PICU Doc On Call

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.

Dr. Courtney Rowan, a pediatric critical care expert, discusses noninvasive ventilation failure in post-hematopoietic cell transplant children. Topics include risk factors, challenges in ventilation, and optimizing outcomes through early intervention.

Welcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.I'm Pradip Kamat and I'm Rahul Damania and we are coming to you from Children's Healthcare of Atlanta - Emory University School of Medicine.Welcome to our episode of a 14-year-old girl with sudden acute outbursts of aggression and severe agitation.Here's the case presented by Dr. Damania:A 14-year-old previously healthy teenager with no significant past h/o presents to the PICU with a three-day h/o of aggressive behavior, agitation, and screaming. Her mother reports that her daughter has recently developed insomnia, abnormal movements and is more irritable with temper tantrums and episodic unintelligible verbal output. Parents report no recent stressors at home or at school. She has been also complaining of headaches for the past week along with things "being too loud". She denies any vertigo symptoms or tinnitus. The patient is brought to the ER due to persistent auditory/visual hallucinations followed by agitation, aggressive behavior, and catatonia. There is no h/o of recent illnesses, head trauma, fevers, rash, abdominal pain, diarrhea, or vomiting. Social history is negative for drugs of abuse in the home. Family h/o negative for seizures, and psychiatric disorders.The patient is sent to the ED and upon arrival has an unprovoked convulsive episode concerning a GTC seizure. The patient was initially admitted to the floor but transferred to the PICU for management of severe agitation, aggressive behavior, and fluctuations of blood pressure and heart rate.Initial vitals in the PICU were notable for tachycardia. The patient was found to be afebrile, normotensive for age, and SpO2 96% on RA. Her physical exam though limited by her aggressive behaviors was normal. The heart, lung, and abdominal exams are normal with no rash or bruising on her body.Initials lab work includes a negative:U pregSerum and Urine tox screenCBC, CMP, and UA are all within normal limitsInflammatory markers — including ESR CRP are unremarkable.A head CT which was normal and an A lumbar puncture revealed colorless CSF with 8 white and 0 red cells. Serum and CSF glucose were within normal limits and protein count in CSF was negligible.An extended multi-disciplinary work-up is initiated.To summarize key elements from this case, Rahul this teenage girl has:Sudden outbursts of agitation, and aggressionRecent difficulty in sleepingIrritability, and decreased verbal outputAuditory and visual hallucinationsPotential autonomic dysfunction as she has fluctuating BP and HR All of which brings up a concern for neuropsychiatric symptoms that could be organic in nature.Let's transition into some history and physical exam components of this case?Rahul, what are key history features in the patient presented this case.Seizures, Agitation, and aggressive behavior which could reflect CNS dysfunction are seen in this case.The patient additionally has concern for hallucinations which point to a primary psychiatric disturbance as well. Remember the incidence of new-onset psychosis or schizophrenia in a child <13 is increasingly rare — 1 in 40K and thus identification and thorough workup for an organic cause is increasingly important.Rahul, are there some red-flag symptoms or physical exam components which you could highlight?The physical examination (although limited by her behavior) in this patient is negativeI would particularly stress the need for a detailed neurological and skin exam.For many of the differentials we will discuss, we must evaluate for rashes, changes in nails or hair, bruising or cutting marks in her arms, and even evidence of trauma to the (head and spine), and considering both an abdominal exam to r/o organomegaly as well as bi-manual pelvic exam is important to perform.Pradip, to continue with our case, the patient’s labs were consistent with?Rahul, actually her labs were normal. Besides the CBC, CMP being normal her presentation CRP & ESR were also normal. This was interesting as CRP and ESR are non-specific highly sensitive markers whose elevations may point to an infectious or inflammatory process.Speaking of infection or inflammation, a lumbar puncture was done and her CSF revealed zero red cells but 8 white cells with a normal protein and glucose.Thyroid studies include the presence of serum thyroid (thyroid peroxidase, thyroglobulin) antibodies. All of which were negative.As we continued to observe this patient's behavior in the PICU we expanded our CSF and serum studies. One of the panels which we sent from the CSF and serum was the auto-immune encephalopathy panel. The panel includes various Ab including:Glutamic Acid Decarboxylase (GAD) AbAquaporin-4 Receptor Ab,Gamma-Aminobutyric Acid Receptor, Type B (GABA-B-receptor) Ab, GFAP Ab,Voltage-Gated Potassium Channel (VGKC) Antibody, and many more.One essential Ab that is tested in the panel, which is an important differential in our case and one that has increased in media popularity, is the N-methyl-D-Aspartate Receptor (NMDA receptor) Ab. The book Brain on Fire by Susannah Cahalan published in 2012 and the subsequent movie released in 2016 has brought this diagnosis to the public limelight.OK to summarize, we have a 14-year-old girl with acute onset of neuropsychiatric symptoms and a working diagnosis of autoimmune encephalitis — the topic of our discussion today.Let's start with a short multiple-choice question: A patient presents with new-onset aggression, irritability, and seizures. A diagnosis of Anti-NMDA encephalitis is suspected, the subsequent test to confirm the diagnosis is:A) MRI chest, abdomen, and pelvisB) Serum antibodies against GLUN1 subunit of the NMDARC) CSF antibodies against GLUN1 subunit of the NMDARD) CSF antibodies against Leucine-Rich, Glioma-Inactivated Protein 1(LGI-1)Rahul the correct Answer is C. CSF antibodies against the GLUN1 subunit of the NMDAR. Answer A (MRI chest, abdomen, and pelvis) is not required for an initial diagnosis but make be required for the detection of teratomas (58% of young females have an ovarian teratoma). ( Answer B (Serum antibodies against GLUN1 subunit of the NMDAR) is wrong because of false-negative results in 14% of cases. False-positive serum results can also be seen in patients without anti-NMDA receptor encephalitis. Answer D (CSF antibodies against Leucine-Rich, Glioma-Inactivated Protein 1(LGI-1)) are typically seen in adults with anti-LGI1 encephalitis who have faciobrachial dystonic seizures, memory loss, hyponatremia, and paroxysmal dizzy spells. In our patient antibodies against the GLUN1 subunit of the NMDAR were detected in the CSF and the serum.As you think about our case, Pradip what would be your differentialAcute Demyelinating encephalopathies would be at the top of my differential. These would specifically be seen after an infectious trigger or vaccinCommon features on MRI would be an abnormality in gray and white matter with CSF testing suggesting Ab