PICU Doc On Call

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.

Explore a medical mystery of a toddler with bilateral wrist hyperflexion, considering systemic causes, familial issues, and nutritional factors. Dive into cases of pediatric hypocalcemia, discussing management and complications. Learn about vitamin D deficiency, genetic factors, and supplementation. Understand the comprehensive management of hypocalcemia in pediatric patients, focusing on lab tests and monitoring for complications.

This episode of the podcast discusses a case of a 16-year-old female with fever, rash, and other symptoms. They explore the diagnosis and management of toxic shock syndrome, including the mechanism of pathogenesis, diagnostic approach, and recommended antibiotic regimen. The use of IVIG in strep TSS and controversy surrounding its use in staph TSS is also discussed.

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 PICU Doc On Call Mini-Case series. In this episode, we present a 15 year old girl who is admitted for shock after returning from her recent travel to NIgeria.Here's the case:13y F with no significant past medical history presents with 4 days of fever, headache, watery, non-bloody diarrhea, non-bloody, non-bilious emesis, decreased PO intake with worsening myalgias, fatigue, and weakness. She had traveled with her mother to Nigeria earlier this month and returned a week ago. Over the weekend mom consulted her pediatrician who prescribed an antiemetic without significant improvement of her symptoms. Once patient progressed to becoming light headed and weak, the mom decided to bring her to ED where she was found to be have tachycardia and hypotension. She required 3 L of crystalloid resuscitation was started an epinephrine continuous infusion and transferred to the PICU. Patient was found to have acute kidney injury with an elevated Cr, as well as a primarily direct hyperbilirubinemia and associated anemia and thrombocytopenia.Her other history elements were notable for fever and difficulty breathing. Prior to traveling to Nigeria she did receive travel vaccinations and took mefloquine prophylaxis. She also had a negative COVID screen. While in Nigeria she denies exposure to animals, raw food intake, and only recalls that she may have had a few mosquito bites but this was well after returning from Nigeria until 7 days prior to presentation to the ED.She presents to the PICU with hypotension, tachycardia at 160 bpm, tachypnea, and normal saturations. Her physical exam is notable for cool peripheral extremities, RUQ tenderness, and bilateral crackles.She had no murmurs or gallops on her initial exam. Pertinently, she had no rash, lymphadenopathy or scleral icterus.This is a teenage girl who has fever and constitutional symptoms after returning from travel abroadShe now presents with fluid refractory shock, tachycardia that is out of proportion to dehydration and signs of end-organ failure.Notable negatives include: No LNadenopathy, hepatosplenomegaly, or a rashSynthesizing these symptoms together → we are thinking that this picture may be related to a contracted infection or inflammatory condition related to her travel.Let's transition into some history and physical exam components of this case.What are key history features in this child who presents with fever and shock after a recent travel outside the US (Nigeria-West Africa)Diarrhea and emesis days before presentationHigh Fever with no rashMental status is maintained although she did have an headacheLight headed and weakness are symptoms suggestive of dehydration and even shockPhysical exam findings of importance here include- patient presenting with tachycardia, signs of poor perfusion such as delayed cap refill, cool extremities, hypotension. It is unique that even though she has RUQ pain there is no jaundice.2. Are there some red-flag symptoms or physical exam components which you could highlight in apatient with the above history and recent travel.Weakness, light-headedness, shock, tachycardia, poor perfusion, fever and evidence of multi-organ dysfunction are suggestive of an acute and possibly life threatening infection acquired during travel. Given her travel to West Africa: I would be worried about falciparum malaria, dengue fever, typhoid fever, and cholera. Other diseases to be concerned about especially given her travel h/o include leptospirosis, chickungunya, Crimean-Congo hemorrhagic fever, African tick bite fever etc. I would be also concerned about bacterial sepsis with a source such as the kidney, bowel, or intrapelvic organs.To continue with our case, the patients labs were consistent with:Anemia 11/33, thrombocytopenia 12, and leukopenia WBC 4.55 with 92% segs. On her smear her RBC morphology was described as normal.Elevated BUN and creatinine with no acidemiaElevated liver enzymes (AST/ALT and Tbilirubin). Although her synthetic liver function was preservedElevated lactate, a BNP of 309 and troponin of 11.5.Given her fever and travel history the ED team also sent a blood culture (large volume) and a thick and thin smears for malaria. In the PICU after consulting with ID service , we sent GI PCR, Dengue serology IgM and IgG) and NS-1 antigen.We also did an EKG, ECHO (given her tachycardia and shock).The lab personnel called to report that a malarial parasite was seen at 0.8% on the smear. The ID attending who examined the smear confirmed multiple ring forms in cells which goes along with Plasmodium falciparum, but unable to exclude different types of Malaria. A PCR for speciation of type of malaria was also sent.OK to summarize, we have a:13 yo female who presented with, fever, shock, and multi-organ dysfunction with a h/o recent travel. Given the findings of falciparum malaria on her blood smears, we confirm a diagnosis of falciparum malaria in this patients. Although her parasitemia level is < 5%, her clinical presentation of shock, AKI suggests she has severe malaria.Let's start with a short multiple choice question:A patient with severe Falciparum malaria who presents in shock, AKI and a parasite level of 10%, and inability to keep PO medications due to emesis, which of the following in the initial drug of choice?A. QuinidineB. ArtemesinC. ArtensunateD. DoxycyclineCorrect answer is C. Artensunate given IV. As recommended by the CDC as well as the American Academy of Pediatrics' Red book. IV Quinidine is no longer available in the US.Artemesin can be used if patient can tolerate PO while awaiting IV Artensunate. Drugs like doxycycline are slow acting antimalarials that would not take effect until well after 24 hours and are not effective in severe malaria. Other PO medications which can be used include artemether-lumefantrine (Coartem™) because of its fast onset of action as well as atovaquone-proguanil (Malarone), quinine, and mefloquine. As for any malaria treatment, the interim regimen should not include the medication used for chemoprophylaxis if possible.As you think about our case, what would be your differential?Broadly speaking you want to think about other causes of fever, and shock with multiorgan dysfunction in a traveler returning to the US, I would think ofSepsis (pyelonephritis, pneumonia, ruptured appendicitis, ovarian abscess etc.): Negative blood cultureLeptospirosis (no exposure to rodent or food contaminated with rodents urine or feces. No conjunctivitis, rash or jaundice)Typhoid fever (GI PCR would confirm)Dengue (no rash or muscle/joint or eye painChickungunya (no joint pain or rash, argues against this)Ebola (lack of conjunctivitis, DIC/hemorrhage)Food poisoning and hypovolemic shock (fever would be unlikely)Always think of SARS-COV-2 especially in this child who is not vaccinated. Her presentation with fever, GI symptoms and shock could be a manifestation of MIS-C. (SARS CoV-2 Ab negative)Rahul if a patient develops a fever or symptoms 21 days after travel to a foreign country certain disease such as dengue, rickettsial