PICU Doc On Call

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.

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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.

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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.

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A nice mnemonic that I use is:

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

P - Pain Management: Analgesics, sedatives, neuromuscular blockers

I - I/Os: Fluids, blood products, estimated blood loss

L - Lines & Tubes: IV/central access, arterial line, drains, NG, Foley

O - Oxygenation/Ventilation: Oxygenation ease, bronchospasm, laryngospasm

T - Time & Position: Duration of case, patient position (supine or prone)

Especially when it comes to access, coordinating with your PICC team, surgery colleagues, or anesthesia teams of long term access or additional PIVs which can be placed while the patient is under anesthesia is key!

Absolutely, Rahul! It’s important for us to also recognize that general anesthesia can cause vasodilation, and when combined with surgical blood loss and insensible losses, it increases the need for fluids postoperatively. Factors like prone positioning and mechanical ventilation can also affect urine output, making it a less reliable indicator of intravascular volume. In the postoperative period, it's important to administer isotonic fluids to avoid hyponatremia and watch for SIADH. Additionally, since operating rooms can be cold, it's crucial to monitor the patient's temperature, especially in infants, to prevent complications like arrhythmias and coagulation disturbances due to hypothermia.

Let’s transition, Pradip. When admitting a postoperative patient to the PICU, what essential questions should we ask the surgeons?

As we have our patient post-op in the PICU, we need to have a clear understanding of the type of surgery performed. Additionally, we should ask these key questions to ensure comprehensive patient management. Communication is essential!

We have arranged this into organ systems, and while not all of these questions would be applicable to every case, this list is relatively comprehensive!

Let’s start with our first organ system:

CNS:

What are the acceptable pain management medications for the immediate post-op period? Can we consider PCA, non-opioids like ketorolac or other NSAIDs, or IV acetaminophen?

Are there any activity restrictions for the patient, or can they be mobilized early? When can we involve PT/OT and speech therapy in the patient's care?

Respiratory:

2) If the patient is admitted to the PICU intubated, when can they be extubated?

If extubation is unsuccessful, can non-invasive positive pressure ventilation, such as HFNC or BiPAP, be used? This is especially true for intra-abdominal procedures.

Is perioperative dexamethasone appropriate?

Are there any procedures like MRI or a revisit to the operating room needed prior to extubation?

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Just to loop back to a prior concept which we discussed, you want to know if the patient at minimum can be bag masked, was the airway difficult, if there is an acute airway event should the PICU team be the primary team to intubate or should this be an intubation by Anesthesia or ENT.

Cardiovascular:

3) What are the target blood pressure goals (systolic or MAP) for the patient postoperatively?

This will be especially true for neurosurgical procedures and even transplant patients.

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If you have yet to check them out, please consider listening to our prior episodes on the post operative approach to Renal transplant and Liver tranplant in the PICU!

Fluid, Electrolytes, and Nutrition/GI:

4) When can the patient begin clear fluids and advance their diet?

Renal:

5) Can the Foley catheter be discontinued, and if so, when?

Talk about urine output goals when applicable.

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Also note that another output which you may have to keep in mind will be how much drainage will be coming out of your peritoneal, penrose, CSF drain — clarifying thresholds of quality and quantity of drainage with your surgical teams can really help with effective recognition of post operative complications. Coordinating a plan to replace the excessive out fluid and with type of fluid is key?

Hematology:

6) Which labs (such as CBC, electrolytes, or coagulation profile) need to be obtained, and how frequently?

Are there any specific transfusion goals?

Infectious Diseases:

7) What antibiotics are prescribed, and for what duration? If the patient becomes febrile, should cultures be obtained?

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Alright summary, analgesia, airway, BP goals, diet/activity, transfusion thresholds, antibiotics & repeat imaging.

Rahul, there seem to be several logistical questions to consider as well. Could you please highlight the key aspects for us?

