PICU Doc On Call

Welcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.I'm Pradip Kamat coming to you from Children’s Healthcare of Atlanta/Emory University School of Medicine. I'm Rahul Damania from Cleveland Clinic Children’s Hospital and we are two Pediatric ICU physicians passionate about all things MED-ED in the PICU. PICU Doc on Call focuses on interesting PICU cases & management in the acute care pediatric setting so let’s get into our episode:Here's the case presented by Rahul:A 21-month-old girl was brought to an OSH ED for somnolence and difficulty breathing, which developed after she accidentally ingested an unknown amount of liquid medicine that was used by her grandfather. Per the mother, the patient’s grandfather was given the liquid medication for the treatment of his opioid addiction. The patient took some unknown amount from the open bottle that was left on the counter by the grandfather. Immediately after ingestion of the medicine, the patient initially became irritable and had some generalized pruritus. The patient subsequently became sleepy followed by difficulty breathing and her lips turned grey. The patient was rushed to an outside hospital ED for evaluation.OSH ED: The patient arrived unresponsive and blue, she was noted to be sleepy and difficult to arouse on arrival, with pinpoint pupils and hypoxic to 88%. , but After receiving Naloxone, however, she became awake and interactive. Her glucose on presentation was 58 mg/dL and Her initial VBG resulted 7.3/49.6/+2. She continued to have intermittent episodes of somnolence without apnea. Poison control called and recommend starting a naloxone infusion; she was also given dextrose bolus. The patient was admitted to the PICU.To summarize key elements from this case, this patient has:Accidental ingestion of an unknown medicationAltered mental statusDifficulty breathing—with grey lips suggestive of hypoventilation/hypoxiaAll of which brings up a concern for a toxidrome which is our topic of discussion for todayThe typical symptoms seen in our patient of pinpoint pupils, respiratory depression, and a decreased level of consciousness is known as the “opioid overdose triad” Given the history of opioid addiction in the grandfather, the liquid medicine given to him is most likely methadone.In fact, in this case, the mother brought the bottle of medicine, which was subsequently confirmed to be prescription methadone given to prevent opioid withdrawal in the grandfather. To dive deeper into this episode, let’s start with a multiple choice question:Which of the following opioids carries the greatest risk of QTc prolongation?A. MethadoneB. MorphineC. FentanylD. DilaudidThe correct answer is methadone. Methadone prolongs QT interval due to its interactions with the cardiac potassium channel (KCNH2) and increases the risk for Torsades in a dose-dependent manner. Besides the effect on cardiac repolarization, methadone is also associated with the development of bradycardia mediated via its anticholinesterase properties and through its action as a calcium channel antagonist. Hypokalemia, hypocalcemia, hypomagnesemia, and concomitant use of other drugs belonging to the family of CYP3A4 system inhibitors such as erythromycin can prolong Qtc. Even in absence of these risk factors, methadone alone can prolong QTc. Thanks for that, I think it is very important to involve your Pediatric Pharmacy team to also help with management as children may be concurrent qt prolonging meds.Rahul, what are some of the pharmacological and clinical features of methadone poisoning?Methadone is a synthetic opioid analgesic made of a racemic mixture of two enantiomers d-methadone and l-methadone. besides its action on mu and kappa receptors, it is also an NMDA receptor antagonist. Due to its long action, methadone is useful as an analgesic and to suppress opioid withdrawal symptoms (hence used for opioid detoxification). Methadone causes constipation, nausea, and vomiting (due to its effect on the chemoreceptor trigger zone).Methadone is well absorbed in the GI tract and can be detected in the plasma within 30 minutes. Although its half-life is 10-18 hours, it can be as high as 25 hours or longer in acute overdoses. In infants and children, a single dose of methadone clinical manifestations can last X 72 hours. The action of methadone is similar to morphine and is primarily on mu, delta, and kappa receptors. It causes drowsiness, respiratory depression, hypotension, and miosis. Cerebral edema has been associated with severe toxicity.Pradip, If you had to work up this patient with methadone ingestion, what would be your diagnostic approach?The classic triad of miosis + respiratory depression and altered mental status with a quick response to Naloxone is diagnostic of opioid poisoning. History of methadone exposure such as in our case above will help clinch the diagnosis.Blood gas, CMP, CBC, Routine and comprehensive drug screens (may help with co-existing toxins).Methadone is usually not tested on a standard drug screen unless specifically requested. Standard urine immunoassays are not able to detect synthetic opioids such as methadone.Methadone ingestion is confirmed when both methadone and methadone metabolite (EDDP) are detected in the urine using high-performance liquid chromatography. However such testing is costly and may take time. The window of methadone detection can