infections, Zika virus infection, and viral hemorrhagic fevers are unlikely, regardless of the traveler’s exposure history.Infectious causes may be further narrowed by pretravel vaccinations and chemoprophylaxis, although neither approach is 100% effective like our patient who did not take her mefloquine correctly. The incubation period (time to onset of malaria symptoms) in most cases ranges from as soon as 7 days after being bitten by an infected mosquito to about 30 days and is shortest for P falciparum and longest for P malariaeIf you had to work up this patient with severe malaria what would be some of the lab investigations you would send:Fever in a returning traveler requires a good history and a physical examination. Besides a complete blood count with differential, comprehensive metabolic panel, CRP, Procal, blood Cx (large volume), UA/UCx and in a patient with shock and poor perfusion- I would send a lactate, get a chest radiograph, EKG and an echocardiograph.After consulting with infectious diseases: I would send thick and thin (to speciate type of parasite) blood films to test for malaria parasite. The thick film allows for concentration of the blood to find parasites that may be present at low density, whereas the thin film is most useful for species identification and determination of the density of red blood cells infected with parasites. If initial blood smears test negative for Plasmodium species but malaria remains a possibility, the smear should be repeated every 12 to 24 hours during a 72-hour period, ideally with at least 3 smears. Serologic testing (rapid diagnostic test or RDT) generally is not helpful. PCR is most useful to confirm species of malaria. If there is diarrhea and vomiting then a GI PCR and testing for SARS-COV-2 maybe useful. If there are respiratory symptoms respiratory viral panel which includes SARS-COV-2 must be performed. Serologic testing for dengue, chikungunya, leptospirosis and rickettsioses may be required. If there is fever with abdominal pain or tenderness- suspect acute cholangitis (stones, liver flukes), liver abscess (pyogenic or amoebic)-may need ultrasound, blood cultures or stool examination. Practitioners to keep in mind that the returning traveler may present with ruptured appendicitis, UTI/pyelonephritis, pancreatitis etc). These conditions need to be sought with appropriate lab and imaging.To summarize - thick smears finds the parasites whereas thin is for species identificationIf our history, physical, and diagnostic investigation led us to severe malaria as our diagnosis what would be your general management of framework?Let me reiterate that a patient is said to have severe malaria if the patient's parasite load is ≥ 5% or the patient has any of the following:Impaired consciousness, Seizures, Circulatory collapse/shock, Pulmonary edema or acute respiratory distress syndrome (ARDS), Acidosis, Acute kidney injury, Abnormal bleeding or disseminated intravascular coagulation (DIC), Jaundice (must be accompanied by at least one other sign) and Severe anemia (Hb <7 g/dL).Cerebral malaria, characterized by altered mental status and manifesting with a range of neurologic signs and symptoms, including generalized seizures, signs of increased intracranial pressure (confusion and progression to stupor or coma), and deathAny patient with severe malaria requires admission to the PICU as there can be rapid decline in the patients clinical status. Initial management of airway, breathing followed by resuscitation with balanced intravenous fluids should be started. Frequent checks as well as correction of glucose and electrolyte imbalances is recommended as well as close monitoring of urine output.Rahul our patient had mild cardiomegaly on CXR, mildly depressed cardiac function (LV and RV) on echo and mild elevation of her BNP and troponin. Can you shed some light on myocardial depression in patients with severe malaria?Pradip-initially our patient presented in shock so a quick echo done at bedside revealed some mild-moderate cardiac dysfunction with no pericardial effusion. An EKG revealed diffuse ST segment elevation. Patient was on epinephrine and MIlrinone for her cardiac dysfunction. Her echo+ekg findings along with elevated biomarkers were strongly suggestive of malarial myocarditis. Mainstay of treatment consists of hemodynamic cardiac support and treatment of the underlying malarial infection. We saw gradual improvement of her cardiac function with malaria therapy. In fact a cardiac MRI done prior to discharge was completely normal.A recent paper by Kotlyar et al in PCCM journal (2018; 19:179–185) reported on myocardial function and Injury by echocardiography and cardiac biomarkers in African Children with severe plasmodium falciparum malaria. The authors reported from their echocardiographic data that most children (96.2%) with severe P. falciparum malaria have normal EF despite some elevation of the cardiac biomarkers. Although there was evidence for myocardial injury (elevated cardiac troponin I), this did not correlate with cardiac dysfunction.Pradip Let's go into specific elements of management, how would you treat severe malariaCDC malaria clinicians are on call 24/7 to provide advice to healthcare providers on the diagnosis and treatment of malaria and can be reached through the CDC Malaria HotlineFor severe malaria: IV artensunate is the drug of choice . If patient is able to take PO, the patient should be treated with artemether-lumefantrine (Coartem™) because of its fast onset of action, or atovaquone-proguanil (Malarone). When IV artesunate arrives, immediately discontinue the oral medication and start parenteral treatment. Each dose of IV artesunate is 2.4 mg/kg. A dose of IV artesunate should be given at 0, 12, and 24 hours. Patients on treatment for severe malaria should have one set of blood smears (thick and thin smear) performed every 12–24 hours until a negative result (no Plasmodium parasites are detected) is reported. If, after the 3rd IV artesunate dose, the patient’s parasite density is >1%, IV artesunate treatment should be continued with the recommended dose once a day for a maximum of 7 days until parasite density is ≤1%. Doses given at 0, 12, and 24 hours count as 1 day, which means up to 6 additional days. Clinicians should proceed with full course of oral follow-on treatment as above as soon as parasite density ≤1% and the patient is able to tolerate oral medications.Intravenous artesunate is safe in infants, children, and pregnant women in the second and third trimesters. The only formal contraindication to IV artesunate treatment is known allergy to IV artemisinins.All persons treated for severe malaria with IV artesunate should be monitored weekly for up to four weeks after treatment initiation for evidence of hemolytic anemia.As for any malaria treatment, the regimen selection should not include the medication used for chemoprophylaxis.Previously, CDC recommended exchange transfusion be considered for certain severely ill persons. However, exchange transfusion has not been proven beneficial in an adequately powered randomized controlled trial. In 2013, CDC conducted an analysis of cases of severe malaria treated with exchange transfusion and was unable to demonstrate a survival benefit of the procedure. Considering this evidence, CDC no longer recommends the use of exchange transfusion as an adjunct procedure for the treatment of severe malaria.This concludes our PICU Mini case Series Episode on Fever and shock in the PICU patient after recent travel . 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!More information can be foundThwaites G and Day Nicholas PJ. Approach to fever in the returning traveler. N Engl J Med 2017; 376:548-560AAP Red Book 2021. Page 493-503Gupta et al, "Malaria and the Heart: JACC State-Of-The-Art Review." J Am Coll Cardiol. 2021 Mar, 77 (8) 1110–1121,Kotlyar S, Olupot-Olupot P, Nteziyaremye J, et al.Assessment of Myocardial Function and Injury by Echocardiography and Cardiac Biomarkers in African Children With Severe Plasmodium falciparum Malaria. Pediatric Critical Care Medicine 2018; 19:179–185