against myelin oligodendrocyte glycoprotein (MOG)Another differential I would consider is the Neuromyelitis Optica spectrum. The classic Ab associated with this condition is towards the aquaporin-4. MRI abnormalities adjacent to periventricular and ependymal regions are seen in these patients.Viral encephalitides are also going to be important to consider. Remember that encephalitis typically causes aberrations in mental status with or without meningeal signs.To transition outside of the CNS, I would also consider Hashimotos encephalopathy (serum antithyroid Ab, absence of neuronal Ab in serum and CSF).Autoimmune diseases like systemic lupus would be an important consideration — specifically the diagnosis of lupus cerebritis.Other rare causes of these neuro-psychiatric disturbances include:Bickerstaff’s brainstem encephalitis (characterized by subacute onset, in less than 4 weeks, of progressive impairment of consciousness along with ataxia and bilateral, mostly symmetrical, ophthalmoparesis). CSF pleocytosis (45%) and brain MRI is normal with brainstem abnormalities in T2- weighted FLAIR imaging is present in 23% of patients.Limbic encephalitis (Ab against GAD, CSF oligoclonal bands)Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) and its subset Pediatric autoimmune neuropsychiatric disorder associated with group A streptococcal infections (PANDAS)- is characterized by OCD and/or tic disorder, and a temporal relationship between symptoms and group A streptococcal (GAS) infection typically in prepubertal children. Controversy exists as to whether these conditions exist as distinct clinical entities. 💡 Great - so for our working diagnosis in this case Anti-NMDA receptor encephalitis let’s go through the diagnostic criteria.4 of the following 6 are required for a diagnosis: 1. abnormal (psychiatric) behavior or cognitive dysfunction, 2. speech dysfunction (pressured speech, verbal reduction, mutism), 3. seizures, 4. movement disorder, dyskinesias, or rigidity/abnormal postures, 5. decreased level of consciousness, 6. autonomic dysfunction or central hypoventilation.These symptoms must be with rapid onset typically less than < 3months.Laboratory study results include abnormal electroencephalogram (EEG) showing focal or diffuse slow or disorganized activity, epileptic activity, or extreme delta brush, cerebrospinal fluid (CSF) with pleocytosis or oligoclonal bands.Rahul, If you had to work up this patient with Anti-NMDA encephalitis, what would be your diagnostic approach in the PICU?MRI brain and spine: In our patient case the MRI showed: hyperintense signal on T2-weighted (FLAIR) sequences highly restricted to both medial temporal lobes involving both the grey and white matter suggestive of demyelination/inflammation.I would also do an EGG. Her EEG showed extreme delta brush pattern (rhythmic delta activity (1–3 Hz) with superimposed beta activity riding on each delta wave)Serum and CSF antibodies against the GLUN1 subunit of the NMDAR as explained previously were detected in this patient.If Anti-NMDA Ab is detected then an MRI of the ches,t abdomen, and pelvis to detect ovarian teratoma is necessary. The frequency of an underlying tumor varies with age and sex, ranging from 0–5% in children (male and female) younger than 12 years, to 58% in women older than 18 years (usually an ovarian teratoma). Adults older than 45 years have a lower frequency of tumors (23%), and these are usually carcinomas instead of teratomas.It is also important to evaluate for infections like herpes simplex virus (CSF PCR), arboviral diseases which can cause infectious encephalitis. A respiratory viral panel that includes SARS COV-2 must be obtained. 💡 Most patients with encephalitis undergo brain MRI at early stages of the disease. The findings could be normal or non-specific, but sometimes they might suggest an autoimmune cause. It may be necessary to repeat the MRI especially if the initial was performed early in the disease process and is normal.Additionally, a team approach with the neurologist, infectious disease, a rheumatologist is necessary prior to sending tests or obtaining imaging for optimal outcomes. The pediatric ICU fellow/attending needs to be the linchpin who updates the family on any results that are obtained from the various tests which are sent. Weekly care conferences with the family to answer the questions the family may have will help alleviate their anxiety and keep them up-to-date on their child's progress. As treatment modalities may have various responses, it is important to also focus on neuro-behavioral rehab for these patients and consider a consultation with in-patient PM&R colleagues.Rahul before we go to the management framework can you briefly inform us about the pathogenesis of anti-NMDA autoimmune encephalitis? The big picture pathophysiologic framework is simple: auto-immune attack and inflammation to neurons leading to neuro-psychiatric changes. To go into more detail:Antigens released from viral destruction of neurons or from tumors elicit an auto-immune reaction.The antigens released are transported by the dendritic cells to the regional lymph nodes, where the naive B cells become differentiated into memory B cells.The memory B cells enter the brain where they differentiate into antibody-producing plasma cells directed against in our case the N-methyl-D-aspartate receptor (NMDAR).In the case of Anti-NMDA encephalitis, there is cross-linking and internalization of the NMDAR leading to a decreased density of the NMDAR. The clinical features thus will resemble those observed with drugs like ketamine or phencyclidine, which work through non-competitive NMDAR antagonists.If our history, physical, and diagnostic investigation led us to Anti NMDA encephalitis as our diagnosis what would be your general management of framework?Good basic supportive care in the PICU, while maintaining patient and staff safety should be a top priority. A collaborative approach with neurologists, infectious disease, rheumatology, and neuroradiologists is necessary for an optimal outcome. The main job of the PICU team is to facilitate early diagnosis by the acquisition of MRI and other diagnostic studies. Intubation and CVL/arterial line may be required for procedure completion, and getting the blood for multiple labs draws and close follow-up labs. Neuroleptic agents such as haloperidol are best avoided in these patients but may be required in extreme agitation. Close monitoring of serum CPK and patient temperature may be required. An EKG to measure a baseline QTc. Sedation of an intubated patient may be challenging and ketamine should be avoided. Continuous EEG monitoring must be initiated if the patient is intubated.Current therapy involves the removal of immunologic triggers such as teratoma, tumors, and immunotherapy. No large randomized trials show the efficacy of any single therapy.In autoimmune encephalitis, most antibody production and inflammatory changes are behind the blood-brain barrier so it is not surprising that treatments that target serum immunologic triggers are rarely effective.Patients are treated with high-dose systemic steroids (followed by a taper), intravenous immune globulin, or plasma exchange. Rituximab may be...

Welcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.I'm Pradip Kamatand I'm Rahul Damania. We are coming to you from Children's Healthcare of Atlanta - Emory University School of Medicine.Welcome to our Episode of a 19 month old female with bloody stool, petechiae and no urine outputHere's the case presented by Rahul:A 19 month old previously healthy female was brought to the pediatric emergency department for blood in her stool. Patient was at daycare the previous day where she developed a low grade fever, congestion and URI symptoms along with non-bloody-non-bilious vomiting and diarrhea. Patient had a rapid COVID test which was negative and was sent home with instructions for oral hydration. That evening, patient began having vomiting/diarrhea which worsened. She was unable to retain anything by mouth and her parents also noted blood in her stool.Due to this, she was rushed to the Emergency Department. In the ED here, she was hypertensive for age BP of 124/103 mm Hg, febrile, and ill. Specks of blood were noted on the diarrheal stool in the diaper.On her physical exam she was noted to be pale with petechiae on neck and chest. Her abdomen was soft, ND, with some hyperactive bowel sounds, and no hepatosplenomegaly. The rest of her physical examination was normal.In the ED, initial labs were significant for WBC 19, Hgb 8.8, and Platelets 34. CMP was significant for BUN of 74mg/dL and Cr of 3.5mg/dL, Na 131 mmol/L, and K of 5.5mmol/L, Ca 8.3mg/dL (corrected for albumin of 2.2g/dL), Phosphorous 8.5 AST 413, and ALT of 227, LDH > 4000. BNP was 142 and troponin negative. She was given 1 dose of CTX 50mg/kg and a 20cc/kg NS bolus. Stool PCR was sent. She was given labetalol for her hypertension, started on maintenance IV fluids and transferred to the PICU for further management.Rahul to summarize key elements from this case, this patient has:We have a 19-month old child withDiarrhea and emesis X 2 daysNo urine output for over 24 hoursBloody stoolPetechiae on the neck and chestAnemia and thrombocytopeniaAll of which bring up a concern for hemolytic uremic syndrome the topic of our discussion todayLet's transition into some history and physical exam components of this case.What are the key historical features in this child who presents with above?Bloody stool which alludes to an invasive diarrheaNo urine output and an ill appearing state which points to a systemic inflammatory condition and end organ dysfunction.Are there some red-flag symptoms or physical exam components which you could highlight?Presence of petechiae which are physical exam features of thrombocytopeniaHer pallor which is a physical exam sign of anemiaHypertension which is related to her renal dysfunctionTo continue with our case, the patient's labs were consistent with:AnemiaThrombocytopeniaElevated BUN and creatinineElevated serum LDHThe patient did not have hyperkalemia, or acidosis on initial presentationOK to summarize, we have a 19 month old girl with:Anemia, thrombocytopenia, and renal failure. This brings up the concern for Hemolytic uremic syndrome →Rahul Let's start with a short multiple choice question:A 2-year old boy is admitted to the PICU with acute respiratory failure secondary to pneumococcal pneumonia. On day # 3 of admission, the nurse reports the patient appears pale and has petechiae on his chest. The patient also has not had urine output for > 12 hours and appears to be fluid overloaded. Of the following the lab findings would be most consistent with the above clinical findings in the patient?A) Elevation of serum haptoglobinB) Low serum lactate dehydrogenase (LDH)C) Negative Direct Coombs testD) Peripheral smear showing schistocytesThe correct answer is D-Peripheral smear showing schistocytes.Patient in the above case most likely has streptococcus pneumoniae associated hemolytic uremic syndrome commonly called as pneumococcal HUS, an uncommon condition, which accounts for 5% of all cases of HUS in children. A peripheral smear will show the presence of schistocytes (which consists of fragmented, deformed, irregular red blood cells). The schistocytes represent RBCs that are partially destroyed as they traverse through the blood vessels partially occluded by microthrombi. Smear may also show giant platelets due to the rapid platelet turnover from peripheral destruction. Because HUS is an intravascular hemolysis serum haptoglobin should be low. Serum LDH along with indirect bilirubin are typically elevated. The Direct Coombs test detects antibodies that coat RBCs and may allude to this pathology. In pneumococcal HUS where there is antigen-antibody interaction on RBC cell surface, the Direct Coombs test may be positive in 90% of the cases. A direct Coombs test is highly sensitive for pneumococcal HUS, but the degree of specificity is unclear.A few points which I want to highlight classically on board exams, schistocytes look like helmet cells on blood smear. Also, presence of COOMBs positivity in the setting of hemolysis think about autoimmune hemolytic anemia (AIHA).Rahul As you think about our case, what would be your differential?            The following may sometimes be difficult to differentiate from HUSBacterial sepsis (History, clinical presentation with hemodynamic compromise and feature of distributive shock, fever with elevated WBC with neutrophil predominance, multiorgan presentation, source of infection, immunocompromised host etc)Disseminated intravascular coagulation (history of sepsis, drug, toxin eg snake venom, abnormal coagulation etc.)-In HUS the fibrinogen, PT, PTT are normal or slightly elevated and there is no active bleeding.Acute hemolysis from any other causes (drugs, toxins, warm-antibody, cold agglutinin disease, paroxysmal nocturnal hemoglobinuria etc.) -typical history, likely older patients, PNH post-viral in children.Hemophagocytic lymphohistiocytosis (HLH), acute macrophage activating syndrome (MAS), liver failure, TMA etc (good history, h/o JRA and other features may be helpful).Thrombotic thrombocytopenic purpura (older patient, neurological symptoms)The classic triad of hemolytic anemia, thrombocytopenia and renal failure is associated with hemolytic uremic syndrome can be seen on the spectrum of TTP — which adds fever and neurological symptoms to the diagnosis. In the pediatric population, TTP can be seen when children have acquired or congenital absence of ADAMS TS 13. Think of ADAMS TS 13 as a pair of scissors that cuts up vWF, an essential component of primary hemostasis. When you have a deficient or mutated ADAMS TS 13, which is a MMP, you end up having large vWF multimers which deposit in between endothelial cells which creates a consumptive thrombocytopenia and intravascular hemolysis. Pradip, do you