PICU Doc On Call

Welcome to PICU Doc On Call, a podcast dedicated to current and aspiring intensivists. My name is Pradip Kamat. My name is Rahul Damania and we come to you from Children’s Healthcare of Atlanta-Emory University School of Medicine.Today's episode Is part two of our pediatric post-cardiac arrest care syndromeIf you have not yet listened to part one, I would highly encourage you to visit that episode prior to delving into this one.Part 1 addressed the epidemiology, causes, and pathophysiology of POST CARDIAC ARREST SYNDROME.Part 2 Today will discuss management and complications related to post-cardiac arrest syndrome in the ICU.To revisit our index case we had a:11 yo previously healthy M who was admitted to the PICU after cardiac arrest. After stabilization: The patient was taken to head CT which showed diffuse cerebral edema and diffusely diminished grey-white differentiation most pronounced in the basal ganglia. He is now 18-24 hours post-cardiac arrest and the team is dealing with hemodynamic changes, arrhythmias, and difficulty with ventilation. The patient’s neurological exam still remains poor with fixed 5 mm pupils and upper motor neuron signs in the lower extremities.Let’s get right into it:What are some of the principles in management of patients with post cardiac arrest syndrome (PCAS)? Where do we keep the patients blood pressure?Hypotension after ROSC is commonly encountered in children with PCAS. Early hypotension occurred in 27% of children after cardiac arrest is associated with lower survival to hospital discharge and unfavorable neurological outcome. When post-cardiac arrest hypotension is present, it is not clear whether increasing the blood pressure through administration of fluids and inotropes/vasopressors can mitigate harm, despite this 41% of patients under 18 receive vasopressor therapy within the first 6 hours after ROSC. Currently, there is no high-quality evidence to support any single specific strategy for post-cardiac arrest hemodynamic optimization in children. Treatment of post-cardiac arrest hypotension and myocardial dysfunction may be assisted by monitoring and evaluating arterial lactate and central venous oxygen saturation. Parenteral fluids, inotropes, and vasoactive drugs are to be used as needed to maintain a systolic blood pressure greater than the fifth percentile for age. Appropriate vasoactive drug therapies should be tailored to each patient and adjusted as needed.What about cardiac arrhythmia's such as Vtach seen in our patient?The rhythm disturbances observed during the post-cardiac arrest period include premature atrial and ventricular contractions, supraventricular tachycardias, and ventricular tachycardias. Heart block is unusual but can be observed as a manifestation of myocarditis. There is inadequate evidence in adults and no published studies in children to support the routine administration of prophylactic antiarrhythmics after ROSC, but rhythm disturbances during this period may warrant therapy. Treatment depends on the cause and hemodynamic consequences of the arrhythmias. Premature depolarizations, both atrial and ventricular, usually do not require therapy other than maintenance of adequate perfusion and normal fluid and electrolyte balance. Ventricular arrhythmias may signify more serious myocardial dysfunction. QT prolonging agents must be avoided. Many of the vasoactive agents used to support myocardial function can increase myocardial irritability and risk of arrhythmias. Premature atrial or ventricular depolarizations are frequently observed and can be controlled by optimizing the dose of the vasoactive drugs. Bradycardia is frequently seen in TTM and typically requires no therapy. During PCAC, mechanical circulatory support (ECMO) may be considered if significant cardiorespiratory instability persists despite appropriate volume expansion and administration of inotropes, vasopressors, and, if indicated, antiarrhythmics.In a study de Mos N et al (CCM 2006) in a PICU population, the use of ECMO within 24 hours after ROSC was associated with reduced mortality. Case series have documented the role of ECMO88 and ventricular assist device support89,90 in children with refractory cardiogenic shock or acute fulminant myocarditis (Blume Ed et al., J Heart Lung Transplant 2016).What about oxygenation and ventilation strategies in our patient with PCASOptimal oxygenation and ventilation of children after ROSC may be hampered by the pathology that precipitated the cardiac arrest (such as drowning with resultant post-pulmonary edema) and by the ensuing post-cardiac arrest pathophysiology. Further management challenges may be caused by aspiration and lung injury occurring during resuscitation efforts as well as ventilator-induced lung injury. Additionally, use of TTM alters the relationship between arterial oxygen saturation and arterial oxygen tension such that, for a given arterial oxygen saturation, the arterial oxygen tension (Pao2) is lower than that observed when the temperature is normal. Hypothermia also decreases the metabolic rate; thus, carbon dioxide production will be lower at any given minute ventilation.Post–cardiac arrest blood gas abnormalities are common in children, particularly in the first hours after ROSC as seen in our patient case. Published evidence has failed to demonstrate a consistent effect of post-cardiac arrest hyperoxia or hypoxemia on outcome. After ROSC, it is reasonable to aim for normal PaO2 (or the value appropriate for the child’s condition if the child has, for example, cyanotic heart disease) and to use the lowest possible fraction of inspired oxygen, weaning to maintain an oxygen saturation of 94% to 99% as a guideline. Throughout PCAC, hypoxemia must be avoided whenever possible, particularly during oxygen titration. The 2010 AHA PALS guidelines recommended prompt arterial blood gas analysis as soon as possible after ROSC and within 10 to 15 minutes of establishing initial mechanical ventilation to guide oxygen administration and titration and to support mechanical ventilation.Post–cardiac arrest derangements in PaCO2 are common. On the basis of available evidence, after ROSC, it is reasonable to target normocapnia (ie, normal for the child, or PaCO2 35–45 mm Hg) or a PaCO2 specific for the patient’s condition, limiting exposure to severe hypercapnia and hypocapnia. Lung protective strategies such as low TV, high PEEP should be used to minimize VILI.Can you comment on targeted temperature management?Post–cardiac arrest pyrexia (elevated core body temperature) is common, and persistent hyperthermia is associated with unfavorable neurological outcomes in children (Bambea MM PCCM 2010).During PCAC, fever (≥38°C) should be aggressively treated. To treat the child who remains comatose after OHCA, the 2015 AHA PALS guidelines update recommended that it is reasonable either to maintain continuous normothermia (TTM to 36°C–37.5°C) for 5 days or to maintain 2 days of continuous hypothermia (TTM to 32C°–34°C) followed by 3 days of continuous normothermia (TTM to 36°C–37.5°C).2 Because increased mortality was associated with temperatures <32°C, if TTM to 32°C to 34°C is used, meticulous care must be provided to prevent temperatures <32°C.Post–cardiac arrest derangements in PaCO2 are common. On the basis of available evidence, after ROSC, it is reasonable to target normocapnia (ie, normal for the child, or Paco2 35–45 mm Hg) or a Paco2 specific for the patient’s condition, limiting exposure to severe hypercapnia and hypocapnia. Lung protective strategies such as low TV, high PEEP should be used to minimize VILI.What about treatment of seizures in PCAS and can you also comment on sedation , analgesia and the use of NMB in these patients ?Seizures occur in 10% to 50% of children who remain encephalopathic after achieving ROSC. (Abend NS et al Neurology 2009). Furthermore, about half of children with post-ROSC seizures experience exclusively non-convulsive (subclinical, EEG only) seizures, which cannot be identified by clinical observation alone. Seizures could not be predicted from any clinical or resuscitation variables. Seizures were associated with unfavorable gross neurological outcomes at discharge but not with higher mortality. Because seizures increase metabolic demand, can worsen metabolic dysfunction, and can increase intracranial pressure, they can contribute to secondary brain injury.For these reasons, many clinicians aim to treat seizures, although the approach is generally guided by the child’s overall medical condition and other prognostic indicators. Typical acute clinical or electrographic seizures are often initially treated with benzodiazepines, levetiracetam, or phenytoin. Myoclonic seizures such as those reported in our patient case may be refractory to treatment. (Ostendorf AP et al PCCM 2016) Providers must be alert for potential adverse effects of anticonvulsants such as cardiac arrhythmias, hypotension, and respiratory depression. In addition, sedation induced by anti-seizure drugs may complicate the neurological examination. Pain and discomfort needs to be controlled using opioids (morphine or fentanyl) and sedatives (dexmedetomidine or benzodiazepines). Neuromuscular blocking agents (eg, vecuronium or pancuronium) with analgesia or sedation (or both) may improve oxygenation and ventilation in case of patient-ventilator dyssynchrony or severely compromised pulmonary function. Providers are cautioned, however, that NMB agents can mask seizures and impede neurological examinations.If TTM is used, practitioners must be aware that the pharmacokinetics and pharmacodynamics of sedatives/hypnotics and neuromuscular blocking agents will be altered, resulting in prolonged time to both hepatic and renal clearance.What about endocrine dysfunction in PCAS patients ? Can you comment on glucose control and treatment of adrenal dysfunction?Both hypoglycemia and hyperglycemia have been associated with unfavorable outcomes in critically ill children and adults. During PCAC, clinicians should avoid and promptly treat hypoglycemia.Severe hyperglycemia can also be problematic because it can lead to uncontrolled osmotic diuresis, which can exacerbate post–cardiac arrest volume depletion and hemodynamic instability. Therefore, it is important to monitor serum glucose concentration, to treat significant hyperglycemia, and to monitor urine volume. There is currently insufficient published evidence to determine the optimal blood glucose concentration during PCAC that will maximize neurological outcome. Approximately 30% of critically ill children have relative adrenal insufficiency, but this has not been evaluated in children resuscitated from cardiac arrest. There is insufficient evidence to support the routine use of corticosteroids after cardiac arrest. Patients should be treated per recommendations for critically ill children.How do we manage Renal failure in these patients?In a recent retrospective study of 296 children during PCAC, 37% had AKI, 11.5% had severe AKI by Acute Kidney Injury Network criteria, and 6.4% required RRT within 48 hours of ROSC.