PICU Doc On Call

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!

In this podcast, the hosts discuss seven habits that can greatly enhance the experience of trainees in pediatric critical care fellowship. They emphasize the importance of setting goals, maintaining a growth mindset, and approaching each day with humility. They also explore the significance of meta awareness in a fellowship, focusing on interpersonal interactions and communication skills. Lastly, they discuss the importance of enjoying the training years in medicine and how having fun enhances leadership skills and teamwork.

Welcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists. I'm Pradip Kamat and I'm Rahul Damania. We are coming to you from Children's Healthcare of Atlanta - Emory University School of Medicine.Welcome to our Episode with a 15 year old Male having hypotension and bradycardia.Here's the case presented by Rahul:A 15 year old M presents to the PICU after sustaining an acute trauma. The patient was brought to the ER by his family after being on a boat and lifting a heavy object. He did not fall, sustain any head or extremity trauma, but did feel an achy non-radiating back pain shortly after the event. His grandmother states that the patient kept complaining about the back-pain and over the next few hours the patient became increasingly fatigued and flushed in the face. The patient was able to move his arms and legs and still walk, however family became concerned when the patient had abdominal fullness and was unable to urinate properly. He presents to the emergency department for further evaluation. In the emergency department he is noted to be awake however intermittently sleepy. His vital signs are notable for a HR of 58 bpm and a blood pressure of 85/60. He has 3/5 motor strength in his lower extremities with decreased sensation in his feet. Patellar reflexes are 1+ bilaterally. Rectal tone is normal. Acute resuscitation is begun for this patient.To summarize key elements from this case, this patient has:Acute triggerBack painVital sign instability and lower motor neuron signs.All of which bring up a concern for a spinal cord injury.Let's transition and discuss some history and physical exam components of this presentation:What are key history features in a child who presents with hypotension and bradycardia?As our worry is primarily spinal cord in etiology you would want to ask about trauma — this could be blunt or penetrating traumaYou also would like to ask about the nature of the injury and scene. It is especially important to inquire with the pre-hospital providers about the nature of the injury and the patient course in transport. Besides our normal ABCs, it is important to ask the care taken regarding spinal cord restriction (such as use of a cervical collar or backboard)Another high yield history component when you think about hypotension and bradycardia is to assess for Numbness, weakness, or changes in bowel or bladder habits. In this case the patient had abdominal fullness which maybe due to bladder dysfunction.This is a great summary of key history findings for patients who present with hypotension and bradycardia as it relates to spinal cord issues. Remember that patients who have Down's syndrome may have a predilection to have lax ligaments especially in the upper verterbrae. As a result, you should have an increased index of suspicion if a Down's Syndrome patient presents with hypotension and bradycardia in the presence or absence of trauma. In a study published in 2017 in Neurocrit Care it was estimated that about 20% of patients with Trisomy 21 may have atlantoaxial instability.A great point which you just highlighted. Remember that when you approach hypotension and bradycardia, it is also important to focus on cardiac etiologies:Bradycardia directly pulls down the cardiac output, potentially causing shock, and especially if you have a blunted vasoconstrictor response you can couple this bradycardia with hypotension.I do not want to delve too much out of the scope of today's episode but there is a wide differential for bradycardia but specifically related to history you should consider intoxication as a cause of bradycardia and hypotension.This includes:Beta-blocker or calcium-channel blocker.Central alpha-2 agonist (e.g., clonidine, dexmedetomidine, guanfacine).Going back to our case, are there