In this episode, we discuss the case of a 15-year-old girl who presents with progressive headache, nausea, vomiting, and difficulty ambulating. Her condition rapidly evolves into altered mental status and severe hydrocephalus, leading to a compelling discussion about the evaluation, diagnosis, and management of hydrocephalus in pediatric patients.

We break down the case into key elements:

• A comprehensive look at acute hydrocephalus, including its pathophysiology and causes
• Epidemiological insights, clinical presentation, and diagnostic approaches
• Management strategies, including temporary and permanent CSF diversion techniques
• A review of complications related to shunts and endoscopic third ventriculostomy

• Patient Presentation:
• A 15-year-old girl with a 3-day history of worsening headaches, nausea, vomiting, and difficulty walking
• Altered mental status and bradycardia upon PICU admission
• CT scan revealed severe hydrocephalus without a clear mass lesion
• Management Steps in the PICU:
• Hypertonic saline bolus improved her mental status and pupillary reactions
• Neurosurgery consultation recommended MRI and close neuro checks
• Initial management included dexamethasone, keeping the patient NPO, and hourly neuro assessments
• Differential Diagnosis:
• Obstructive (non-communicating) vs. non-obstructive (communicating) hydrocephalus
• Consideration of alternative diagnoses like intracranial hemorrhage and idiopathic intracranial hypertension

• Hydrocephalus Overview:
• Abnormal CSF buildup in the ventricles leading to increased intracranial pressure (ICP)
• Key distinctions between obstructive and non-obstructive types

Epidemiology and Risk Factors:

• Congenital causes include genetic syndromes, neural tube defects, and Chiari malformations
• Acquired causes: post-hemorrhagic hydrocephalus (e.g., from IVH in preemies), infections like TB meningitis, and brain tumors

Clinical Presentation:

• Infants: Bulging fontanelles, sunsetting eyes, irritability
• Older children: Headaches, vomiting, papilledema, and gait disturbances

Management Framework:

• Temporary CSF diversion via external ventricular drains (EVD) or lumbar catheters
• Permanent interventions include VP shunts and endoscopic third ventriculostomy (ETV)

Complications of Shunts and ETV:

• Shunt infections, malfunctions, over-drainage, and migration
• ETV-specific risks, including delayed failure years post-procedure

Clinical Pearl:

• Communicating hydrocephalus involves symmetric ventricular enlargement and is often linked to inflammatory or post-treatment changes affecting CSF reabsorption.

Hosts’ Takeaway Points:

• Dr. Pradip Kamat emphasizes the importance of timely recognition and intervention in hydrocephalus to prevent complications like brain herniation.
• Dr. Rahul Damania highlights the need for meticulous neurological checks in PICU patients and an individualized approach to treatment.

• Hydrocephalus Clinical Research Network guidelines.
• Recent studies on ETV outcomes in pediatric populations.

If you enjoyed this discussion, please subscribe to PICU Doc On Call and leave a review. Have a topic you’d like us to cover? Reach out to us via email or on social media!

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• Twitter: @PICUDocOnCall
• Email: contact@picudoconcall.com

Stay tuned for more cases that challenge and inspire us as PICU clinicians!

Today, Dr. Rahul Damania, Dr. Pradip Kamat, and their guest,  Dr. Jordan Dent, discuss a critical case involving a 15-year-old male who collapsed during football practice due to exertional heat stroke. The discussion emphasizes the clinical presentation, risk factors, pathophysiology, and evidence-based management of heat stroke and other heat-related illnesses in pediatric patients. The episode also delves into the role of rapid cooling interventions and long-term care to minimize mortality and morbidity.

Case Summary: A 15-year-old male with ADHD collapsed during football practice on a hot, humid day. He presented with:

• Normotension (BP: 101/67 mmHg)
• Tachycardia (HR: 157 bpm)
• Tachypnea (RR: 40 breaths/min)
• Febrile (Rectal temp: 41.8°C/107.2°F)
• Dry, hot skin, GCS of 9
• Lab abnormalities: hyponatremia, hypokalemia, hypoglycemia, elevated creatinine, liver enzymes, lactate, CK, and troponin

After suffering cardiac arrest and undergoing resuscitation, the patient developed multiorgan dysfunction, including seizures, encephalopathy, and cerebral edema. Despite severe initial complications, the patient demonstrated neurological improvement with left-side hemiparesis before discharge.

Key Discussion Points:

1. Etiology and Pathophysiology of Heat Stroke:

• Heat stroke occurs when the body’s thermoregulatory mechanisms fail, leading to dangerous elevations in core body temperature. Exertional heat stroke is common during strenuous physical activity in hot, humid environments.
• Key physiological breakdowns include inadequate sweating, vasodilation dysfunction, and subsequent cellular damage due to hyperthermia.

1. Risk Factors for Exertional Heat Stroke:

• Environmental factors: High temperature, humidity, lack of hydration, and breaks.
• Athlete-related factors: Hypohidrosis, dehydration, medical conditions, and medications (e.g., Adderall).
• Heat illness is the third leading cause of death in high school athletics, with American football players particularly at risk.

1. Spectrum of Heat-Related Illness:

• Heat Cramps: Involuntary muscle contractions due to dehydration and electrolyte imbalance.
• Heat Syncope: Transient loss of consciousness due to heat exposure.
• Heat Exhaustion: Milder heat illness with core temperature < 104°F, potentially progressing to heat stroke if untreated.
• Heat Stroke: Life-threatening with core temperature ≥ 104°F, CNS dysfunction, and risk of multiorgan failure.

1. Management of Heat Stroke:

• Rapid Cooling: Immediate cooling to bring core temperature down to 39°C within 30 minutes is critical. Methods include ice packs, cold water immersion, and core cooling techniques (cold IV fluids, gastric lavage).
• Supportive Care: Management of shock, electrolyte imbalances, rhabdomyolysis, DIC, and ARDS.
• Monitoring and Long-Term Care: Continuous EEG, fluid management, and rehabilitation are key in managing neurological and systemic complications.

1. Differentiating Heat Stroke from Fever:

• Fever results from a reset of the hypothalamic setpoint due to pyrogens, while heat stroke involves the failure of thermoregulation without a change in the hypothalamic setpoint.

1. Case Outcome:

• The patient initially suffered significant neurological damage but improved with intensive care and rehabilitation. By discharge, the patient showed notable recovery, though with some lasting deficits.

Key Takeaways:

1. Heat stroke is a medical emergency with a high risk of mortality and long-term complications if not treated promptly.
2. Early recognition, rapid cooling, and a multidisciplinary approach are critical to improving outcomes.
3. Athletes and children engaging in strenuous activities in hot environments should be closely monitored for signs of heat-related illness.

References:

1. Fuhrman, B., & Zimmerman, J. J. (2020). Hyperthermic Injury. In Textbook of Pediatric Critical Care (pp. 1327-1331).
2. Rogers, M. C., et al. (2016). Thermoregulation. In Rogers' Textbook of Pediatric Intensive Care (pp. 546-552).
3. Ishimine, P. (2022). Heat Stroke in Children. UpToDate. Retrieved from www.uptodate.com/contents/heat-stroke-in-children.
4. Jardine, D. S. (2007). Heat Illness and Heat Stroke. Pediatrics in Review, 28(7), 249–258. https://doi.org/10.1542/pir.28-7-249.
5. Patel, J., et al. (2023). Critical illness aspects of heatstroke: A hot topic. Journal of Intensive Care Society, 24(2), 206-214. https://doi.org/10.1177/17511437221148922.
6. Ramirez, O., Malyshev, Y., & Sahni, S. (2018). It’s Getting Hot in Here: A Rare Case of Heat Stroke in a Young Male. Cureus, 10(12), e3724. https://doi.org/10.7759/cureus.3724.

Today’s case presentation involves a 2-year-old girl who was previously healthy and was admitted to the Pediatric Intensive Care Unit (PICU) for acute respiratory distress characterized by increased work of breathing and wheezing.