(Neumayr TM et al. PCCM 2017). Risk factors for severe AKI after cardiac arrest included abnormal baseline creatinine, lack of a chronic lung condition, in-hospital arrest location, higher number of doses of epinephrine during arrest, and worse post–cardiac arrest acidosis.Throughout PCAC, it is important to monitor kidney function, including urine output and creatinine, because patients are at risk for developing AKI, and RRT may be indicated. Nephrotoxic medications and medications excreted by the kidneys should be used with caution, and dose adjustment may be needed. Serum concentrations of nephrotoxic medications should be closely monitored.Do we need antibiotics during post cardiac arrest care (PCAC) ? Can you also comment on management of inflammation and coagulation abnormalities?Infection is common after pediatric cardiac arrest. Most studies reporting the incidence of infection during PCAC enrolled children treated with THAPCA trial. The incidence varied from < 5 infections per 100 days in IHCA to 11.1 infections per 100 days for OHCA patients. The incidence of culture-proven infection did not differ between patients treated with TTM 32-34 and those treated with TTM to 36-37.5. During ECMO therapy for PCAS, the infection rate was ~ 10%. Monitoring for signs of infection is important during PCAC. The decision to obtain cultures and to initiate empirical antimicrobial coverage should follow local PICU protocols.Inflammatory pathways are activated as part of PCAS, including disturbances of the coagulation cascade. The effects of blocking or modulation of these pathways have been studied in adults and in animal models; we identified no studies to date involving infants or children. Extensive animal research into blocking or modifying inflammatory pathways has yielded promising results. However, to date, most attempts to translate this work to humans have been unsuccessful. Because inflammation can alter the coagulation cascade, providers should monitor for signs of bleeding or coagulopathies; this is particularly important for patients receiving ECMO support. At this time, there is insufficient evidence to support specific treatments to modulate inflammatory pathways during PCAC.To summarize, Infection is common after pediatric cardiac arrest. Inflammatory pathways are activated as part of PCAS, including disturbances of the coagulation cascade. The effects of blocking or modulation of these pathways have been studied in adults and in animal models; we identified no studies to date involving infants or children.Can you comment on rehabilitation and recovery after cardiac arrest ?Children surviving cardiac arrest are at high risk for physical, cognitive, and emotional disabilities that can affect quality of life, family function, activities of daily living, school performance, and employment. There is little evidence on specific interventions during PCAC that will improve functional outcomes of children after cardiac arrest. Small observational studies of children after critical illness or injury suggest that children with anoxic injury have more severe disability and demonstrate less improvement compared with children with traumatic brain injury. There is insufficient evidence to support specific rehabilitation interventions or the optimal timing of initiation of such interventions. However, on the basis of the benefits of rehabilitation for patients with traumatic brain injury and stroke, it is reasonable for providers to consult rehabilitation experts within the first 72 hours after cardiac arrest to tailor a plan of rehabilitation interventions for survivors of cardiac arrest.As we look into the future, What about biomarkers for post arrest prognostication?Currently, there is insufficient evidence to support the use of serum biomarker concentrations alone to predict outcome after pediatric cardiac arrest. Although specific biomarkers have shown promise, they have yet to be validated in prospective pediatric studies after cardiac arrest. After cardiac arrest, elevations in lactate concentration may reflect not only severe post–cardiac arrest systemic hypoperfusion but also severe cerebral hypoperfusion. In several pediatric cardiac arrest studies, higher serum lactate concentrations in the first 12 hours after cardiac arrest were associated with increased mortality, and higher concentrations within 12 hours of ROSC were modestly predictive of unfavorable outcome (area under the curve: for IHCA, 0.76; for OHCA, 0.75). (Meert K et al. PCCM 2009; Topjian A PCCM 2013). Numerous other promising biomarkers of neurological injury, systemic inflammation, and genetic polymorphisms are currently under evaluation. An ongoing trial is investigating concentrations of NSE, S100B, glial fibrillary acid protein, and ubiquitin carboxy-terminal hydrolase L1 in the first 72 hours after pediatric OHCA and their association with 1-year neurological outcomes. (Prout AJ et al. Curr Opin Pediatr 2017).To summarize, In several pediatric cardiac arrest studies, higher serum lactate concentrations in the first 12 hours after cardiac arrest were associated with increased mortality, and higher concentrations within 12 hours of ROSC were modestly predictive of unfavorable outcomeHow do we prognosticate PCASProviders must consider multiple variables when attempting to prognosticate outcomes during and after cardiac arrest. Providers must consider multiple variables when attempting to prognosticate outcomes during and after cardiac arrest. Although there are factors associated with better or worse outcomes, no single factor studied predicts outcome with sufficient accuracy to recommend termination or continuation of CPR or to enable prognostication after ROSC (de Caen AR et al. Circulation 2015).Several prearrest conditions and therapies have been independently associated with worse survival to discharge and unfavorable neurological outcomes after pediatric cardiac arrest: Worse outcomes from OHCA are associated with decreased age and some causes of arrest, including sudden infant death syndrome and blunt trauma. (Meert KL et al. PCCM 2016. Matos RI et al. Circulation 2013). Factors associated with lower survival after IHCA include older age; presence of preexisting conditions; interventions such as tracheal intubation, mechanical ventilation, and use of vasopressors at the time of arrest; and arrests occurring...

Welcome to PICU Doc On Call, a podcast dedicated to current and aspiring intensivists. My name is Pradip Kamat.My name is Rahul Damania, a current 2nd-year pediatric critical care fellow. We come to you from Children’s Healthcare of Atlanta-Emory University School of Medicine.Today's episode is dedicated to pediatric post-cardiac arrest care.We are going to split this topic into two episodes, part one of pediatric post-cardiac arrest syndrome will address the epidemiology, causes, and pathophysiology.I will turn it over to Rahul to start with our patient case...11 yo previously healthy M who is admitted to the PICU after cardiac arrest.The patient was noted to be found unresponsive and submerged in a neighborhood pool.He was pulled out by bystanders and CPR was started for 5 minutes with two rounds of epinephrine prior to achieving ROSC.During transport to the OSH, the patient developed hypotension requiring a continuous epinephrine infusion.His initial blood gas was notable for a mixed respiratory and metabolic acidosis:7.0/60/-20His initial serum lactate was 6.8 mmol/L.He presents to the PICU with a temperature of 36.6, HR 130s, MAPs 50s on Epinephrine infusion at 0.03mcg/kg/minHe is mechanically ventilated with notable settings PEEP of 10, FiO2 65%.The patient is taken to head CT which shows diffuse cerebral edema and diffusely diminished grey-white differentiation most pronounced in the basal ganglia.Great Rahul, can you please comment on his physical exam & PMH?Important physical exam findings include an unresponsive intubated patient with a cervical collar and bilateral non-reactive pupils at 4mm. The patient received mechanical ventilation with coarse breath sounds. A heart exam revealed tachycardia with no murmur or gallop. The patient does not respond to stimuli, intermittent jerking movements of arms and legs were observed. There was no evidence of rash or trauma. No past medical history of seizures or any heart disease. No home medications or toxic ingestions are suspected.So now he is transferred to the ICU, what did we do?An arterial line, central venous line, urinary catheter, esophageal temperature probe was placed. The patient was ventilated using a TV of 6cc/kg and a PEEP of 10 (FIO2 ~65%) to keep SPO2 >94%. The patient initially had runs of ventricular tachycardia for which lidocaine was used. Although the initial EKG showed mild QTc prolongation, it subsequently normalized and was considered to be due to his cardiac arrest and resuscitation. An echocardiogram revealed normal biventricular systolic function (on epinephrine) and also showed normal origins of the coronary arteries. Comprehensive Arrhythmia Panel did not identify a specific genetic cause for the patient's sudden cardiac arrest. The patient was placed on continuous EEG, which demonstrated severe diffuse encephalopathy with myoclonic status likely from anoxic brain injury Patient was also started on Levetiracetam and valproic acid. Initial portable CT scan done on day # of admission showed diffuse cerebral edema and diffusely diminished gray-white differentiation (most pronounced in the basal ganglia). MRI was deferred due to patient instability.The case we talked about highlights a patient who had a trigger that then resulted in cardiac arrest is common is one of the common reasons for admission to the PICU at Children's hospitals whether from submersion injury, trauma, ingestion, cardiac arrhythmia, sepsis, etc. Can we start by defining post-cardiac arrest syndrome?Successful resuscitation from cardiac arrest results in a post-cardiac arrest syndrome, which can evolve in the days to weeks after the return of spontaneous circulation. The components of post-cardiac arrest syndrome are brain injury, myocardial dysfunction, systemic ischemia/reperfusion response, and persistent precipitating pathophysiology. Prior to 2008, the AHA pediatric advanced life support (PALS) guidelines focused chiefly on the prevention of cardiac arrest, immediate recognition of cardiac arrest, and provision of early CPR because outcomes of pediatric cardiac arrest were poor. The past decade has led to focused efforts by resuscitation experts to address specific pediatric post-cardiac arrest knowledge gaps. In the 2019 Aug issue of Circulation (Vol 140, issue 6) published a scientific statement from the American Heart Association, which summarizes the epidemiology, pathophysiology, management, and prognostication after the return of sustained circulation after cardiac arrest, and it provides consensus on the current evidence supporting elements of pediatric post-cardiac arrest care.In order to provide post-cardiac arrest care (PCAC), caregivers need to understand the phases of cardiac arrest. Can you give us more information on the phases of cardiac arrest care?Let me start by defining ROSC or return of spontaneous circulation: ROSC refers to a return of sustained circulation, which can include circulation that results either from a perfusing spontaneous heart rhythm or from the establishment of extracorporeal circulation with extracorporeal membrane oxygenation (ECMO).The immediate phase: the first 0 to 20 minutes after ROSCThe early phase: the period after ROSC from 20 minutes up to 6 to 12 hoursThe intermediate phase: 12 to 72 hoursThe recovery phase: approximately 72 hours to day 7. Starts at different times for different patients; the timing may be influenced by factors such as cardiovascular function or use of targeted temperature management (TTM)The rehabilitation phase: traditionally began with the application of care after discharge from the acute care hospital, but rehabilitation services are now often initiated during the intermediate phase or the recovery phase.What is the epidemiology of post-cardiac arrest syndrome (PCAS)?The timing and severity of