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 9 year old girl with worsening seizures in the setting of an electrolyte abnormality.Here's the case:A 9 year old girl presents to the ED with increased frequency of seizures, dehydration and listlessness. She has h/o of global developmental delay, congenital hydrocephalous (with VP shunt in place with her last revision 3 years prior, and seizure d/o treated with Leviteracetam. She usually has one or two focal seizures per day but on day of admission she had multiple prolonged seizures which were also generalized tonic clonic in semiology. Per her caregiver, the patient usually eats by mouth and mother typically gives her 3 cups of water daily. There is no history of diarrhea but patient has had 2-3 bouts of non-bloody non-bilous emesis on day of presentation. Looking at her growth chart, the patient has also lost ~ 2KG of her weight in the last 3 months and has had poor follow up with her PCP. In the ED she has a hypovolemic shock picture as she is hypothermic, tachycardic, tachpneic, and hypotensive with appropriate saturations. Blood gas is notable for a mild metabolic acidosis. Patient receives abortive seizure rescue. A head CT showed no increased in hydrocephalus, no mass or hemorrhage and a shunt series confirms patency of her VP shunt. Most pertinently to this case, her serum sodium on her RFP was undetectable at a value of = >200mEQ/dL; this was confirmed by a repeat lab draw and POC value. Other notable findings included an elevated Cr for age, an elevated BUN and a microcytic anemia. Patient was given a NS bolus, had cultures drawn, was started on broad spectrum abx therapy, stabilized and sent to the PICU.To summarize key elements from this case, this patient has:A history of GDD with epilepsy and shunted hydrocephalus.A stigmata of cachexia.And a presentation of hypovolemic shock secondary to decreased intake, increased loss, and potential underlying concern for sepsis.The most important element of this case is her extreme hypernatremiaAll of these factors in this case point to our topic of discussion today → the approach to hypovloemic hypernatremia 2/2 to dehydration.Let's transition into some history and physical exam components of hypovolemic hypernatremia?Key history features in patients who present with Hypovolemic HyperNa include:Increased losses such as emesisDecreased intake, and in this setting potentially lack of access to free waterListlessness which could be related to cerebral hypoperfusionIncrease in seizure frequency due to increased rapid depolarization of Na channels in the brain and fluid shiftsAnd weight loss → all of these factors were seen in our case.Of note if this patient was a neonate considering a high-pitched cry in the setting of hyperNa & dehydration could be a subtle history finding.Are there some red-flag symptoms or physical exam components which you could highlight?Our patient is Non verbal and has global delay secondary to a remote neurological insultShe may not have intact ability to communicate or vocalize thirst.Apart from her mucous membranes, dry cracked lips, decreased skin turgor that can be described as doughy, and prolonged capillary refill, I think it is important to highlight her hypotension - as BP is one of the last vital signs in pediatrics to be abnormal in intravascular volume depletion. To me, this really stratifies this patient into severe dehydration and potentially septic shock.This is a great point — understanding % volume loss and its correlation to vital sign and PE anomalies is key. Remember a sensitive marker for dehydration in pediatrics is tachycardia and a late finding if you are primarily dealing with dehydration is hypotension. This indicates that counter-regulatory responses are unable to maintain adequate systemic vascular resistance (SVR) and that there is a significant loss of intravascular volume. In our patient, we also noticed her weight loss on presentation which not only brings up the concern for malnutrition but it also serves as an adjunct measure of dehydration. In fact, in a 2009 paper assessing dehydration in pediatrics it was noted that the gold standard for confirming the diagnosis of hypovolemia in children is comparison of body weight before and after rehydration.To continue with our case, the patients labs were consistent with:Severe HypernatremiaElevated BUN and Cr which point to an AKIAnd interestingly mild anemia → this could be a nutritional aberrancy such as iron deficiency anemia or anemia of chronic disease in the setting of her complex underlying condition but it also brings up the concern for hypovolemic shock secondary to bleeding. Pertinently she had no signs of external or internal bleeding, but it is important to stratify this element as your resuscitation efforts — i.e. whether you would give crystalloid or colloid can be guided by this subtlety.Correct, it is important to highlight that in the setting of dehydration Hct values would be increased. In a 2006 Study in Transfusion, Valeri and colleagues concluded that the Hct values in hypovolemic anemic patients are elevated because the plasma volume does not increase to achieve the normovolemic anemic state.OK to summarize, we have:9 year old with global developmental delay who has emesis, dehydration and a serum Na of 200 mEq/L. This brings to the topic of our discussion today namely hypernatremia in the PICU.Let's start with a short multiple choice question: 15 year old with h/o diabetes insipidus presents with a serum Na of 175mEq/L. 4 months ago his serum Na was 140mEq/L. Currently patient is obtunded with decreased skin turgor, fever and a blood pressure of 140/80 mmHg. Patient has been stressed due to school work and been non compliant with his DDAVP resulting in polyuria for almost 5 days.Treatment goal for this patient isa. Reduce serum sodium concentration to normal in first 12 hoursb. Reduce serum sodium concentration to normal in 24 hoursc. Reduce serum sodium concentration to 150 mEq/L in 24 hoursd. Reduce serum sodium concentration by 10 mEq/L in 24 hoursThe correct answer is d. Reduce serum concentration by 10-12 mEq/L in first 24 hours; you can also think of this as not correcting the sodium more than 0.5 meQ/L per hour → thus in 24 hrs you should not lower the sodium by more than 12. I think listeners should remember that it is important to gradually lower the sodium in patients who have developed hypernatremia slowly over a period of days especially when Na is > 165mEq/L. Pradip, why is this?Patients with hypernatremia develop idiogenic osmoles to protect the brain from dehydration within hours. Numerous fatal cases of cerebral edema and herniation have occurred with rapid correction over a 24-hour period, leading to recommendations for correction over no less than 48 hours. General trend is for slow correction over 48 hours.A mnemonic that can be useful is high to low the brain will blow; i.e. if a patient has chronic hypernatremia that is corrected too acutely, you have the potential to develop cerebral edema. In a landmark study published in NEJM in 2015, the authors concluded that rapid correction of hypernatremia can lead to cerebral edema to the relative inability of the brain to extrude idiogenic osmoles. Furthermore a study published in pediatric emergency care in 2013 showed that serum sodium correction rate > 0.5 mEq/L/hour was associated with increased risk of mortality and convulsion in neonates with hypernatremia dehydration admitted to neonatal intensive care unit.Rahul: what would be some of the anatomic changes seen in the brain due to the resultant hyperosmolarity from hypernatremia?Anatomic changes seen with the hyperosmolar state include loss of volume of brain cells with resultant