some red-flag symptoms or physical exam components which you could highlight when you approach?Yes, in this patient who we suspect spinal cord injury, we would like to perform a comprehensive neurological exam:Motor strength should be tested especially in the lower extremitiesKey muscle groups should be tested to determine level of injuryKnee extensors are at L3Whereas your triceps and biceps can be assessed C5-C7.On physical exam, this patient had a flushed face, and this could be related to an Interruption of sympathetic chain causing a horner's syndrome like presentation.Recall that Horner's Syndrome is a triad of ptosis, miosis, and anhidrosis which can present as facial flushing.During this spinal cord assessment it is important to perform a rectal exam to check for perianal sensation and rectal toneIf at least 1 is normal in the acute setting, this suggests a sacral-sparing injury and thus an incomplete injury with the potential for some motor recoveryOther physical exam components includes assessing for priapism in male patients. Priapism in male patients may be present from abrupt loss of sympathetic tone to pelvic vasculature, causing a high-flow arterial priapism.This is a great review of history & physical components for hypotension and bradycardia as a presentation of spinal cord injury — I think the key point here is to remember that this presentation is related to a loss of sympathetics and thus unopposed vagal tone which leads to the acute symptamology of Distributive shock with hypotension and bradycardiaTo continue with our case, the patients labs were consistent with:Blood gas consistent with a metabolic acidosisA lactic acid of 4.6 mg/dLHis coagulation panel and basic metabolic panel was within normal limitsEKG was notable for sinus bradycardia with no evidence of heart block.I would also like listeners to note that in patient with high cervical spinal cord injuries, the presence of hypercarbia suggesting hypoventilation may prompt for the need for early intubationWhat did the imaging show in this patient?After stabilization, our patient underwent CT showing an T2 spinal cord injury. There was an associated T5 vertebral fracture.Interesting this may have been related to his boat trauma. Remember listeners, that CT is very sensitive for defining bone fractures in the spine. Because CT is more sensitive than plain films, patients who are suspected to have a spinal injury and have normal plain films should also undergo CT. CT also has advantages over plain films in assessing the patency of the spinal canal. CT also provides some assessment of the paravertebral soft tissues and perhaps of the spinal cord as well, but is inferior in that regard to MRI.OK, to summarize, we have:A 15 yo M who presents after trauma with hypotension, bradycardia, facial flushing and bladder dysfunction. This brings up the concern for spinal or neurogenic shock, the topic of our discussion today.Let's start with a short multiple choice question:After a MVA, a 16 yo M presents with a HR 50 and MAP 45. Patient is obtunded, gurgling, and resuscitation efforts are begun. His hypotension does not improve with fluid resuscitation. A diagnosis of neurogenic shock is suspected. Stimulation of which of the following receptors is most likely to benefit this patient acutely?nicotinic ach receptorsmuscarinic ach receptorsvasopressin -2 receptorsalpha-1 receptors.The correct answer is D. alpha-1 receptors. Remember that patients with neurogenic shock are devoid of sympathetics. Thus, you want to initiate sympathomimetics early. Some patients may require continuous infusion of norepinephrine, phyenlephrine, or dopamine.As you think about our case, what would be your differential?First off I would make a distinction between Conus medullaris syndrome & Cauda Equina Syndrome.To start, the Conus medullaris is the terminal end of the spinal cord. If damaged, these children will have UMN weakness.They make have impaired sphincter control early, and Disturbances in urinationOlder children may be able to communicate a feeling of saddle anesthesia.Pradip, what about cauda eqina syndrome?Great question. So the Cauda equina is the lumbar and sacral roots caudal from the conus medullaris. These patients are going to have multiple nerves affected and may also have progressive incontinence.In fact, studies have shown that Finding of urinary retention (post void residual > 100-200 mL) has 90% sensitivity for cauda equina syndrome.A key distinction between the two is that cauda equaina syndrome in general has an asymmetric weakness with primarily LMN signs. These patient are going to have urinary retention that presents later from the onset of injury.OK, to summarize, Conus medullaris syndrome you damage spinal cord, think early onset issues of bowel and bladder with UMN vs CE syndrome you have more damage of peripheral nerve roots and you in general will have a progressive inconitence with UMN signs.RAHUL, I have also heard of this acronym, SCIWORA. What is this clinical entity?SCIWORA stands for Spinal Cord Injury WithOut Radiographic Abnormality (SCIWORA)In the pediatric population this differential is greater concern in pediatric population due to laxity of ligaments and weaker musclesIn this disorder, there is No discernible fracture on conventional films or computed tomography scans however patients may have spinal cord injury or on exam neurological deficits. The Mechanism is transient subluxation, stretching, or vascular compromise.Finally, let's contrast neurogenic shock with spinal shock — this is a subtle distinction clinically but has been described in the literature Rahul can you shed some light on that?Spinal Shock Syndrome with a temporary loss of neurologic function and tone below a level of an acute lesionPresents as flaccid paralysis, loss of sensation, loss of deep tendon reflexes, and urinary bladder incontinenceSpinal reflexes often return in a predictive manner with the reflexes in the genital region among the first to reappearSpinal shock, when accompanied by hemodynamic compromise with loss of vasomotor tone, is generally going to be known as neurogenic shock. Neurogenic shock typically occurs in patients with a T5 injury and above however can be seen in any lesion throughout the spinal cord.If our history, physical, and diagnostic investigation led us to neurogenic shock related to acute traumatic spinal cord injury as our diagnosis, what would be your general management of framework?We have made a key theme today regarding the interruption of autonomic pathways in the spinal cord causing decreased vascular resistance and bradycardia. As such, your management should be focused on resuscitation and re-initiation of sympathetic tone in the form of vasopressors.Remember that Patients with traumatic spinal cord injury may also suffer from hemodynamic shock related to blood loss and other complications.An adequate blood pressure is believed to be critical in maintaining adequate perfusion to the injured spinal cord and thereby limiting secondary ischemic injury.Bradycardia caused by cervical spinal cord or high thoracic spinal cord disruption may require external pacing or administration of atropine. However in studies atropine has not been shown to completely reverse neurogenic shock.What about steroid use in spinal cord injuries?Methylprednisolone is the only treatment that has been suggested in clinical trials to improve neurologic outcomes in patients with acute, nonpenetrating TSCI. However, the evidence is limited, and its use is debated.In animal experiments, administration of glucocorticoids after a spinal cord injury reduces edema, prevents intracellular potassium depletion, and improves neurologic recovery - this is especially true within the first eight hours after injury.In 2013, based upon the available evidence, the American Association of Neurological Surgeons and Congress of Neurological Surgeons stated that the use of glucocorticoids in acute spinal cord injury is not recommended. Use of glucocorticoids in this setting appears to be declining.Let's focus our management on the vasopressor use — as mentioned prior, vasopressors should be considered in cases of neurogenic shock esp if there is failure to respond to crystalloid, and no alternative diagnosis for hypotension.Your go to agents are going to be those that have a-lpha 1 activity to reestabllish vasomotor tone:Norepinephrine or Phenylephrine are your medications of choice in this settingNote phenylephrine may cause reflex bradycardia as this is a pure alpha one agonist.In terms of prognosis:Adult studies have cited: 10%-20% of patients with spinal cord injuries do not survive to hospitalization.Most recovery starts within the first few weeks and plateaus in the