the phases of post-cardiac arrest syndrome (PCAS) may differ between patients with out-of-hospital cardiac arrest (OHCA) and those with in-hospital cardiac arrest (IHCA) because witnessed status, preexisting conditions, cause of arrest, and timing and quality of bystander actions, such as immediate administration of high-quality CPR, may differ between OHCA and IHCA.It is estimated that >5000 children experience OHCA annually in the United States with an estimated incidence of non-traumatic OHCA of 8.04 per 100 000 person-years.11 With current ROSC rates of ≈36%. The reported survival to discharge in OHCA remains poor- 6.7-10.2% although favorable neurological outcome has been reported in 77% of pediatric OHCA survivors. One study using PECARN data (Moler FW et al. CCM 2011) of TTM in comatose children who survived OHCA to be admitted to a pediatric intensive care unit (ICU), reported that 38% survived to hospital discharge.An estimated 6000 infants and children develop IHCA annually. Non–risk-adjusted ICU ROSC occurred in 78%, with 45% surviving to discharge; 89% of survivors had a favorable neurological outcome (Berg RA et al. CCM 2016)Approximately 6500 children per year in the US have PCAS. The goal of PCAC is to increase not only survival to hospital discharge but also survival with favorable neurological outcomes.Can we take a deeper dive into the pathophysiology of PCAS? Let's start with brain injuryPost–cardiac arrest brain injury remains a leading cause of morbidity and mortality in adults and children because the brain has limited tolerance of ischemia, hyperemia, or edema. The first 3 phases of PCAS involve hypoxemic-hypotensive perfusion with energy deprivation. With ROSC, there is a burst of reactive oxygen species, and oxidative stress may ensue in tissue that is depleted of antioxidants. As a result, reperfusion is associated with excitotoxicity, calcium accumulation, and free radical-mediated cell injury or death. The myoclonic status seen in your case is probably due to this excitotoxicity. Both neuronal cellular necrosis and apoptosis result from this cascading injury and can continue in the days to weeks after ROSC. A variety of post-cardiac arrest clinical conditions, including hyperoxia, hypoxemia, and hypotension, can exacerbate the neuronal injury.What about cardiac injury in PCAS?Global myocardial dysfunction occurs even in the absence of a cardiac cause of the arrest, and the severity of the myocardial dysfunction may be related to the duration of no-flow time during cardiac arrest. Myocardial dysfunction has been associated with early mortality despite successful initial resuscitation in children and adults. The onset of post-cardiac arrest myocardial dysfunction begins within hours of the arrest, peaks at ≈8 hours, begins to improve at 24 hours, and typically resolves within 48 to 72 hours. The pathophysiology contributing to this frequently reversible deterioration of cardiac function after cardiac arrest is not fully understood but is associated with cardiovascular ischemia/reperfusion injury, cytokine-mediated cardiovascular dysfunction, and induced myocardial injury secondary to catecholamines or electric shocks. (Adrie C et al. Circulation 2002).Children may initially demonstrate a hyperdynamic state and then develop cardiac dysfunction over time. Because myocardial dysfunction is likely to develop in approximately two-thirds of patients after ROSC and subsequently improve, it is thought to be a modifiable risk factor.Clinical manifestations of myocardial dysfunction include hypotension, left ventricular and RV systolic or diastolic dysfunction resulting in reduced cardiac output, arrhythmias, and pulmonary edema, which can result in recurrent cardiac arrest. Cardiac arrhythmias such as Vtach noted in the patient in your case are common during PCAC and may be exacerbated by catecholamine administration, which is required to maintain adequate cardiac output.Rahul**: What about systemic ischemia/reperfusion ?**The combination of systemic ischemia/reperfusion produces a state similar to the sepsis syndrome, with elevated cytokines, the presence of endotoxin in plasma, activation of coagulation pathways, and inhibition of anticoagulant pathways. Transient critical illness hyperglycemia occurs after cardiac arrest from a relative insulin-resistant state that is associated with high levels of endogenous catecholamines and cortisol secretion, with resulting gluconeogenesis and glycogenolysis. In children, the serum glucose is typically elevated in the first 12 to 18 hours after the insult and then falls to normal. Clinical manifestations of systemic ischemia/reperfusion include capillary leak with intravascular hypovolemia, vasoplegia, coagulopathy, hyperglycemia, adrenal insufficiency, and impaired oxygen utilization and delivery, contributing to multisystem organ dysfunction. I would like to advise our listeners that management of the child after cardiac arrest includes diagnosis and treatment of the precipitating cause of cardiac arrest. Failure to identify and correct the original cause of cardiac arrest leaves the patient at risk for secondary injury and even recurrence of cardiac arrest. A team approach using experts from cardiology, genetics, infectious disease, radiologists and toxicologists, etc., may be required to investigate the cause of cardiac arrest.To summarize, the combination of systemic ischemia/reperfusion produces a state similar to the sepsis syndrome, with elevated cytokines, the presence of endotoxin in plasma, activation of coagulation pathways, and inhibition of anticoagulant pathways. Transient critical illness hyperglycemia occurs after cardiac arrest from a relative insulin-resistant state that is associated with high levels of endogenous catecholamines and cortisol secretion, with resulting gluconeogenesis and glycogenolysis. In children, the serum glucose is typically elevated in the first 12 to 18 hours after the insult and then falls to normal.Let's discuss monitoring typically used in patients with PCAS?In the post-cardiac arrest period, it is important for the healthcare team to anticipate and assess for evolving systemic and organ dysfunction and to proactively support organ function. This requires ongoing monitoring to guide intensive care therapies. Monitoring in the field continues through transport and includes ECG, pulse oximetry, capnography, noninvasive blood pressure measurement, and point-of-care glucose testing.General monitoring: General intensive care monitoring includes continuous cardiac telemetry, pulse oximetry, continuous capnography, continuous temperature monitoring, and measurement of blood pressure and urine output. Monitoring includes laboratory analysis of venous or arterial blood gases, serum electrolytes, and glucose and calcium concentration. Arterial lactate and central venous oxygen saturation assist in evaluation of the adequacy of tissue oxygen delivery. A chest x-ray aids evaluation of endotracheal tube position, heart size, and pulmonary status.52 Additional monitoring includes evaluation of renal function, measurement of hemoglobin concentration, monitoring of coagulation function, and assessment for signs of inflammation and infection.Hemodynamic monitoring includes: arterial line placement for intra-arterial blood pressure monitoring to facilitate the identification and treatment of hypotension. In addition, central venous catheters may be useful to monitor central venous oxygen saturation and to provide a route for the administration of fluids and medications. Pulmonary artery catheters are now rarely used in pediatrics. An echo and ECG should be performed. The optimal timing or frequency of echo acquisition remains unknown.Neuro-monitoring: Serial neurological examinations may help identify evolving hypoxic-ischemic brain injury. Given the high incidence of electrographic seizures after ROSC(Abend NS et al. Neurology 2011) monitoring with an electroencephalogram (EEG) is increasing in pediatric PCAC. Neuroimaging can be helpful to identify a cerebral cause of cardiac arrest and the presence of severe brain injury. One small pediatric study (36 patients) by Lee JK et al (Resuscitation 2014) evaluated the role of cerebral autoregulation in guiding hemodynamic management and oxygen delivery and assisting in neuroprognostication in comatose children after cardiac arrest, but more studies are needed.This concludes our episode today on PCAS. We hope you found value in this short podcast. We welcome you to share your feedback & place a review on our podcast. PICU Doc on Call is co-hosted by Dr. Pradip Kamat, and my cohost Dr. Rahul Damania.Stay tuned for our next episode which covers Part 2 of PCAS focused on Management! Thank you

Welcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.I'm Pradip Kamat and I'm Rahul Damania. We are coming to you from Children's Healthcare of Atlanta - Emory University School of Medicine.Welcome to our Episode a 2-year-old with severe pallor and O2 desaturation.Here's the case presented by Rahul:A two-year-old presents to the PICU with severe pallor + O2 requirement. The patient went for a routine check with her primary care who noted the patient appeared severely pale. He sent the patient to the ED. An initial Hgb check revealed a Hgb of 1.5gm/dL. Per mother, she is otherwise healthy but a very picky eater. She also reports the patient drinks milk as a soothing adjunct at night, consuming between 12 - 36oz a day. No family h/o of anemia or any other blood disorders.No h/o recent illness. Mother had a normal spontaneous full-term delivery. The patient is up to date on her immunizations. Per mother, developmental milestones are normal. The mother also denies any history of decreased activity in the child. Given the low Hgb, the patient was admitted to the PICU.Let's transition into some history and physical exam components of this case?What are key history features in this child?Severe pallor in a 2-year-oldH/o being a picky eaterH/o excessive milk consumptionPertinent negatives include: No obvious blood loss, No petechia, bruising, or jaundiceWhat did the physical exam show?The patient was hypertensive, tachycardic to the 140s, and 10th% weight for growth percentilesOn physical exam, the patient was in no acute distress. Her lips, gums, and conjunctiva were pale. She had a systolic ejection murmur. As a pertinent negative, she had no hepatosplenomegaly. She also has no rash, bruising, or petechiae.The lack of hepatosplenomegaly may indicate that the patient has no signs of extramedullary hematopoiesis. Patients with hemolytic processes resulting in anemia may present with signs of scleral icterus, jaundice, and hepatosplenomegaly resulting from increased red cell destruction. In fact, in an emergency department setting, the clinical detection of jaundice was found to have sensitivity and specificity of only approximately 70 percent.To continue with our case, then what were the patient's labs consistent with:Initial CBC showed: WBC 8.5K, RBC 1.14 (L), Hgb 1.5gm/dL; Hct 6.1, MCV 53.5, and an elevated RDW 37.7. Initial platelet count was 50K, reticulocyte count 1.1%Peripheral smear revealed no blasts, thrombocytopenia - with occasional medium-sized platelets - ghost cells and anisocytosis/poikilocytosis- which appears most consistent with iron deficiency.It was interesting that the patient had thrombocytopeniaAbsolutely, typically with Iron deficiency, there is thrombocytosis (erythropoietin is increased which closely mimics thrombopoietin stimulates platelets). In fact, both act via the non-TK, JAK-STAT pathway.OK, to summarize, we have:Two year old