intubation for the patient with severe metabolic acidosis are necessary to prevent cardiovascular collapse and pulmonary hypertension.
                                                                          • How systolic dysfunction from either ventricle plays into the process of intubation
                                                                          • Factors to consider to mitigate risk in intubation include preparation, a multidisciplinary approach, intubation equipment nearby, and management of the post-intubation period.
                                                                          • Dr. Viamonte shares her perspectives on sedation and other medications to consider with intubation.
                                                                          • Takeaway clinical pearls regarding intubation of the critically-ill, high-risk patient include maintaining the patient’s cardiopulmonary reserve, leveraging team potential and resources, and mitigating chaos. “Advance preparation is the key to success.”
                                                                          
                                                                          
                                                                          ]]>b2edcedd-b35b-490b-aceb-6f5662b7aa7dSun, 02 May 2021 03:00:00 -040021:12falsefull1111Anterior Mediastinal MassToday’s episode is dedicated to the acute management of anterior mediastinal mass in the PICU. Join us as we discuss the patient case, symptoms, and treatment. We are delighted to be joined by Dr. Lisa Lima and Dr. Tom Austin. 

                                                                          Dr. Tom Austin is the Director of General Pediatric Anesthesiology at Children’s Healthcare of Atlanta-Egleston. He is also an Associate Professor of Anesthesiology and Pediatrics at Emory University School of Medicine.

                                                                          Dr. Lisa Lima is a Fourth Year Advanced Technology Fellow in the Division of Critical Care at Children’s Healthcare of Atlanta. She’s also the Senior Associate in the Department of Pediatrics at Emory University School of Medicine. She’s one of the only pediatric-trained ECMO Fellows in the country. 

                                                                          Show Highlights:

                                                                          • Our case, symptoms, and diagnosis: A 17-year-old female has facial swelling and shortness of breath. She recently went to her primary care physician and received a steroid burst and Benadryl for the facial swelling. On the day of admission, her mother noticed that the patient had a deep voice and a “funny” inspiratory sound. The patient presented to the ER and was noted to have a widened mediastinum on a chest x-ray, bringing up concern for an anterior mediastinal mass.
                                                                          • Key presentation features for mediastinal masses
                                                                          • What defines a widened mediastinum?
                                                                          • Important differentials to consider with mediastinal masses:
                                                                          • Take the patient’s history and presentation into context, like if there was a high-impact motor vehicle collision, history of congestive heart failure, lupus, transplant, leukemia, or lymphoma
                                                                          • Pay attention to the Four T’s: thymoma, teratoma, ATLL(lymphoma), and thyroid masses
                                                                          • Key principles that might put pediatric patients with mediastinal masses at risk for anesthetic agents
                                                                          • Important pathophysiologic issues for patients with mediastinal mass include compressed trachea, blocked access to lungs, and right ventricular failure; these effects can be magnified under general anesthesia
                                                                          • Why we need to have great appreciation of the risk of cardiovascular collapse in patients in a tenuous physiological state
                                                                          • General management strategies for those patients who are unable to lie flat or may not tolerate a diagnostic scan: patient history, personal physical exam, determining a rescue position
                                                                          • Key considerations for the patient in the PICU:
                                                                          • Keep the patient spontaneously breathing
                                                                          • Have adequate access with large-bore IVs in sites with no anatomic compression
                                                                          • Have a rescue position
                                                                          • Have a backup plan for rapid deterioration
                                                                          • Communicate with others on the patient care team
                                                                          • Why the Chamberlain procedure is used to obtain a tissue biopsy when there isn’t another primary biopsy site
                                                                          • Key anesthesia principles for patients needing intrathoracic biopsies:
                                                                          • Have clear role assignments in the multidisciplinary team approach
                                                                          • Keep the patient spontaneously breathing
                                                                          • Manage the patient’s pain
                                                                          • Employ liberal use of local anesthetics
                                                                          • Avoid intubation if possible
                                                                          • If necessary, use fiber optic intubation
                                                                          • Keep large-bore IVs in extremities
                                                                          • Why it’s important to stress interdisciplinary involvement early in management
                                                                          • Key factors to consider in patients headed to the OR about airway compression and vascular compression
                                                                          • Takeaway clinical pearls regarding anterior mediastinal masses:
                                                                          • Remember the Four T’s
                                                                          • The pathophysiology of local compression
                                                                          • Emphasize a streamlined multidisciplinary approach with important considerations for contingency planning
                                                                          
                                                                          ]]>Today’s episode is dedicated to the acute management of anterior mediastinal mass in the PICU. Join us as we discuss the patient case, symptoms, and treatment. We are delighted to be joined by Dr. Lisa Lima and Dr. Tom Austin. 

                                                                          Dr. Tom Austin is the Director of General Pediatric Anesthesiology at Children’s Healthcare of Atlanta-Egleston. He is also an Associate Professor of Anesthesiology and Pediatrics at Emory University School of Medicine.

                                                                          Dr. Lisa Lima is a Fourth Year Advanced Technology Fellow in the Division of Critical Care at Children’s Healthcare of Atlanta. She’s also the Senior Associate in the Department of Pediatrics at Emory University School of Medicine. She’s one of the only pediatric-trained ECMO Fellows in the country. 

                                                                          Show Highlights:

                                                                          • Our case, symptoms, and diagnosis: A 17-year-old female has facial swelling and shortness of breath. She recently went to her primary care physician and received a steroid burst and Benadryl for the facial swelling. On the day of admission, her mother noticed that the patient had a deep voice and a “funny” inspiratory sound. The patient presented to the ER and was noted to have a widened mediastinum on a chest x-ray, bringing up concern for an anterior mediastinal mass.
                                                                          • Key presentation features for mediastinal masses
                                                                          • What defines a widened mediastinum?
                                                                          • Important differentials to consider with mediastinal masses:
                                                                          • Take the patient’s history and presentation into context, like if there was a high-impact motor vehicle collision, history of congestive heart failure, lupus, transplant, leukemia, or lymphoma
                                                                          • Pay attention to the Four T’s: thymoma, teratoma, ATLL(lymphoma), and thyroid masses
                                                                          • Key principles that might put pediatric patients with mediastinal masses at risk for anesthetic agents
                                                                          • Important pathophysiologic issues for patients with mediastinal mass include compressed trachea, blocked access to lungs, and right ventricular failure; these effects can be magnified under general anesthesia
                                                                          • Why we need to have great appreciation of the risk of cardiovascular collapse in patients in a tenuous physiological state
                                                                          • General management strategies for those patients who are unable to lie flat or may not tolerate a diagnostic scan: patient history, personal physical exam, determining a rescue position
                                                                          • Key considerations for the patient in the PICU:
                                                                          • Keep the patient spontaneously breathing
                                                                          • Have adequate access with large-bore IVs in sites with no anatomic compression
                                                                          • Have a rescue position
                                                                          • Have a backup plan for rapid deterioration
                                                                          • Communicate with others on the patient care team
                                                                          • Why the Chamberlain procedure is used to obtain a tissue biopsy when there isn’t another primary biopsy site
                                                                          • Key anesthesia principles for patients needing intrathoracic biopsies:
                                                                          • Have clear role assignments in the multidisciplinary team approach
                                                                          • Keep the patient spontaneously breathing
                                                                          • Manage the patient’s pain
                                                                          • Employ liberal use of local anesthetics
                                                                          • Avoid intubation if possible
                                                                          • If necessary, use fiber optic intubation
                                                                          • Keep large-bore IVs in extremities
                                                                          • Why it’s important to stress interdisciplinary involvement early in management
                                                                          • Key factors to consider in patients headed to the OR about airway compression and vascular compression
                                                                          • Takeaway clinical pearls regarding anterior mediastinal masses:
                                                                          • Remember the Four T’s
                                                                          • The pathophysiology of local compression
                                                                          • Emphasize a streamlined multidisciplinary approach with important considerations for contingency planning
                                                                          
                                                                          ]]>536f0de8-7ab2-4ceb-b041-59377feab63fSun, 25 Apr 2021 03:00:00 -040018:03falsefull1010Tumor Lysis Syndrome in the Pediatric Intensive Care UnitToday’s episode is dedicated to Tumor Lysis Syndrome management in the PICU. Join us as we discuss the patient case, symptoms, and treatment.

                                                                          We are delighted to be joined by Dr. Himalee Sabnis, Assistant Professor of Pediatrics at Emory University School of Medicine. She is also a pediatric hematologist/oncologist and the Co-Director of the High-Risk Leukemia Team at the AFLAC Cancer & Blood Disorders Center at Children’s Healthcare of Atlanta. 

                                                                          Show Highlights:

                                                                          • Our case, symptoms, and diagnosis: A three-year-old female with pre-B ALL presents on Day 2 of chemotherapy to the PICU. She is admitted with telemetry findings of arrhythmia, decreased urine output, and an EKG notable for peaked T waves. Her labs are notable for elevated WBC, hyperkalemia, hyperphosphatemia, and low ionized calcium.
                                                                          • Tumor Lysis Syndrome is a life-threatening medical emergency stemming from rapid tumor cell destruction that overwhelms the usual metabolic and excretory pathways. 
                                                                          • Why TLS is the most common pediatric oncologic emergency for pediatric cancer patients
                                                                          • When the tumor cells die or lyse, what’s inside those cells comes out into the blood
                                                                          • Key metabolic abnormalities that affect organ function are too much potassium and phosphorus, low calcium, and uric acid buildup.
                                                                          • Those metabolic abnormalities can result in cardiac arrhythmia and kidney failure.
                                                                          • Certain patient populations have an increased risk for TLS:
                                                                          • Hematological cancers have a higher risk than solid tumors
                                                                          • Patients with fast-growing tumors, like lymphoma and leukemia, are at high risk
                                                                          • Key pathophysiologic principles that drive TLS:
                                                                          • The imbalance of electrolytes can impact heart function
                                                                          • TLS is characterized by hyperkalemia, hyperphosphatemia, hypocalcemia, and uric acid, which is a by-product of DNA breakdown
                                                                          • If untreated, the uric acid can lead to acute kidney injury and renal failure
                                                                          • Electrolyte and metabolic disturbances can progress to renal insufficiency, cardiac arrhythmias, seizures, and death
                                                                          • TLS releases cytokines that can cause a systemic inflammatory response and multi-organ failure
                                                                          • Other lab markers in patients with TLS include uric acid, LDH, CBC, DIC panel, and daily blood gas (these are typically trended every 4-6 hours).
                                                                          • Key factors in TLS management are to understand the risk and know your resources.
                                                                          • Steps taken would be continuous cardiac monitoring, uric acid control, administering Allopurinol to combat uric acid formation, and managing electrolyte disturbances in conjunction with an intensivist.
                                                                          • Chemotherapy would not be delayed due to TLS because the patient’s condition won’t improve until the cancer is treated.
                                                                          • How the complications of TLS are treated:
                                                                          • Hyperphosphatemia should be treated by using oral phosphate binders such as aluminum hydroxide.
                                                                          • Hypocalcemia does not require therapy unless cardiac function is affected.
                                                                          • How renal replacement therapy might be required and indications are similar to other forms of acute kidney injury.
                                                                          • Besides Allopurinol being given at the initiation of chemotherapy, patients at high risk for TLS may receive low-intensity initial therapy to prevent rapid cell lysis.
                                                                          • Takeaway clinical pearls regarding TLS:
                                                                          • Know what you’re dealing with because every cancer is different.
                                                                          • Fluid management is important and will vary from patient to patient.
                                                                          • Be proactive in monitoring. Intervene early and quickly.
                                                                          
                                                                          

                                                                           

                                                                          ]]>Today’s episode is dedicated to Tumor Lysis Syndrome management in the PICU. Join us as we discuss the patient case, symptoms, and treatment.

                                                                          We are delighted to be joined by Dr. Himalee Sabnis, Assistant Professor of Pediatrics at Emory University School of Medicine. She is also a pediatric hematologist/oncologist and the Co-Director of the High-Risk Leukemia Team at the AFLAC Cancer & Blood Disorders Center at Children’s Healthcare of Atlanta. 