A 2-year-old girl with acute respiratory distress due to RSV infection

• Presented with increased work of breathing, wheezing, and no fever
• Started on High Flow Nasal Cannula (HFNC) therapy in the PICU

Key Elements:

• Prodrome of URI symptoms
• Increased respiratory effort (nasal flaring, intercostal retractions, decreased lung base air entry)
• HFNC improved the work of breathing and oxygen saturation

Washout of Nasopharyngeal Dead Space:

• HFNC clears nasopharyngeal dead space, improving oxygen efficiency.
• Reduces re-breathing of CO2 from the anatomical dead space.
• Enhances ventilation efficiency and oxygenation.

Reduction in Upper Airway Resistance:

• HFNC reduces resistance in the upper airway.
• Delivers rapid gas flow matching or exceeding natural inhalation rate.
• Eases breathing, especially in neonates and infants with narrow airways.

Optimal Conditioning of Gas:

• HFNC delivers heated and humidified oxygen, matching the body's conditions.
• Reduces energy expenditure and risk of airway irritation
• More comfortable and effective compared to cold, dry air delivery

• HFNC generates minimal and variable PEEP.
• Amount of PEEP depends on factors like flow rate and cannula size
• Not as high or consistent as other respiratory support devices

• A 2022 CHEST study by Khemani et al. on children with bronchiolitis challenged the conventional understanding of HFNC's mechanisms.
• HFNC primarily reduces breathing effort but does not consistently increase lung volume (EELV) or tidal volume (VT).
• Reduction in the pressure rate product (PRP) indicates decreased breathing effort, but not significant alterations in EELV or VT.

• HR, RR, and SpO2 are key indicators of HFNC efficacy.
• HR and RR should approach normal ranges for the child's age.
• Improvement in SpO2 levels while maintaining or reducing FiO2 indicates a positive response.

• HFNC is a valuable tool in pediatric care for alleviating respiratory distress.
• Not a one-size-fits-all solution; vigilant monitoring and reassessment are crucial
• Recognizing HFNC's mechanisms allows for optimized bedside application.

Closing Remarks:

• Subscribe, share feedback, and leave a review on the podcast.
• Visit picudoconcall.org for more episodes and management cards.
• Hosted by Dr. Pradip Kamat and Dr. Rahul Damania

Miller AG, Gentle MA, Tyler LM, Napolitano N. High-Flow Nasal Cannula in Pediatric Patients: A Survey of Clinical Practice. Respir Care 2018; 63:894.

Wraight TI, Ganu SS. High-flow nasal cannula use in a pediatric intensive care unit over 3 years. Crit Care Resusc 2015; 17:197.

Hutchings FA, Hilliard TN, Davis PJ. Heated humidified high-flow nasal cannula therapy in children. Arch Dis Child 2015; 100:571.

Lee JH, Rehder KJ, Williford L, et al. Use of high flow nasal cannula in critically ill infants, children, and adults: a critical review of the literature. Intensive Care Med 2013; 39:247.

Wing R, James C, Maranda LS, Armsby CC. Use of high-flow nasal cannula support in the emergency department reduces the need for intubation in pediatric acute respiratory insufficiency. Pediatr Emerg Care 2012; 28:1117.

Bressan S, Balzani M, Krauss B, et al. High-flow nasal cannula oxygen for bronchiolitis in a pediatric ward: a pilot study. Eur J Pediatr 2013; 172:1649.

Mayfield S, Bogossian F, O'Malley L, Schibler A. High-flow nasal cannula oxygen therapy for infants with bronchiolitis: pilot study. J Paediatr Child Health 2014; 50:373.

Kelly GS, Simon HK, Sturm JJ. High-flow nasal cannula use in children with respiratory distress in the emergency department: predicting the need for subsequent intubation. Pediatr Emerg Care 2013; 29:888.

Welcome to PICU Doc on Call, a podcast dedicated to current and aspiring intensivists. I'm Pradeep Kumar 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 medical education in the PICU.

Episode Overview: 

PICU.com call focuses on interesting PICU cases and management in the acute care Pediatric setting. In this episode, we discuss the case of an eight-year-old boy with chest pain, fatigue, and shortness of breath. This case presentation by Rahul highlights the complexity of pediatric care in the PICU.

Case Presentation: 

An eight-year-old boy with up-to-date immunizations and no recent travel or pet exposure presented to the PICU with chief complaints of chest pain, fatigue, and decreased oral intake. His history over the preceding two weeks included a diminishing appetite, episodes of vomiting, and shortness of breath.

On examination, he exhibited various cardiac findings, including a hyperdynamic left ventricle, murmurs, and a noted gallop. Abdominal and neurological findings were also concerning. Diagnostic studies revealed an enlarged heart, and sinus tachycardia with left ventricular hypertrophy, and echocardiography confirmed severe valvular and ventricular abnormalities.

Laboratory Findings:

Laboratory findings included elevated BNP, slightly elevated troponin, and elevated inflammatory markers (ESR and CRP). Strep throat culture was negative, but ASO and anti-DNAse B titers were markedly elevated. MRI confirmed multiple punctate infarctions, likely due to valvular heart disease.

Diagnosis: 

Given the complex multisystem presentation, the child was admitted to the PICU for intensive monitoring and comprehensive management of this multisystem pathology. The working diagnosis is rheumatic fever.

The episode is organized into three parts:

• Pathophysiology of Acute Rheumatic Fever
• Approach to Diagnosis and Investigations
• Management and Prevention

Pathophysiology of Acute Rheumatic Fever: 

Acute rheumatic fever is an autoimmune disease initiated by a response to group A strep infection, primarily due to molecular mimicry. The streptococcal M protein has structural similarities with host proteins, leading to organ damage, especially in the heart.

Epidemiology: 

Acute rheumatic fever is most prevalent in low to middle-income areas, affecting over 80% of cases. It mainly affects children between 5 to 14 years of age, and overcrowded households and limited healthcare access increase the risk. Globally, rheumatic heart disease affects millions of people annually and claims many lives.

Jones Criteria for Diagnosis: 

The Jones criteria help diagnose acute rheumatic fever. For a definitive diagnosis, evidence of a preceding group A strep infection is required. Major manifestations include carditis, arthritis, erythema marginatum, subcutaneous nodules, and Sydenham's chorea. Minor criteria include fever, elevated inflammatory markers, prolonged PR interval on EKG, and mild joint issues.

Differentiating Low and High-Risk Populations: 

The criteria differentiate between low and high-risk populations based on the epidemiology of acute rheumatic fever. The presentation of arthritis varies, and the thresholds for fever or inflammatory marker elevation are lower in high-risk populations.

Diagnostic Approach:

Diagnosis includes throat swab, anti-streptolysin O antibody titers, anti-DNAse B titers, CBC with differential, blood cultures, inflammatory markers, EKG, chest X-ray, and echocardiography. Joint analysis may be performed if needed.

Sydenham's Chorea:

Sydenham's chorea is marked by involuntary movements, primarily in the trunk and limbs, and it often resolves within 12 to 15 weeks with treatment.

Management of Acute Rheumatic Fever: 

Management includes eradicating the remaining strep infection, controlling inflammation, and preventing recurrence. Penicillin or amoxicillin is used to treat the infection, while aspirin or NSAIDs are used to manage inflammation. In severe cases, systemic steroids may be considered. Cardiac surgery should be delayed until acute inflammation resolves. Prophylactic antibiotics are used for prevention.

Conclusion: 

Rheumatic fever management requires a holistic approach, encompassing infection control, inflammation management, and long-term prevention. Early recognition, thorough diagnostics, and prophylactic antibiotics play essential roles in managing this condition.

Future Directions: 

Research is needed for early detection using biomarkers and the development of a group A strep vaccine.