Certainly, it's crucial to address logistical factors in postoperative care. Firstly, we need to determine when a patient, who is extubated and on room air and hemodynamically stable, can be transferred out, especially if bed capacity is limited. Secondly, it's essential to verify whether the child's family or guardians have been updated on their condition. Lastly, we should inquire about any additional consults that need to be placed for the PICU team to ensure comprehensive patient care.

We want to conclude this episode by delving deep into a few of the patients which are commonly admitted to the PICU post operatively. Our goal here is to apply the principles of management we just learned.

The first case we want to return to is our post-operative spinal fusion.

How does their pre-op status influence the post-op course?

The post-op course depends on pre-op status, pulmonary function, degree of curvature, and extent of repair. Key concerns include paralysis, pain management, airway maintenance, and pulmonary hygiene.

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The key here is to work closely with your pulmonary colleagues and RT to coordinate an effective bronchopulmonary hygiene regimen while admitted in the hospital as effective airway clearance can optimize cardiorespiratory status.

What complications should we watch for due to spinal cord manipulation?

Watch for SIADH and check sodium levels if urine output decreases. A high heart rate might be due to pain, so check intra-operative records for more information.

Alright our next Rapid Fire Case: ENT or OMFS procedures like tracheostomy, TNA, SGP, and airway reconstruction!

What should we know about post-op management for typical ENT procedures like tracheostomy or airway reconstruction?

Get information on bag-mask ventilation and intubation options in case of unplanned extubation. Check if NIPPV is contraindicated. Be prepared for blood loss, post-op swelling, and airway emergencies with wire cutters and spare tracheostomy.

How should we handle a dislodged tracheostomy in a fresh case?

Consult the ENT surgeon for a fresh tracheostomy dislodgment. Forcing a trach can create a false track. Some trachs have stay sutures for guidance. Difficult airway patients may need deep sedation or paralysis until the first tracheostomy change.

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In airway emergencies it is vital to remember that what...

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 proportion to their body, constituting about 15-20% of total body weight as opposed to 2-3% in adults.

So, we've discussed how the pathophysiology of abusive head trauma in infants is complex and multifactorial. Can you tell me more about how the soft and malleable skull of a neonate plays a role in this type of injury?

• A heavier head with a lack of nuchal muscular strength predisposes the head to sustain severe injury as opposed to an older child. Furthermore, due to a lack of coordination of the head and body motion, the infant is unable to protect themselves. Injuries in abusive head trauma can be due to blunt impact, shaking with blunt impact, or shaking alone. Whiplash shaking and jerking subjects the brain to rotational acceleration and deceleration forces, which explains brain injuries and retinal hemorrhages in the absence of external trauma. The resulting traumatic brain injuries can have devastating and long-lasting effects on the child's cognitive and physical development.

Rahul, how would an intensivist assess a child with physical abuse?

• As the pediatric intensive care unit is a team sport, it's important to consult with multiple teams early on in cases of suspected abusive head trauma. This includes the trauma and neurosurgery teams, radiologists, child advocacy services, and social workers. In some states, early referral to Child Protective Services or law enforcement is mandatory to protect other siblings from harm. By involving these specialized teams and agencies, we can ensure a comprehensive approach to the diagnosis and management of abusive head trauma in pediatric patients.
• Absolutely, Rahul. The first step in diagnosing abusive head trauma is to obtain a detailed history from parents or caregivers. It's important to determine if the child was brought for medical attention or neglected after the traumatic event. Additionally, we need to assess whether the child's development level is consistent with the proposed mechanism of injury and whether the alleged events account for all injuries.

What are some key historical features that can help diagnose child abuse in cases of suspected abusive head trauma?

• In a retrospective study of 163 children, 30% of whom met the criteria for physical abuse, certain historical features had high specificity and positive predictive value for diagnosing child abuse. Having no history of trauma had a specificity of 0.97 and a positive predictive value of 0.92 for abuse. Among the subgroup of patients with persistent neurological abnormality at hospital discharge, having a history of no or low-impact trauma had a specificity and positive predictive value of 1.0 for definite abuse.