                                                                          Show Highlights:

                                                                          • Our case, symptoms, and diagnosis: A three-year-old female with pre-B ALL presents on Day 2 of chemotherapy to the PICU. She is admitted with telemetry findings of arrhythmia, decreased urine output, and an EKG notable for peaked T waves. Her labs are notable for elevated WBC, hyperkalemia, hyperphosphatemia, and low ionized calcium.
                                                                          • Tumor Lysis Syndrome is a life-threatening medical emergency stemming from rapid tumor cell destruction that overwhelms the usual metabolic and excretory pathways. 
                                                                          • Why TLS is the most common pediatric oncologic emergency for pediatric cancer patients
                                                                          • When the tumor cells die or lyse, what’s inside those cells comes out into the blood
                                                                          • Key metabolic abnormalities that affect organ function are too much potassium and phosphorus, low calcium, and uric acid buildup.
                                                                          • Those metabolic abnormalities can result in cardiac arrhythmia and kidney failure.
                                                                          • Certain patient populations have an increased risk for TLS:
                                                                          • Hematological cancers have a higher risk than solid tumors
                                                                          • Patients with fast-growing tumors, like lymphoma and leukemia, are at high risk
                                                                          • Key pathophysiologic principles that drive TLS:
                                                                          • The imbalance of electrolytes can impact heart function
                                                                          • TLS is characterized by hyperkalemia, hyperphosphatemia, hypocalcemia, and uric acid, which is a by-product of DNA breakdown
                                                                          • If untreated, the uric acid can lead to acute kidney injury and renal failure
                                                                          • Electrolyte and metabolic disturbances can progress to renal insufficiency, cardiac arrhythmias, seizures, and death
                                                                          • TLS releases cytokines that can cause a systemic inflammatory response and multi-organ failure
                                                                          • Other lab markers in patients with TLS include uric acid, LDH, CBC, DIC panel, and daily blood gas (these are typically trended every 4-6 hours).
                                                                          • Key factors in TLS management are to understand the risk and know your resources.
                                                                          • Steps taken would be continuous cardiac monitoring, uric acid control, administering Allopurinol to combat uric acid formation, and managing electrolyte disturbances in conjunction with an intensivist.
                                                                          • Chemotherapy would not be delayed due to TLS because the patient’s condition won’t improve until the cancer is treated.
                                                                          • How the complications of TLS are treated:
                                                                          • Hyperphosphatemia should be treated by using oral phosphate binders such as aluminum hydroxide.
                                                                          • Hypocalcemia does not require therapy unless cardiac function is affected.
                                                                          • How renal replacement therapy might be required and indications are similar to other forms of acute kidney injury.
                                                                          • Besides Allopurinol being given at the initiation of chemotherapy, patients at high risk for TLS may receive low-intensity initial therapy to prevent rapid cell lysis.
                                                                          • Takeaway clinical pearls regarding TLS:
                                                                          • Know what you’re dealing with because every cancer is different.
                                                                          • Fluid management is important and will vary from patient to patient.
                                                                          • Be proactive in monitoring. Intervene early and quickly.
                                                                          
                                                                          

                                                                           

                                                                          ]]>df9450f5-1b0c-408c-b848-05817dbf8c9eSun, 18 Apr 2021 03:00:00 -040019:46falsefull99Acute Management of the Post-operative Renal TransplantToday’s episode is dedicated to post-operative management in the PICU of the pediatric renal transplant patient. Join us as we discuss the patient case, symptoms, and treatment. 

                                                                           Joining the conversation is Dr. Rouba Garro, Associate Professor of Pediatrics at Emory University School of Medicine and the Medical Director of the Kidney Transplant Program at Children’s Healthcare of Atlanta. Children’s Healthcare of Atlanta has one of the largest kidney transplant programs in the country and is the largest in the Southeast US with excellent patient and graft survival. 

                                                                          Show Highlights: 

                                                                          • Our case, symptoms, and diagnosis: a five-year-old is transferred to the PICU after a related living kidney transplant for end-stage renal disease due to obstructive uropathy. The patient has a history of post-urethral valves and is on room air, IV fluids, an arterial line, and a Foley catheter is in place.
                                                                          • The top indicators for renal transplant in pediatrics vary according to age, but congenital anomalies are the most common in children younger than six.
                                                                          • The criteria for being considered for kidney transplantation include several factors, including when kidney function drops below 20%.
                                                                          • The keys for successful transplantation:
                                                                          • An experienced pre-transplant team
                                                                          • A robust and experienced team for perioperative care and graft outcome
                                                                          • A comprehensive and multidisciplinary post-transplant team
                                                                          • The process of organ procurement for cadaveric and living donor renal transplants includes the following:
                                                                          • Multiple factors determine the points a patient receives toward transplant priority
                                                                          • Deceased donor kidneys are classified using the KDPI (kidney donor profile index)
                                                                          • A thorough evaluation is performed for living donors
                                                                          • Advantages to living donation include a shorter time on dialysis and waitlists, improved graft survival, and shorter ischemia time than from a deceased donor
                                                                          • Information from the operating team that is vital for the PICU team to know for post-op success includes patient history, transplant details, ischemia time, and transplant complications.
                                                                          • Red flags for the critical care post-op team are in the three categories of blood pressure, urine output, and kidney function/electrolytes. 
                                                                          • The need to watch for signs of infection in the post-op phase
                                                                          • How immunosuppressive medications might be used for the pediatric renal transplant patient
                                                                          • Why the post-op transplant patient might need dialysis
                                                                          • Clinical pearls for post-op care of the pediatric renal transplant patient in the PICU:
                                                                          • Teamwork and collaboration are key elements for success.
                                                                          • The most important task is to monitor blood pressure, urine output, and electrolytes. 
                                                                          
                                                                          
                                                                          ]]>Today’s episode is dedicated to post-operative management in the PICU of the pediatric renal transplant patient. Join us as we discuss the patient case, symptoms, and treatment. 

                                                                           Joining the conversation is Dr. Rouba Garro, Associate Professor of Pediatrics at Emory University School of Medicine and the Medical Director of the Kidney Transplant Program at Children’s Healthcare of Atlanta. Children’s Healthcare of Atlanta has one of the largest kidney transplant programs in the country and is the largest in the Southeast US with excellent patient and graft survival. 