with severe anemia most likely secondary to iron deficiency.As you think about our case, what would be your differential?For any patient with acute severe anemia presenting to the PICU- One has to think in terms of blood loss, decreased or impaired production (i.e bone marrow failure), or peripheral blood destruction (i.e hemolysis).Here would be the organizations:Blood lossDecreased or impaired productionIncreased destructionLet’s go into detail for each:Blood loss can be internal or external (due to trauma, excessive blood draws, due to surgery)-typically gives rise to normochromic normocytic anemia.Decreased or impaired production: Deficiency of substances needed for Hgb & RBC production such as iron Vit B12 etc. Depression of BM due to infection (parvo B), chemicals, pharmacologic agents or immune mechanisms. Bone marrow aplasia can be idiopathic with or without congenital anomalies. Infiltration of BM due to malignancies such as leukemia, Hodgkin disease, neuroblastoma, etc.Increased blood destruction:Can be due to intrinsic defects of the RBC such as hereditary spherocytosis, defects of Hgb such as sickle cell disease, thalassemia syndromes, enzyme defects.Extrinsic factors include immune mechanisms which can be related to drugs, infections, and non-immune mechanisms such as drugs, toxins, sepsis, HUS, TTP.Also a combination of intrinsic and extrinsic defects such as PNH, Favism, G-6PD. Patients with peripheral destruction in addition to pallor, typically have evidence of hemolysis such as jaundice, red cell breakdown (erythrocyte fragmentation) on the peripheral smear is seen typically in microangiopathic hemolytic anemias.There is typically an increase in the reticulocyte count, which keeps the MCV in the macrocytic range. Bone marrow will typically reveal erythroid hyperplasia. The sine qua non of immune hemolysis is the demonstration of the presence of antibodies or complement components bound to the erythrocyte membrane using the Direct Coombs test.A prospective study by Bateman ST et al (Am J Respir Crit Care Med. 178:26-33 2008) reported 73% of blood loss in the PICU is attributable to blood draws. We need to limit both the number as well as the frequency of blood tests in our patients especially if these are not helping make a change in patient management. Conservative blood draws will help reduce blood transfusions in patients in the PICU. The SCCM’s “Choose Wisely” campaign recommendations from 2015 advises us not to order diagnostic tests at regular intervals (such as every day) but rather in response to specific clinical questions.Rahul, can you give us a brief synopsis on the physiology of iron metabolism in the human body?Iron metabolism is unique in that iron balance is achieved by control of absorption rather than by excretion.About 1.5mg/day of iron is lost due to cell exfoliation from the skin, gut, and urinary tract.About twice this amount is lost by menstruating women and about three one-half times lost during pregnancy.Dietary iron is either in form of heme iron (from hemoglobin and myoglobin of animal sources) or non-heme iron from salts of non-animal sources. The mucosal cell of the small intestine (mostly duodenum and ileum) ultimately controls the absorption of iron in the body. Once taken up by the mucosal cell the iron is either incorporated into the ferritin of the mucosal cell (sloughed off in 3-4 days) or transferred to the portal circulation of the liver with help of mucosal cell transferrin.The cellular metabolism of iron is mediated by three proteins:Transferrin, transferrin receptor, and ferritin.Transferrin production is increased in iron deficiency states. Iron storage exists in the soluble easily available form ferritin or insoluble more stable fraction hemosiderin. Ferritin is widely distributed in all cells whereas hemosiderin is deposited primarily in the liver, spleen, and bone marrow. Serum ferritin < 10 or 12 microgm/ml indicated depletion of iron reserves.To summarize, iron metabolism uptake occurs primarily in the duodenum. Thus, always watch out for patients with duodenal disease, for example, short gut, celiac, IBD, etc. Also, transferrin transports iron, and ferritin represents your storesRahul, a frequently asked question on the Peds CCM boards is about oxygen content and oxygen delivery. Can you shed some light on this with the respect to this case?We have discussed this in detail in episode 33: Oxygen Content and Oxygen Delivery. Definitely worth a listen.As a review, the formula for O2 content is 1.34 X Hgb X O2 saturation +0.003X PaO2.If we assume PaO2 is 100 and O2 saturation is 100%, our O2 content for this patient = (1.34 X 1.5 X 1) +0.003 X 100 = 2.01+ 0.3 = 2.31 ml O2/dLIf patient is transfused to a Hgb of 6, O2 content = 8.04+0.3 = 8.34Conversely, If patient is given 100% O2, the PaO2 = 713, The O2 content of above patient is 2.10+ 0.003 X 713 =4.239,So we either have to increase the Hgb or if unable to transfuse, increase PaO2 as shown in the calculations above.What gives us more bang for our buck is increasing Hgb concentration — this will in turn increase our O2 content.I think it is great to practice calculations of the O2 content, anytime they are faced with a patient with low Hgb or a patient for whom blood transfusion on is indicated. I would also recommend folks read the TAXI guidelines for pRBC transfusion in the Peds ICU. (PCCM)If you had to work up this patient with severe anemia, what would be your diagnostic approach?CBC with differential, reticulocyte count, peripheral smearCMP, urine analysis, stool guaiacInfectious workup should include RVP, ParvovirusHgb electrophoresisSerum lead levelIf the patient has pancytopenia despite PRBC replacement, she would need workup for bone marrow arrest/failure process - such as peripheral flow, BMA/BxNo single test or combination of tests reliably documents iron deficiency in all clinical situations. I would also add that review of the peripheral smear is an essential part of any anemia evaluation. Even if the patient's RBC indices are normal, a review of the blood smear may reveal abnormal cells that can help identify the cause of anemia.If our history, physical, and diagnostic investigation led us to severe most likely due to iron deficiency anemia as our diagnosis what would be your general management of framework?When a patient is admitted to the PICU with severe anemia the usual principles of good PICU care in terms of monitoring, management of airway, and hemodynamics should precede the workup and therapy. I also make sure the patient has at least two good peripheral IVs of which one can be used to send the required labs. We work very closely with our hematology colleagues and the nutritionist.When Hgb is < 5gm%, the patient should be administered a sequential small aliquot 2.5mL/kg very slowly (typically over 3-4 hours). Frequent rechecking of hgb/hct is required as well as close monitoring for any signs of heart failure. Once Hgb is > =5gm%, we can give 5ml/kg over 2-3 hours and wait at least 2 hours in between aliquots.Absolutely, Rahul, Iron supplementation should also be started at around 3mg/kg/dose BID.Nutritionists recommended limiting milk intake and encouraging iron-containing foods and eating a healthy toddler diet. iron should not be taken with Calcium but Vitamin C, which promotes its absorption.Social work referral to get family the necessary support may be needed. Especially if there is a concern for lead in the home.It is also essential to involve the Pediatric Hematology team for appropriate workup, management and follow-up!This concludes our episode on acute anemia in the PICU. We hope you found value in our short, case-based podcast. We welcome you to share your feedback, subscribe & place a review on our podcast! Please visit our website picudoconcall.org which showcases our episodes as well as our Doc on Call management cards. If you are interested in learning more regarding acute severe anemia please refer to Fuhrman & Zimmerman - Textbook of Pediatric Critical Care Chapter 91. Transfusion Medicine. PICU Doc on Call is co-hosted by myself Dr. Pradip Kamat and Dr. Rahul Damania. Stay tuned for our next episode! Thank you!Cummings BM, Shailam R, Rosales AM, Huang MS, Nardi V. Case 37-2019: A 20-Month-Old Boy with Severe Anemia. N Engl J Med. 2019 Nov 28;381(22):2158-2167. doi: 10.1056/NEJMcpc1904048. PMID: 31774963Mattiello V, Schmugge M, Hengartner H, von der Weid N, Renella R; SPOG Pediatric Hematology Working Group. Diagnosis and management of iron deficiency in children with or without anemia: consensus recommendations of the SPOG Pediatric Hematology Working Group. Eur J Pediatr. 2020 Apr;179(4):527-545. doi: 10.1007/s00431-020-03597-5. Epub 2020 Feb 4. PMID: 32020331.Powers JM, McCavit TL, Buchanan GR. Management of iron deficiency anemia: a survey of pediatric hematology/oncology specialists. Pediatr Blood Cancer. 2015 May;62(5):842-6. doi: 10.1002/pbc.25433. Epub 2015 Feb 7. PMID: 25663613; PMCID: PMC4376588.Fuhrman & Zimmerman - Textbook of Pediatric Critical Care Chapter 91. Transfusion Medicine.

Welcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.I'm Pradip Kamat and I'm Rahul Damania. We are coming to you from Children's Healthcare of Atlanta - Emory University School of Medicine.Welcome to our episode, which is Part 2 of our acute severe asthma management. Today we discuss invasive mechanical ventilation of the acute asthmatic.A patient with a history of asthma presents to the PICU with decreased air entry. Somnolence. Hypercarbia and drooling. The patient is hypoxemic and has see-saw breathing.Rahul: Let’s dive right into this. What are the indications for intubating a child with acute severe asthma?Absolute indications include:Altered mental status which may be preceded by obtundation, agitationCardiac and respiratory arrestRelative indications decided on a case by case basis:Progressive exhaustion-despite, despite maximal therapy. Profound hypoxemia refractory to supplemental oxygen administration, and respiratory failure.The decision to intubate should not be solely determined based on blood gas results.Pradip, can you shed light on how we prepare for the intubation of the patient with acute severe asthma?Rahul, first and foremost- we take the intubation of an asthmatic very seriously. In fact we try the whole “kitchen sink” to avoid intubation. But there will be times when we have to intubate especially for the indications you mentioned above.The intubation will worsen the patient’s bronchospasm, put the patient at risk for barotrauma as well as cardiovascular collapse.Preparation is the key- A team huddle and mapping prior to proceeding to intubate is the key. Every person in the room should have clear roles and responsibilities. Scenarios of what to do if “X” happens should be clearly laid out to the team by the team leader (preferably the attending or a senior fellow). The senior-most experienced person should manage the airway. At least two dedicated RTs to provide bag-mask ventilation as well as manage the ventilator are required. Nursing roles to push meds, chart the vitals and other activities as well a role for the resource nurses to help in case of cardiac arrest should be clearly laid out. Additionally, facilities that have access to isoflurane should have that ready to go. We typically give a heads up to our ECMO team to be on stand-by.Prior to Intubation: Have central access or multiple large-bore PIVs if possible. Keep crystalloids boluses ready for hypotension. We also have peri-arrest epinephrine as well as an epinephrine infusion ready for any hypotension, bradycardia, or cardiac arrest. For