tearing of cerebral vessels due to local ECM shear stress forces. As you have an imbalance in frank starling capillary mechanics and subsequent flow through your cerebral vasculature, you may also see capillary and venous congestion, subcortical or subarachnoid bleeding, and interestingly, venous sinus thrombosis.I'd like to make a big point about the phenomena of sinus venous thrombosis as this has been well described in Pediatric Review articles. Taking it back to the basics, Virchow's triad gives us a framework on how to think about mechanisms of thrombosis. During hypernatremic dehydration at a micro-level there is endothelial stress and subsequent injury which can subsequently lead to venous sinus thrombosis. These patients can present with altered mental status, severe headache, and seizures.Rahul, that was a great framework → as we conclude our podcast, Iets hone in on three areas: a schema in understanding hypernatremia, a diagnostic approach, and finally a management framework.In general, how do you think about hypernatremia?I think Pradip one easy way to approach hypernatremia is to think of it as a water loss problem or a salt gain problem. Hypernatremia can exist as any of the following 3 scenarios, and these are all correlated to total body water.First, low total body water: Patients with a low total body water and hypernatremia have a loss of water in relative excess of sodium losses. This can occur from vomiting and diarrhea or renal losses from osmotic diuresis.Second Normal Total body Water: Loss of water occurs without excessive sodium losses in some conditions → these patients are going to be relatively euvolemic. Extrarenal losses result from increased respiratory losses as may occur with tachypnea, hyperventilation, or mechanical ventilation with inadequate humidification are examples of this phenomena.We also think about further insensible loss scenarios such as transcutaneous losses associated with fever, burns, extreme prematurity, or use of phototherapy or radiant warmers in the neonate without adequate water replacement. In general, another well-described cause of euvolemic hypernatremia is DI which can be a podcast in and of itself!Finally we think about increase in total body sodium and subsequent total body water: Usually from iatrogenic causes such as administration of Na HCO3, hypertonic saline or improperly concentrated infant formula.In a 2017 systematic review the authors looked at acute sodium toxicity due to dietary intake. They cited factors such as social media challenges and even charities that advocated eating small amount of salt to empathize with Syrian refugees. They concluded that a lethal dose of <5 teaspoons of salt ingested acutely can lead to pediatric fatality.If you had to work up this patient with hypernatremia what would be your diagnostic approach?I would highly suggest getting a nephrology consult in this patient.A comprehensive metabolic panel, Urine analysisUrine analysis especially of the first urine specimen preferably prior to rehydration to determine specific gravityIf you are suspecting DI, getting urine Na and electrolytes may be indicatedIn this our patient case, she presented with increased seizures and altered sensorium, thus A CT scan of the head is recommended to evaluate for hemorrhage and shunt malfunction.Due to hypothermia a blood culture, urine CX, a CBC with diff, CRP and procal would be useful. As this child has concern for increased catabolism in the setting of failure to thrive and lack of access getting a CPK to rule out rhabdomyolysis as a cause of intrinsic AKI would be useful.Finally a renal US may be necessary based on laboratory and urinary findings.I like this list Pradip, totally agree that a coordinated effort with nephrology can help in this setting as these patients may have renal dysfunction and there can be a collaborative effort in tracking electrolytes after we choose the appropriate rehydration fluid management. I would also recommend tracking weights as a part of your initial diagnostic plan!Our history physical and investigational undertaking has led us to severe hypernatremia as our diagnosis what would be your general management of framework? Patient needs to be adequately resuscitated to correct hypotension, protection of airway, and if necessary AEDs to control of seizures. Continuous EEG monitoring must be considered especially if patient is intubated. Most importantly, correction of underlying disease process giving rise to hypernatremia should be the goal. In our case it was dehydration due to lack of access to free water.Gradual correction of serum hypernatremia ~ 12-15 mEq/L/day. Frequent monitoring of serum Na(Q2 hr initially), as well as close eye on UOPAs hypernatremia is toxic to the beta islet cells, their dysfunction can lead to associated hyperglycemia.Estimated deficits, ongoing maintenance requirements, and additional excessive losses must be accounted for in calculations of the amount of fluid replacement required. In general 2-2.5 times maintenance IVF fluids usually with NACl is necessary especially with severe dehydration.In a precise academic approach calculating the free water deficit may be helpful:The equation is:0.6 x wt (kg) x [(current Na+/140) – 1] = this gives you liters of fluids:In acute dehydration you can take this fluid deficit and resusicate 50% of the volume you calculate over the first 12 hrs, and the remaining in the next 24 hrs could be a potential management strategy.If patient has central DI: Vasopressin, DDAVP along with replacement of UOP may be needed.In hypernatremic dehydration, the intracellular fluid moves into the extravascular space due to hypernatremia hence the patients dehydration may be underestimated.If patient has renal failure dialysis may be necessary

Welcome to PICU Doc On Call, a podcast dedicated to current and aspiring intensivists. My name is Pradip Kamatand my name is Rahul Damania and we come to you from Children's Healthcare of Atlanta Emory University School of Medicine. Today's episode is dedicated to the rational use of antibiotics in the PICUWe are delighted to be joined by two brilliant Pediatric clinical pharmacists Ms Whitney Moore and Ms. Stephanie Yasechko from Children's Healthcare of Atlanta.I will turn it over to Rahul to start with our patient case...CaseAn 8-year-old female (24 kg, 130 cm) with PMH significant for severe persistent asthma and history of multiple PICU admissions presents to the ED with swelling, redness and inability to bear weight in her (L) lower leg.Patient had just finished soccer practice the evening prior to her ED visit when she first noticed swelling and redness of her left lower leg. She also had a fever as well as some non-bloody, non-bilious emesis. Her past h/o is significant for poorly controlled asthma with multiple admissions to the PICU.Upon arrival to the ED, patient's BP was hypotensive, tachycardic, and tachypneic. She was given two 20 mL/kg NS boluses, and blood cultures were drawn in addition to a CBC, BMP, and UA.Labs were notable for an elevated white count, lactate, and serum Cr. Patient was given a dose of antibiotic, and transported to the PICU for further workup and management.Whitney and Stephanie welcome to PICU Doc on call.Thanks Rahul and Pradip for having us. Neither one of us have any financial disclosures or conflicts of interest.We want to divide today's discussion into 3 segments- antibiotic selection, transition into dosing and end with therapeutic monitoringWhitney, what are some of the factors to consider prior to choosing an antibiotic regimen in our patient case with a preliminary diagnosis of cellulitis of the left lower extremity with possible sepsis?Whitney: First and foremost you want to consider your host so really diving deep into the patient’s past medical history and secondly we should consider the likely pathogens that are causing the patient’s infection. In this case given the