                                                                          Show Highlights: 

                                                                          • Our case, symptoms, and diagnosis: a five-year-old is transferred to the PICU after a related living kidney transplant for end-stage renal disease due to obstructive uropathy. The patient has a history of post-urethral valves and is on room air, IV fluids, an arterial line, and a Foley catheter is in place.
                                                                          • The top indicators for renal transplant in pediatrics vary according to age, but congenital anomalies are the most common in children younger than six.
                                                                          • The criteria for being considered for kidney transplantation include several factors, including when kidney function drops below 20%.
                                                                          • The keys for successful transplantation:
                                                                          • An experienced pre-transplant team
                                                                          • A robust and experienced team for perioperative care and graft outcome
                                                                          • A comprehensive and multidisciplinary post-transplant team
                                                                          • The process of organ procurement for cadaveric and living donor renal transplants includes the following:
                                                                          • Multiple factors determine the points a patient receives toward transplant priority
                                                                          • Deceased donor kidneys are classified using the KDPI (kidney donor profile index)
                                                                          • A thorough evaluation is performed for living donors
                                                                          • Advantages to living donation include a shorter time on dialysis and waitlists, improved graft survival, and shorter ischemia time than from a deceased donor
                                                                          • Information from the operating team that is vital for the PICU team to know for post-op success includes patient history, transplant details, ischemia time, and transplant complications.
                                                                          • Red flags for the critical care post-op team are in the three categories of blood pressure, urine output, and kidney function/electrolytes. 
                                                                          • The need to watch for signs of infection in the post-op phase
                                                                          • How immunosuppressive medications might be used for the pediatric renal transplant patient
                                                                          • Why the post-op transplant patient might need dialysis
                                                                          • Clinical pearls for post-op care of the pediatric renal transplant patient in the PICU:
                                                                          • Teamwork and collaboration are key elements for success.
                                                                          • The most important task is to monitor blood pressure, urine output, and electrolytes. 
                                                                          
                                                                          
                                                                          ]]>d7ebf10b-a25b-476d-a4bc-21951dda177cSun, 11 Apr 2021 03:00:00 -040025:28falsefull88Acute Management of Post Op Liver TransplantToday’s episode is dedicated to post-operative management of liver transplant patients in PICU. Join us as we discuss the patient case, symptoms, and treatment. 

                                                                          Joining us is Dr. Joe Magliocca, Associate Professor of Surgery in the Department of Surgery at Emory University School of Medicine. He is also the Surgical Director of Adult and Pediatric Liver Transplantation at Children’s Healthcare of Atlanta. 

                                                                          Also joining the conversation is Dr. Rene Romero, Professor of Pediatrics at Emory University School of Medicine and Medical Director of the Liver Transplant Program at Children’s Healthcare of Atlanta, which is one of the largest liver transplant programs in the country with over 600 pediatric liver transplants to date. 

                                                                          >>Click here to download the PICU card for this episode<<

                                                                          Show Highlights:

                                                                          • Our patient, symptoms, and treatment: An 18-month-old with a history of biliary atresia is admitted to PICU after an orthotopic whole liver transplant. The patient is intubated, and Doppler ultrasound shows vascular patency post-operatively. AST and ALT are pending. 
                                                                          • Common indications for pediatric liver transplantation:
                                                                          • 500-700 pediatric liver transplants are performed annually in the US
                                                                          • 40% of the transplants are done on children born with biliary atresia
                                                                          • 10-15% of the transplants are due to acute liver failure
                                                                          • 5% of the transplants are due to malignancies
                                                                          • The rest of the transplants are due to different childhood diseases and metabolic diseases
                                                                          • How the PELD (Pediatric End-Stage Liver Disease in children under 12) score relates to prioritization for liver transplant
                                                                          • Criteria for the PELD score are bilirubin, albumin, age, growth parameters, and INR
                                                                          • The major differences between whole organ vs. split liver transplantation (long-term outcomes are similar and good for both situations)
                                                                          • Why liver transplantation requires less immunosuppression than other organ transplants
                                                                          • Three phases of the liver transplant process are the hepatectomy phase, anhepatic phase, and reperfusion phase
                                                                          • Specifics of the time intervals during the transplant process, where the major risk is for primary non-function during cold ischemia and warm ischemia times
                                                                          • Major red flags to look for during the immediate post-operative period
                                                                          • Acute post-op management includes extubation in the OR, CV monitoring, pain management, checking urine and electrolyte levels, and communication with the transplant surgeon and liver team
                                                                          • How treatment and management have evolved over time with standardized post-op management, protocols, and parameters
                                                                          • Two important aspects of post-op management are nutrition and immunosuppression
                                                                          • Clinical pearls of wisdom:
                                                                          • The need for organ donors is great. 
                                                                          • Teamwork and collaboration are essential for good patient outcomes. 
                                                                          • The transformation in the field of liver transplantation has saved many children’s lives.
                                                                          
                                                                          ]]>Today’s episode is dedicated to post-operative management of liver transplant patients in PICU. Join us as we discuss the patient case, symptoms, and treatment. 

                                                                          Joining us is Dr. Joe Magliocca, Associate Professor of Surgery in the Department of Surgery at Emory University School of Medicine. He is also the Surgical Director of Adult and Pediatric Liver Transplantation at Children’s Healthcare of Atlanta. 

                                                                          Also joining the conversation is Dr. Rene Romero, Professor of Pediatrics at Emory University School of Medicine and Medical Director of the Liver Transplant Program at Children’s Healthcare of Atlanta, which is one of the largest liver transplant programs in the country with over 600 pediatric liver transplants to date. 

                                                                          >>Click here to download the PICU card for this episode<<

                                                                          Show Highlights:

                                                                          • Our patient, symptoms, and treatment: An 18-month-old with a history of biliary atresia is admitted to PICU after an orthotopic whole liver transplant. The patient is intubated, and Doppler ultrasound shows vascular patency post-operatively. AST and ALT are pending. 
                                                                          • Common indications for pediatric liver transplantation:
                                                                          • 500-700 pediatric liver transplants are performed annually in the US
                                                                          • 40% of the transplants are done on children born with biliary atresia
                                                                          • 10-15% of the transplants are due to acute liver failure
                                                                          • 5% of the transplants are due to malignancies
                                                                          • The rest of the transplants are due to different childhood diseases and metabolic diseases
                                                                          • How the PELD (Pediatric End-Stage Liver Disease in children under 12) score relates to prioritization for liver transplant
                                                                          • Criteria for the PELD score are bilirubin, albumin, age, growth parameters, and INR
                                                                          • The major differences between whole organ vs. split liver transplantation (long-term outcomes are similar and good for both situations)
                                                                          • Why liver transplantation requires less immunosuppression than other organ transplants
                                                                          • Three phases of the liver transplant process are the hepatectomy phase, anhepatic phase, and reperfusion phase
                                                                          • Specifics of the time intervals during the transplant process, where the major risk is for primary non-function during cold ischemia and warm ischemia times
                                                                          • Major red flags to look for during the immediate post-operative period
                                                                          • Acute post-op management includes extubation in the OR, CV monitoring, pain management, checking urine and electrolyte levels, and communication with the transplant surgeon and liver team
                                                                          • How treatment and management have evolved over time with standardized post-op management, protocols, and parameters
                                                                          • Two important aspects of post-op management are nutrition and immunosuppression
                                                                          • Clinical pearls of wisdom:
                                                                          • The need for organ donors is great. 
                                                                          • Teamwork and collaboration are essential for good patient outcomes. 
                                                                          • The transformation in the field of liver transplantation has saved many children’s lives.
                                                                          