A detailed history is crucial in diagnosing abusive head trauma, as certain negative historical features such as no history of trauma and low-impact trauma have high specificity and positive predictive value for diagnosing child abuse when the clinical suspicion is high

• Certainly. In our case, the mother's boyfriend claimed that the baby fell from the crib onto the hardwood floor. However, falls from less than five feet are unlikely to cause moderate or large subdural hematomas in children and are rarely fatal. It's important to note that scalp contusions or lacerations are common in such falls, while a skull fracture is typically linear and located in the parietal region without associated intracranial hemorrhage.
• Rahul, in our case the patient had mild transaminitis, can you comment on abusive abdominal trauma?
• Certainly, abdominal trauma in the PICU is an important topic to discuss. In our case, the patient had mild transaminitis which leads us to question the possibility of abusive abdominal trauma. It's important to note that AAT is actually the most common cause of abdominal injuries in children under two years of age.
• The outcome for patients with AAT is also worse than those with accidental trauma, with a mortality rate ranging from 9-30%, as opposed to 4.7% for those with accidental injuries. Symptoms such as vomiting may be initially attributed to medical conditions like gastroenteritis, which can lead to a delay in diagnosis. The most common injuries in AAT involve the liver, kidney, spleen (with the liver being more common than the spleen), and the stomach/intestines. If a child presents with pancreatitis after a "reported fall," it should raise suspicion for abusive abdominal trauma.

Let’s keep building on this diagnostic framework, besides history what else would you emphasize?

• Certainly, in addition to obtaining a thorough history, the next step in evaluating a child for non-accidental trauma in the PICU is to conduct a comprehensive physical exam. It's essential to document any skin findings, oral lesions, or eye findings, as well as to take photographs and place them in the patient's electronic medical records with the appropriate date/time. The next step is to obtain imaging, with CT being most helpful in the acute phase to determine the need for neurosurgical intervention, while MRI may be needed to evaluate for diffuse axonal injury, ischemia, cranial shearing, or infarction.
• A skeletal survey should also be obtained to assess for fractures, and if abdominal injuries are suspected, a CT or MRI of the abdomen should be obtained. Additionally, CBC, CMP, coagulation studies, and pancreatic enzymes should be ordered. An ophthalmology consult for retinal hemorrhages is crucial, as they cannot be specifically dated and may clear quickly, so early examination is important. Lastly, postmortem examination is recommended for children who died from unexplained causes or abusive injuries.

To summarize, retinal hemorrhages are a common finding in fatal cases of AHT seen in 85% of cases with a spectrum of disease such as extensive hemorrhages leading to retinal tears, detachment, and vitreal hemorrhage. While retinal hemorrhages are not specific to AHT, they can be easily distinguished based on history, imaging, and clinical evaluation. Conditions such as birth trauma can cause retinal hemorrhages; the presence of these retinal hemorrhages can be correlated with the mode of delivery, with vacuum extractions having a higher correlation compared to NSVD and C-sections. It is important to note that retinal hemorrhages should not be attributed to birth trauma after 6 weeks of age. Other differentials for retinal hemorrhages in infants to keep in mind include leukemia, meningitis, vasculitis, and severe hypertension. However, by and large, please keep NAT on top of your differential.

How would you outline your general management framework if the history, physical examination, and diagnostic investigation suggest a diagnosis of abusive head trauma?

• In managing a child with NAT, the first step is to prioritize acute medical and surgical management of the child's clinical condition, which includes following the same principles used for traumatic brain injury and polytrauma. This involves early consultation with neurosurgery and trauma teams, implementing cerebroprotective measures for intracranial pressure management and prevention of secondary brain injury, using lung protective ventilation strategies, providing adequate analgosedation, maintaining judicious fluid balance, and correcting any necessary laboratory abnormalities. The TAXI guidelines can be followed for blood and platelet transfusion. These topics have been discussed in detail in previous podcast episodes.