first 3-6 monthsBetter prognosis for ambulation includeYounger age, decreased severity of impairment, incomplete injury, and lower level of injuryThis is a great time for us to highlight the multi-disciplinary effort that goes into caring for these children. It is important in the acute setting to work closely with neurosurgery, ortho, neurology, and the critical care team and further in the subacute setting involving the rehabilitation team.Leading causes of death in children with spinal cord injury are respiratory conditions and pnuemonia so working closely with speech therapy for oromotor function is imperative in management.I would advise trainees and anyone interested to consider reading chapter 34 entitled shock states in Fuhrman & Zimmerman - Textbook of Pediatric Critical Care to review the hemodynamic patterns seen in our discussion of neurogenic shock.This concludes our episode on Neurogenic shock. We hope you found value in our short, case-based podcast. We welcome you to share your feedback, subscribe & place a review on our podcast! Please visit our website picudoconcall.org which showcases our episodes as well as our Doc on Call management cards. PICU Doc on Call is hosted by myself Pradip Kamat and my cohost Dr. Rahul Damania. Stay tuned for our next episode! Thank you!References:Powell A, Davidson L. Pediatric spinal cord injury: a review by organ system. Phys Med Rehabil Clin N Am. 2015 Feb;26(1):109-32. doi: 10.1016/j.pmr.2014.09.002. PMID: 25479784.Farrell CA, Hannon M, Lee LK. Pediatric spinal cord injury without radiographic abnormality in the era of advanced imaging. Curr Opin Pediatr. 2017 Jun;29(3):286-290. doi: 10.1097/MOP.0000000000000481. PMID: 28306628.Yue JK, Tsolinas RE, Burke JF, Deng H, Upadhyayula PS, Robinson CK, Lee YM, Chan AK, Winkler EA, Dhall SS. Vasopressor support in managing acute spinal cord injury: current knowledge. J Neurosurg Sci. 2019 Jun;63(3):308-317. doi: 10.23736/S0390-5616.17.04003-6. Epub 2017 Mar 1. PMID: 28252264.

Welcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.I'm Pradip Kamat and I'm Rahul Damania. We are coming to you from Children's Healthcare of Atlanta - Emory University School of Medicine.Welcome to our Episode of 17-year old with h/o of SLE and now acute liver failure.Here's the case presented by Rahul:A 17-year old teenage female year old presents to the PICU with acute liver failure. Important past h/o includes a diagnosis of SLE on therapy with prednisone, mycophenolate (cellcept), and plaquenil.4 days prior to this admission, patient presented to an OSH with RUQ pain, vomiting (non bloody & no bilious), fever & malaise. Initially due to concern for "lupus Flare" patient was given steroids at the OSH.At the OSH notable initial labs included a mild transaminitis and an INR of 1.5. She suddenly at the OSH developed fluid refractory hypotension and was started on a pressor. Due to continued worsening of her transaminitis well as a rising INR on her repeat labs she was referred to our tertiary PICU for further management.Pertinent history also includes a negative urine pregnancy test. No recreational drug use, and only as needed use of Tylenol.She now is in the PICU. She generally appears tired and ill. She is tachypneic on 4 LPM of nasal canulla and her oxygen saturation is 98%. She has a non-focal lung exam.Her cardiac exam is notable for tachycardia, and pertinently no gallop, rub or murmur.Her abdominal exam is non-focal except for mild discomfort on palpation of the RUQ with a palpable liver edge. Her extremities are cool with 3-4 capillary refill time. She is able to answer questions but intermittently doses off. No rash is noted.To summarize key elements from this case, this patient has:H/o of lupus and is on immunosuppressive medicationsNew onset fever/malaiseThis sounds like a LUPUS flare as she has a clinical picture of generalized inflammation.Rahul: Lets pause right here and take a look at key history and physical exam components in a patient who has a chronic auto-immune condition:Fever, malaise and feeling tired all signs of constitutional symptoms.She has abdominal pain and vomiting that could again be related to systemic inflammation but also an intra-hepatic lesion.Are there some red-flag symptoms or physical exam components which you could highlight?This patient has signs of shock!Tachycardia with delayed cap refill and