                                                                          ]]>7ea070ce-df2a-45aa-a31d-6f2dc42b4169Sun, 04 Apr 2021 03:00:00 -040028:47falsefull77Acute Liver FailureToday’s episode is dedicated to pediatric acute liver failure. Join us as we discuss the patient case, symptoms, and treatment. 

                                                                           Joining the conversation is Dr. Rene Romero, Professor of Pediatrics at Emory University School of Medicine and the Medical Director of the Liver Transplant Program at Children’s Healthcare of Atlanta. 

                                                                          >>Click here to download the PICU card for this episode<<

                                                                          Show Highlights: 

                                                                          • Our case, symptoms, and diagnosis: a three-year-old child presents in the PICU with decreased arousal; the patient is hypoglycemic. The coagulation panel is significant for increased PTT and INR, and AST and ALT are significantly elevated. The patient is hyperammonemic, and the acetaminophen level is normal. The diagnosis is acute liver failure.
                                                                          • Basic functions of the liver, the “workhorse of the body” that plays major roles in interactions with other organs
                                                                          • Why pediatric acute liver failure is more difficult to diagnose than in adults; key indicators are coagulopathy along with biochemical disruptions
                                                                          • The most important contributing factors to pediatric acute liver failure, and why most pediatric cases are children under four years of age
                                                                          • Causes of pediatric acute liver failure in the US include HSV, adenovirus, enterovirus, metabolic causes, and acetaminophen, especially in older children
                                                                          • The diagnostic approach considers infectious etiologies, toxins, vascular issues, and immune dysregulation
                                                                          • In treatment, care should be given to the correction of abnormal lab values and possible renal replacement therapy
                                                                          • Why the use of prophylactic antifungal antibiotics is controversial and varies from institution to institution
                                                                          • How to discern hyperammonemia and neurologic status
                                                                          • The role of intracranial pressure monitoring for cerebral edema, which is the mode of death for these patients
                                                                          • Key Clinical Pearls: acute liver failure is a systemic disease that requires a broad diagnostic approach, and the need for standardized approaches still exists.
                                                                          
                                                                          ]]>Today’s episode is dedicated to pediatric acute liver failure. Join us as we discuss the patient case, symptoms, and treatment. 

                                                                           Joining the conversation is Dr. Rene Romero, Professor of Pediatrics at Emory University School of Medicine and the Medical Director of the Liver Transplant Program at Children’s Healthcare of Atlanta. 

                                                                          >>Click here to download the PICU card for this episode<<

                                                                          Show Highlights: 

                                                                          • Our case, symptoms, and diagnosis: a three-year-old child presents in the PICU with decreased arousal; the patient is hypoglycemic. The coagulation panel is significant for increased PTT and INR, and AST and ALT are significantly elevated. The patient is hyperammonemic, and the acetaminophen level is normal. The diagnosis is acute liver failure.
                                                                          • Basic functions of the liver, the “workhorse of the body” that plays major roles in interactions with other organs
                                                                          • Why pediatric acute liver failure is more difficult to diagnose than in adults; key indicators are coagulopathy along with biochemical disruptions
                                                                          • The most important contributing factors to pediatric acute liver failure, and why most pediatric cases are children under four years of age
                                                                          • Causes of pediatric acute liver failure in the US include HSV, adenovirus, enterovirus, metabolic causes, and acetaminophen, especially in older children
                                                                          • The diagnostic approach considers infectious etiologies, toxins, vascular issues, and immune dysregulation
                                                                          • In treatment, care should be given to the correction of abnormal lab values and possible renal replacement therapy
                                                                          • Why the use of prophylactic antifungal antibiotics is controversial and varies from institution to institution
                                                                          • How to discern hyperammonemia and neurologic status
                                                                          • The role of intracranial pressure monitoring for cerebral edema, which is the mode of death for these patients
                                                                          • Key Clinical Pearls: acute liver failure is a systemic disease that requires a broad diagnostic approach, and the need for standardized approaches still exists.
                                                                          
                                                                          ]]>1c40e58a-7c97-48c4-a817-8673e9615acaSun, 28 Mar 2021 03:00:00 -040021:46falsefull66Acute Metabolic EmergenciesToday’s episode is dedicated to acute metabolic emergencies. Join us as we discuss the patient case, symptoms, and treatment. 

                                                                          Joining us is Dr. Lori-Anne Schillaci, trained in clinical pediatric genetics with additional training in metabolism. She had a dual appointment in the Department of Pediatric Emergency Medicine at Rainbow Babies and Children’s Hospital, as well as an appointment in the Department of Genetics and Metabolism. Dr. Schillaci is currently embarking on a fellowship in Pediatric Emergency Medicine at Wake Forest Brenner Children’s Hospital. 