invasive nature of her infection and recent hospital admissions I would start Vancomycin and Cefepime. Once blood cultures results are back, we can then tailor or narrow her antibiotics based on susceptibilities.Stephanie what are some of the other factors to consider prior to starting antibiotics in this patient?Other things to consider include her multiple previous hospitalizations, significant exposure to broad-spectrum antibiotics, whether or not she is immunocompromised, the presence of chronic conditions like lung disease, ventilator/trach dependency, and if patient was a resident of a long term care facility. Additionally any history of organ or bone marrow transplant or malignancy with use of chemotherapy/radiation, and/or a history of growth of multiple drug resistant organisms.This is an important point - infectious disease is not just about the relevant pathogen or "bug" but it is also about understanding the host status!Stephanie -why vancomycin and cefepime in this case?In this patient the major pathogens to consider include: P. aeruginosa (give her multiple previous PICU admissions).Also she has extensive cellulitis which necessitates antibiotic coverage against Methicillin resistant staph aureus (MRSA) and Streptococcus pyogenes . So our options in this case include vancomycin for broad-spectrum gram positive coverage, and generally either piperacillin/tazobactam or cefepime for broad-spectrum gram negative and pseudomonal coverage.As you can see by patient’s Scr, it appears that she is presenting in AKI since we have no history of her having any type of renal impairment at baseline; therefore, to minimize additional AKI risk, cefepime would be our most appropriate choice for the time being. There is literature that shows us that the combination of vancomycin and piperacillin/tazobactam specifically has a much higher risk of AKI than other nephrotoxic combinations and should be avoided if possible.Whitney lets now transition from abx selection to dosing — how would you dose vancomycin and cefepime in our patient case?An appropriate dose of vancomycin to start out here would be 15 mg/kg, with a maximum of 1000 mg. However, instead of scheduling a defined frequency, pharmacy would recommend a x1 dose, and check a level in a couple of hours in patients who present with any type of unstable renal function. However, traditional vancomycin dosing in patients with normal renal function is either 20 mg/kg/dose IV every 8 hours or 15 mg/kg/dose IV every 6 hours with a max of 1000 mg/dose.Cefepime is traditionally dosed at 50 mg/kg/dose IV every 8 hours; however, since our patient has AKI, we should calculate her CrCl or estimated GFR to renally adjust the dose. As you all know there are a couple of equations we could use to calculate her clearance. But the modified Bedside Schwartz equation is the gold standard for pediatric patients. Once the GFR or CrCl is calculated we can then adjust the dose for her AKI.I think this is a great time to start to highlight the importance of collaboration between the intensivists, nursing & the pharmacy team. These children already are tenuous and as we treat with broad spectrum abx it is important to also consider the side effects such as nephrotoxicity of broad spectrum antibiotics.As we discussed specifics of dosing of Vanc and Cefepime, Stephanie, if we take a step back what are some of the other factors to consider prior to antibiotic dosing?In terms of selecting the most appropriate dose, we always want to consider factors like age, weight, renal/hepatic function, as well as the area in the body we wish to penetrate (CNS, bone, blood, etc.).Additionally, it is very important to identify whether or not the patient is currently receiving continuous renal replacement therapy(CRRT), plasma exchange, ECMO, or fluids and/or diuretics, because all of these can affect drugs quite significantly from a pharmacokinetic standpoint.Lexicomp (available either as a paper-back or online) is the gold standard for pediatric dosing. And of course your clinical pharmacist specialist is always available to help with dosing references, and can provide recommendations on how to most appropriately dose your specific patientWhitney how would you monitor the patient given evidence of AKI and the need for a nephrotoxic antibiotic such as vancomycin?Depending on the severity of the renal dysfunction, the vancomycin level can be checked anywhere from 8-24 hours post administrationA therapeutic steady-state drug concentration is generally reached after the administration of about 3-4 doses (or 4 to 5 half-lives). The therapeutic goal trough level is 10-15 mcg/mL for all infections, except for those harder to penetrate areas like the CNS or the heart. In these cases the target trough is higher at 15-20 mcg/mL.To summarize, those "hard to reach areas" such as the blood brain barrier or the heart — we should ensure a higher trough in order for us to reach therapeutic effect.Stephanie, what are important points regarding trough monitoring for vancomycin?Trough monitoring represents a therapeutic controversy within the pharmacy community, as recent vancomycin dosing guidelines have changed to now recommend area under the curve (AUC) guided monitoring as the most efficacious and safe way to monitor the drug given its narrow therapeutic range and increased nephrotoxic risk with trough monitoring.Here at our institution, we have not yet fully incorporated this new monitoring technique. We are reserving AUC monitoring for patients with MRSA bacteremia or unable to achieve therapeutic troughs with traditional dosing.This is a great practical example, as the bedside staff it is important to optimize communication as antibiotic troughs are time sensitive.Now that we have discussed vancomycin, Stephanie what about dosing and monitoring of cefepime in our patient?Cefepime, does not require therapeutic drug monitoring, so determination of an appropriate dose is dependent on CrCL, and it is important to recognize that continuous adjustments may need to be made as renal function improves or declines.Refer to Lexicomp for all renal dose adjustments. Rule of thumb, if CrCL > 50, a patient can be dosed normally. Anything less should be evaluated.Let's wrap up this section by summarizing some important dosing points for Vancomycin and Cefepime. Whitney, as your patient improves how would you approach de-escalation of abx?There are two important points I want you to remember when dosing vancomycin and cefepime. First, is knowing the maximum dose of each medication. Cefepime we max the dose at 2000 mg per dose, and our initial starting dose maximum for vancomycin is 1000 mg, as mentioned. We can go up to 1250 but only after we have drawn levels and need to. But knowing the maximum dose is an important point to consider when dosing a large patient because you don’t want to exceed an adult dose. The second important point I want you to remember is calculating the patient’s clearance and adjusting the dose and/or frequency based on the patients renal function if needed.Now, in regards to de-escalation of antibiotics, once the patient is no longer septic, with a resolved AKI, and cultures and susceptibilities have resulted, the team will determine if a full treatment course is warranted or not. If it is, then broad-spectrum antibiotics can be discontinued, and we can narrow to an antibiotic that the patient's pathogen is susceptible to.This is an important point — narrowing broad spectrum antimicrobials optimizes antibiotic stewardship.As we build on our case, Stephanie, if the blood culture grew Methicillin sensitive staph Aureus (MSSA) what antibiotic would be used and how will it be dosed?When a patient's blood culture is positive for MSSA, it is considered an invasive infection. Most common sources of bacteremia include endocarditis, skin and soft tissue infections, intravascular catheter infections, bone and joint