Closing Remarks: 

As pediatric intensivists, we play a pivotal role in primary prevention by advocating for awareness and prompt treatment of group A strep infections.

Thank you for listening to PICU Doc on Call. Please subscribe, share your feedback, and visit our website at picudoconcall.org for more information. Stay tuned for our next episode.

Introduction: 

Welcome to "PQ Doc On Call," a podcast dedicated to current and aspiring intensivists. Hosted by Dr. Pradeep Kamar from Children's Healthcare of Atlanta, Emory University School of Medicine, and Dr. Rahul Damia from Cleveland Clinic Children's Hospital, both passionate PICU physicians.

You will hear:

This episode dives into the management of pediatric drowning cases in the PICU, providing valuable insights into assessment, pathophysiology, and practical management strategies.

Case Presentation: 

An 18-month-old girl was admitted to the PICU following a submersion incident in a residential pool. The child's initial unresponsiveness and subsequent clinical deterioration presented challenges for the PICU team, including respiratory distress, electrolyte imbalances, and potential neurological complications.

Key Elements from the Case:

• Severe acute respiratory failure following submersion
• Abnormal electrolytes (hyponatremia)
• Neurological insult requiring ongoing monitoring

Definitions and Terminology:

Clarification of drowning terminology, emphasizing uniform definitions and avoiding outdated terms like "near drowning." Key terms include primary vs. secondary drowning, saltwater vs. freshwater, intentional vs. non-intentional, and fatal vs. non-fatal drowning incidents.

Pathophysiology:

• Airway Reflexes: Initial reflex laryngospasm triggered by liquid penetration, followed by relaxation due to hypoxia, hypercarbia, and acidosis.
• Gas Exchange Compromise: Decreased functional residual capacity leading to impaired oxygen uptake and CO2 elimination.
• Pulmonary Complications: Pulmonary edema, surfactant washout, increased pulmonary vascular resistance, and shunting, impacting oxygen delivery.

Management Strategies:

• Out-of-Hospital: Aggressive on-site CPR and advanced life support are crucial for favorable outcomes. Swift control of hypoxia and acidosis is vital.
• In-PICU: Ventilation strategies resembling ARDS management (low tidal volume, low plateau pressures, high PEEP). Consider neurological exam, continuous EEG, and neuromuscular blockade if needed.
• Prognostic Factors: Duration of submersion, time to effective CPR, initial GCS, apnea persistence, pH levels, and neurologic status.

Prevention:

Empowering prevention through measures like fencing around pools, teaching children to swim, and vigilant adult supervision can significantly reduce the risk of pediatric drowning incidents.

Conclusion:

"PQ Doc On Call" underscores the importance of timely, effective CPR, swift management of hypoxia and acidosis, and vigilant neurological assessment in pediatric drowning cases. Prevention remains paramount in avoiding such incidents.

Stay tuned for more engaging episodes from PICU Doc On Call! Don't forget to subscribe, share your feedback, and review the podcast on your preferred platform. For more information and resources, visit picudoconcall.org.

In this episode of PICU Doc On Call, your hosts Pradip Kamat and Rahul Damania, experienced Pediatric ICU physicians, take you on an enlightening journey through the intricate landscape of lactic acidosis. Join us as we unravel the complexities, share clinical insights, and provide practical guidance on diagnosing and managing this critical condition in the acute care pediatric setting.

You will hear:

Case Presentation:

4-year-old boy with hypotension, fatigue, rash, and respiratory distress

Recent COVID-19 exposure, concerning respiratory symptoms

Hypotensive, tachycardic, tachypneic, low pulse oximetry reading

Swollen red lips, erythematous rash, hepatomegaly

High-flow nasal cannula, resuscitation, epinephrine infusion

Initial arterial blood gas: pH 7.22, lactate 4.5 mMol/L

Definition of Lactic Acidosis:

• Hyperlactatemia and lactic acidosis criteria
• Causes: impaired tissue oxygenation or mitochondrial dysfunction

Types of Lactic Acidosis:

• Type A: Impaired O2 delivery, shock-related
• Type B: Impaired O2 utilization, toxins, infections

Lactate Measurement:

• Comparability between POCT and central lab analysis
• Role of lactate measurement in pediatric sepsis

Lactic Washout:

• Rising lactate with re-established oxygen delivery
• Impaired clearance in microcirculation, liver, kidney
• Monitoring trends with clinical exams and lab surrogates

Bicarbonate Therapy:

• Role in Type A lactic acidosis
• Controversy, indications, and potential complications

Conclusion:

PICU Doc On Call podcast explores the intriguing case of a 4-year-old boy with lactic acidosis, highlighting the clinical intricacies of diagnosing and managing this condition. The hosts, Pradip Kamat and Rahul Damania provide insightful discussions on the different types of lactic acidosis, the physiological mechanisms behind it, and the role of bicarbonate therapy. The episode emphasizes the importance of addressing underlying causes and offers valuable clinical pearls for managing pediatric patients with lactic acidosis.

Stay tuned for more engaging episodes from PICU Doc On Call! Don't forget to subscribe, share your feedback, and review the podcast on your preferred platform. For more information and resources, visit picudoconcall.org.

In this episode of PICU Doc On Call, Dr. Pradip Kamat and Dr. Rahul Damania discuss a case of a 4-year-old girl with bite marks and swelling of her foot, presenting with concerning vital signs and abnormal labs. They explore snake envenomation and its management in the pediatric critical care setting.

Snakes with venom-delivering fangs, primarily Elapidae and Viperidae, are responsible for most human envenomations and fatalities. We're focusing on Pit Vipers today, including rattlesnakes, cottonmouths, and the copperhead. Elapids, such as the coral snake, differ by having round pupils, short fangs, and no facial pit.

Snakebite incidents can happen when toddlers unintentionally disturb snakes, particularly in low-light conditions or grassy areas. Teenagers trying to capture snakes are another frequent group presenting with upper extremity bites. 

Pathophysiology of Snake Envenomation

Snake venoms contain toxic proteins that affect various physiological systems, leading to neurotoxic, hemotoxic, myotoxic, or cytotoxic effects. Envenomation can happen immediately or be delayed, presenting with various clinical and laboratory anomalies.

The impact of a snakebite depends on the snake type, fang size, and venom injection site. Effects may include cytotoxicity, lymphatic system damage, platelet dysfunction, neurotoxicity, cardiotoxicity, hypotension, and nephrotoxicity.

In snakebite cases, prehospital care involves immediate EMS call and ensuring airway, breathing, and hemodynamic stability. In the hospital, general supportive care is crucial, and antivenin administration depends on clinical presentation and snake type.

Antivenin dosage is challenging due to unknown venom load, and its choice depends on safety, kinetics, cost, and the specific snake involved. Smaller fragments of antivenin have larger distribution volumes and shorter half-lives. Recurrence, anaphylaxis, and serum sickness are potential side effects of antivenin.

• A high index of suspicion is required to diagnose snake envenomation.
• Antivenin is the mainstay of therapy, and rapid transport to a facility with antivenin is crucial.
• Patients should be educated about recurrence, serum sickness, and lifestyle adjustments after a pit viper bite.

Thank you for listening to this episode on snake envenomation in the PICU. For more episodes, visit our website picudoconcall.org. Stay tuned for our next episode! Don't forget to share your feedback and subscribe to our podcast.

In this episode PICUDoc On Call, we discuss the case of a six-month-old ex-preemie with bacterial meningitis who presents with symptoms of cerebral sinus venous thrombosis. We explore the anatomy of the venous distribution in the brain and the clinical syndromes associated with sinus venous thrombosis. Our focus is on the imaging techniques, laboratory tests, and management strategies involved in diagnosing and treating this challenging condition.