cool extremitiesTachypnea& hepatomegaly which could indicate increased central venous pressures.Initially her outside presentation of fluid refractory shock is of utmost concern!Fluid refractory shock with multi organ presentation involving liver, kidney and the blood/coagulation systemsAll of these elements bring up a concern for some acute life threatening process such as sepsis, or even immune dys-regulation due to her h/o of LupusTo continue with our case, the patients labs were consistent with:Acute liver dysfunction (Elevated AST and ALT in the thousands, Total bilirubin 1.6, GGT 56) although the total bilirubin is not elevated to a degree I would expect.AKI (creatinine 2.18)An uptrending Coagulopathy with elevated PT and INR: PT 120 and a peak INR of 16Thrombocytopenia: Platelets < 50KShe had a peak lactate 9.2and concurrent Metabolic acidemia: serum HCO3 7, and pH 7.18.A Pertinent negative: Normal serum ammonia <38 micromol/L (nl < 50)Finally, she had an elevated WBC 20.5K/ Hgb 9.7, Platelet 42. CRP 4.2/ESR 5OK to summarize, we have: a 17 yr old female with SLE on mycophenolate (cellcept) who presents with fever, hypotension, AKI and liver dysfunction with severe coagulopathy, although we do not have other labs- This brings up the concern for acute macrophage activation syndrome (MAS) the topic of our discussion today.Let's start with a short multiple choice question:12 year old male with h/o systemic onset juvenile idiopathic arthritis (JIA) presents with fever, rash, hypotension, acute respiratory distress with hypoxia. Mental status is normal. He also has acute kidney injury, transaminitis, coagulopathy, metabolic acidemia as well as anemia and thrombocytopenia. His liver and spleen are enlarged and he has scattered lymphadenopathy. The laboratory findings most suggestive of acute macrophage activation syndrome in this patient is:Erythrocyte Sedimentation Rate > 100ADAMS13 activity < 10%Serum Ferritin > 20, 000ng/mLFibrinogen (> 500mg/dL)The correct answer is serum ferritin > 20,000ng/mL. Any patient with systemic JIA who presents with high fever, heptao-splenomegaly with evidence of multi-organ dysfunction should be considered to have the potentially life threatening complication of systemic inflammatory disorders: acute macrophage activation syndrome (MAS) unless proven otherwise. The 2016 Classification criteria for MAS was published (Ravelli A. et al. Ann Rheum Dis 2016; 75:481-489) requires a Ferritin > 684ng/mL and any two of the following:A platelet count < 181 X 109/L (181K)AST > 48unitsTriglycerides > 156 mg/dLFibrinogen ≤ 360mg/dLOK lets summarize, platelets less than 180K, fibronogen <360, transaminitis >AST 48 and hypertriglcyeridemia! Remember many of these values are acute phase reactantsCorrect Rahul, also the above Laboratory abnormalities should not be otherwise explained by another patient condition, such as concomitant immune-mediated thrombocytopenia, infectious hepatitis, visceral leishmaniasis or familial hyperlipidemia.Are there any other inflammatory mediators or subtleties you would like to highlight with this disease?A falling ESR, especially with a high CRP, is concerning for MAS and is secondary to low fibrinogen in the setting of consumptive coagulopathy.In the question, patient's ESR is elevated. Low or absent ADAMS T-13 activity is more suggestive of thrombocytopenic purpura (TTP), which is not the case here as mental status is preserved indicating no CNS involvement. In MAS there is typically consumption of fibrinogen not its elevation. The elevated ferritin (> 10,000ng/mL) along with other systemic findings in the patient in the question is highly suggestive of MAS. Additional labs that would suggest MAS include demonstration of hemophagocytosis in bone marrow or other tissue, elevated D-dimers, lactic acid dehydrogenase (LDH), triglycerides, low natural killer (NK) cell function, and elevated soluble IL-2 receptor levels.Great highlight of the incorrect answers the pathophysiology of increased immune activation is key along with dysfibrinogenemia — this is likely due to microangiopathic consumptionRahul can you briefly tell us a bit about macrophage activation syndrome?MAS is classified among the group of hemophagocytic lymphohistiocytosis (HLH), so HLH is the umbrella term.HLH includes familial HLH and secondary HLH. Secondary HLH is triggered by several causes, including