                                                                          >>Click here to download the PICU card for this episode<<

                                                                          Show Highlights:

                                                                          • Our case: A three-month-old infant presents with seizures and decreased oral intake
                                                                          • History, symptoms, and treatment: The child is hypothermic and tachypneic. Blood gas is notable for anion-gap metabolic acidosis. Blood cultures are drawn, and antibiotics are started. Urine organic acids and serum ammonia are both pending. 
                                                                          • A metabolic emergency is defined as a defect in the breakdown or storage of the body’s energy sources (sugar, fat, and protein) at the cellular level
                                                                          • Why metabolic conditions can be inherited or result from a spontaneous mutation
                                                                          • How the toxic products form in the body and can affect children in three categories (protein, fat, and sugar metabolism)
                                                                          • Common lab tests would be for ammonia, gas, and blood sugar
                                                                          • Why the physician should save a purple top tube before any transfusion
                                                                          • General management should include treatment of the underlying acute issues, early dextrose fluids, normal saline fluid boluses, IV lipid emulsion (except in patients with known fatty acid oxidation defects)
                                                                          • Advice to colleagues in managing a patient with inborn error:
                                                                          • Keep in mind that the presentation can occur in older kids
                                                                          • Get early labs when they are sick
                                                                          • Start high dextrose fluids
                                                                          • Keep the patient NPO
                                                                          • Treat fever, hypoglycemia, seizures, infection, etc. 
                                                                          • The goal is to prevent catabolism and be aggressive early in treatment
                                                                          • Dr. Schillaci’s final thoughts: “Be vigilant. Assume an inborn error of metabolism unless proven otherwise. Be aware of late presentations of inborn errors of metabolism.”
                                                                          
                                                                          ]]>Today’s episode is dedicated to acute metabolic emergencies. Join us as we discuss the patient case, symptoms, and treatment. 

                                                                          Joining us is Dr. Lori-Anne Schillaci, trained in clinical pediatric genetics with additional training in metabolism. She had a dual appointment in the Department of Pediatric Emergency Medicine at Rainbow Babies and Children’s Hospital, as well as an appointment in the Department of Genetics and Metabolism. Dr. Schillaci is currently embarking on a fellowship in Pediatric Emergency Medicine at Wake Forest Brenner Children’s Hospital. 

                                                                          >>Click here to download the PICU card for this episode<<

                                                                          Show Highlights:

                                                                          • Our case: A three-month-old infant presents with seizures and decreased oral intake
                                                                          • History, symptoms, and treatment: The child is hypothermic and tachypneic. Blood gas is notable for anion-gap metabolic acidosis. Blood cultures are drawn, and antibiotics are started. Urine organic acids and serum ammonia are both pending. 
                                                                          • A metabolic emergency is defined as a defect in the breakdown or storage of the body’s energy sources (sugar, fat, and protein) at the cellular level
                                                                          • Why metabolic conditions can be inherited or result from a spontaneous mutation
                                                                          • How the toxic products form in the body and can affect children in three categories (protein, fat, and sugar metabolism)
                                                                          • Common lab tests would be for ammonia, gas, and blood sugar
                                                                          • Why the physician should save a purple top tube before any transfusion
                                                                          • General management should include treatment of the underlying acute issues, early dextrose fluids, normal saline fluid boluses, IV lipid emulsion (except in patients with known fatty acid oxidation defects)
                                                                          • Advice to colleagues in managing a patient with inborn error:
                                                                          • Keep in mind that the presentation can occur in older kids
                                                                          • Get early labs when they are sick
                                                                          • Start high dextrose fluids
                                                                          • Keep the patient NPO
                                                                          • Treat fever, hypoglycemia, seizures, infection, etc. 
                                                                          • The goal is to prevent catabolism and be aggressive early in treatment
                                                                          • Dr. Schillaci’s final thoughts: “Be vigilant. Assume an inborn error of metabolism unless proven otherwise. Be aware of late presentations of inborn errors of metabolism.”
                                                                          
                                                                          ]]>3380c3b1-69c2-491a-9990-f62518e82b19Thu, 04 Mar 2021 03:00:00 -040014:33falsefull55PICU Applications of Lipid Emulsion TherapyToday’s episode is dedicated to PICU applications of lipid emulsion therapy. Join us as we discuss the patient case, symptoms, and treatment. 

                                                                          Joining us is Dr. Ziad N. Kazzi, Associate Professor of Emergency Medicine at Emory University School of Medicine, Director of the International Toxicology Fellowship Program at Emory, and Assistant Medical Director of the Georgia Poison Center. Dr. Kazzi is also a board member of the American College of Medical Toxicology and current president of the Middle East North Africa Toxicology Association. 

                                                                          >>Click here to download the PICU card for this episode<<

                                                                          Show Highlights:

                                                                          • Our case: a 14-year-old girl has been admitted to PICU after acute ingestion of the calcium channel blocker Amlodipine in a suicide attempt
                                                                          • Symptoms: profound hypotension
                                                                          • Acute management: After fluid resuscitation, norepinephrine infusion, and high-dose insulin therapy, lipid emulsion therapy is considered
                                                                          • How lipid emulsion therapy began
                                                                          • How lipids work in the toxicology realm
                                                                          • Applications in PICU for indicators and efficient doses of lipid emulsion therapy
                                                                          • Examples of cases that call for lipid emulsion therapy
                                                                          • Considerations of propofol as a substitute for lipid emulsion therapy
                                                                          • To minimize complications from lipid emulsion therapy, pay attention to dosing guidelines, limit the duration of the infusion, and focus on systemic toxicities
                                                                          • Final thoughts: Know when to use (and when not to use) antidotes and be aware of publication bias with any studies
                                                                          
                                                                          

                                                                          Resources:

                                                                          Download the PICU Card for this episode here

                                                                          www.lipidrescue.org  

                                                                          ]]>Today’s episode is dedicated to PICU applications of lipid emulsion therapy. Join us as we discuss the patient case, symptoms, and treatment. 

                                                                          Joining us is Dr. Ziad N. Kazzi, Associate Professor of Emergency Medicine at Emory University School of Medicine, Director of the International Toxicology Fellowship Program at Emory, and Assistant Medical Director of the Georgia Poison Center. Dr. Kazzi is also a board member of the American College of Medical Toxicology and current president of the Middle East North Africa Toxicology Association. 