You will learn:

• A six-month-old ex-preemie presents with persistent fever, recurrent emesis, and increased somnolence.
• The patient experiences eye rolling and decreased oxygen saturation, prompting a visit to the emergency department.
• Physical examination reveals rigidity in all four limbs, and a head CT shows dilated ventricles and encephalomalacia.
• Lumbar puncture confirms an infection, and the patient is admitted to the hospital.
• After a 14-day course of antibiotics, the patient's clinical status worsens, leading to intubation and neurosurgery consultation.
• An MRI confirms cerebral venous sinus thrombosis.

Anatomy of Venous Distribution in the Brain:

• Dural venous sinuses serve as conduits for venous blood return from the brain to the internal jugular veins.
• The superior sagittal sinus, cortical veins, transverse sinus, sigmoid sinus, and internal jugular vein are key components of the venous drainage system.

Clinical Syndromes of Sinus Venous Thrombosis:

• Symptoms can be related to elevated intracranial pressure or focal brain damage from venous ischemia, infarction, or hemorrhage.
• Headache, seizures, focal neurologic deficits, and cranial nerve paralysis are common presentations.
• Cavernous sinus thrombosis can cause periorbital pain, ocular chemos, and paralysis of cranial nerves passing through the sinus.

Risk Factors for Cerebral Sinus Venous Thrombosis:

• Dehydration, CNS or sinus infections, intracranial surgery, autoimmune disorders, genetic syndromes, metabolic syndromes, medications, and genetic thrombophilic states can predispose children to thrombosis.
• Thorough evaluation for risk factors, including thrombophilia, is recommended in children with cerebral venous thrombosis.

Imaging and Laboratory Tests:

• CT and MRI with contrast-enhanced venography are preferred imaging tools to detect cerebral sinus venous thrombosis.
• Non-enhanced CT scans and T1/T2-weighted MRI scans show characteristic signs of thrombosis.
• Lab tests include CBC with differential, DIC panel, comprehensive metabolic panel, ESR, and specific thrombophilia tests.

Management Strategies:

• Supportive care, including airway management, hemodynamics, and neurologic monitoring, is crucial.
• Consultation with a multidisciplinary team (neurosurgeons, neuro-interventional radiologists, hematologists, etc.) is necessary.
• Anticoagulation therapy with heparin is initiated and closely monitored.
• Surgical interventions (e.g., EVD placement, ventricular peritoneal shunt, decompressive hemicraniectomy) may be required in severe cases.
• Long-term rehabilitation may be necessary for neurological deficits.

In summary:

Cerebral sinus venous thrombosis in pediatric patients requires a multidisciplinary approach for prompt diagnosis and management. Recognizing the clinical signs, conducting appropriate imaging and laboratory tests, and initiating timely interventions are crucial for improved outcomes.

Welcome to PICU Doc on Call, a podcast dedicated to intense wisdom in the field of pediatric critical care. In this episode, hosts Pradeep Kama and Rahul Damania, both pediatric ICU physicians, discuss the case of a five-year-old male who presents to the emergency department with unexplained fatigue and fever. The patient's symptoms include fatigue, intermittent fevers, tachycardia, and significantly low hemoglobin levels.

The hosts delve into the possible causes of the patient's condition, considering a blood cell disorder and the potential for severe anemia due to aplastic crisis. They explain the physiological adaptations that occur in severe acute anemia, including the shifting of the oxyhemoglobin curve to the right and the increase in cardiac output through tachycardia and increased stroke volume.

The podcast episode also covers different forms of hemolytic anemia, including extravascular and intravascular hemolysis, autoimmune hemolytic anemia, and paroxysmal nocturnal hemoglobinuria. The hosts discuss the workup for hemolytic anemias, such as complete blood count, peripheral smear, LDH levels, haptoglobin levels, and Coombs tests. They emphasize the importance of involving hematology and infectious disease specialists for accurate diagnosis and management.

The case of the five-year-old with hereditary spherocytosis is explored, highlighting the characteristic spherocytic shape of red blood cells and potential complications like hemolytic crisis, splenic sequestration, and aplastic crisis. The hosts provide insights into the pathophysiology and presentations of these complications, emphasizing the need for prompt recognition and appropriate interventions.

In summary, this episode of PICU Doc on Call provides valuable information on the evaluation and management of a pediatric patient with fatigue, fever, and anemia, shedding light on different forms of hemolytic anemias and their associated complications.

Welcome to "PICU Doc On Call," a podcast dedicated to current and aspiring intensivists. In this episode, Dr. Pradip Kamat and Dr. Rahul Damania discuss an interesting case of a 16-year-old male with high-grade fever and abdominal pain. The patient also presents with a rash and other concerning symptoms, leading to urgent medical attention. They provide a summary of the key elements from the case, including vital signs, physical examination findings, and laboratory and imaging results.

Dr. Kamat then shares his thought process regarding the working diagnosis for this patient, considering several possibilities such as severe bacterial infection, atypical appendicitis or cholecystitis, toxic shock syndrome, and systemic inflammatory processes like Multisystem Inflammatory Syndrome in Children (MIS-C) and atypical Kawasaki disease.

Moving on to the topic of vasopressors, Dr. Damania explains the importance of understanding how these medications work and their specific pharmacological properties. They discuss the classification of shock as cold or warm and the limitations of relying solely on clinical signs to categorize septic shock in children.

They highlight the challenges in selecting the appropriate vasopressor, such as a lack of standardization in clinical examination and individual variability in response to medications. They emphasize the need for a comprehensive approach when evaluating and managing pediatric shock patients, considering multiple factors beyond traditional bedside signs.

The hosts then engage in a rapid review of pressors, starting with a multiple-choice question regarding the choice of vasoactive infusion for a patient with toxic shock syndrome. They discuss the pros and cons of using norepinephrine (NE) in distributive shock and highlight its vasoconstrictive effects, inotropic activity, and potential side effects.

They proceed to compare NE with epinephrine, explaining the differences in their actions on adrenergic receptors and their effects on various circulations. They mention that epinephrine acts on all adrenergic receptors and has hemodynamic and metabolic effects, redirecting cardiac output and increasing myocardial oxygen demand.

Lastly, the hosts touch on phenylephrine, a vasopressor that acts on the alpha-1 receptor and elevates systemic vascular resistance (SVR) and pulmonary vascular resistance (PVR). They stress the importance of securing central line access when administering vasopressors to avoid harm to peripheral and systemic tissues.

In conclusion, this episode provides valuable insights into the diagnosis and management of a complex pediatric case involving high-grade fever, abdominal pain, and shock. The hosts also offer a rapid review of common vasopressors, highlighting their mechanisms of action, pros, and cons.

Today’s episode of "PICU Doc On Call," with Dr. Pradip Kamat and Dr. Rahul Damania, pediatric ICU physicians, delves into intriguing case and management strategies within the acute care pediatric setting.

This episode focuses on a 2-year-old child transferred to the PICU due to pneumonia-induced respiratory distress. As the child's condition deteriorates, intubation becomes necessary to address acute hypoxemic respiratory failure.

We discuss the significance of minimizing unnecessary blood cultures in febrile patients with central lines in the PICU. A study implementing a quality improvement program is referenced, which successfully reduces blood culture rates, broad-spectrum antibiotic usage, and CLABSI rates without impacting mortality or length of stay.

Next, we’ll explore the comparison between a high-flow nasal cannula (HFNC) and continuous positive airway pressure (CPAP) in pediatric patients experiencing respiratory distress. Findings from a randomized controlled trial revealed that HFNC is non-inferior to CPAP in terms of time required for liberation from respiratory support.

We further investigate the application of pediatric early warning scores (PEWS) and automated clinical prediction models to identify patients at risk of deterioration and transfer to the PICU. The importance of employing clinical judgment and a combination of assessment tools to determine the need for transfer is emphasized.

Lastly, we’ll highlight the significance of screening for social determinants of health in critically ill children and their families. A study demonstrates that a substantial number of participants had unmet social needs, underscoring the importance of screening to provide appropriate interventions and resources.