mind building a framework between typical HUS versus Atypical HUS? Typical HUS is seen in patients with STEC diarrhea, or invasive pneumococcal disease, such as pneumonia. The atypical HUS is a term reserved for complement mediated HUS in which there is uncontrolled complement activation using the alternative pathway.Rahul, before we go into the diagnostic and management framework can you shed some light on the pathogenesis of HUS?The hemolytic uremic syndrome comes under an umbrella term called Thrombotic microangiopathy (TMA) syndromes. The clinical features of TMA include microangiopathic hemolytic anemia, thrombocytopenia, and organ injury. The pathological features are vascular damage that is manifested by arteriolar and capillary thrombosis with characteristic abnormalities in the endothelium and vessel wall.Let’s breakdown the three pathogenesis or sub-diagnoses:In STEC HUS (accounts for most of the HUS seen in children):Enterohemorrhagic E coli expresses adhesin called intimin, allowing the Shiga Toxin to enter the bloodstream.Once in the bloodstream the Shiga Toxin binds to globotriaosylceramide (Gb3, also known as CD77 or ceramide trihexoside) on endothelial cells, as well as to renal mesangial cells and epithelial cells.After endocytosis, the toxin causes ribosomal inactivation leading to cell death.Shiga Toxin is pro-inflammatory and pro-thrombotic and induces endothelial Von Willebrand factor resulting in thrombosis.Multiple E Coli species produce the Shiga toxin but E Coli 0157:H7 is the most common in Europe and North America. S. dysenteriae Type 1 is an important cause of Shiga toxin HUS in other countries. STEC HUS is seen in younger children (3-5 years). Severe disease is seen in those with high white counts on initial presentation, female gender and younger age.Pradip, what is the second subtype?Pneumococcal HUS (accounts for 5% of all HUS seen in children): Neuraminidase produced by the pneumococci cleaves the n-acetyl neuraminic acid from cell surface of platelets, RBC and glomerular cells and exposes the Thomsen Friedenreich (TF) crypt antigen. The TF antigen is typically hidden by the neuraminic acid. Once the TF antigen is exposed, preformed IgM antibodies bind to the TF antigen resulting in a cascade of events leading to hemolytic uremic syndrome.Finally, let’s talk about atypical HUS.Atypical HUS or complement mediated HUS accounts for approximately 10% of cases seen in children - what is the pathophysiology of this disease?In Atypical or complement mediated HUS the gain or loss of function mutations in complement regulatory protein results in uncontrolled activation of the alternative pathway of complement.Unlike the other two pathways of complement activation, the alternative pathway is constitutively active as a result of spontaneous hydrolysis of C3 to C3b.In the absence of normal regulation, C3b deposition on tissues may increase markedly, resulting in increased formation of the C5b-9 terminal complement complex (also called the membrane-attack complex) leading to endothelial injury and TMA.30% of patients may not have any mutation in complement genes at presentation. 80% of patients present with a fulminant course (after acute URI or viral gastroenteritis). Low C3 with normal C4 indicates alternative pathway activation. Extra-renal manifestations such as seizures, hemiplegia, diplopia, blindness, coma, cardiac and lung involvement are also seen.Rahul: If you had to work up this patient with HUS, what would be your diagnostic approach?Before we get into this, lets create a mental model: 1) Show evidence of hemolysis, 2) find a source/cause and 3) determine severity of organ involvementExcellently said, Initial tests include CBC with differential, peripheral smear, DIC panel, Direct Coombs test.A comprehensive metabolic panel, serum LDH, serum haptoglobin, complement levels (C3 and C4), urinary NGAL.Blood culture, stool PCR/culture, respiratory culture from ETTImaging and other diagnostics include: Chest radiograph, echocardiography, and renal ultrasound. Daily weights are highly recommended for the patient.Disease severity can be gauged by acidosis, hyperkalemia, LDH level and platelet count. Recovery of platelet count followed by decrease in LDH suggests improvement of hemolysis. Persistent hyperkalemia/acidosis suggests an urgent need for dialysis along with decreased UOP, fluid overload and weight gain.Other labs that may be needed on a case by case basis include ADAMTS-13 (needed for diagnosis of TTP) or complement 3 glomerulopathy (C3G) functional panel (Includes Complement Antibody Panel, Complement Biomarker Panel, Complement Pathway Panel). This will require great coordination between the nephrology, hematology, and ICU team.Pradip, If our history, physical, and diagnostic investigation led us to HUS as our diagnosis what would be your general management of the framework?After careful attention to airway, breathing circulation and good basic PICU care, supportive therapy is the cornerstone of the treatment of HUS patients admitted to the PICU.Let’s organize our management model into key PICU management components: fluid and electrolyte management, blood pressure control, transfusion thresholds, plasma exchange and antimicrobialFluid, Electrolytes and Nutrition:Early volume expansion especially prior to development of acute kidney injury has been shown to have also proven to lessen the need for renal replacement therapy (RRT) as well as reduce central nervous system-associated complications.Once AKI develops, the intensivist will have to work with the nephrologist to provide dialysis. Typically at our institution this is done using CVVH although peritoneal dialysis can also be used.CVVH will help reduce volume overload, correct electrolytes, acidosis and allow provision of nutrition. We typically use citrate regional anticoagulation.Blood pressure control:Hypertension is common in HUS.Early use of titratable IV nicardipine especially for severe hypertension followed by transition to PO meds is recommended.Blood and platelet transfusion:Transfusion of pRBCs should be considered only in symptomatic children whose hemoglobin is < 7gm/dL.Platelet transfusion must be restricted to active bleeding or invasive surgical procedures.Transfusion of fresh frozen plasma also should be avoided unless there is active bleeding.You're absolutely correct, FFP which contains clotting factors & complement mediators may actually fuel your inflammatory cascade. A discussion with blood bank/hematology may be required to see if there is a role for "dextran washed RBCs" which removes more than 95% of plasma from donor pRBCs.Rahul, is there a role for plasma exchange in these patients?Plasma exchange:No role for...