infections, pneumonia, etc. and in 25% there is no source.MSSA can give rise to sepsis syndrome and septic shock with a mortality of 10-20%.We typically use nafcillin or oxacillin 2 gm IV Q4 hours or even an infusion. One retrospective study reported that continuous oxacillin was an effective alternative to intermittent oxacillin for the treatment of infective endocarditis caused by MSSA and may improve microbiological cure.Cefazolin can also be used. Patients who cannot be treated with beta-lactams, should be administered vancomycin or daptomycin. For uncomplicated bacteremia, a two week regimen is used. For complicated infection we typically do a 4-6 week course.Finally, understanding that patients who have toxic shock syndrome from staphylococcal species, Clindamycin has been shown to have bacteriostatic effects and reduce production of bacterial toxins!Key points: MSSA likes to form a biofilm especially on internal hardware, and continuous oxacillin may be an effective option for treatment prior to consider removing the hardware for source control.Our final portion of this podcast relates to specific clinical scenarios. We will be covering broad spectrum therapy for specific patient populations. We will cover anti-microbial coverage for patients who have:Hematologic malignanciesSolid organ transplant on immunosuppressionNeontal sepsisSickle celland ...Children with:VP shuntsPerforated appendicitisLemierre's disease...and finally the undifferentiated, critically ill, child.Whitney lets start with patients who have an underlying hematologic malignancies. What would be an initial empiric anti-microbial regimen for these patients?We typically use Cefepime, or zosyn, for gram negative coverage to cover bugs like pseudomonas & enterobacteriaceae. And for enhanced Gram positive coverage for your staph and strep we add vancomycin especially if there is presence of a central line associated bloodstream infection (BSI), or if the patient has severe mucositis, a skin and soft tissue infection, pneumonia or is hemodynamically unstable).If the patients fever continues with no source identification by about day 5 (4 to 7 window), consider adding an antifungal agent like micafungin or caspofungin. And if patient happens to already be on an antifungal for prophylaxis, consider adding voriconazole.And what about the the patient who has a solid organ transplant on immunosuppression who presents with septic shock?In transplant patients or those on immunosuppression we should first consider the fact that some immunosuppressive medications are known to be nephrotoxic and interact with other medications. Second thing we should consider like I mentioned before is our host. If they are immune compromised they will need broader coverage. Therefore, the most appropriate choices would be vancomycin and cefepime. If the patient continues to clinically decompensated, then it would be appropriate to add on that antifungal coverage with micafungin.This is an important point - immuno-suppresants may compound end organ dysfunction and further, may have key drug interactions, such as CYP enzymes, which may alter your antimicrobial or antifungal kinetics.Stephanie, let's continue with our specific patient populations which antibiotics would we consider in neonatal sepsis?Ampicillin +Cefotaxime OR Ampicillin +gentamicin but given shortage of cefotaxime we should consider ampicillin with ceftazidime.We want to cover Group B streptococci, E Coli and other gram negatives along with listeria species.Discontinue antibiotics if cultures are negative after 48 hours and suspicion for infection is low based on inflammatory markers.(Stephanie) What about the patient with fever, headache, altered sensorium concerning for bacterial meningitis, can you also comment on the patient with ventriculoperitoneal shunt infection and brain abscess?So in this scenario, it is essential to select antimicrobials that penetrate the CNS. Therefore, generally speaking, an appropriate selection would be vancomycin and ceftriaxone. The more inflamed the meninges are, the greater CNS penetration you are going to get with vancomycin. We would also add metronidazole for brain abscess to vancomycin and ceftriaxone to cover for anaerobic organisms.The addition of Vancomycin combined with Ceftriaxone especially in patients who have meningitis and no hardware is important in overcoming resistant S. Pneumo strains.Whitney, what is our coverage for perforated appendicitis with sepsis?For a perforated appendicitis with sepsis, piperacillin/tazobactam (Zosyn) is our preferred agent. Also the combination of Ampicillin +gentamicin + metronidazole can be used. When thinking of appendicitis you want to cover for your GI bugs like klebsiella, proteus, bacteroides and other anaerobes.One thing to note when thinking about gut coverage is clindamycin's resistance to B. fragilis is increasing and is up to 60% worldwide, therefore, it’s no longer recommended for intra-abdominal infections.Stephanie, What about neck abscesses and septic thrombophlebitis (such as Lemierre syndrome)A beta-lactamase resistant beta-lactam antibiotic (ampicillin/sulbactam) is recommended as an empiric therapy due to case reports of treatment failures with penicillin secondary to beta-lactamase producing F. necrophorum.Antibiotics should of course be tailored to the culture results and susceptibility data when available.Alternative options include clindamycin or metronidazole for patients with significant clinical allergy to beta-lactams. Clindamycin is preferred (for head, neck and lung anaerobic infections) as it has activity against metronidazole-resistant organisms such as actinomycetes and peptostreptococci.(Allen BW, Anjum F, Bentley TP. Lemierre Syndrome. [Updated 2020 Dec 4]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK499846.)It is important for us to highlight that the likely microbe associated with Lemierre's is Fusobacterium necrophorum!Whitney, lets conclude with our final patient population. What is your typical coverage in patient with Sickle cell disease who presents with sepsis, or acute chest syndrome?Levofloxacin is our agent of choice in this scenario to provide routine bacterial coverage as well as atypical coverage. Traditionally we would have done a 3rd generation cephalosporin, but we try to avoid the empiric use of ceftriaxone due to the association with life threatening hemolysis after administration.Though this incidence is rare, it is important to understand that CTX can cause intravascular hemolysis in these patients who already have compromised Oxygen delivery due to their anemia.Alright Stephanie, we have reached the end of our episode today... but I have one more question, as a fellow, when I am on call and we have a previously healthy child who presents to the PICU who is critically ill and hemodynamically unstable, what antibiotics should we consider ?Once again, the concept of where exactly we think the source of the infection is will drive antibiotic selection with the goal of providing the best empiric therapy for the most likely pathogen(s). In a previously healthy patient who has really had no recent hospitalizations or antibiotic exposure, we could start with ceftriaxone. If the patient, however, has MRSA of PSE risk factors, at that point we would then need to broaden to vancomycin and either cefepime/ceftazidime/or piperacillin/tazobactam.To take this episode home, remember to consider host status, source of infection, and likely microbes prior to initiation of broad spectrum therapy!Whitney and Stephanie thank you so much for your expertise on common bugs and drugs — this was a great discussion, and we value your expertise. What are your take home clinical pearls for anti-microbials in the PICU..Stephanie: Your clinical pharmacist can always help with choice of antibiotics as well as dosing and monitoring, especially in critically-ill children with AKI or hepatic dysfunction.Whitney: The...