                                                                          >>Click here to download the PICU card for this episode<<

                                                                          Show Highlights:

                                                                          • Our case: a 14-year-old girl has been admitted to PICU after acute ingestion of the calcium channel blocker Amlodipine in a suicide attempt
                                                                          • Symptoms: profound hypotension
                                                                          • Acute management: After fluid resuscitation, norepinephrine infusion, and high-dose insulin therapy, lipid emulsion therapy is considered
                                                                          • How lipid emulsion therapy began
                                                                          • How lipids work in the toxicology realm
                                                                          • Applications in PICU for indicators and efficient doses of lipid emulsion therapy
                                                                          • Examples of cases that call for lipid emulsion therapy
                                                                          • Considerations of propofol as a substitute for lipid emulsion therapy
                                                                          • To minimize complications from lipid emulsion therapy, pay attention to dosing guidelines, limit the duration of the infusion, and focus on systemic toxicities
                                                                          • Final thoughts: Know when to use (and when not to use) antidotes and be aware of publication bias with any studies
                                                                          
                                                                          

                                                                          Resources:

                                                                          Download the PICU Card for this episode here

                                                                          www.lipidrescue.org  

                                                                          ]]>8aadf9de-e49d-4aaa-a2f6-0b7f977b3efcThu, 25 Feb 2021 03:00:00 -040018:04falsefull44Acute Management of Pediatric StrokeToday’s episode is dedicated to the acute management of pediatric stroke. Join us as we discuss the patient case, symptoms, and treatment. 

                                                                          Joining us is Dr. Elissa Ortolani, Assistant Professor of Pediatrics in the Division of Child Neurology and Assistant Professor of Neurology at Emory University School of Medicine. Dr. Ortolani has a strong clinical interest in pediatric vascular disease and is one of the few pediatric neurologists who has completed a formal adult stroke fellowship. She is actively helping to develop a pediatric stroke program at Children’s Healthcare of Atlanta.

                                                                          >>Click here to download the PICU card for this episode<<

                                                                          Show Highlights:

                                                                          • Our case: a five-year-old male, previously healthy, has had cold symptoms for two days; he presents to the ER with possible stroke symptoms
                                                                          • Symptoms: the patient has had left arm and left leg weakness during the past day, and his mother noticed a subtle left side lip droop with drooling
                                                                          • Acute management: In the ER, a CT revealed a subtle hypodensity in the right basal ganglia region; the patient was admitted to PICU for further monitoring and workup
                                                                          • Causes of an acute pediatric vascular event can include stroke, seizure, migraine, and toxidrome
                                                                          • Definition of stroke: an acute neurologic change identified by advanced imaging
                                                                          • Practical tools in evaluating stroke include F-facial droop, A-arm weakness, S-speech difficulty, T-time. (Now, amended to FASTER to include stability and eyes/vision)
                                                                          • Risk factors for pediatric stroke include vascular issues like sickle cell disease, congenital heart problems, thrombophilia, and mitochondrial, inflammatory, or connective tissue disease
                                                                          • In pinpointing pediatric stroke or stroke mimic, which is very common, MRI is the preferred imaging method 
                                                                          • Important considerations in the diagnosis of pediatric stroke are that mild sedation is sufficient for the 10-12 minutes needed for MRI
                                                                          • In the management of pediatric stroke, TPA should be administered within 4.5 hours, and endovascular therapy (if needed) should be administered within 24 hours
                                                                          • Why the diagnosis and management of pediatric stroke is delayed, and how ER and ICU physicians can change that
                                                                          • Developing a pediatric stroke program is a collaborative effort among emergency care providers, radiologists, pharmacists, adult neuro interventionalists, ICU team, neurosurgeons, hematologists, and rehab physicians
                                                                          • A key in the diagnosis of pediatric stroke is recognizing altered mental status
                                                                          
                                                                          ]]>Today’s episode is dedicated to the acute management of pediatric stroke. Join us as we discuss the patient case, symptoms, and treatment. 

                                                                          Joining us is Dr. Elissa Ortolani, Assistant Professor of Pediatrics in the Division of Child Neurology and Assistant Professor of Neurology at Emory University School of Medicine. Dr. Ortolani has a strong clinical interest in pediatric vascular disease and is one of the few pediatric neurologists who has completed a formal adult stroke fellowship. She is actively helping to develop a pediatric stroke program at Children’s Healthcare of Atlanta.

                                                                          >>Click here to download the PICU card for this episode<<

                                                                          Show Highlights:

                                                                          • Our case: a five-year-old male, previously healthy, has had cold symptoms for two days; he presents to the ER with possible stroke symptoms
                                                                          • Symptoms: the patient has had left arm and left leg weakness during the past day, and his mother noticed a subtle left side lip droop with drooling
                                                                          • Acute management: In the ER, a CT revealed a subtle hypodensity in the right basal ganglia region; the patient was admitted to PICU for further monitoring and workup
                                                                          • Causes of an acute pediatric vascular event can include stroke, seizure, migraine, and toxidrome
                                                                          • Definition of stroke: an acute neurologic change identified by advanced imaging
                                                                          • Practical tools in evaluating stroke include F-facial droop, A-arm weakness, S-speech difficulty, T-time. (Now, amended to FASTER to include stability and eyes/vision)
                                                                          • Risk factors for pediatric stroke include vascular issues like sickle cell disease, congenital heart problems, thrombophilia, and mitochondrial, inflammatory, or connective tissue disease
                                                                          • In pinpointing pediatric stroke or stroke mimic, which is very common, MRI is the preferred imaging method 
                                                                          • Important considerations in the diagnosis of pediatric stroke are that mild sedation is sufficient for the 10-12 minutes needed for MRI
                                                                          • In the management of pediatric stroke, TPA should be administered within 4.5 hours, and endovascular therapy (if needed) should be administered within 24 hours
                                                                          • Why the diagnosis and management of pediatric stroke is delayed, and how ER and ICU physicians can change that
                                                                          • Developing a pediatric stroke program is a collaborative effort among emergency care providers, radiologists, pharmacists, adult neuro interventionalists, ICU team, neurosurgeons, hematologists, and rehab physicians
                                                                          • A key in the diagnosis of pediatric stroke is recognizing altered mental status
                                                                          
                                                                          ]]>37d7d221-c48a-4b37-aa40-8d5da5194be3Wed, 17 Feb 2021 05:00:00 -040014:56falsefull33Acute Management of LaryngospasmToday’s episode is dedicated to acute management of laryngospasm. Join us as we discuss the patient case, symptoms, and treatment. 

                                                                          Joining us is Dr. Tom Austin, director of General Pediatric Anesthesiology at Children’s Healthcare of Atlanta-Egleston. He’s also an associate professor of anesthesia and pediatrics at Emory University School of Medicine. 