Welcome to PICU Doc On Call, a podcast dedicated to current and aspiring intensivists. My name is Pradip KamatMy name is Rahul Damania, a current 2nd year pediatric critical care fellow. We come to you from Emory University,School of Medicine, Children’s Healthcare of Atlanta, Atlanta, GA.Today's episode is dedicated to O2 delivery in the PICU. We would like to highlight in this episode Stanford University School of Medicine Pediatric Critical Care's LearnPICU website. The LearnPICU.com website Is dedicated to reviewing clinical topics related to pediatric critical care, and is an open access resources which Is widely accessed worldwide. The website has over 10,000 visits each month, and is managed by Dr. Kevin Kuo - Clinical associate professor of pediatrics pediatric critical care at Stanford University. Dr. Kuo has Been featured on our prior episode entitled seven habits of highly effective Picu fellows, and we are very excited to collaborate with his educational resources to provide you the listener a comprehensive educational experience.Rahul, let's go ahead and get into today's case.A 17-year old boy is admitted after he was struck by a car at slow speed while crossing the street.He is has SPO2 of 98%, HR 98 bpm with a normal capillary refill and perfusion.His blood gas at admission to the PICU reveals a ph of 7.3/PCO2 35/PaO2 196 mm Hg on 50% NRB with 100% O2 flowing at 12LPM.His admission hgb is 10.5 gm%.4 hours post admission, the nurses noticed that the patient is tachycardic to 150s, with a drop in his BP, delayed capillary refill, with cool extremities and increased output from the chest tube.His SpO2 has decreased to 86% and PaO2 on his blood gas is now 65mm HG. He is found to have a POC Hgb of 6.8 mg/dL.Let’s take this case and highlight key components of O2 delivery and O2 consumption.Lets focus on O2 delivery first. Rahul What are the components of O2 delivery ? Pradip, O2 delivery is made of O2 content X Cardiac outputSimply put, O2 content is the amount of blood present in 100ml of arterial or venous blood. Its is denoted by CaO2 or CvO2 and its unit is mL O2 / dL blood or mL O2 per 100 mL of blood.Before we introduce the complicated formula, let's just appreciate the variables within the equation.Oxygen content is going to be a function of three variables:This is going to be Hgb, Saturations on the hemoglobin also known as SaO2, and the amount of oxygen that is dissolved within the blood also known as your PaO2.Pradip, Can you elucidate further about O2 content?O2 content is given by the formula: CaO2 = (1.34X Hgb gm/dl X SaO2) + (0.003X PaO2)Important points to remember about above formula is that the constant 1.34 (or 1.36 as given by some textbooks) is the amount of O2 in mL bound by one gm of Hgb and is called as the O2 carrying capacity of Hgb. In a healthy person say with 15gm% of Hgb, the O2 carrying capacity is about 15X1.34 = 20gm%.Now many times amount of O2 bound to Hgb may not always reflect 100% saturation So we need to factor the % oxygen saturation into the oxygen carrying capacity of the Hgb.The final element is to understand that some oxygen is dissolved in the plasma and is calculated using a constant 0.003 X PaO2. Typically 100ml of arterial blood with a saturation of 100 will contain 100 X 0.003 = 0.30ml of dissolved oxygen.Rahul can you calculate the pre-decompensation oxygen content in the above case?The above patients hgb pre-decompensation = 10.5gm%. His room air saturation 98% and his PaO2 is 196.CaO2 = (1.34X10.5X0.98) + 0.003 X 196 = 13.7 + 0.58 = 14.2ml O2/dL blood.Great - what is the post decompensation CaO2.?The post decompensation CaO2 can be estimated using same formula as above: CaO2 = (1.34 X 6.8 X0.86) + (0.003 X 65) = 7.8 + 0.195 = 7.9 O2/dL blood.Exactly So if you see the pre and post bleed O2 content just with a drop in Hgb from 10.5 to 7.5gm/dL: There is almost a 38% decrease in patients O2 content (8.83/14.2 = 62%,)What is the best strategy to increase the patients O2 content?First we can increase the patients FiO2 from 50% to 100% (immediate bedside action). We can get consent from family to order blood for transfusion.Increasing FiO2 will result in an CaO2 = (1.34 X 6.8 X1 ) + (0.003 X 65) = 7.8 + 0.195 of about 9. O2/dL blood.If we transfuse to a hgb of 10gm% with no increase in FiO2: we will get an CaO2 of (1.34X10X0.86) + (0.003 X 65) = 11.52 + 0.195 = 11.71 ml O2/dL.The summary of this is to understand that modulating the patients hemoglobin via transfusion gives greatest bang for your buck in terms of optimizing O2 contentExactly. Now, there is some value of increasing PaO2 in patients with acute severe hgb (say a Hgb of < 3gm/dL). Placing a child on 100% FIO2 NRB or placing child in hyperbaric chamber (diving & increasing PaO2) can increase CaO2 significantly. This is rarely used however may be indicated in patients who present with severe anemia with difficulty finding blood for transfusion due to antibody development etc.Except for acute severe symptomatic anemia,Hgb should not be the sole criteria to transfuse to improve O2 content. In fact recent studies report that liberal policy of transfusion may be associated with increased mortality compared to a more restricted (transfused only if Hgb < 7gm/dL). So you want to assess the clinical picture fully and identify, intervene, and reassess.Rahul, can you create a mental model related to O2 content in the blood for our listeners?Absolutely, I would like to create 2 mental models:As we reviewed, the variables in the oxygen content equation are:HgbSaO2PaO2So how do we measure these clinically?Well, in order to get the Hgb you order a CBCIn order to get your SaO2 you would place the patient on a pulse oximeterIn order to obtain your PaO2 to you or draw an ABGThus, your total oxygen content can be thought of as CBC, pulse ox, an ABG.This is great - What’s another way to think about CaO2?You can think about CAO2 by visualizing a car.Many of us have heard that hemoglobin is the car which carries oxygen throughout our body. So the car and its frame represents hemoglobin. The wheels on the car represents the saturations. Four wheels on a car, for binding sites on hemoglobin. And finally thinking about a car needing to travel on a fluid road, helps you remember that PaO2 is the dissolved O2 in the plasma.Pradip, we also talked about Venous oxygen content. How is that calculated?CvO2 is similar to CaO2 and it is calculated using the formula: 1.34XHgbXSvO2 + 0.003 X PvO2Typically, mixed venous O2 sat is used instead of SaO2 and PVO2 is used instead of PaO2. The blood gas is typically obtained from a central venous line with tip at SVC-RA junction.Now thtat we have defined CaO2 and CvO2 lets talk about the other component of O2 delivery and that is CO. remember DO2 = CaO2 x CO.Exactly, going into our Car analogy:Hgb representing the frame SaO2 being the wheels on a car and PaO2 being the fluid road which the car travels on,Remember that a car cannot run without a motor. SO what is that motor? It is CO.So just to summarize DO2 = CaO2 x CO.So Rahul, what is the AVO2 difference?It