infection, drugs, malignancy, and rheumatic disorder. Remember in our case the patient had LupusIn MAS A common hypothesis in MAS is that there is a defect in lymphocyte cytolytic activity, which means that lymphocytes are not able to kill cells appropriately.Let's break down the pathophysiology a bit further.There is a genetic predisposition, and that is to having increased macrophage responsivenessThere is some form of background inflammatory activity. What cytokines are elevated?IL-6IL-1IL-18What does IL-6 do?Decreases NK cell functionSo now you have bad T cell cytolytic function and decreased NK cell cytolytic function. What does this lead to?Prolonged cell to cell interactions and amplification of a pro0inflammatory cascade.So now we have genetic predisposition some background cytokine inflammatory activity with cytokine production and now we layer in the third element of the pathophysiology — A trigger!What are triggers: acute on chronic inflammation & especially infection!This trigger will be important to capture in our understand as management will be geared towards reversing this trigger. So where does the hemophagocytosis come about in the term hemophagocytic lymphohistiocytosis? Well, the cytokine storm results in activation of macrophages which are known as hemophagocytes. There's a particular cytokine IFN gamma that make macrophages angry and it is this response that can lead to multi-organ dysfunction.Pradip, now with this summary let's dive into MAS and how it relates to HLH?MAS is a life threatening illness is a form of secondary hemophagocytic lymphohistiocytosis (HLH) and a common complication of rheumatologic conditions, such as systemic JIA. The occurence of MAS has been well reported in other autoimmune or auto-inflammatory conditions, such as, adult-onset and childhood-onset systemic lupus erythematosus, Kawasaki disease, and periodic fever syndromes.Characteristic clinical features of MAS are high, non-remitting fever, hepatosplenomegaly, generalized lymphadenopathy, central nervous system dysfunction and hemorrhagic manifestations.Typical laboratory abnormalities include pancytopenia, increased levels of ferritin, liver enzymes, lactate dehydrogenase, triglycerides, D-dimers and soluble interleukin 2 (IL-2) receptor α (also known as soluble CD25 (sCD25)), and decreased fibrinogen levels.A typical histopathological feature of MAS is the accumulation of well differentiated macrophages exhibiting hemophagocytic activity in bone marrow biopsy specimens or aspirates. Although the prevalence of MAS among patients with systemic JIA has been estimated to be ∼10%, recent reports suggest that subclinical MAS may occur in as many as 30–40% of patients with systemic JIA.MAS can result in progressive multiorgan failure and eventually a fatal outcome if unrecognized. Recent studies indicate a mortality rate of 8%. Early recognition of MAS is often challenging, given the lack of a single pathognomonic clinical or laboratory feature. Furthermore, histopathological features of hemophagocytosis may not be present in the initial stages and lack specificity for hemophagocytic syndromes. In addition, features of MAS may be difficult to distinguish from other conditions that may present with overlapping manifestations, such as flares of systemic JIA, lupus or systemic infections.MAS associated with SLE is rare and the incidence is about 0.9–4.6% but survival from MAS in febrile SLE patients who are admitted to the hospital ranges is 64% vs 97%.(p<0.001) in those without MAS. The odds of in-hospital mortality was 64.5, 95% CI: 7.6-544; p<0.001).OK so HLH is the umbrella term and if a patient has signs and symptoms of acute inflammation + end organ dysfunction with a chronic rheumatological disease, you defintiely want to consider MAS. MAS in febrile SLE patients has a poor outcome.As you think about our case, what would be your differential?Sepsis with DIC or liver dysfunctionFlare of systemic JIA, lupus or primary rheumatologic diseaseRemember cytokine release syndrome in patients who get CAR-T therapy is a form of MAS.Pradip: If you had to work up this patient with MAS what would be your diagnostic approach?Initial labs include: CBC with diff, DIC panel, CMP, Ferritin, Soluble IL-2R. Blood/urine analysis/cultures. Patient in MOF, I would also trend lactates, blood gas, CMP and DIC panel at least every Q12 