                                                                          >>Click here to download the PICU card for this episode<<

                                                                          Show Highlights:

                                                                          • Our case: a two-year-old male with a history of Wilms’ tumor presents in a sedation suite for post-surveillance MRI
                                                                          • History, symptoms, and treatment: One-week history of nasal congestion with no active nasal discharge and clear lung sounds. Patient was placed on continuous pulse ox symmetry and CO2 monitoring. With sedation for the MRI, the patient had a sudden cough, which progressed to perioral cyanosis and loss of end-tidal CO2.
                                                                          • How this case illustrates laryngospasm
                                                                          • Definition of laryngospasm: complete or partial closure of the larynx due to some manner of external stimulation
                                                                          • Why laryngospasm leads to acute respiratory failure in children
                                                                          • How laryngospasm differs from airway obstruction
                                                                          • Characteristic breathing pattern with laryngospasm
                                                                          • Acute management of laryngospasm includes a bag-mask and positive pressure ventilation, followed by deepened sedation, and a breathing tube
                                                                          • Why early recognition of laryngospasm is the key
                                                                          
                                                                          ]]>Today’s episode is dedicated to acute management of laryngospasm. Join us as we discuss the patient case, symptoms, and treatment. 

                                                                          Joining us is Dr. Tom Austin, director of General Pediatric Anesthesiology at Children’s Healthcare of Atlanta-Egleston. He’s also an associate professor of anesthesia and pediatrics at Emory University School of Medicine. 

                                                                          >>Click here to download the PICU card for this episode<<

                                                                          Show Highlights:

                                                                          • Our case: a two-year-old male with a history of Wilms’ tumor presents in a sedation suite for post-surveillance MRI
                                                                          • History, symptoms, and treatment: One-week history of nasal congestion with no active nasal discharge and clear lung sounds. Patient was placed on continuous pulse ox symmetry and CO2 monitoring. With sedation for the MRI, the patient had a sudden cough, which progressed to perioral cyanosis and loss of end-tidal CO2.
                                                                          • How this case illustrates laryngospasm
                                                                          • Definition of laryngospasm: complete or partial closure of the larynx due to some manner of external stimulation
                                                                          • Why laryngospasm leads to acute respiratory failure in children
                                                                          • How laryngospasm differs from airway obstruction
                                                                          • Characteristic breathing pattern with laryngospasm
                                                                          • Acute management of laryngospasm includes a bag-mask and positive pressure ventilation, followed by deepened sedation, and a breathing tube
                                                                          • Why early recognition of laryngospasm is the key
                                                                          
                                                                          ]]>8cd6917b-edae-49ee-961b-78e18b769eefWed, 17 Feb 2021 03:00:00 -040010:15falsefull22Treating Anaphylaxis in the PICUWelcome to the first episode of our podcast for current and aspiring intensivists. Our panel of medical professionals and students will examine specific patient cases, symptoms, and treatments. Today’s episode focuses on anaphylaxis. Join us!

                                                                          >>Click here to download the PICU card for this episode<<

                                                                          Show Highlights:

                                                                          • Our case: a four-year-old is admitted to PICU, and TPN has been administered.
                                                                          • Symptoms: dyspnea, wheezing, strider, and urticaria
                                                                          • Vitals: hypotensive, tachycardic, with stats dropping rapidly
                                                                          • What is anaphylaxis? An acute, life-threatening, systemic allergic reaction that can lead to death by airway obstruction or cardiovascular collapse.
                                                                          • Anaphylaxis symptoms include skin, mucosal, respiratory, cardiovascular, and gastrointestinal symptoms that develop within one hour of exposure to the allergen.
                                                                          • Anaphylaxis triggers can include allergens, biologics, immunotherapy, and radio-contrast media.
                                                                          • The anaphylaxis reaction ends with distributive shock, manifested by low cardiovascular output, low systemic vascular resistance, and high pulmonary vascular resistance.
                                                                          • Acute management of an anaphylaxis reaction includes airway, circulation, and breathing management, and epinephrine (the dosing is different from code dose).
                                                                          • Watch out for hypotension and lower airway obstruction as possible complications, which can be managed with fluids and nebulized albuterol.
                                                                          • Adjunctive therapies include histamine blockers and steroids.
                                                                          • Post-anaphylaxis care:
                                                                          • Focus on observation of the patient for 10-24 hours.
                                                                          • Watch for a biphasic reaction.
                                                                          • At discharge, provide two prescriptions for epinephrine, education for the patient and family, and a medical alert bracelet for the patient to wear. 
                                                                          
                                                                          ]]>Welcome to the first episode of our podcast for current and aspiring intensivists. Our panel of medical professionals and students will examine specific patient cases, symptoms, and treatments. Today’s episode focuses on anaphylaxis. Join us!

                                                                          >>Click here to download the PICU card for this episode<<

                                                                          Show Highlights:

                                                                          • Our case: a four-year-old is admitted to PICU, and TPN has been administered.
                                                                          • Symptoms: dyspnea, wheezing, strider, and urticaria
                                                                          • Vitals: hypotensive, tachycardic, with stats dropping rapidly
                                                                          • What is anaphylaxis? An acute, life-threatening, systemic allergic reaction that can lead to death by airway obstruction or cardiovascular collapse.
                                                                          • Anaphylaxis symptoms include skin, mucosal, respiratory, cardiovascular, and gastrointestinal symptoms that develop within one hour of exposure to the allergen.
                                                                          • Anaphylaxis triggers can include allergens, biologics, immunotherapy, and radio-contrast media.
                                                                          • The anaphylaxis reaction ends with distributive shock, manifested by low cardiovascular output, low systemic vascular resistance, and high pulmonary vascular resistance.
                                                                          • Acute management of an anaphylaxis reaction includes airway, circulation, and breathing management, and epinephrine (the dosing is different from code dose).
                                                                          • Watch out for hypotension and lower airway obstruction as possible complications, which can be managed with fluids and nebulized albuterol.
                                                                          • Adjunctive therapies include histamine blockers and steroids.
                                                                          • Post-anaphylaxis care:
                                                                          • Focus on observation of the patient for 10-24 hours.
                                                                          • Watch for a biphasic reaction.
                                                                          • At discharge, provide two prescriptions for epinephrine, education for the patient and family, and a medical alert bracelet for the patient to wear. 
                                                                          
                                                                          ]]>07fa8d6b-355d-4783-9564-0a221c96ea03Mon, 08 Feb 2021 03:00:00 -040004:17falsefull11