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 Children's Healthcare of Atlanta and the Emory University School of Medicine Atlanta, GAToday's episode is dedicated to How to Read And Critically Review a Paper not only for the Journal club presentation at the fellows conferences but also for use in your clinical practice as a pediatric intensivist.We are delighted to be joined by Jocelyn Grunwell, MD, PhD. Dr. Grunwell is an Assistant Professor of Pediatrics-Pediatric Critical Critical Care at Emory University School of Medicine in Atlanta, GA. She is a K-scholar with research interests in mitochondrial dysfunction in critical illness, the airway immune response in pediatric acute respiratory distress syndrome, and near-fatal asthma. She is on twitter @GrunwellJocelyn.Rahul: Dr Grunwell welcome to picu doc on call. We are delighted to have you on our podcast today to discuss how to read & critically review a manuscript.Grunwell: Thank you Rahul and Pradip for having me on PICU DOC on Call. I have no conflicts of interest or financial disclosures.Q1. Rahul: Dr Grunwell: Why should a pediatric intensivist (whether in training or as a faculty) read journal articles?Grunwell: There are several reasons you might want to read journal articles, and your reading should be tailored to your goals. For example, first, you may want to learn more about a clinical topic to understand how to diagnose, treat or manage a disease. 2nd you may want to find the best evidence for how to treat a patient. 3rd, you may want to learn about the basic biology or mechanisms of a disease. Finally, you may want to identify gaps in a particular field of research to develop a research plan and write a proposal to explore a new research area.Q2: Dr Grunwell: Where do you find manuscripts relevant to intensivists?First, I would like to suggest that the learners and faculty in pediatric critical care make a habit of reading at the very least the abstracts in various pediatric journals even if they don't have the time to read an entire article. I generally go to Pediatric Critical Care Medicine, Critical Care Medicine, Critical Care Explorations, Pediatrics, Journal of Pediatrics, NEJM, JAMA Pediatrics, and the family of American Thoracic Society journals on a weekly basis. You can set-up your account so that the table of contents of these journals will be emailed to you. There are apps available, such as ReadQxMD, where you can be alerted to new content of interest to you. You can sign up and follow the accounts of several journals of interest to you on Twitter. There is also a useful, free website sponsored by Dr. Hari Krishnan called picujournalwatch.com in which Dr Krishnan has journal articles well-organized. The website is constantly updated to show the latest manuscripts relevant to our field. You can keep your articles organized by topic in software such as EndNote. Also doing a search on PubMed, OVID etc. can also be helpful to find latest information on a topic. Talking to a medical library scientists is very useful to structure a systematic search for articles or to get a article from a journal that is not available at your institution.Q3: Dr Grunwell can you define the term level of evidence?Grunwell: the term level of evidence - or traditional hierarchy of evidence - refers to what degree that information can be trusted based on the study design.The most common question is related to therapy or an intervention. Levels of therapy are typically represented as a pyramid with systematic reviews or meta-analyses positioned at the top of the pyramid followed by well-designed randomized control trials, and then observational studies. Observational studies include cohort studies or case-control studies. Case studies, laboratory-based studies with animal or in vitro models (aka: preclinical studies), and consensus or expert opinion lie at the bottom of the pyramid hierarchy. Based on this pyramid structure of evidence, the message is clear: Not all evidence and information is equivalent.Q3. Pradip: Dr. Grunwell what is a critical appraisal of a manuscript and how does it help us?Grunwell: Critical appraisal is the systematic evaluation of clinical research papers and it is used to judge the article's trustworthiness, its value and relevance in a particular context. Critical appraisal helps you to systematically evaluate whether:The study addresses a CLEARLY FOCUSED QUESTIONThe study uses VALID METHODS to address this questionThe valid results of the study are IMPORTANTThe VALID, IMPORTANT results are APPLICABLE to your patients or populationSo the goal of learning critical appraisal helps you:identify the most relevant papersdistinguish evidence from opinion, assumptions, misreporting, and beliefsPassess the validity of the studyassess the usefulness and clinical applicability of the studyrecognize any potential for bias.Q4. Dr Grunwell what are some of the key components of the appraisal process of a manuscript?I generally ask 3 preliminary questions when I look at a paper:What was the research question and why was the study needed? ( After a brief background about the topic under study, the paper's introduction should clearly state the research question and the hypothesis.)What was the research design? (For example, is this a primary or secondary study; If primary, then was it a laboratory experiment, clinical trial, survey, observational, or a case series study? If secondary, then was it a review or a clinical guideline, decision analyses, or economic analyses)?Was the research design appropriate to the question? It can be helpful to categorize the study into a therapeutic, diagnostic, prognostic, randomized control trial, qualitative, an epidemiologic/descriptive study, or a meta-analysis. There are evidence-based medicine worksheets that can help you structure a formal review and make sure you consider all aspects of the study. These worksheets can be found in many different languages at the Centre for Evidence-Based Medicine at The University of Oxford in the United Kingdom under Critical Appraisal Tools. The web address will be in the show notes (https://www.cebm.ox.ac.uk/resources/ebm-tools/critical-appraisal-tools) The Evidence-Based Medicine Toolbox from Toronto, Canada also have critical appraisal worksheets and resources to learn evidence-based medicine. This link will also be available in the show notes? https://ebm-tools.knowledgetranslation.net/.OK to summarize, understand the question and the study design and then assess whether the appropriate design was used to answer a central question!Q5. Dr Grunwell what is a general framework of how we should approach a manuscript?Dr Grunwell: In order to explain the structure of a scientific paper, I use the analogy of a story. Think about your favorite fairy tale: there is a beginning - where the scene is set and the characters are introduced; there is a middle - where the action happens, and there is an ending - where there is a lesson learned or a moral of the story. By analogy, every scientific paper has an introduction - where you set the background and importance of the question and introduce the subject matter - the who, the what, and the why of the study). The middle of the article is where the action happens - you explain how you did the study in the methods section and what happened (what you found) in the results section. Finally, the article has an ending where you discuss the results within a larger context of other studies by comparing and contrasting, noting similarities and explaining discrepancies to other work, and acknowledging limitations. Finally you make a conclusion based on your results - can you recommend this therapy or diagnostic study for your patients?.I really like the story analogy as this really frames our next segment of how to systematically read a scientific paper.Q6. Dr Grunwell: What is the first step in the critical appraisal of the scientific paper?A good first step would be just to skim through an article (start with the abstract) to understand the aims, key data and conclusions. Early considerations as you are skimming through the manuscript)-Main question - Relevant? Interesting?Original topic - Address a gap? Clear & easy to read?Conclusions consistent with the evidence presented?Do the experiments/data address the main question?Is there a disagreement with current consensus & is this disagreement justified by the data gathered?Do the Tables & Figures tell the story/add to the paper?This is a bird's eye view to get yourself oriented.Dr. Grunwell, in general, how does the introduction help you as you critically appraise a manuscript?Grunwell: When we look at the introduction we can formulate the problemDefine who the question is about? (how would I describe a group of patients similar to this one)Define which maneuver you are considering in this patient or population and if necessary, a comparison maneuver: (drug treatment vs. standard therapy or placebo)Define the outcome: Reduced mortality, length of stay, better quality of life cost savings, etc.Q7 Pradip: As you read further after your broad overview how do you identify areas for improvement or major flaws in study design?Dr Grunwell: I would encourage listeners to closely look at Tables, figures and images— What story are these data telling you? Can you recreate the story from the data presented WITHOUT reading a single word of the text? You should be able to follow the experimental argument and draw conclusions based solely on the evidence presented in the tables and figures.Some things to watch for:Are the authors drawing a conclusion that is contradicted by the author’s own statistical or qualitative evidence.Are they using a discredited or flawed method?how are they sampling a population, do they have appropriate controls, how precise are their measurements, was the analysis conducted in a systematic manner?Are they asking a valid question?