is The difference between CaO2 and CvO2 can be used as a measure of the adequacy of O2 delivery. Typically in a normal patient the CaO2 is about 20.5 mL O2/dL and the CVO2 is about 14.5mL O2/dL giving us an AVDO2 of 5mL O2/dL. The normal range is 4-6mL O2/dL.A decrease in DO2 will lead to higher O2 extraction and therefore a higher AV O2 difference. A lower AV O2 difference is seen when there is decreased O2 extraction such as in cyanide toxicity or sepsis.Rahul, lets shift gears to the next heading of our talk O2 consumption or VO2 - can you introduce this to us?VO2 is the amount of oxygen consumed by the tissues per minute. Certain condition can result in low VO2 such as hypothermia in the absence of shivering sedation/paralysis, coma, brain death, cyanide poisoning etc. Increased VO2 is seen with fever, pain, shivering, increased work of breathing, positive inotropes etc. VO2 (mL/min) is given by (CaO2-CvO2) X cardiac output, which uses the reversed Fick equation. VO2 = CI X AVDO2. IN ARDS or sepsis, VO2 may continue to increase even as DO2 increases above normal values. VO2 remains supply dependent to much higher levels of DO2 leading to pathologic supply dependency. The exact reason for this pathologic supply dependency is unknown.Pradip, help us understand O2 Extraction a bit more?It is important to understand that the DO2 in humans is around 620+/- 50mL/min per square meter. The O2 consumption in humans is typically in the range of 120-200mL/min per square meter. The body normally extracts only about 25% of the oxygen delivered to the tissues overall. O2 extraction (ERO2) is given by DO2/VO2 = 25%. OR AVDO2/CaO2. O2 extraction can vary by organ-the heart, brain extract a lot of oxygen but the kidneys, liver utilize little oxygen.Global impairment in oxygen delivery can thus be determined by monitoring central venous oxygen saturation (measured at SVC-RA junction with a central venous line) or mixed venous oxygen saturation (measured with a Swan Ganz catheter at the pulmonary artery).Normal ScvO2 = 70-75% reflecting an O2 extraction of 25%It is important to note that in humans: O2 consumption or VO2 is independent of O2 delivery or DO2.As the oxygen delivery decreases (or as oxygen demand increases), the body responds by extracting more oxygen and hence, the mixed venous saturation (ScvO2) or its oxygen saturation of blood at the SVC-RA junction gradually decreases to reflect this increasing oxygen extraction. However, the body can only extract so much oxygen and eventually, a critical extraction threshold (critical point of oxygen delivery) is met and cellular metabolism becomes anaerobic with the subsequent production of lactate. I would advise listeners to visit learnpicu.com to see an important graph drafting the relationship between DO2 and VO2.An important component of oxygen delivery is Cardiac output: Rahul can you tell us the components of cardiac output?Rahul: CO (liters per minute) = HR(beat per minute) X SV(mL). Cardiac output is typically indexed to BSA. CI is given as CO/BSAListeners need to remember that newborns and children with heart disease cannot increase stroke volume and are therefore heart rate dependent to increase cardiac output. Any rate or conduction anomalies can affect heart rate as in myocarditis, arrhythmias or poisoning.SV is amount of blood pumped at each contraction and is dependent on preload, pump function and afterload.Preload is the stretch of the cardiac myocytes just prior to contraction. Left ventricular end-diastolic volume, which is the volume of blood in the (L) ventricle just prior to contraction is the best surrogate marker of systemic preload. Preload is decreased in hypovolemia, hemorrhagic shock and cardiac tamponade.Stroke volume is also determined by cardiac contractility which is defined as the extent of shortening that occurs in cardiac myocytes when stimulated independent of preload or afterload. It a function of cardiac muscle performance. Echocardiographic measures of shortening fraction and ejection fraction are typically used as estimates of contractility. Listeners need to remember that multiple factors affect contractility such as catecholamines as well as optimization of the so called cardiac lytes:- calcium, magnesium and potassium. contractility is decreased in cardiogenic shock, drugs/toxins or cardiomyopathy.Afterload: is defined as the force opposing the contraction of the left ventricular myocytes during systole. Increased or decreased SVR can affect afterload in shock statesIn the next section Lets us discuss the assessment of O2 delivery & consumption clinically at the bedside where it matters.:How can you assess oxygen delivery and consumption at the bedside?A physical exam we can assess peripheral perfusion, heart rate, blood pressure, urine output, and mental status.Serial arterial blood gases, measures of serum lactate, SmVO2 (if available as SmvO2 requires pulmonary artery catheter), ScvO2, measure of Hgb, SaO2 can be obtained. A rise in lactate with falling ScVO2 or SmvO2 suggest anaerobic metabolism. A rising base deficit, persistent acidosis, decreasing pH may suggest declining DO2 in the right circumstances.Blood lactate can be used as an indirect measure of perfusion. A temporal trend is more valuable than a single number. Rate of production and clearance is affected by liver metabolism.Rahul, any serum biomarkers for assessment of cardiac function ?Paige: B-type Brain natriuretic peptide (BNP):, troponin (specific to myocardium) Troponin increase is seen in myocarditis, pericarditis, coronary injury or occlusion, and sepsis. BNP is released in response to ventricular wall stress due to volume or pressure overload. High levels of circulating BNP have been correlated with congestive heart failure states—a trend over time is likely the most helpful for the clinicianPradip, what can you tell us about Near-infrared spectroscopy?NIRS helps assess the systemic and regional O2 transport. NIRS is commonly used, particularly in patients with CHD, as a means of trending regional DO2 or as a surrogate for mixed venous O2 saturation or systemic DO2. Frequently used on patients undergoing VA ECMO. Rahul, how can we improve oxygen delivery?We can give patient a blood transfusion (although not ideal unless hgb < 7gm%) increase FIO2 to increase SAO2. We can decrease VO2 by reducing fever/catabolic states, treating infection, treating agitation with sedation/paralysis, cooling (while avoiding shivering), inducing coma etc. We can also decrease VO2 by early intubation if necessary in a patient with severe respiratory distress. Avoiding vasopressors can also decrease myocardial oxygen requirement and O2 consumption.Pradip How can we tackle O2 consumption?Let’s break this down in a systems based manner:Resp:Reduce respiratory distress by supporting using Ni or Inv MVReduce arrythmia as this can increase VO2 but also derail CO and thus DO2Reduce pain agitation fever seizure or shivering. At times you may not have a great clinical assessment of subclinincal status so consider placing eeg on patient or intiating...