and as needed. Consult with rheumatology, infectious disease experts for their help with diagnosis and management. Given difficulty with distinguishing acute liver failure with DIC from MAS, factor V, VII and VIII levels (decreased in sepsis but not in liver disease) may be helpful. Additionally, PICU docs must be vigilant for neutropenic sepsis and opportunistic fungal infections, correct electrolyte imbalances, and use blood products to correct anemia, thrombocytopenia and coagulopathy.Alternative biomarkers for MAS—such as soluble IL-2 receptor, CD163, and IL-18—have shown promise. However, these tests are not universally available and generally have long turnaround times.It is important to r/o infection early but that may be difficult to do. I would send a viral panel which includes SARS COV-2 PCRImaging: CXR, abdominal ultrasound, and echocardiographyFerritin > 10K with evidence of hemophagocytosis in the bone marrow is most suggestive of MAS in a patient who has a presentation suggestive of MAS.Pradip: If our history, physical, and diagnostic investigation led us to Macrophage activation syndrome (MAS) as our diagnosis what would be your general management of framework?Good basic PICU care with close attention to airway, breathing and hemodynamics. As modern medicine is a team sport consult with ID, rheumatology, hepatology etc. These patients typically need mechanical ventilation (On CMV use a high PEEP, low FIO2, low TV lung protective strategies). Patients may need HFOV for pulmonary hemorrhage. CVL, arterial lines should be placed. Avoid benzodiazepines for sedation, and prevent secondary kidney or liver toxicity (avoid nephrotoxic medications, dose antibiotics based on levels, avoid acetaminophen). As MAS is not readily distinguishable from sepsis-initial broad-spectrum antibiotics should be initiated.Although previously steroids/cyclosporine were the first line therapy: More recently, cytokine specific therapy with agents like anakinra an IL-1 receptor antagonist (2-4mg/kg s.c. every 6-24 hours) is rapidly effective. Anakinra blocks the biologic activity of both IL-1α and IL-1β by competitively inhibiting their binding to IL-1R. IV anakinra may be indicated if platelets < 20, neurologic symptoms and subcutaneous skin edema. A distinct advantage of anakinra is that the drug is less hepatotoxic, less immunosuppressive and has shorter half-life compared to etoposide or tocilizumab. Anakinra may help avoid steroids especially if diagnosis is not clear and there is a danger of masking lymphoma due to the steroids.Rahul its important to note that 2 other drugs (IL-1 beta receptor antagonist canakinumab and IL-6 inhibitor tocilizumab) while decreasing some of the clinical findings of MAS- such that patients may present with less fevers and hepatomegaly, as well as change lab features and the patient can thus have lower ferritin, lower fibrinogen, and lower CRP. Moreover, the excellent response of sJIA features to canakinumab and tocilizumab with simultaneous development of MAS features in some patients also suggests that the role of IL-1beta and IL-6 in MAS development might be limitedIn addition, plasma exchange and high-flow continuous veno-venous hemofiltration have shown promise. The use of extracorporeal cytokine removal therapies (CytoSorb) may show some selective efficacy in such patients with MAS.That was a great summary, I would also advocate for treating the underlying cause!This concludes our episode on acute macrophage activating syndrome We hope you found value in our short, case-based podcast. We welcome you to share your feedback, subscribe & place a review on our podcast! Please visit our website picudoconcall.org which showcases our episodes as well as our Doc on Call management cards. PICU Doc on Call is co-hosted by myself Dr. Pradip Kamat and Dr. Rahul Damania. Stay tuned for our next episode! Thank you!

In this podcast, a 17-year-old teenage female with a history of lupus presents with acute liver failure. The case discussion includes her initial treatment, concerns of lupus flare, fluid refractory hypotension, tachycardia, and abnormal lab results. The podcast also covers the analysis of lupus flare symptoms, critical condition assessment, and the importance of identifying life-threatening complications in systemic JIA patients.

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