Rahul, let's close this episode with some key summary take-homes.

Our case highlighted the importance of maintaining a high index of suspicion for non-accidental trauma in infants and young children. The infant in our case had clinical findings inconsistent with the history provided by the caregiver, leading to a diagnosis of abusive head trauma. Abusive abdominal trauma should also be considered in cases of non-accidental trauma, with a high mortality rate and common injuries to the liver, kidney, spleen, and intestines. A team approach is crucial in the management of NAT in the PICU, involving specialists from trauma, neurosurgery, child advocacy, radiology, and social services. Early recognition and intervention are essential in improving outcomes for these vulnerable patients.

This concludes our episode on child abuse We hope you found value in our short, case-based podcast. We welcome you to share your feedback, subscribe & place a review on our podcast! Please visit our website picudoconcall.org which showcases our episodes as well as our Doc on Call management cards. PICU Doc on Call is co-hosted by...

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 enzymes, urine analysis, and even a toxicology screen. Cardiac genetic testing should be considered on a case-by-case basis.

Rahul, what is the management of such a patient in the PICU?

Usual good supportive care with attention to airway, breathing, and circulation should be provided. CVL and arterial lines should be placed and continuous cardiac monitoring initiated. The child may initially require a pressor, like epinephrine, immediately after the arrest for cardiogenic shock. Early extubation when a child is clinically stable should be attempted. Maintenance of judicious fluid balance and correction of electrolytes must be done. Physical and occupational therapy should be initiated early as should the early mobility program to prevent de-conditioning. In the absence of any underlying cardiac disease, there is no indication for any medical or device therapy for survivors of commotio cordis. Such individuals, generally, should have no restrictions for returning to athletic activity.

Check out our episode on post-cardiac arrest care. This two-part episode provides a systems-based breakdown of how to manage the multi-system dysfunction after cardiac arrest.

Pradip, what are some of the community approaches we can use in commotio cordis?

Improved design of sports equipment (using air-filled balls over the dense hardcore balls-although may not be practical as this may change the nature of the game).

Coaching young players to avoid getting hit in the chest by an errant pitch or avoid defending the goal in hockey or lacrosse using the player's chest

Chest protection devices, commercially available protectors, which were originally designed to reduce the likelihood of trauma from blunt bodily injury, do not offer absolute protection from arrhythmia after a blow to the chest. Wearing chest protectors is ineffective in consistently preventing ventricular fibrillation and reducing the risk of sudden death.

AEDs have substantial life-saving capability, and it is appropriate to disseminate them widely at youth sporting events and recreational settings where commotio cordis may occur. Prevention of sudden cardiac death from commotio cordis should be focused on the wider availability of automated external defibrillators and prompt recognition and resuscitation of victims.

Commotio cordis is usually, although not invariably, fatal. The availability of AEDs, public awareness, and early activation of the survival chain has improved survival.

As we close our episode, Rahul, can you summarize some key take-home points?

Commotio cordis 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.

Early recognition of cardiac arrest with prompt initiation of CPR and defibrillation can improve outcomes in patients who suffer severe blunt trauma & commotio cordis.

AEDs should be made available as a public health measure in youth sports or recreational settings! We are pediatricians at heart; thus prevention is key!

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

References

Fuhrman & Zimmerman - Textbook of Pediatric Critical Care. Fitzgerald T and Reed C. Pediatric Thoracic trauma. Chapter 119: page 1405

Marron BJ, Estes N. A.M. Commotio Cordis. N Engl J Med 2010; 362:917-927

Estes, N A M; Weinstock, J. My APPROACH to Commotio Cordis. Trends in cardiovascular medicine, 2019, Vol.29(4), p.248

Clinical Profile and Spectrum of Commotio Cordis. Marron BJ et al. JAMA. 2002;287(9):1142-1146. doi:10.1001/jama.287.9.1142

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

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

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

Here is the case presented by Rahul

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

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

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

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

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

Traumatic brain injury (TBI)

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

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

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

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

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

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

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

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

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

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

Rahul, what about NMB?