intubation, we typically use Ketamine, fentanyl, and rocuronium (some centers may use succinylcholine). We use cuffed endotracheal tube. We don't bag-mask at fast rates but rather wait for a full expiration prior to the next breath being delivered. These patients require slow respiratory rates with very prolonged expiratory times to allow for adequate gas exchange and lung volumes. A helpful technique is to use a stethoscope to auscultate at the lower neck for the disappearance of expiratory wheezes prior to starting the next inspiration. We sometimes place a nasogastric tube to prevent gastric distension.If there is hypoxemia, hypotension, not improving with fluids, ventilator manipulation, - A consideration for tension pneumothorax should be given especially if there is asymmetric chest rise. Bedside POCUS can be used to make a diagnosis.Intubation of an asthmatic is a high-risk procedure and requires a team approach, proactiveness, and anticipation. Intubation should be approached cautiously in patients with severe acute asthma exacerbations because manipulation of the airway can cause laryngospasm and worsening bronchoconstriction.Rahul, what are some of the principles we should all follow prior to initiation of mechanical ventilation in an asthmatic after intubation?It is important to note that most complications of intubating an asthmatic happen in the immediate post-intubation period. Hypoxemia, hypotension, tension PTX/air leaks as well as cardiac arrest can happen immediately upon initiation of positive pressure ventilation. An important cause of hypotension is hyperinflation and decreased venous return. So slowing down manual bag-mask ventilation of even disconnecting the bag and allowing for a brief period of apnea while applying manual pressure to the rib cage may help decrease hyperinflation. Hypotension should respond to fluid boluses and decrease manual bagging.Dynamic Hyperinflation: Severe airflow obstruction results in incomplete exhalation resulting in dynamic hyperinflation (DHI). Progressive DHI leads to an end-expiratory lung volume reaching a new equilibrium that exceeds the functional residual capacity. In the early stages of asthma, the increased lung volume increases pulmonary elastic recoil pressure thus increasing pulmonary expiratory flow and expanding small airways thus decreasing expiratory resistance. Thus lung volume will reach a point where the entire tidal volume can be expired during the available exhalation time. However, this process becomes maladaptive in severe asthmatic such that hyperinflation required to maintain normocapnia cannot be maintained as it would expand total lung capacityPositive pressure ventilation worsens DHI especially if ventilator settings are aimed at normocapnia. This will also increase the risk of hypotension and pneumothorax. The initial rule of thumb would be to use low Tidal volumes and low respiratory rates to allow for controlled hypoventilation and permissive hypercapnia.Pradip, with the above is mind what are your initial ventilator settings?We typically use pressure regulated volume control (PRVC) to set a TV of 8-12m//kg (reduce to generate a plateau pressure of ~30 cm H2O), respiratory rate of 6-10/minute time of 1-1.5 seconds, which allows for an expiratory time of 4-9seconds. in the patient with NMB, we set PEEP initially at zero. Peak pressures in the 50s are expected initially due to airflow obstruction but plateau pressures of 30 or below should be reassuring.An inspiratory hold will determine the plateau pressure whereas an expiratory hold will give us information about the auto-PEEP. The applied PEEP should be set below the auto peep in a spontaneously breathing patient in order to decrease the trigger work.Another ventilation strategy, which is comfortable for the patient is the use of pressure support ventilation with PEEP. PEEP narrows the gap between proximal and distal airway pressures during the hyperinflated obstructed state. Pressure support facilitates inspiration while decreasing the work of breathing. The patient determines the time, respiratory rate, and depth. of each breath.In summary: RR 10-12/min; Tidal volume: 6 to 8 mL/kg; set the sensitivity for triggering a ventilator-assisted breath at -2. Allow increased expiratory time by decreasing the I:E ratio (1:3 or 1:4 up to 1:5).Rahul, What are the variables you closely monitor during the ventilation of a child with acute severe asthma?Frequent auscultation of the patients’s chest at the bedside, observing vital signs including hemodynamics is helpful. Watching flow volume, PV loops gives useful information about patient’s condition. Monitoring peak-to-plateau pressure differences tell us about improvement in airway resistance. in response to therapy.Following the capnography waveform can give us information about lung emptying.Rahul, what are the sedation-analgesia-neuromuscular blockade therapies used in the child intubated for Near-fatal asthma.We prefer to use ketamine with low-dose benzodiazepines such as midazolam. We initially chemically paralyze the patient using rocuronium to abolish spontaneous respirations which can add to the DHI and hypercapnia. If we use isoflurane gas we D/C all other sedatives a, analgesics and NMBs. The use of steroids along with NMB can add to the neuromuscular weakness in such critically ill patients. Consideration for early stooping of NMB should be given.Pradip, can you talk about the use of isoflurane in a child with NEAR fatal asthma?Inhalational anesthetics such as isoflurane can be delivered by means of an anesthesia machine that feeds into the low-pressure gas port of a conventional mechanical ventilator or via a dedicated anesthesia ventilator with its own vaporizer. Isoflurane is preferred over others has it has no negative inotropic effects although it can cause hypotension due to peripheral vasodilatation. Typical concentration used is 0.5-2%. Appropriate scavenging of the waste gas is important so as to not expose the staff. The exact mechanism of action remains unclear. although studies indicate that inhaled anesthetics reduce vagal tone and reflexes as well as alter circulating catecholamines and ß receptor sensitivity. Inhaled anesthetics may also have a direct relaxation effect on the airway smooth muscle. Potential neurotoxicity especially in the very young is a concern and withdrawal with prolonged use has been seen. Improvement is seen as early as within 30 minutes of initiation of isoflurane and typically by 12 hours. Some refractory cases may need isoflurane for 2-3 days. Inhaled anesthetics should not be used in patients at risk for malignant hyperthermia.To summarize, isoflurane is an inhaled anesthetic that can be employed in near-fatal asthma by creating smooth muscle relaxation in the respiratory tree. As isoflurane is a potent anesthetic that has a smooth muscle relaxation effect, we must be mindful of the Rahul, what is the role of ECMO in NEAR Fatal asthma?Some refractory cases of NFA that do not respond to isoflurane or have severe air leaks, cardiac arrest may be candidates for ECMO. Mechanical ventilation of patients with NFA is challenging, and high ventilator settings may cause lung injury and hemodynamic instability secondary to barotrauma and dynamic hyperinflation.A more recent ELSO registry query (Crit Care. 2017;21(1):297.) for ECMO support for adults with asthma found successful decannulation in 86.7% and survival to discharge of 83.5%, with nonsurvivors being older in age, with lower pH and higher PEEP, higher post-ECMO oxygen requirement, and post ECMO driving pressures significantly associated with in-hospital mortality. The use of full-flow VV ECMO for refractory asthma in children is not uncommon and has been described previously as case reports and small studies. An ELSO registry report (published in CCM 2009) on ECMO use in children with SA reported a median time of ECMO support of 94 hours and was associated with 94% survival. Nine percent of the children placed on ECMO had a cardiorespiratory arrest before ECMO initiation. The presence of cardiorespiratory arrest or neurological injury was not associated with higher mortality.A more recent study of children with rhinovirus (Pediatric pulmonology 2020) reported a survival rate of 100%.Pradip, as these patients have hypoventilation due to obstruction, what are some of the cutting-edge therapies recently highlighted in the literature?ECCO2R (or AVCCO2R-requires double lumen cannula) is a more recent strategy and is designed to remove CO2, but, unlike ECMO, does not provide significant oxygenation. Essentially, ECCO2R consists of a drainage cannula placed in a large central vein, a pump, a membrane lung, and a return cannula, or a double lumen VV cannula. Blood is pumped through the membrane and CO2 is removed by diffusion. In contrast to ECMO, where the need for oxygenation requires high blood flow rates, ECCO2R allows much lower blood flow rates. ECCO2R does not provide for oxygenation which ultimately most NFA patients require due to viral or bacterial infection, as well as doesn't provide hemodynamic support as ECMO would. There are no randomized controlled trials or large studies to compare the outcomes of ECMO versus ECCO2R in children with asthma to assess the superiority or benefit of one over the other.In Chapter 50 in Furhman, Zimmerman’s textbook of Pediatric Critical Care, Dr. Steve Shein, and colleagues highlight that the use of extracorporeal life support (ECLS) has been reported in the management of the very few patients with near-fatal asthma who continue to exhibit a profound degree of clinical instability despite maximal therapy. Moreover, only 4% of patients in the Extracorporeal Life Support Organization registry have had runs for near-fatal Asthma. The survival rate for persons with near-fatal asthma necessitating ECLS is approximately 81%, which is remarkable considering that the vast majority of these patients were extraordinarily sick and had failed to respond to very aggressive treatment.To Summarize:Intubation of an asthmatic is a high-risk procedure and requires a team approach, proactiveness, and anticipation.Ventilator strategies include allowing time for expiration by modulating the I:E ratio and decreasing the RR and TV.Isoflurane & ECMO are last-ditch efforts in near-fatal asthma and should be performed in quaternary care facilities.References:Medar SS, Peek GJ, Rastogi D. Extracorporeal and advanced therapies for progressive refractory near-fatal acute severe asthma in children. Pediatr Pulmonol. 2020 Jun;55(6):1311-1319. doi: 10.1002/ppul.24751. Epub 2020 Mar 30. PMID: 32227683.Werner HA. Status asthmaticus in children: a review. Chest. 2001 Jun;119(6):1913-29. doi: 10.1378/chest.119.6.1913. PMID: 11399724.Demoule A, Brochard L, Dres M, Heunks L, Jubran A, Laghi F, Mekontso-Dessap A, Nava S, Ouanes-Besbes L, Peñuelas O, Piquilloud L, Vassilakopoulos T, Mancebo J. How to ventilate obstructive and asthmatic patients. Intensive Care Med. 2020 Dec;46(12):2436-2449. doi: 10.1007/s00134-020-06291-0. Epub 2020 Nov 9. PMID: 33169215; PMCID: PMC7652057.More information can be foundFuhrman & Zimmerman - Textbook of Pediatric Critical Care Chapter 50 entitled AsthmaThis concludes our episode on Near-Fatal Asthma. We hope you found value in our short, case-based podcast. We welcome you to share your feedback, subscribe & place a review on our podcast! Please visit our website picudoconcall.org which showcases our episodes as well as our Doc on Call management cards. PICU Doc on Call is co-hosted by myself Dr. Pradip Kamat and Dr. Rahul Damania. Stay tuned for our next episode! Thank you!

Welcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.I'm Pradip Kamat and I'm Rahul Damania. We are coming to you from Children's Healthcare of Atlanta - Emory University School of Medicine.Welcome to our Episode a 15 mo F with respiratory distress and runny nose.Here's the case:A 15 mo F presents to the ED with cough, runny nose, and increased work of breathing. Her mother states that the patient has had these symptoms for the past three days, however, the work of breathing progressed. The patient has had 2 fevers during this course, with the highest 101F. She says that her 3 yo cousin who she visited for the holidays had similar symptoms. Mother notes decreased PO and wet diapers. The patient presented to the ED with the following vital signs: T 38.5C, HR 155, BP 70/48 (MAP 50), RR 48, 92% on RA. The patient on the exam was noted to be tachypneic with abdominal retractions, grunting, and nasal flaring. The patient was nasally suctioned and initiated on 12 L 40% of HFNC. The patient was then transferred to the PICU for further management.To summarize key elements from this case, this patient has:Increased work of breathing indicates respiratory distress.She has a prodrome of symptoms that worsened prior to presentationAnd a sick contact.All of which brings up a concern for acute respiratory failure requiring non-invasive positive pressure ventilation in the form of HFNC.Let's transition into some history and physical exam components of this case?What are key history features in this child who presents with respiratory distress & URI sx?Usually, children under the age of two with bronchiolitis will present with cough, respiratory distress, and crackles on lung exam.The crackles indicate atelectatic alveoli that are filled with fluid which occurs due to inflammatory processes in the lung triggered by respiratory viruses.Respiratory distress, increased work of breathing, respiratory rate, and oxygenation all can change rapidly with crying, coughing, and agitation.Are there some red-flag symptoms or physical exam components in a child with acute respiratory distress which you could highlight?That is a great question. We really want to highlight the distinction between respiratory distress and respiratory failure.Children with respiratory failure in our case may have issues with oxygenation or ventilation as well as increased work of breathing that necessitates higher levels of respiratory support like HFNC.In a 2003 Journal of Pediatrics study, infants who were most severely affected with bronchiolitis were born prematurely, <12 weeks of age, or who have underlying cardiopulmonary disease or immunodeficiency. These children are at risk for apnea and respiratory failure which may require escalation to mechanical ventilation.Finally, Infants with bronchiolitis may have difficulty maintaining adequate hydration because of increased fluid needs and metabolic demand. Remember these children will have increased insensible losses due to fever and tachypnea, as well as decreased oral intake related to their systemic illness.To continue with our case, the patient's labs were consistent with:Mild hyper NA 149All other electrolytes were within normal limits.The patient had a respiratory viral panel which was positive for Rhino/Entero and RSV. Her COVID PCR was negative.A CXR was performed and showed alveolar airspace disease consistent with I would like to highlight an important point, with the exception of otitis media, a secondary bacterial infection is uncommon among infants and young children with bronchiolitis. In a nine-year prospective study of 565 children (<3 yo) hospitalized with documented RSV infection published in the Journal of Pediatrics, subsequent bacterial pneumonia was present in only 0.9 percent of these. Yes, Rahul, that is a great point. The risk of secondary bacterial pneumonia is increased among children who require admission to the intensive care unit, particularly those who require intubation.Ok to summarize, we have:A 15 mo F who presented with URI symptoms and respiratory distress was admitted to the PICU with Rhino/Entero, & RSV+ bronchiolitis with concurrent community-acquired PNA. We would like to focus the rest of this podcast on discussing the use of HFNC, its principles of action, and the data surrounding its use in the PICU.Before we get into this topic, let’s start with a short multiple-choice question:A 13 mo ex-34 week infant presents to the ED with increased work of breathing, tachypnea, and hyperthermia. The patient is on a home 1/8 L nasal cannula and has no echocardiographic evidence of pulmonary hypertension on prior follow-up. HFNC is initiated at 1.5 L per kg. Which of the following responses best describes the MOA of HFNC?A. Increased nasopharyngeal dead spaceB. Decreased humidification of gasC. Negative distending pressureD. Reduction in upper airway resistance.The correct answer here is D. Reduction in upper airway resistance. By providing gas flows that match or exceed spontaneous inspiratory flow rates, HFNC minimizes inspiratory resistance across the nasopharynx. The resultant reduction in work of breathing has been demonstrated in studies in neonates and infants by measuring diaphragmatic electrical activity and respiratory plethysmography.Rahul, what does the literature say regarding positive distending pressure with the use of HFNC?The data is definitely mixed but leans towards not HFNC not providing clinically significant PEEP. In a study of infants with bronchiolitis published in 2013 in Intensive Care Medicine, a flow rate of 2 L/kg per minute resulted in mean pharyngeal pressures >4 cm H2O as measured by transesophageal probes and improved breathing.Subsequent studies have documented a difference in increased pharyngeal pressure during HFNC when the mouth is closed compared with when it is open. So if you are going to use HFNC to promote distending pressure concurrent use of a pacifier may be helpful in achieving the full benefit of HFNC.To summarize key principles of how HFNC let’s review some respiratory physiology:Rahul, what is Dead Space?Dead space is the volume of air that is inhaled that does not take part in the gas exchange, because it either remains in the conducting airways or reaches alveoli that are not perfused or poorly perfused.This means that not all the air in each breath is available for the exchange of oxygen and carbon dioxide.HFNC creates a washout of nasopharyngeal dead space and creates a richly oxygenated reservoir of air. This reserve in the upper airway is what the patient draws from with each breath, minimizing the entrainment of room air and also decreasing the amount of CO2 in the anatomic zone of the respiratory tree.What are key concepts related to Airway Resistance in Pulmonary Dynamics?West Physiology defines airway resistance as the change in transpulmonary pressure needed to produce a unit flow of gas through the airways of the lung.More simply put, it is the pressure difference between the mouth and alveoli of the lung, divided by airflow. Bronchiolitis creates a decrease in airflow thus increasing airway resistance. As HFNC increases flow, i.e. the denominator of our equation, It reduces resistance in the airway tree.By providing gas flows that match or exceed spontaneous inspiratory flow rates, HFNC minimizes inspiratory resistance across the nasopharynx.In a study published in 2009 in Respiratory Care, it was hypothesized that the resultant reduction in airway resistance which high flow provides the decrease in WOB. This was especially studied by measuring infant diaphragmatic electrical activity.Rahul, what is the last major mechanism of a high-flow nasal cannula?HFNC reduces the energy expenditure required by the body to condition air. It does this by delivering heated and humidified gas. This also promotes less bronchospasm which would occur with the delivery of cold air.Pradip, in your experience, what are disease states we see in the PICU that are most amenable to HFNC?Many causes of respiratory distress can respond to the use of HFNC. In this state, I would recommend that providers start HFNC, and then ensure close monitoring and frequent reassessment of these patients to ensure response as well as the need to escalate respiratory support.Conditions for which HFNC can be used to include conditions such as Asthma, Tracheomalacia, Apneic Oxygenation, and Bronchiolitis.HFNC should not delay advanced airway management in a patient deemed to require immediate endotracheal intubation. This may include patients with acutely impaired mental status, risk of aspiration, or other needs for airway protectionYes, thank you for highlighting this, HFNC should be avoided in patients who have facial anomalies that preclude appropriate nasal cannula fit (like choanal atresia). Children who have active vomiting, bowel obstruction, or even sensory issues which may create Agitation may be some relative contraindications for HFNC. Lastly, I would also not delay escalation in invasive respiratory support especially if the patient does not have a significant change in hemodynamic (such as a decrease in HR) or oxygenation parameters after about 4 hrs on HFNC therapy.Finally, HFNC oxygen therapy is considered an aerosol-generating procedure. Thus, appropriate infection control precautions are required when it is being administered to patients with unknown or positive coronavirus disease 2019.This concludes our episode on bronchiolitis and HFNC. We hope you found value in our short, case-based podcast. We welcome you to share your feedback, subscribe & place a review on our podcast! Please visit our website picudoconcall.org which showcases our episodes as well as our Doc on Call management cards. PICU Doc on Call is co-hosted by myself Dr. Pradip Kamat and Dr. Rahul Damania. Stay tuned for our next episode! Thank you!

Welcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.I'm Pradip Kamat and I'm Rahul Damania. We are coming to you from Children's Healthcare of Atlanta - Emory University School of Medicine.Welcome to our discussion today on airway clearance in the critically-ill patient in the PICU. We will focus on the use of pharmacological as well as non-pharmacological techniques in critically ill children admitted to the ICU. This episode will be a general overview as specific clinical scenarios such as NM disease may warrant specific therapeutics.Let’s get started with the case:We have an 8-month old ex-34 week premie intubated for acute respiratory failure secondary to RSV bronchiolitis. The patient is on a conventional mechanical ventilator receiving a TV of 6ml/kg, rate of 20, PEEP 6, 40% FiO2 inspiratory time of 0.7CXR shows a pattern suggestive of viral pneumonia with minimal hyperinflation and atelectasis of the right middle lobe. The patient has excessive secretions when the suction catheter is assessed. The patient is hemodynamically stable and is on feeds via a NG tube.Rahul, Can you comment on how a child clears his/her pulmonary secretions normally when not ill?That's an excellent question. Normally some baseline secretions are produced by all humans. Normal bronchial secretions are made up of contributions from mucus-secreting (goblet)cells as well as cells secreting serous fluid. The ciliary epithelium made of columnar cells line the entire tracheobronchial tree up to the alveolar ducts. This ciliary epithelium provides the coordinated rhythmic force that propels the overlying “mucus blanket” towards the central airways and upper respiratory tract.Primary mechanisms of tracheobronchial clearance of these secretions consist of (1) The mucociliary (MC) escalator in the smaller airways and (2) Cough in central and larger airways. The co-ordinating activity of the beating cilia and their interaction with the overlying viscoelastic layer of mucus makes up the mucociliary escalator. The MC escalator helps remove both healthy and pathologic secretions from the airways as well as the removal of inhaled particles. This MC transport can be affected by mycoplasma, influenza and other viruses as well as exposure to toxins (cigarette smoke, vaping) as well as in CF, asthma, COPD, and ciliary dyskinesia just to name a few.Once the secretions are in large or central airways they are coughed out or swallowed.Let’s transition and talk a little on how one generates an effective cough:For an effective cough one needs firstly to take a sufficiently deep breath in.The glottis needs to close briefly to allow an increase in intrathoracic pressureThis is followed by expulsive glottic opening together with abdominal contraction, which results in air being forcibly expelled. Individuals with neuromuscular disease, bulbar insufficiency, obtunded patients, those on MV with chemical neuromuscular blockade, severe skeletal deformity may have decreased cough expiratory airflow. Reduced ability to cough results in secretion retention, mucus plugging, atelectasis and pre-disposition to infection even if the MC escalator