To summarize, this podcast episode covers key topics such as reducing unnecessary blood cultures, comparing HFNC and CPAP in respiratory distress, utilizing PEWS and clinical prediction models for patient identification, and the importance of screening for social determinants of health.

Be sure to listen in entirety as we discuss the case.

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.

Today, we are going to discuss the management of the postoperative patient admitted to the PICU. Our discussion will focus on the non-cardiac and non-transplant admission. Our objective in this episode is to create a framework on what areas of care to focus on when you have a patient admitted to the PICU post-operatively. Each surgery and patient is unique; however, we hope that you will garner a few pearls in this discussion so you can be proactive.

in your management. Without any further delay, let’s get started with today’s case:

We begin with a 13-year-old child, Alexa, with h/o of a genetic syndrome, who presents today with a history of thoracolumbar kyphoscoliosis. Over the years, Alexa's curvature has progressively worsened, resulting in difficulty breathing and chronic back pain. The decision was made to proceed with a complex spinal surgery, including posterior spinal fusion and instrumentation.

In the weeks leading up to the surgery, Alexa underwent a thorough preoperative evaluation, including consultations with specialists and relevant imaging studies. Pulmonary function tests revealed a restrictive lung pattern, while the echocardiogram showed no significant cardiac abnormalities. Preoperative labs, including CBC, electrolytes, and coagulation profile, were within normal limits.

During the surgery, Alexa was closely monitored by the anesthesia team, who administered general anesthesia with endotracheal intubation. The surgery was performed by the pediatric neurosurgery and orthopedics, with intra-operative neuromonitoring to assess spinal cord function. The surgical team encountered an unexpected dural tear, which was repaired using sutures and a dural graft. Due to the prolonged surgical time, a temporary intra-operative loss of somatosensory evoked potentials was noted. However, signals were restored after adjusting the patient's position and optimizing blood pressure. The posterior spinal fusion and instrumentation were completed successfully, but the surgery lasted 8 hours. Total intra-operative blood loss was 800 mL, and Alex received 2 units of packed red blood cells and was on NE for a little over half the case before weaning off.

Alexa was admitted to the PICU intubated and sedated for postoperative care. The initial assessment showed stable vital signs, with a systolic blood pressure of 100 mmHg, heart rate of 90 bpm, and oxygen saturation of 99% on mechanical ventilation. Postoperative pain was managed with a continuous morphine infusion. The surgical team placed a closed suction drain near the surgical site and a Foley catheter for urinary output monitoring. You are now at the bedside for OR to PICU handoff…

To summarize key components from this case:

This is a patient with thoracolumbar kyphoscoliosis, underwent complex spinal surgery (posterior spinal fusion and instrumentation) due to progressive curvature, breathing difficulties, and chronic pain.

She had a course intra-operatively, where an unexpected dural tear occurred, requiring repair with sutures and a dural graft. Temporary loss of somatosensory evoked potentials was resolved through patient repositioning and blood pressure optimization with NE.

She had a moderate amount of blood loss in the case and is back intubated, sedated, with surgical drains in place.

So Pradip, we see patients such as Alex in our PICU commonly, if we take a step back what is your general approach with children who are admitted to the PICU post operatively?

I think it's crucial to approach the care of postoperative children in the PICU systematically and proactively. This involves closely monitoring their changing physiology, anticipating potential complications, and collaborating with the surgical team to address any concerns. By maintaining open communication and following evidence-based guidelines, we can optimize patient outcomes and facilitate a smooth recovery process.

💡

Just as a quick tid-bit, while some of these PICU admissions are scheduled, there is literature to suggest that up to 24% of non-cardiac surgeries may result in unanticipated admissions to the PICU. An single center study published in 2017 in PCCM looked at their rates of unanticipated PICU admissions from the OR, and they found that these children spend twice as much time on mechanical ventilation and that airway abnormalities, anesthetic factors, and intra-operative hypoxia contribute to such admissions.

Alright, Pradip, we are now at the post operative handoff and the first person who is going to be giving report is the anesthesia team. Can you please highlight what are some key things to listen out for during their sign out and what are some questions to ask?

Great question! The anesthesiologist plays a crucial role in ensuring the patient's airway and hemodynamics are properly managed during surgery, which is essential for a safe and successful procedure. It's important for the anesthesiologist to communicate with the PICU team regarding: induction, intraoperative course, line & tubes, as well as pain management.

Let’s break these down:

So for induction, you want to know were the anesthetics administered through IV or general anesthesia, was it a smooth process or were there difficulties, and what was used for anesthesia maintenance.

Next you want to know about the airway.

You want to gather essential information about the patient's airway management. Find out if an LMA or ETT was used during the procedure. If the patient was intubated, inquire about the ease of bag-mask ventilation and laryngoscopy, as well as the grade of the glottic view (e.g., Grade 1) and the type of laryngoscope used, including if video laryngoscopy was employed. It's also important to know the number of intubation attempts. Additionally, gather details about the type of ETT (regular or neo-cuff), its size, and the length at which it is taped to the gum or teeth. Finally, ask if any airway adjuncts were utilized during bag-mask ventilation or intubation.

🚨

Remember that a key management point as soon as handout is completed is to obtain a CXR to confirm tube placement, and work closely with your RT to secure the tube in the correct position.

That’s so true!

As you wrap up anesthesia sign out, here are some other things to think about:

Oxygenation/Ventilation: Determine if the patient was easily oxygenated and ventilated, or if any bronchospasm or laryngospasm occurred during the case.

Lines & Tubes: Inquire about IV or central access, arterial line usage, and the presence of any drains or tubes (e.g., NG, Foley).

I/Os: Understand the management of fluid, electrolyte, and glucose homeostasis during anesthetic care, including the types and rates of fluids administered, blood product usage, and estimated blood loss.

Pain Management: Gather information on the analgesics, sedatives, and neuromuscular blockers used.

Other Medications: Be aware of antibiotics, antiemetics, anticholinergics, and other medications administered during the procedure.

Duration of the Case & Patient Position: Obtain information on the duration of the surgery and the patient's position (e.g., supine or prone, as in spinal cases).

Latest Set of Vital Signs: Ensure you have the most recent vital signs recorded.

⚖️

A nice mnemonic that I use is:

A - Airway: LMA/ETT, ease of ventilation, glottic view, laryngoscope type

P - Pain Management: Analgesics,...

Welcome to PICU Doc On Call, a podcast dedicated to current and aspiring pediatric intensivists. I'm Dr. Pradip Kamat from Children’s Healthcare of Atlanta/Emory University School of Medicine, and I’m Dr. Rahul Damania from Cleveland Clinic Children’s Hospital. We are two Pediatric ICU physicians passionate about medical education in the PICU. This podcast focuses on interesting PICU cases and their management in the acute care pediatric setting.

In today’s episode, we are excited to welcome Dr. Karen Zimowski, Assistant Professor of Pediatrics at Emory University School of Medicine and a practicing pediatric hematologist at Children’s Healthcare of Atlanta at the Aflac Blood & Cancer Center. Dr. Zimowski specializes in pediatric bleeding and clotting disorders.

A 16-year-old female with a complex medical history, including autoimmune thyroiditis and prior cerebral infarcts, was admitted to the PICU with acute chest pain and difficulty breathing. Despite being on low-dose aspirin, her oxygen saturation was 86% on room air. A CT angiography revealed a pulmonary embolism (PE) in the left lower lobe and signs of right heart strain. The patient was hemodynamically stable, and thrombolytic therapy was deferred in favor of anticoagulation. She was placed on BiPAP to improve her respiratory status. Her social history was negative for smoking, illicit drug use, or oral contraceptive use.