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

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

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

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

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

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

Pradip, What about fluid status?

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

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

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

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

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

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

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

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

What about blood transfusion?

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

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

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

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

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

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

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

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

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

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

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

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

Dear Listeners & Peds ICU community, WE are back on air!

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

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

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

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

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

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

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

Let’s get into our first learning objective,

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

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

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

The first concept here is that many podcasts provide narratives.

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

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

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

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

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

trainees preferred podcast learning over reading for many topics.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Start with a case to highlight the PICU topic at hand

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

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

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

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

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

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

References:

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

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

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

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

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

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

Here's the case presented by Rahul—

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

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

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

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

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

Basic Urine drug screen was positive for THC

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

References

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

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

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

Welcome to our Episode: A Somnolent Toddler.

Here's the case:

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

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

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

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

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

The correct answer is A, verapamil toxicity.

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

 What is the mechanism of toxicity with beta-blockers?

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

• Clonidine: Grandma's purse may have clonidine patches or tabs (used for sleep, hypertension, etc.). Most patients present with somnolence, along with bradycardia or hypotension.
• First things first: maintain airway, breathing, and hemodynamics. Especially in this patient with marked central nervous system depression, we should consider trialing intravenous naloxone(0.1 mg/kg, maximum single dose: 2 mg). This may be repeated every one to two minutes up to 10 mg total dose. Please note, Naloxone has been utilized to treat seriously poisoned clonidine overdose patients with inconsistent results. Finally, in symptomatic patients with enteral clonidine overdose, it is important to note that HD or CRRT has a limited role. Another important point to remember in a child who may have an overdose with clonidine is to have the child fully exposed and have any adherent transdermal patches be removed.
• We advocate the early use of activated charcoal + supportive care with attention to airway, breathing, and circulation. The antidote Flumazenil can be used to reverse severe benzodiazepine toxicity.

1. ACE inhibitors → Include drugs like captopril, and enalapril, which block the conversion of angiotensin I to angiotensin II, thereby lowering arteriolar resistance to decrease BP. Mild toxicity may be produced with a single, supra-therapeutic dose; however, severe toxic effects and deaths are rare and are often attributed to co-ingestants. There are reports of children 6 years of age and younger who have ingested up to 8mg/kg captopril or up to 2mg/kg enalapril or lisinopril and remained asymptomatic. The primary toxic effect of ACE inhibitor ingestion is hypotension. Asymptomatic patients should be observed for at least four hours post-ingestion with frequent monitoring of vital signs. Hyperkalemia and hyponatremia may be seen due to the aldosterone blocking effect of ACE inhibitors.

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

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

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

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

As pediatric intensivists, we are pediatricians at heart and our job is to educate parents/grandparents to keep children safe: Keep all purses out of reach of small children, Keep...

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

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

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

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

Here's the case presented by Rahul:

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

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

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

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

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

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

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

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

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

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

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

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

So these children can get cataracts, why is that?

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Let’s summarize today’s podcast:

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

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

References

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

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

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

Here's the case presented by Rahul:

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

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

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

Accidental ingestion of an unknown medication

Altered mental status

Difficulty breathing—with grey lips suggestive of hypoventilation/hypoxia

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

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

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

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

A. Methadone

B. Morphine

C. Fentanyl

D. Dilaudid

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

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

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

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

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

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

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

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

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

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

EKG

beta-HCG in a female teenager.

Always follow your state's poison control recommendations.

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

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

Administer oxygen and assist ventilation for respiratory depression.

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

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

Monitor for QT prolongation and dysrhythmias. Torsades de pointes

Correct electrolyte abnormalities. Intravenous magnesium and overdrive pacing as indicated

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

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

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

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

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

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

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

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

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

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

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

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

References:

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

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

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

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

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

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

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

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

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

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

Here's the case presented by Rahul:

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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