Acute pulmonary Hypertensive Crises.Welcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.I'm Pradip Kamat and I'm Rahul Damania. We are coming to you from Children's Healthcare of Atlanta - Emory University School of Medicine.Welcome to our Episode a 7 month old boy ex-26 week premature infant with acute hypoxemia, bradycardia episodes, poor perfusionHere's the case:A 7 month old ex-26 week male was transferred from the outside hospital to our PICU for tracheostomy evaluation. Patient was intubated on second day of life. He had a prolonged course, on inhaled Nitric Oxide for first 2-3 months of life in the setting of severe pulmonary hypertension, requiring HFOV for a prolonged period of time. Failed extubation attempts multiple times. Received steroid burst x2. BPD settings trialed (lower rate, longer iTime, high PEEP, larger TV) without improvement. At time of transfer he was in PRVC mode on the ventilator — TV ~10ml/kg, 50%, PEEP 8, rate 28 (Peak pressures 27-32). Patient received albuterol Q4 for bronchospasm/wheezing and pulmicort BID. Patient was deeply sedated with morphine and midazolam. Interstitial lung disease panel was negative. ECHO showed: systolic septal flattening, moderate RV hypertrophy with normal systolic functioning. Patient was not on any PH medications at transfer. Patient is also on furosemide, hydrochlorothiazide and spironolactone.Patient has completed a course of antibiotics for klebsiella tracheitis from a ETT CX a week prior to admission to our picu. Patient tolerated feeds via an NJ tube.The team continues to evaluate his case as the Patient continues to have episodes of acute desaturation, tachycardia, cool extremities and poor perfusion.To summarize key elements from this case, we have a 7month old who is ex-26 week premiePatient has BPD and is on high vent settings and failing extubationAbnormal echocardiogram with flat septum and hypertrophied Right ventricleEpisodes of cold shock-tachycardia, poor perfusion, and cool extremitiesHypoxiaAll of which bring up a concern for acute pulmonary hypertensive crisisRahul Let's transition into some history and physical exam components of this case?What are key history features in this infants who presents with an acute pulmonary hypertensive crisisPrematurityBPDRemember BPD is defined by a requirement of oxygen supplementation either at 28 days postnatal age or 36 weeks postmenstrual age.Are there some red-flag symptoms or physical exam components which you could highlight?Presence of cold shock: tachycardia, cool extremities and poor perfusionHypoxiaCardiac exam will reveal a bounding right ventricle, prominent loud single S2Although not obvious in this patient: some patients can have a palpable liver, cardiac gallop, peripheral edema and jugular venous distentionS2 heart sound represents the closure of the PV very close to AV — In pulmonary hypertension this PE sign is seen with equal right and left ventricular pressures.To continue with our case, the patient's labs were consistent with:Respiratory acidosis (PCO2 > 100)CMP, CBC are normalBNP < 100, serum lactate normalEchocardiography findings in these patients can show tricuspid regurgitation. We can estimate right ventricular systolic pressure on echo and, by extension, systolic PAP (sPAP), by using tricuspid regurgitant (TR) jet velocity in combination with other echocardiographic findings. Using the modified bernoulli principle 4 x TR jet velocity squared, we can estimate the sPAP. If sPAP >2/3 systemic sBP with severe flattening or posterior bowing of the interventricular septum the patient can be diagnosed with severe pHTN.Pradip, what if the patient had a PDA on echo — what would you see?Rahul, when you see Predominantly right-to-left shunting across the PDA suggests suprasystemic sPAP. And as a result these patients can be hypoxemicOk, to summarize, we have:A 7-month ex-26 week premie infant old with shock with signs of poor perfusion +bounding right ventricle and loud single second heart sound, which brings us to the concern for acute pulmonary hypertensive crises.Let's start with a short multiple choice question:The best treatment for an acute pulmonary hypertension crises in an six month old ex-26 week with premie without congenital heart disease who is mechanically ventilated secondary to RSV bronchiolitis isA) SildenafilB) HypoventilationC) MilrinoneD) Sedation and paralysisRahul the correct answer is D sedation and paralysis. Although not a choice the I would recommend giving 100% O2 which is a potent vasodilator preferably with bag-mask hyperventilation (which causes alkalemia and causes pulmonary vasculature vasodilatation). Of the choices given in the above question none will be helpful in an acute PH crises although they are frequently used to treat PH in children. Milrinone is a PDE-3 inhibitor (increases cAMP) where as sildenafil is a PDE-5 inhibitor (increases cGMP). Hypoventilation will increase PCO2 which is a potent stimulus for PH crises. If available nitric oxide could be used.To summarize, acute pHtn you have to think about the pulmonary vasculature — which is responsive to changes in 02, pH, and Co2.As you think about our case, what would be your differential?Cold shock (although the in patients without PH-the cardiac exam will not reveal a loud single S2 or hyperdynamic right ventricle"Tet spell"-cyanotic spells typically seen in infants with congenital heart disease with a VSD such as tetralogy of fallot. deoxygenated blood is shunted across fro the right to the left across the VSD due to increased PVR. Cardiac exam may reveal reduced intensity or no murmur (as the murmur due to right ventricular outflow tract obstruction is proportional to the blood flow to the pulmonary circuit).We should also be vigilant of obstruction/Kinking of ETT in