• Diagnosis: Pulmonary embolism (PE)
• Hemodynamics: Stable with no right ventricular (RV) strain on echocardiogram
• Management Focus: Anticoagulation and consultation with the hematology/thrombosis team

• Pathophysiology: Venous thromboembolism (VTE) in children involves components of Virchow’s triad: stasis of blood flow, endothelial injury, and hypercoagulability.
• Incidence: VTE is rare in the general pediatric population but increases significantly in hospitalized children.
• Age Distribution: Bimodal peaks in infants and adolescents aged 15-17 years.
• Risk Factors: Central venous lines, infections, congenital heart disease, cancer, and autoimmune disorders.

• Symptoms: Swelling, pain, warmth, and skin discoloration in the affected extremity.
• Specific Presentations:
• SVC syndrome from superior vena cava thrombosis
• Abdominal pain from portal vein thrombosis
• Hematuria from renal vein thrombosis
• Neurological symptoms from cerebral sinus venous thrombosis

• Imaging:
• Compression Doppler Ultrasonography: Primary method for diagnosing DVT in pediatric patients.
• MR Venography (MRV) and CT Venography (CTV): Used for abdominal and cerebral sinus thrombosis.
• Laboratory Studies:
• D-dimer: Useful in adults; limited specificity in children.
• Other Labs: Renal and liver function tests, CBC with differential, DIC panel.

• Unfractionated Heparin (UFH):
• Targets factors IIa and Xa; requires frequent monitoring.
• Adverse events: Bleeding and thrombocytopenia.
• Low Molecular Weight Heparin (LMWH):
• More predictable pharmacokinetics than UFH.
• Advantages include ease of administration and lower risk of HIT.
• Vitamin K Antagonists (VKAs):
• Used for long-term anticoagulation.
• Requires regular INR monitoring.
• Direct Oral Anticoagulants (DOACs):
• Dabigatran, Rivaroxaban, and Apixaban used in pediatric VTE.
• Advantages: No routine monitoring required, predictable effects.

In this episode, we discussed the intricacies of VTE diagnosis and management in pediatric patients. We thank Dr. Karen Zimowski for sharing her expertise on anticoagulation and hemostasis in the PICU. For more episodes and our Doc on Call management cards, visit picudoconcall.org.

Stay tuned for our next episode, and thank you for listening!

1. Fuhrman & Zimmerman - Textbook of Pediatric Critical Care: Thrombosis in Pediatric Critical Care.
2. American Society of Hematology 2018 Guidelines for Management of Venous Thromboembolism: Treatment of Pediatric Venous Thromboembolism.
3. Antithrombotic Therapy in Neonates and Children: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines.
4. O’Brien, SH, Stanek JR, Witmer CM, Raffini L. The Continued Rise of Venous Thromboembolism Across US Children’s Hospitals. Pediatrics (2022).

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.

Here's the case of a 12-week-old girl old who is limp and seizing presented by Rahul.

• Chief Complaint: A 12-week-old previously healthy female infant was found limp in her crib and developed generalized tonic-clonic seizures on the way to the hospital.
• History of Present Illness: The mother returned from work on a Saturday to find her daughter unresponsive in her crib. The infant had been left in the care of her mother's boyfriend, who stated that the daughter had been sleeping all day and had a small spit up. As the patient continued to have low appetite throughout the day and continued to be unresponsive in her crib, mother called EMS to bring her to the emergency department. En route, the patient had tonic movement that did not resolve with intranasal benzodiazepines.
• ED Course: The infant presents to the ED being masked. Upon arrival at the ED, the infant was in respiratory distress, with a heart rate of 190 beats per minute, respiratory rate of 50 breaths per minute, and oxygen saturation of 85% with bagging. She was intubated for seizure control upon arrival at the ED. Physical examination in the ED revealed bruising on the right neck region but was otherwise unremarkable. A non-contrast head CT showed no acute intracranial abnormalities. The initial diagnostic workup revealed normal CBC, mildly elevated hepatic enzymes, and pancreatic enzymes which were within normal limits. The blood gas showed metabolic acidemia with PCO2 in the 60s.
• Admission to PICU: Upon admission to the PICU, neurosurgery and trauma teams were consulted. A skeletal survey and ophthalmology consult for a fundoscopic examination were ordered, as there were concerns of non-accidental trauma. Further investigation is underway to determine the cause of the infant's condition.

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

• Patient left with mother's boyfriend
• Infant found limp and had seizures requiring intubation
• Neck bruise
• All of these bring up a concern for Non-Accidental Trauma (NAT) the topic of our discussion.

Let's start with a short multiple-choice question:

Which imaging modality is the most appropriate for establishing a diagnosis of abusive head trauma (AHT) in a 12-week-old infant with an open fontanelle on the exam?

• A. CT scan of the brain without contrast B. MRI of the brain without contrast C. Skull X-ray D. Doppler ultrasound of the head

Rahul, the correct answer is A.

Though ultrasound may be less invasive, the penumbra effect in cranial ultrasound makes it hard to visualize the parts of the brain located just under the convexity of the skull such as a subdural hematoma. Regardless of the small radiation risk, noncontrast head CT is the method of first choice in imaging traumatic brain injury for both fractures and intracranial pathology. CT scan has a short scan time and is widely available. Non-contrast-enhanced CT has a high sensitivity for detecting acute hemorrhage and midline shift.

Thanks for that detailed explanation, I agree CT scan is a valuable diagnostic tool that provides detailed recon images for understanding the mechanism of fractures.

What about the role of MRI in diagnosing abusive head trauma?

• MRI has lower sensitivity for acute hemorrhage compared to a CT scan and takes longer to acquire images, which may require anesthesia to provide immobility. However, a systematic review by Kemp and colleagues published in 2009 (Clin Radiol. 2009;64:473–483) reported that MRI performed following an abnormal CT scan in children with abusive head trauma revealed new information in at least 25% of cases, such as cranial shearing, ischemia, infarction, parenchymal hemorrhages, and cerebral contusions. It's important to note that the role of MRI in cases where the initial CT scan is normal is unclear. Additionally, MRI is more accurate in evaluating time points in certain lesions, making it a valuable tool in the diagnosis and management of abusive head trauma in pediatric patients.

💡 In summary, a CT scan is the preferred imaging modality for assessing traumatic brain injury in cases of suspected abusive head trauma, while cranial ultrasonography may be useful in some cases. It's important to remember that interpretation of imaging in cases of suspected AHT requires complete clinical information.

Alright, Pradip, very interesting that our initial CT scan did not show any signs of bleeding, once the patient became more stable in the PICU, what did the skeletal survey show?

• The skeletal survey showed multiple fractures of varying ages, including multiple rib fractures, and an unhealed clavicle fracture. The team closely monitored the infant's condition and initiated treatment as necessary.

Rahul, can you give us a brief introduction to non-accidental trauma in the pediatric ICU?

• Child abuse, also known as battered child syndrome, can take multiple forms such as physical abuse, sexual abuse, neglect, psychological maltreatment, general neglect, and medical neglect. Today, we'll focus on physical abuse that intensivists may encounter in their practice.
• In the Pediatric Intensive Care Unit (PICU), the team is more likely to see cases of abusive head trauma, abdominal trauma, burns, complex fractures, and rib fractures, which may be identified when a chest radiograph is obtained after intubation. These are serious and often life-threatening conditions that require a multidisciplinary team approach and specialized care.

💡 To summarize, physical abuse in children, particularly infants, can present with nonspecific symptoms and signs, such as vomiting or apnea. This highlights the importance of considering the possibility of abusive head trauma in such cases.

Please also remember that the term, abusive head trauma replaced "shaken baby syndrome," and it's a serious and often life-threatening condition that requires prompt recognition and intervention. Therefore, it's essential for us as intensivists to be familiar with the various forms of physical abuse, including abusive head trauma, and work closely with other specialists to ensure that the patient receives the best possible care.

Pradip, let’s dive deep into abusive head trauma, do you mind talking about the spectrum of symptoms we can see?

Abusive head trauma is the most common presentation of child abuse in the PICU: As seen in our case presentation infants may present with apnea, altered mental status, loss of consciousness, limpness, vomiting, seizure, poor feeding, or have subtle signs like swelling of the scalp.