function is normal.Q2. Pradip can you tell us about atelectasisThis is a great question. The term atelectasis means “imperfect expansion” and indicates reversible loss of aerated lung with otherwise normal lung parenchyma.Thats a nice concise definition, so if atelectasis reperesents imperfect expansion, what are mechanisms which keep our lungs open?There are three major mechanisms:1. Pulmonary Surfactant 2. Collateral Ventilation 3. Lung & Chest Wall BalanceLet’s go into each of these in more detail:A pulmonary surfactant that covers the large alveolar surface is composed of phospholipids (mostly phosphatidylcholine), neutral lipids, and surfactant-specific apoproteins (termed surfactant proteins A , B , C , and D ). By reducing alveolar surface tension, pulmonary surfactant stabilizes the alveoli and prevents alveolar collapse.There is a collateral ventilating mechanism (intra-alveolar pores & bronchiole-alveolar communications) that prevents alveolar collapse. Inter-alveolar pores by which alveoli are connected to each other via are called the Pores of Kohn. There also exist connections between distal bronchioles and neighboring alveoli called channels of Lambert. These structures can aerate hundreds of alveoli adjacent to a bronchiole preventing the collapse of one in case there is resorption of the air from that alveolus. Resorption occurs when an airway becomes occluded, the air is trapped in lung units ventilated by that airway, and the trapped gases are absorbed by the blood perfusing that part of the lung. Oxygen is absorbed faster than nitrogen from the alveolus into the blood resulting in collapsed lungs postoperatively especially if high O2 concentrations are used.The balance between Inward recoil of lung tissue and outward expansion of the chest wall (myo-elastic element: smooth muscle fibers interwoven with elastic fibers in distal airways and alveolar sacs) is is opposed by an outward recoil of the chest wall. An exact balance of these forces is essentially FRC at end of exhalAnion. An imbalance of these forces which keep lungs open can predispose to atelectasis. An example of chest wall inability to provide outward recoil is the reason a patient with pneumothorax develops lung collapseAwesome, let’s quickly summarize, atelectasis represents airway collapse, in order to keep alveoli open, our body’s mechanisms include pulmonary surfactant, collateral ventilation, and FRC.Let's transition and talk about the various types of atelectasis and the diseases we encounter in the PICU which can create an imperfect expansion of the alveoli? Surfactant deficiency or dysfunction: Infant with surfactant deficiency or neonate with prematurity.Children with ARDS or Near drowning, as well as hydrocarbon ingestion, can all have surfactant dysfunction which can lead to atelectasis.Resorption atelectasis (most common): high FIO2 concentration, intra-bronchial obstruction due to inflammation, infection, mucus plugs, and foreign body.Another mechanism is an extrinsic compression of the small airways. c) Compression of normal lung tissue: Pleural effusion, chylothorax, cardiac enlargement or tumors, Extra bronchial compression: vascular ring, lobar emphysema or by lymph nodesAll in all, when you have atelectasis you run the risk of having decreased lung compliance, impairment of oxygenation, increased pulmonary vascular resistance, and development of lung injury.In asthma and bronchiolitis, the right middle lobe and the lingula segment are the most common localization of the atelectasis and this is called the middle lobe syndrome. It is possible that hilar Lymph node enlargement due to viral infection and subsequent compression of middle lobe bronchus may be a cause of its preferred location.Pradip, what are the clinical consequences of atelectasis?This is a great question, and like many processes, clinical consequences Depend on the patient’s age, rate of formation, extent and of course the underlying cause of the atelectasis, however, let’s talk in general:Going back to our case, a critically -ill patient such as an intubated infant with bronchiolitis on moderate ventilator settings, development of atelectasis can lead to rapid deterioration. This is contrasted, In a clinically stable child admittedly postoperatively for a non-pulmonary reason who is on RA, a significant atelectasis may go completely unnoticed and detected only on a chest radiograph.5) Rahul how is atelectasis treated in the PICU patient admitted for acute illness (i.e without chronic neuromuscular condition)?One of the primary approaches to tackle atelectasis involves Airway clearance or chest physiotherapy or pulmonary toilet (an outdated term) refers to a spectrum of physical and mechanical interventions aimed at interacting therapeutically with acute and chronic respiratory disorders.Over the next few minutes we will cover some primary approaches, ranging from suctioning to manual CPT. To start,One of the simplest modality is suctioning. In infants and toddlers with small ETT tubes transport of secretions may be hampered by the size of the ETT. Sedation/NMB use may diminish the cough reflex. So the suction acts like a cough substitute. Type of catheter, its size, depth of insertion are all standardized and moist centers gave their own policies/procedures. Pre-oxygenation prior to suctioning or mechanical hyperinflation post suctioning can also be used.Another useful technique is postural drainage which is easily achieved in intubated patients: Gravity helps mobilize and transport secretions. If the atelectasis is in the right lung, then placing the patient in a left lateral decubitus position so that the right side is up will help open the right lung. This can be helped with chest percussion (RTs cupped hands or small cushioned mask or mechanical percussion devices), vibration, and even compression. I use this technique in small infants, and toddlers especially if they are intubated.That’s great and I should add that it is important to have a sedation management plan or algorithm adequately balanced to the patient’s needs during these interventions.Additionally, gentle bagging-(sometimes with saline lavage)-leading to an increase in lung volume and manual hyperinflation may help open a lung segment up. We need to be careful not to de-recruit the lung by frequent disconnection of the ventilator to do bag-lavage.Pradip what are some of the mechanical devices you use in the PICU to help conventional chest physiotherapy?This is a great question and to be honest, each type of chest PT has its risks and benefits, lets's review the most common. We will talk about:ISIPVMechanical In Ex (Cough Assist)Flutter/AcapellaVest therapyIncentive spirometry (IS): The basis of incentive spirometry involves having the patient take a sustained, maximal inspiration (SMI). An SMI is a slow, deep inspiration from the FRC up to the total lung capacity (TLC) followed by ≥5 seconds breath hold. An incentive spirometer is a medical device that facilitates SMI. The device gives the individual visual feedback regarding flow and volume and also prevent and reverse atelectasis when used appropriately and regularly.Patients who are at risk for developing atelectasis due to immobility especially post-operatively may be helped by the use of incentive spirometer. It can help improve lung volume, optimize oxygenation and maintain inspiratory muscle strength. One study by Fahd et al (Journal of Pediatric Hematology/Oncology) reported that mandatory IS for sickle cell disease patients admitted without respiratory complaints reduces transfusions and acute chest syndrome, particularly for those presenting with back pain.IPV: Intrapulmonary percussive ventilator: The IPV device delivers high-flow jets of air to the airways by a pneumatic flow interrupter at a rate of 100 to 300 cycles/min through a mouthpiece. The patient controls variables such as inspiratory time, peak pressure, and delivery rates. IPV has been shown to be beneficial for secretion clearance (particularly for cystic fibrosis patients) and improvement in atelectasis in intubated patients.Mechanical insufflator-exsufflator: CoughAssist is a portable, electric mechanical insufflation-exsufflation device that attempts to simulate a cough by using a blower and valve to alternately apply a positive and then a negative pressure to a patient’s airway to assist the patient in clearing retained bronchopulmonary secretions.Flutter and Acapella devices are small, handheld devices that provide positive expiratory pressure (PEP). Exhaling through the device creates oscillations in the airway, resulting in loosening of mucus.Percussive vests: A high-frequency chest wall vibrating/oscillating vest device has been shown to mobilize secretions in patients with cystic fibrosis and is commonly used as an adjunct airway clearance device in children with a reduced ability to clear secretions due to neuromuscular abnormalitiesRahul can you comment on some pharmacological approaches in the PICU?Saline: 0.9% saline enables clearance of secretions, especially in an intubated patient. 0.9% saline loosens secretions, lubricates the ETT, enhances cough as well as decreases viscosity of the secretions. Studies are mixed as to the benefit of using saline instillation prior to suctioning in intubated patients.One pediatric RCT (Riddling DA et. al. Am J Crit Care 2003) in postoperative patients with congenital heart disease showed no benefit with regard to incidence of VAP or mucus plugging. They also found (similar to adult studies) a drop in SpO2 from baseline in the group that used saline.Hypertonic Saline: Although shown to be beneficial in children with cystic fibrosis who are > 6 years of age, One study showed no benefit in children under 6 years of age.In bronchiolitis HS is believed to help by decreasing airway edema and thinning of mucus to alleviate plugging via the osmotic effect of HS. Literature about 3% HS has been conflicting at best with some studies showing benefit with regards to the length of stay and symptom score and others showing no benefit.A 2017 Cochrane database review published by Zhang et al reported that nebulised hypertonic saline may modestly reduce length of stay among infants hospitalised with acute bronchiolitis and improve clinical severity score. Treatment with nebulised hypertonic saline may also reduce the risk of hospitalisation among outpatients and emergency department patients. However, we assessed the quality of the evidence as low to moderate. Quality of evidence is moderate due to substantial clinical heterogeneity between studies and large multicenter trials are still warranted.Yes, Pradip, actually — One PICU randomized study by Shein et al (2016) reported on 18 intubated patients (9 in each group)- receiving either hypertonic saline or 0.9%NS used 4 times a day for 7 days. They found no difference in any outcomes measures between the two group after adjustment for baseline differences in respiratory parameters.So Pradip, I have heard of N-Acetylcysteine or Mucomyst used as a pharmacological — how does it work?N-acetylcysteine (mucomyst) : It hydrolyzes the disulfide bonds of mucins and other proteins. The sodium salts of NAC may also disrupt DNA. Animal studies suggest there may be some benefit to the airway due to its antioxidant effect, its use in ARDS has not shown any benefit although in one study in pediatric burn patients, the combination NAC and heparin resulted in lower rates of reintubation, atelectasis, and mortality. (Desai MH et al. J burn care rehabilitation).What about Dornase Alpha?Dornase alfa: is a recombinant human DNAase, which degrades DNA of the neutrophils, which migrate to the airway in inflammatory conditions. DNA from neutrophils increases the viscosity of the sputum and mucus plugging in the airway. Dornase decreases mucus viscosity and helps its clearance from the airway.A Cochrane database review from 2018 (Yang et al)reported improved lung function in patients with cystic fibrosis in trials lasting from one month to two years. There was a decrease in pulmonary exacerbations in trials of six months or longer. A meta-analysis from 2012 (Enriquez et al.) reported no benefit with respect to clinical scores in patients with bronchiolitis but longer duration of...

Join the PICU Docs as they discuss a case of a 3-year-old girl with cough and difficulty breathing. Explore topics like pediatric respiratory distress, asthma management, clinical respiratory score, risk factors of acute asthma, and management strategies for pediatric acute severe asthma.

The podcast discusses a case of an 8-year-old with altered mental status and seizures due to multi-system inflammatory syndrome, leading to intensive care and diagnostic tests. Topics include posterior reversible encephalopathy syndrome, lab trends correlating with steroid dosage changes, differential diagnosis, occurrence in various medical scenarios, general management framework, and prognosis of PRES.

Welcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.I'm Pradip Kamat and I'm Rahul Damania, and we are coming to you from Children's Healthcare of Atlanta - Emory University School of Medicine.Welcome to our Episode a 24-month-old girl with increased seizure frequency.Here's the case:A 24-month old girl presents to the ED with h/o shaking/jerking episodes in her sleep. The patient was in the care of her aunt when this acute episode occurred. When the father arrived from work, he saw his daughter having episodes of her body shaking alternating with heavy breathing. The patient would not wake up in between episodes. There was pertinently no history of trauma. 911 was called and when EMS arrived, she was starting to arouse and respond to stimuli. The patient was transported to the ED. In the ambulance, the patient continued to have similar shaking and jerking episodes and was given rectal diazepam. On arrival to ED, the patient had a fever of 38.5 Centigrade. Due to ongoing seizures, the patient was loaded with Fosphenytoin, after having been given a total of two doses of IV Lorazepam. The patient was subsequently intubated for airway protection and respiratory failure. A respiratory viral panel was negative for SARS-COV-2 but positive for Rhino-enterovirus. The patient was admitted to the PICU with cEEG monitoring and placed on mechanical ventilation with fentanyl + dexmedetomidine infusions with as needed Midazolam administrationsHer physical examination on arrival to the PICU was unremarkable. She wasn't interactive as she had just received sedation after intubation. On her neuro-examination, Pupils are equal and punctiform. The face is symmetric. The tongue is midline. Normal bulk and tone. No spontaneous movements were noted. No withdrawal to painful stimuli. Tendon reflexes were equal throughout. No clonus is noted.Rahul, to summarize key elements from this case, this patient has:FeverViral infection with Rhinoentero virusGeneralized Tonic clonic seizure lasting > 5minutesAcute respiratory failureAll of which brings up a concern for status epilepticusAbsolutely, we will get to this later on in the episode; however, remember that Status epilepticus is historically defined as single epileptic seizure of >30 minutes duration or a series of epileptic seizures during which function is not regained between ictal events in a 30-minute periodLet's transition into some history and physical exam components of this case?What are key history features in this child who presents with status epilepticus?Prolonged SeizuresFever with viral symptomatology which may act as a triggerA pertinent negative is that this patient had no history of trauma or co-morbid conditions such as a genetic syndrome.The patient also had no presumed ingestions as well.Are there some red-flag symptoms or physical exam components which you could highlight?Important to look for rash (darkening of the skin = adrenoleukodystrophy), genetic facies, evidence of trauma —-all of which are absent in this girlTo continue with our case, the patients labs were consistent with:Initial Labs: WBC 27K, with neutrophilic predominance, Hgb and platelets were normal. Initial CMP was normal except for a glucose of 233. Gas prior to intubation in the ED was 6.9/102/85/-9. (repeat after intubation 7.19/49/40/-9). Ionized ca 4.9mg/dl. A urine analysis was unremarkable.Head CT negativeOK to summarize, we have: 24-month-old girl who presented with prolonged seizures and acute respiratory failureAll of which brings up the concern for status epilepticus the topic of our discussion today.Let's start with a short multiple-choice question:A 14-year-old girl is brought to the PICU from the floor with new-onset status epilepticus. She was admitted to the floor on her second day after a posterior spinal fusion surgery and is still receiving intravenous fluids. Her seizure is described as generalized tonic-clonic. After initial stabilization and maintenance of her airway and hemodynamics, which of the following is most likely to reveal the cause of her seizures?A) Serum electrolytesB) Stat MRI brainC) Lumbar punctureD) cEEGRahul, the correct answer here is A) serum electrolytes. Patients especially after posterior spinal fusion surgery are at risk for hyponatremia secondary to SIADH or even hypotonic fluids used for maintenance. Correction of hyponatremia in a child with seizures requires 3% hypertonic saline. The seizure threshold is typically a serum Na of 125meQ/L. Serum electrolytes will also reveal the serum glucose which is especially important to check in infants who have seizures. A stat MRI is not warranted in this patient especially if she is alert and awake prior to the seizure. Additionally, it would be dangerous to send an unstable patient for an MRI. As the patient is afebrile, LP is less likely to be illuminating about the cause of her seizures. LP could be needed especially if there is a strong suspicion of infection such as meningitis but can be delayed if the patient is unstable and antibiotics initiated. While a CEEG may be needed especially if the patient is intubated or comatose and there is a risk of non-clinical seizures, it is not the first-line diagnostic tool.Excellent explanation Pradip, it is of utmost importance to make sure you assess for electrolyte disturbances or glucose abnormalities in your rapid diagnostics when patients are seizing. Remember hyponatremia, hypoglycemia, and hypocalcemia. If you have a child with Seizures As you think about our case, what would be your differential for rhythmic jerking movements that mimic or are associated with seizures?Movement disorders: Any abnormal involuntary movements such as Tics, tremor, chorea, athetosis, dystonia, myoclonus, ballismus, asterixis. Dyskinesia is a generalized term used for abnormal involuntary movementsMigraine (its paroxysmal nature + association with neuro-deficits or altered consciousness) may lead to confusion with seizures.In infants paroxysmal non-epileptic disorders such as jitteriness, benign neonatal myoclonus may be confused with seizureMyoclonus from drugs such as etomidate or post drowning due to hypoxia reperfusion injury may be mistaken for seizuresLet’s transition and highlight key definitions of status epilepticus:Previously defined as a seizure lasting > than 30minutes or recurrent seizures lasting > 30minutes without patient regaining consciousness between seizures. The new definition refers to SE as 5minutes or more of either continuous seizure or 2 or more discrete seizures between which there is incomplete recovery of consciousness.Refractory SE = SE that persists despite the administration of first and second-line anti-seizure medications with different mechanisms of action.Super refractory SE refers to SE that continues 24 hours or more after the onset of anesthetic therapy for SE and includes recurrence during reduction or withdrawal of anesthetic therapy.Pradip what is the most common cause of seizures in the pediatric population?The majority of pediatric SE (30-50%) involved febrile seizures. About 9-17% involved either acute metabolic derangement or a CNS infection. 12% of first seizures in children present with status epilepticus (Shinnar, Pediatrics 1996)What is the pathophysiology of seizures and its progression to status epilepticus?There is an imbalance between excitation and inhibition. Ineffective recruitment of GABA neurons coupled with excessive excitatory NMDA neuronal stimulation leads to initiation and propagation of the electrical disturbance in SE. Prolonged seizures lead to selective neuronal loss in the hippocampus, cortex, and thalamus.There is neurotoxicity due to excitotoxicity (via excess stimulation from glutamate on NMDA and AMPA receptors) as well as hypoxic-ischemic injury (imbalance between increased metabolic demand and cerebral blood flow/oxygenation). Hypoxia, acidosis, hypotension, and hypercarbia add to the ongoing damage.There are early (< 30minutes) and late (> 30minutes) time-related complications of status epilepticus which are nicely elucidated in the LearnPICU status epilepticus-pathophysiology. (http://www.learnpicu.com/neurology/status-epilepticus)The risk of subsequent epilepsy after status epilepticus is 26-36% (Barnard, J child Neurol 1999 and Eriksson, Develop Med Child Neurol 1997).Would you also mind highlighting the way seizures are classified?Seizures are classified as Partial or generalized based on clinical presentation or EEG FINDINGS. Partial Seizures arise in specific areas of the brain and are further classified as simple, local, or focal. Generalized seizures arise from diffuse cortical areas at one time. They involve both cerebral hemispheres and consciousness is typically impaired. Generalized can present as motor movements or absence seizures during which no convulsions are seen.If you had to work up this patient with status epilepticus what would be your diagnostic approach?I would start with some basic labs such as glucose, serum electrolytes including magnesium and calcium. I also typically add a DIC panel and CPK for especially for prolonged seizures.If there is concern for infection then CBC with differential, Lumbar puncture, CRP, procal, appropriate cultures (urine, blood, and CSF) should be sent. Virals studies such as HSV PCR from blood/CSF as well as a respiratory viral panel.Another thing to look at is the drug levels of any previous anti-epileptic agents (as agent withdrawal or change can precipitate seizures).In selected cases where inflammation is suspected- ESR, CRP, vWF antigen may be required. additionally, oligoclonal bands, testing for antibodies including neuronal and ion channel antibodies may be required from blood as well as the CSF.Rarely evaluation for toxins, metabolic disease, ophthalmologic evaluation may be needed in selected cases.In patients with established epilepsy- imaging is typically not necessary. Otherwise, brain imaging (either a CT or MRI) is required especially for a new status epilepsycEEG in the PICU is required especially if the patient is intubated or comatose as the patient could continue to have non-clinical status. The overall incidence of electrographic seizures in critically-ill patients was ~ 26%.Yes, Rahul - I would also like to highlight a “new-age technology” with regards to EEG.One study (Fung F. et al. Epilepsia 2020) devised a predictive model for capturing electrographic seizures in critically ill pediatric patients. The model had a sensitivity of 92% with a negative predictive value of 93%. Variables associated with increased capturing of seizures on this monitor included:age (<1 or >1 year of age)acute encephalopathy categoryclinical seizures prior to CEEG initiationEEG background (slow disorganized, discontinuous, or burst suppression background)epileptiform discharges during the initial 30minutes of the recording. We should be cognizant that equipment for cEEG, as well as staffing, may not be available at all centers.To summarize, these are the common causes of seizures in the PICU — AED withdrawal or change, drug toxicity or withdrawal, electrolyte problems, hypertensive encephalopathy, tumor, TBI, vasculitis, renal/hepatic dysfunction, fever, hypoxia/ischemia, and postoperative conditions. Pre-existing epilepsy, genetic and central nervous system disorders can also present with seizures. Intensivists should be vigilant about non-convulsive status especially in children who have hypoxic injury s/p cardiac arrest, submersion injury, TBI, and stroke.If our history, physical, and diagnostic investigation led us to status epilepticus as our diagnosis what would be your approach to general management?In the initial phase (0-5minutes): I would focus on stabilization of the patient’s airway/breathing and hemodynamics. Establish IV/IO access and supplement patients’ oxygenation and focus on correcting any abnormal glucose or electrolytes.Medications: Benzodiazepines (BZDs) are the first-line agents for status epilepticus.The BZDs work by potentiating the neuro-inhibitory effects of Gamma-aminobutyric acid (GABA).Lorazepam, diazepam and midazolam are frequently used.Zhao ZY et al. (J Child Neurol. 2016) in a network meta-analysis of 16 RCTs including 1821 patients which compared the efficacy of midazolam, lorazepam, and diazepam in treating pediatric status epilepticus concluded that non-IV midazolam and IV lorazepam were superior to IV or non-IV diazepam, and IV lorazepam was at least as effective as non-IV midazolam.Summary: IV Ativan and IV Midazolam if your patient has good access are equally effectiveYes, All the aforementioned benzodiazepines are lipid-soluble entering the brain within 2 minutes of IV administration.Diazepam has the highest lipid solubility and is also highly protein-bound and thus has a large volume of distribution of the unbound drug. Thus the effective duration of action for diazepam in SE is 20-30minutes resulting in rapid redistribution compared to lorazepam which has a much smaller volume of distribution of unbound drug and thus has a longer duration of action in SE. Hence lorazepam is the preferred agent in the initial management of SE.Midazolam can be given intranasally or intramuscularly inpatient without IV access. In fact, one study (Silbergleit R et al. NEJM 2012) showed that IM midazolam was as effective and safe as IV lorazepam for prehospital seizure termination. Rectal Diazepam is an option if unable to get IV access.How many doses of benzodiazepines would you give Rahul, and what is the pharmacokinetics to keep in mind?More than two doses of benzodiazepines are associated with side effects without a substantial increase in efficacy. The potency of BZDs decreases 20 fold over 30 minutes of SE. Receptor trafficking of GABAa receptors resulting in movement of the receptors from the synaptic membrane into the cytoplasm where they become functionally inactive. This reduces the number of GABAa receptors available on the synaptic surface to bind BZD, and in turn, leads to a single seizure becoming self-sustaining a time-dependent resistance to BZD develops. Additionally > 2 doses increases risk of respiratory depression (43% risk compared to 13% with < 2 doses). Furthermore, only 13% of patients achieved seizure termination

A podcast discusses the case of a 3-year-old girl with a cough and leg weakness, exploring the diagnosis and management of Guillain-Barre syndrome. They also delve into neurological conditions and their corresponding lesions, as well as the diagnostic approach and autonomic dysfunction in Guillain-Barre syndrome.