a patient resulting in hypoxia, bradycardia and cardiac arrest- which may look like a PH crisesRemember due to inc RV afterload you are going to have impairment of forward flow thus clinically presenting with hypoxemia and signs of poor perfusionIf you had to work up this patient with what would be your diagnostic approach?Really you don't need any investigation during an acute crises especially in a patient with h/o PHTN, h/o chronic lung disease, BPD or an infant with known cyanotic heart disease. Once patient is stable- consider chest radiograph (to check ETT tube position), blood gas for adequacy of ventilation. If patient is febrile then a CBC with differential + blood culture should be considered. An EKG may show RAH, RVH, ECHO may reveal findings suggestive of PH such as enlarged RA/RV, increased RV pressure, systolic flattening of the septum.Rahul: What is the pathophysiology of an acute PHTN crises?A pulmonary hypertensive crisis occurs when the pulmonary vasculature presents such a high resistance that there is little or no preload to the left ventricle and a massive, unsustainable afterload to the failing right ventricle. This can be triggered by multiple causes including parenchymal lung disease, Fever,pain, anxiety, tracheal suctioning, hypovolemia, increased cardiac demand, acidemia, aspiration, GE reflux, accidental interruption of prostanoid infusion. The acute massive loss of left ventricular preload and right ventricular afterload results in a drop in systemic cardiac output and coronary blood flow. Decreased coronary flow causes worsening right ventricular function. The higher than systemic right ventricular pressure pushes the interventricular septum into the left ventricle and that further worsens left ventricular filling. A vicious cycle ensues resulting in worsened left ventricular performance, syncope, bradycardia, and asystole. Once this point is reached, it is rare that cardiopulmonary resuscitation will successfully return sufficient cardiac output without significant multiorgan damage.If our history, physical, and diagnostic investigation led us to acute PH crises as our diagnosis what would be your general management of framework?Although PH management depends on the underlying cause-during a acute PH crises the following can be tried:If patient is on the ventilator-bag-mask ventilation with 100% O2 will vasodilate the pulmonary vasculature. O2 is a potent vasodilator and hyperventilation will decrease the PCO2 also causing vasodilationBolus of sedation (decreases sympathetic drive) and a dose of NMB such as rocuronium will further relax the vasculatureNitric oxide can be used (start at 20-40ppm) if available-as it is a direct pulmonary vasodilator (works by increasing cGMP), causes selective pulmonary vasodilation (improves VQ matching as well as PVR)Great rahul - further, Correct metabolic acidosis using NAHCO3Treat bradycardia and hypotensionUse fluid bolus if patient is dehydrated or over diuresed.After acute crises is mitigated - consideration for anti-reflux therapy of treatment of infection should be highly considered. A short course of steroids can also be used to decrease inflammation although these may not help in an acute crises.We have used epoprostenol (PGI2) infusion more to treat acute PH rather than in a crises. Typically started at 2ng/kg/min and slowly increased by 2ng/kg/min to a max of 9-11ng/kg/min.OK to summarize, long term management focuses on modulating NO pathway, endothelin pathway, and prostacyclin pathway.Are there any recent publications related to acute PH crises?We have posted references on our website picudoconcall.org (should NOT go through all below but just say posted in our shownotes)Lau EMT, Giannoulatou E, Celermajer DS, Humbert M. Epidemiology and treatment of pulmonary arterial hypertension. Nat Rev Cardiol. 2017 Oct;14(10):603-614. doi: 10.1038/nrcardio.2017.84. Epub 2017 Jun 8. PMID: 28593996.Hansmann G. Pulmonary Hypertension in Infants, Children, and Young Adults. J Am Coll Cardiol. 2017 May 23;69(20):2551-2569. doi: 10.1016/j.jacc.2017.03.575. PMID: 28521893.Krishnan U, Feinstein JA, Adatia I, Austin ED, Mullen MP, Hopper RK, Hanna B, Romer L, Keller RL, Fineman J, Steinhorn R, Kinsella JP, Ivy DD, Rosenzweig EB, Raj U, Humpl T, Abman SH; Pediatric Pulmonary Hypertension Network (PPHNet). Evaluation and Management of Pulmonary Hypertension in Children with Bronchopulmonary Dysplasia. J Pediatr. 2017 Sep;188:24-34.e1. doi: 10.1016/j.jpeds.2017.05.029. Epub 2017 Jun 20. PMID: 28645441.Del Pizzo J, Hanna B. Emergency Management of Pediatric Pulmonary Hypertension. Pediatr Emerg Care. 2016 Jan;32(1):49-55. doi: 10.1097/PEC.0000000000000674. PMID: 26720067.Rahul, where can more information can be found:Fuhrman & Zimmerman - Textbook of Pediatric Critical Care Chapter 53: Diseases of the Pulmonary Circulation by Zhang H et al.Rahul what are the key objective take-aways:Acute PHTN crises is a life threatening event that requires immediate therapy using oxygen, sedation+paralysis, inhaled nitric oxide, prevention of bradycardia and hypotension.A multidisciplinary team approach with specialists from cardiology, pulmonary teams are needed in the management of patients with PH in the picu. Intensivists should understand the triggers for acute PH crises and try to avoid these triggers to prevent such crises.This concludes our episode on acute pulmonary hypertensive crises. We hope you found value in our short, case-based podcast. We welcome you to share your feedback, subscribe & place a review on our podcast! Please visit our website picudoconcall.org which showcases our episodes as well as our Doc on Call management cards. PICU Doc on Call is hosted by myself Pradip Kamat and Dr. Rahul Damania. Stay tuned for our next episode! Thank you!