In a third of abusive head trauma cases, the infant was seen by another physician in the preceding 2-3 weeks. The diagnosis requires a high level of suspicion especially in an infant with fractures, ecchymosis, and failure to gain weight. AHT is the leading cause of fatal injuries in children.

📖 AHT is responsible for 53% of all severe TBI cases in infants.

What is the pathophysiology of injury in abusive head trauma?

The pathophysiology of abusive head trauma in infants is complex and multifactorial. The skull of a neonate is soft and malleable, which allows forces applied to the skull to propagate directly to the brain tissue. Additionally, the higher water content and lack of myelination make the brain more susceptible to shearing forces, which occur with shaking. Infants have a larger head in...

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 14-year-old male who collapsed on the baseball field.

Here’s the case presented by Rahul:

A 14-year-old male athlete was playing in a high school baseball tournament when he was hit in the chest with a pitched ball. The impact caused him to collapse on the field. Bystander CPR was begun given his unresponsiveness and emergency medical services were immediately called. The patient was transported to the hospital. Upon arrival, he was unresponsive and had no pulse. An electrocardiogram (ECG) showed ventricular fibrillation, and advanced cardiac life support was initiated. After several shocks and cardiac compressions, the patient regained a pulse and was transferred to the pediatric intensive care unit for further evaluation and management.

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

• Been struck by a high-velocity object in the chest
• Suffered a cardiac arrest, likely due to an arrhythmia from the blunt chest trauma

The presentation brings up a concern for Commotio Cordis, our topic of discussion today!

We wanted to create this educational episode in light of the recent medical event experienced by the Buffalo Bill’s safety Damar Hamlin. His blunt chest trauma, which led to cardiac arrest, has been postulated to be due to commotio cordis. At the date of this record, we are glad that Damar Hamlin is on the road to recovery.

Absolutely, let’s dive in more into this topic, Let's start with a short multiple-choice question:

The 14-year-old described in our case suffered cardiac arrest after blunt chest trauma. Based on the working diagnosis of comottio cordis, what is the most likely EKG finding which may be seen in this patient?

A. Ventricular fibrillation

B. Ventricular tachycardia

C. Complete heart block

D. Asystole

The correct answer is A. In a study published in JAMA (2002; 287(9):1142-1146) which used data from the US Commotio Cordis registry maintained by the Minneapolis Heart Institute Foundation, reported that the most common arrhythmia out of the 128 confirmed cases, 82 of which had EKGs which could be analyzed was ventricular fibrillation. Three patients had Vtach, 3 had Bradyarrhythmia and 1 had complete heart block. Although 40 patients had asystole, this was unlikely to be the initial rhythm after impact. Interestingly, the majority of these rhythms were recorded at the scene.

Rahul, What is the definition of Commotio Cordis?

Commotio cordis is Latin for "commotion of the heart." It refers to a type of sudden cardiac arrest that occurs when a blunt impact to the chest disrupts the normal electrical activity of the heart and causes ventricular fibrillation. It is a primary arrhythmic event that occurs when the mechanical energy generated by a blow is confined to a small area of the precordium and profoundly alters the electrical stability of the myocardium, resulting in ventricular fibrillation. (NEJM Marron BJ et al. N Engl J Med 2010; 362:917-927)

So Pradip, the case we have involves an athlete, do you mind talking a bit about the demographics and epidemiology of this condition?

Absolutely! As you mentioned, Commotio cordis is Latin for agitation of the heart. Interestingly, it is the 3rd most common cause of sudden death in athletes after hypertrophic cardiomyopathy and congenital coronary-artery anomalies. Commotio cordis shows a predilection for children and adolescents with 26% of victims being younger than 10 years of age, & a minority of patients 25 years of age or older. It has a predilection for males, up to 95% in some reports. Commotio cordis can result from blows to the chest from projectiles (predominantly baseballs, softballs, lacrosse balls, or hockey pucks) or blunt bodily contact with other athletes, especially in children < 15 years of age group.

In summary, here are some patients at risk:

• Male gender
• Young age (typically between 5 and 25 years old)
• Participation in high-impact sports such as baseball, ice hockey, and lacrosse.
• Chest wall size and anatomy

Heart rate and rhythm at the time of impact.

It is important to note that commotio cordis can occur in anyone who sustains a sudden blow to the chest, regardless of age or level of physical fitness.

Rahul, what is the pathophysiology of Commotio Cordis?

The ventricular fibrillation seen after the mechanical energy of the blow is delivered to the chest has been shown to have certain determinants and triggers from animal studies.

Important determinants include:

 1. Location of the blow must be directly over the heart (near the center of the cardiac silhouette);

 2. Timing of the blow, which must occur within a narrow window of 10 to 20 msec on the upstroke of the T wave, just before its peak. That is an electrically vulnerable period, when inhomogeneous dispersion of repolarization is greatest, creating a susceptible myocardial substrate for provoked ventricular fibrillation.

Contributing variables include greater hardness of the projectile, small sphere, direct orientation, and thinner more compliant chest wall (with immature intercostal musculature).

At a molecular level: It is possible that ventricular depolarization induced by a blow to the chest in commotio cordis, has something in common with the pathophysiological mechanisms that give rise to primary arrhythmogenic conditions, such as ion channelopathies. The increased pressure in the ventricle after the impact, causes the cell membranes to stretch and activates ion channels. The candidate ion channels include the ATP-sensitive potassium channel, which contributes to the initiation of ventricular fibrillation in commotio cordis.

The incidence of Commotio Cordis in adults is low even in sports like kickboxing and boxing. A probable explanation for this may be that their mature and fully developed chest cage may be protective.

Pradip, if a child collapses during sports, what should be the approach of the bystanders prior to the arrival of the paramedics?

Early recognition of cardiac arrest is important. Sudden collapse with unresponsiveness, or no breathing or agonal breathing and no pulse, is cardiac arrest unless proven otherwise. 

Immediate high-quality chest compressions should be initiated without interruptions while 911 call is initiated. If an AED is available, then the pads need to be applied to the chest without delay.

Another common scenario is that the child starts to seize after the collapse. This should not be erroneously blamed on a seizure disorder but could be most likely due to brain hypoxia from cardiac arrest.

Rahul, after the initial resuscitation, what are some of the investigations which should be considered?

Early consultation with the cardiologist and electro-physiologist is necessary. Electrocardiography, echocardiography, stress testing, ambulatory ECG monitoring, and cardiac MRI must be considered provided the patient is stable for transport. Electrocardiographic features suggestive of long QT and Brugada syndrome should be pursued if appropriate. Other tests include- CBC, CMP, cardiac...

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...

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...

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...

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...

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,...

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...

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,

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...

Welcome to PICU Doc On Call, where Dr. Pradip Kamat from Children’s Healthcare of Atlanta/Emory University School of Medicine and Dr. Rahul Damania from Cleveland Clinic Children’s Hospital delve into the intricacies of Pediatric Intensive Care Medicine. In this special episode of PICU Doc on Call shorts, we dissect the Alveolar Gas Equation—a fundamental concept in respiratory physiology with significant clinical relevance.