-Are the authors ignoring a process that is known to have a strong influence on the area under study?Asking questions which correlate to the author's point of view is essential.Correct, using this process it is important to summarize the research question by:Stating the main question addressedand Summarizing the goals or objectives.This helps to conceptualize the research, and allows focus on the successful aspects of the paper.Transitioning to the methods section of a paper, Do Grunwell how do we assess the quality of the methods used in a study?I guess the real question is whether the study in question is original and what does the new research add to the scientific literature? For example, is this a continuation of a large study or field of research.Does it address previous methodological shortcomings? Will numerical results add significantly to a meta-analysis?Is the study population different?Is the clinical issue important enough, or does there exist sufficient doubt in key-decision makers, to make new evidence ‘politically’ desirable?Dr Grunwell as we assess the methods section how do we narrow in on the population of interest and specifically relate the methodology and paper to our patient cohort whom we serve clinically?This is a great question. I would think about whether the patientsAre the subjects more, or less, ill than who you see?Are the subjects of a different ethnicity, live a different lifestyle, from your own patients?Did the subjects receive more, or different, attention during the study that you can give your patients?Unlike most patients you care for, did the subjects have nothing wrong with them apart from the condition being studied?Did the subjects have potentially confounding exposures similar to your patients?To summarize a central theme of our episode thus far is to read a paper with a perspective on how this applies to your setting - in our case it is critically ill childrenLets transition and talk about the layers of bias which may be present in the results or even discussion portion of the manuscript, Dr Grunwell can you highlight the sources of bias in a study?Bias occurs when there is a systematic difference between the results from a study and the true state of affairs. Bias is often introduced when a study is being designed, but can be introduced at any stage. Appropriate statistical methods can reduce the effect of bias, but may not eliminate it. Increasing the sample size does not reduce bias.We need to look at the treatment group and control group very closely to make sure both are treated equally.Selection bias: can result from incomplete randomization. So patients included in the study are not representative of the population which you intended to analyze.Performance bias can result from systematic differences in care received by the intervention and control groups because either the participant or the researcher know what group they were assigned - so there are differences in care received other than the intervention being comparedExclusion bias refers to systematic differences in withdrawal or participants from a study arm. For example, there may be more withdrawals from the intervention compared to the placebo arm of a trial due to side effects; alternatively, there may be more withdrawals from the placebo arm of the trial compared to the intervention arm due to lack of improvement in clinical condition.Detection bias is the systematic differences in outcome assessment between groups. Blinding (or masking) of outcome assessors may reduce the risk that knowledge of which intervention was received, rather than the intervention itself, affects outcome measurement.Alright listeners lets summarize the various types of bias — selection is due to incomplete randomization, performance bias involves a lack of blinding, exclusion bias refers to the element of attrition, and detection bias refers to the impact the intervention has with respects to the control.Dr Grunwell what are the preliminary statistical questions which need to be addressed in a manuscript?Grunwell: Three statistical questions should be addressed:First, there should be a sample size calculation to determine the power to detect a true difference between groups–To calculate a sample size, there needs to be a defined amount of difference between 2 groups that is a clinically significant effect–You will need to know the Mean and Standard deviation (or variance) of the principal outcome variableSecond, the study must be continued for long enough for the effect to be reflected in the primary outcome.Third, the completeness of follow-up should be high. For example, < 70% follow-up may be sub-optimal. You can make an assessment of completeness by looking at the rate of withdrawal from the study (some reasons for low completeness include suspected adverse reaction, loss of motivation, loss to follow-up (moving from study area), or death).Dr Grunwell lets conclude our podcast by going into how do you evaluate the Results and Discussion section of a manuscript?The results should tell us what was discovered or confirmed. I make sure to see if it tells a coherent story. The authors should describe in simple terms what the data show and refer to statistical analyses such as significance and goodness of fit. Its should evaluate observed trends.Explains significance of results to a wider understanding. Outcome should be a critical analysis of the data collected.How do you look at the conclusion of a study?The conclusion should basically reflect upon whether or not the aims are achieved. Conclusion should not have surprises in them and should be evidence-based. It typically is short and relates directly to the question and outcome.Dr Grunwell this was a wonderful summary and discussion today — what our resources our listeners can utilize to improve their understanding about research methodology:How to read a paper by Trisha GreenhalghUsers' Guide to medical literature by Gordon GuyattI also would recommend writing science by Joshua Schimel.I always give my fellows a paper by my undergraduate research mentor, Professor George M. Whitesides titled the "Whitesides' Group: Writing a Paper" in the journal Advanced Materials.I recommend that PCCM fellows keep reading papers in PCCM and CCM journal - at the very least peruse through the abstracts especially when they are busy on-service, etc. Structured and interactive journal clubs can help practice critical appraisal skills.A community approach is definitely essential in staying current on new research?Dr. Grunwell we appreciate your insights on today's podcast, as we wrap up, would you mind highlighting your personal pearls with respect to critical appraisal of manuscript ?To develop a new habit, such as skimming abstracts and journal articles, its best to start small. For example, choose 1-2 journals to peruse and get the table of contents emailed to you.Be curious and start a journal club and try using the critical appraisal templates or worksheets when assessing the article. Make the journal club a fun and social experience.Learning new skills takes practice, and any investment you make in learning critical appraisal skills will help you become a better writer, researcher and clinician.Tables and figures should stand alone and tell the story. Invest time in trying to understand what the evidence supports in the article by interpreting the information in the tables and figures yourself before reading the text of the paper in its entirety.We went through a systematic process on how to collect, organize, synthesize & apply journal articles from manuscript to bedside! Having close collaboration with your medical librarian is essential along with a curiosity to learn is essential to optimize your evidence based knowledge and stay up to date on the literatureThis concludes our episode today on how to read a paper. We thank Dr Jocelyn Grunwell for her expertise on this topic. We hope you found value in this short podcast. We welcome you to share your feedback & place a review on our podcast. PICU Doc on Call is co-hosted by me Pradip Kamat and myself Dr. Rahul Damania.Stay tuned for our next episode! Thank youReferences:How to read a Paper 5th Edition by Trisha Greenhalgh. Wiley Blackwell publishersWhite J....