Key Concepts Covered:

• Alveolar Gas Equation Demystified: Dr. Rahul explains the Alveolar Gas Equation, which calculates the partial pressure of oxygen in the alveoli (PAO2). This equation, PAO2 = FiO2 (Patm - PH2O) - (PaCO2/R), is essential in understanding hypoxemia and the dynamics of gas exchange in the lungs.
• Calculating PAO2: Using the Alveolar Gas Equation, the hosts demonstrate how to calculate PAO2 at sea level, emphasizing the influence of atmospheric pressure, fraction of inspired oxygen (FiO2), water vapor pressure, arterial carbon dioxide pressure (PaCO2), and respiratory quotient (R) on oxygenation.
• A-a Gradient and Hypoxemia: The A-a gradient, derived from the Alveolar Gas Equation, is discussed in the context of hypoxemia evaluation. Understanding the causes of hypoxemia, including ventilation/perfusion (V/Q) mismatch, anatomical shunt, diffusion defects, and hypoventilation, is crucial for clinical diagnosis and management.
• Clinical Scenarios and A-a Gradient Interpretation: Through a clinical scenario, the hosts elucidate how different conditions affect the A-a gradient and oxygenation, providing insights into respiratory pathophysiology and differential diagnosis.
• Clinical Implications and Management Strategies: The hosts highlight the clinical significance of the Alveolar Gas Equation in assessing oxygenation status, diagnosing gas exchange abnormalities, and tailoring respiratory management strategies in the pediatric intensive care setting.

Key Takeaways:

• Utility of the Alveolar Gas Equation: Understanding and applying the Alveolar Gas Equation is essential for evaluating oxygenation and diagnosing respiratory abnormalities.
• Interpreting A-a Gradient: A normal A-a gradient suggests alveolar hypoventilation as the likely cause of hypoxemia, whereas elevated gradients indicate other underlying pathologies.
• Clinical Relevance: Recognizing the clinical implications of the Alveolar Gas Equation aids in accurate diagnosis and optimal management of respiratory conditions in pediatric intensive care patients.

Conclusion:

Join Dr. Kamat and Dr. Damania as they unravel the complexities of the Alveolar Gas Equation, providing valuable insights into respiratory physiology and its clinical applications. Don’t forget to subscribe, share your feedback, and visit picudoconcall.org for more educational content and resources.

References:

• Fuhrman & Zimmerman - Textbook of Pediatric Critical Care Chapter: Physiology of the respiratory system. Chapter 42. Khemani et al. Pages 470-481
• Rogers textbook of Pediatric intensive care: Chapter 44. Respiratory physiology. Akong K et al. Pages 691-721
• Respiratory Physiology for the Anesthesiologist. Bigatello L and Pesenti A, Anesthesiology 2019; 130: 1064-77

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....

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...

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...

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,...

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...

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...

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...

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...

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

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.

• Hosts:
• Dr. Pradip Kamat: Children’s Healthcare of Atlanta/Emory University School of Medicine
• Dr. Rahul Damania: Cleveland Clinic Children’s Hospital

Introduction:

• Pediatric Intensive Care Unit (PICU) physicians passionate about medical education in the acute care pediatric setting
• Episode focus: A case of a 23-month-old ex-28 week premie presenting with sudden high fever and rapidly rising ETCO2 during surgery

Case Presentation:

• Presented by Dr. Rahul Damania
• 23-month-old ex-28 week premie intubated during hernia repair surgery
• Noticed rapidly rising ETCO2, unprovoked tachycardia, and elevated temperature
• Transferred to PICU, exhibiting rigidity, clenched jaw, metabolic acidosis, and elevated lactate.
• Consideration of Malignant Hyperthermia (MH) crisis

Key Points:

• Elevated temperature, hypercapnia, metabolic acidosis, and unprovoked tachycardia raise concern for MH
• Organized discussion on pathophysiology, clinical signs, symptoms, and management

Multiple Choice Question:

• Diagnosis of MH crisis during scoliosis repair
• Correct Answer: D) Sarcoplasmic reticulum
• Dantrolene acts on the sarcoplasmic reticulum to inhibit calcium release, crucial in MH management

Clinical Presentation of MH Crisis:

• Tachycardia, acidosis, muscle stiffness, and hyperthermia are hallmark features
• Potential life-threatening complications underscore the urgency of recognition and treatment

Triggers and Pathophysiology of MH Crisis:

• Triggered by inhalational agents and depolarizing neuromuscular blocking agents
• Pathophysiology involves defective Ryanodine receptor leading to uncontrolled calcium release

Differential Diagnosis:

• Includes sepsis, thyroid storm, pheochromocytoma, and neuroleptic malignant syndrome
• Differentiation from similar conditions crucial for accurate management

Diagnostic Approach:

• High clinical suspicion
• Genetic testing (ryanodine receptor gene sequencing) and Caffeine Halothane Contracture Test (CHCT) for diagnosis
• Immediate workup during crisis includes blood gas, lactate, CPK, CMP, and urine analysis

General Management Framework:

• MH crisis is a medical emergency requiring rapid intervention
• Dantrolene Na administration, supportive measures, and continuous monitoring in PICU
• Utilization of Malignant Hyperthermia carts and involvement of specialized hotlines

Clinical Pearls and Pitfalls:

• Early recognition is crucial.
• Proper administration of Dantrolene Na without delay
• Extended monitoring period in PICU to ensure stability

Conclusion:

• Importance of recognizing and managing MH crisis
• Feedback, subscription, and reviews encouraged
• Website picudoconcall.org for additional resources

References:

• Fuhrman & Zimmerman - Textbook of Pediatric Critical Care Chapter
• Malignant Hyperthermia Association of the United States
• What is MH?
• [Managing a crisis](https://www.mhaus.org/ healthcare-professionals/managing-a-crisis/)
• Rosenbaum HK, Rosenberg H. UpToDate: Malignant hyperthermia: diagnosis and management of acute crisis.

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 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. 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, 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.

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, 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 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 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 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 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...

Show Introduction

• Welcome to PICU Doc On Call, a podcast dedicated to current and aspiring intensivists.
• Hosted by Dr. Pradip Kamat and Dr. Rahul Damania

Case Presentation

• A 14-year-old female with a history of depression and oppositional defiant disorder presents with dizziness, slurring speech, and is pale appearance.
• The mother noticed symptoms of dizziness, stumbling, and sleepiness.
• The patient had a prior suicide attempt.
• Vital signs: HR 50 bpm, BP 75/40, GCS 10.
• The initial workup reveals hyperglycemia, and she is stabilized and admitted to the PICU.

Key Aspects of Ingestion Work-up

• History and physical exam are crucial.
• Stratify acute or chronic ingestions.
• Consider baseline medications and coingestants.
• Perform initial screening examination to identify immediate measures for stabilization.

Diagnostic Studies

• Pulse oximetry, continuous cardiac monitoring, ECG, capillary glucose measurement.
• Serum acetaminophen, ASA levels
• Consider extended toxicology screen.

Differentiating CCB vs. Beta-Blocker Overdose

• ECG findings: PR interval prolongation and Bradydysrhythmia suggest CCB poisoning.
• Hyperglycemia in non-diabetic patients may indicate CCB overdose

Approach to CCB Overdose

• Initial resuscitation and stabilization
• ABC approach
• Consult Poison Control Center
• Empiric use of glucagon, IV fluids, and vasopressors
• Consideration of orogastric lavage and activated charcoal

Specific Medical Therapies

• Vasopressors: norepinephrine/epinephrine infusion
• Atropine for bradycardia
• IV calcium salts to overcome cardiovascular effects
• High-dose insulin and dextrose for myocardial function
• Investigational therapies: methylene blue, lipid emulsion

Procedures

• Transvenous pacemaker placement if needed
• ECMO in refractory hypotension

Key Takeaways

• Hypotension and bradycardia indicate life-threatening toxidromes.
• Differential includes CCB, BB, digoxin, clonidine, and CNS depressants.
• Stepwise approach includes close monitoring of ABCs and specific medical therapies.

Thank you for listening to PICU Doc On Call. We would love for you to share your feedback, subscribe, and review our podcast.

Visit picudoconcall.org for more information and resources.

Stay tuned for our next episode!

References

• Fuhrman & Zimmerman - Textbook of Pediatric Critical Care Chapter 125 and 126.
• St-Onge M et al. Treatment for calcium channel blocker poisoning: a systematic review.
• DeRoos F. Calcium channel blockers. In: Goldfrank's Toxicologic Emergencies, 8th edition.

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...

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....

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.

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.

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.

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...