range from 3-4 days (rarely up to 14 days).EKGbeta-HCG in a female teenager.Always follow your state's poison control recommendations.If our history, physical, and diagnostic investigation led us to methadone ingestion as our diagnosis, what would be your general management of framework?Symptomatic and good supportive PICU care with continuous monitoring of airway patency is the mainstay of treatment in patients who present with mild to moderate methadone toxicity. Charcoal lavage may be tried in mild intoxication in a patient who is not altered.Administer oxygen and assist ventilation for respiratory depression.Naloxone is an opioid antagonist and the antidote of choice, especially in severe toxicity. For children under 5years of age (or < 20Kg): Use 0.1mg/kg. For children > 5 years or over 20Kg 2mg IV every 2-3hours. Naloxone can be administered SC, IM, IV, via the endotracheal tube or even intranasally. Continuous infusion is likely to be necessary for patients who have ingested methadone, as the duration of action of Naloxone is 1 to 2 hours, compared with a duration of action of 24 hours for methadone. The infusion should be started at a rate such that two-thirds of the dose effective for initial reversal is administered each hour, and titrated as needed. Naloxone can potentiate withdrawal in opioid-dependent patients. A side effect of naloxone use can be transient hypertension or pulmonary edema (both rare) and such risks should not preclude its use.Early intubation and ventilation assistance should be performed if respiratory depression does not respond to naloxone. Adequate circulatory support with IV fluids and vasopressors (if needed) should be assured if a patient presents with a circulatory collapse that does not reverse with naloxone. Treat seizures with benzodiazepines, propofol, and/or barbiturates.Monitor for QT prolongation and dysrhythmias. Torsades de pointesCorrect electrolyte abnormalities. Intravenous magnesium and overdrive pacing as indicatedVery rarely ECMO may be required if life-threatening pulmonary edema refractory to standard measures.Pradip, it was found in our case that the patient had significant hypoglycemia. Can you shed some light on this in relation to the methadone overdose?Blood glucose needs to be carefully monitored. Most studies report hypoketotic, hyperinsulinemic, and hypoglycemia after an acute, unintentional methadone exposure, especially with high doses. Possible etiologies of hypoglycemia may include promotion of pancreatic insulin release, suppression of counter-regulatory mechanisms such as glucagon, epinephrine, and sympathoadrenal responses to hypoglycemia as well as impairment of glycogenolysis and gluconeogenesis.As we wrap up today, let’s also go through the criteria for observation, admission, and ICU-level care. All patients who develop CNS or respiratory depression should be admitted for observation (for at least 24 hours) even after adequate response to naloxone therapy. Patients who require intubation or a naloxone infusion will obviously require an intensive care unit admission. Patients should not be discharged until they have remained awake and alert for 4 to 6 hours after the Naloxone infusion has been discontinued.Patients with mild toxicity who do not require Naloxone should be observed for at least 8 hours.Please also work closely with toxicologists and local poison control as well!Pradip, what are some clinical pearls or pitfalls to avoid?Remember the triad of pinpoint pupils+respiratory depression+altered mental status is highly suggestive of opioid poisoningNaloxone is the drug of choice in opioid overdose, an infusion may be needed for longer-acting agents such as methadone.In addition to Naloxone, close attention to airway patency and maintenance of respiration is required in the PICUSo today we learned about the management of methadone ingestion in a toddler. Liquid methadone is highly toxic and even as one little teaspoon can lead to fatality in a toddler. Besides appropriate storage of methadone to prevent accidental ingestion by toddlers, early recognition of the classic opioid triad (AMS+Pinpoint pupils+respiratory depression) and prompt medical intervention can be life-saving.This concludes our episode on Methadone ingestion. We hope you found value in our short, case-based podcast. We welcome you to share your feedback, subscribe & place a review on our podcast! Please visit our website picudoconcall.org which showcases our episodes as well as our Doc on Call management cards. PICU Doc on Call is co-hosted by myself Dr. Pradip Kamat and Dr. Rahul Damania. Stay tuned for our next episode! Thank you!References:Fuhrman & Zimmerman - Textbook of Pediatric Critical Care Chapter 126 Toxidromes and Their treatment by Prashant Joshi. Page 1497.Reference 1: Sachdeva DK, Stadnyk JM. Are one or two dangerous? Opioid exposure in toddlers. J Emerg Med. 2005 Jul;29(1):77-84. doi: 10.1016/j.jemermed.2004.12.015. PMID: 15961014.Reference 2: Boyer EW, McCance-Katz EF, Marcus S. Methadone and buprenorphine toxicity in children. Am J Addict. 2010 Jan-Feb;19(1):89-95. doi: 10.1111/j.1521-0391.2009.00002.x. PMID: 20132125.Reference 3: Glatstein M, Finkelstein Y, Scolnik D. Accidental methadone ingestion in an infant: case report and review of the literature. Pediatr Emerg Care. 2009 Feb;25(2):109-11. doi: 10.1097/PEC.0b013e318196faff. PMID: 19225381.

Welcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.I'm Pradip Kamat coming to you from Children’s Healthcare of Atlanta/Emory University School of Medicine. Today we are joined by two wonderful clinical pharmacists — Whitney Moore & Stephanie Yasechko.Whitney is a Clinical Pharmacy Specialist at Children’s Healthcare of Atlanta. She is on Twitter at @MoorephinRx.Stephanie is a Pediatric Lung Transplant Clinical Pharmacy Specialist at Cincinnati Children’s Hospital Medical Center.We are so excited to have you both on today. My name is Rahul Damania and I am a Pediatric Intensivist at Cleveland Clinic Children’s Hospital; Welcome to PICU Doc On Call where we focus on all things MED-ED in the PICU. Our podcast focuses on interesting PICU cases & management in the acute care pediatric setting so let’s get into our episode:Welcome to our Episode an 18 yo immunocompromised patient with headache & sore throatHere's the case presented by Rahul:An 18-year-old female (40 kg) with PMH significant for fibrolamellar carcinoma of the liver, presents to the ED with headache and sore throat. She is febrile to 38.3, tachycardic, tachypneic, and has a WBC of 27K on her CBC. She is markedly hypotensive with BP on the arrival of 99/65. Cultures were drawn, the patient was given x1 doses of vancomycin and meropenem, and she was transported to the PICU for further workup and management. Due to her progressive hemodynamic instability, increased inflammatory markers, and marked immunocompromised state, the team is considering broadening her anti-microbial coverage.To summarize key elements from this case, this patient has:Fibrolamellar carcinoma of the liverA presentation of headache, sore throat, and hemodynamic instability with concern for sepsisA current regimen of just antibacterials, which brings up the consideration of adding anti-fungal coverage in her clinically ill state.Our episode today will be covering anti-fungal agents in the PICU.We will review general mycology, understand different classes of antifungals, and highlight practical clinical pearls in the acute care setting.As mentioned, this patient has risk factors for an immunocompromised state due to her underlying liver condition. As we dive deeper into antifungals, Whitney, can you please give us an overview of common fungal pathogens in the PICU?Before we discuss the major drugs, it’s important that we take some time to briefly review the most common fungi we encounter clinically since it’s hard to choose the right agent when you don’t know exactly what you are treating.Clinically, Candida is probably the most common fungal pathogen encountered, especially in warm, moist environments. It is important to determine what type of species is growing. The three major species known to cause infection are C. albicans, C. glabrata, and C. krusei, but it is important to differentiate these species when identified since they have different resistance patterns.Cryptococcus is another type of fungus that is known to cause meningitis or fungemia, especially in immunocompromised or cirrhotic patients. Both Candida and Cryptococcus are classified as yeast on Gram stain. Treating cryptococcus will require the use of an agent that has good penetration to the CNS.Endemic fungi known as Coccidia, Histoplasma, and Blastomyces are known to cause disseminated infections in immunocompromised hosts; however, each fungus is associated with a different geographic region in the United States. With any type of infection, it is always very important to consider your patients’ exposures and recent travel history.And finally, there are two major molds that have the potential to be pathogenic. The first is Aspergillus which is identified via hyphae (tall filaments) on Gram stain well known to cause invasive pulmonary infections in the immunocompromised, specifically those who are neutropenic and/or received a lung transplant. Cystic fibrosis patients are also well-known hosts to aspergillus. The next mold is Mucorates, otherwise known as Mucor. Mucor has the propensity to cause an aggressive infection that necessitates surgical debridement. While rare, you can see this pathogen affect patients who are diabetic, neutropenic, taking chronic steroids or other immunosuppressants, or who have just sustained a trauma.So now that we have some background on fungal pathogens and who they most commonly affect, let’s now dive into the medications we have available to treat them, but first, let’s circle back to our case.While cultures remained negative for bacteria, the patient’s headache and sore throat worsened, congestion developed, and ENT was consulted to evaluate nasal cavities which appeared concerning for necrosis. The patient was then taken to the OR for investigation and debridement, and fungal cultures were taken.After a close consult with ID, the recommendation was made to empirically treat with liposomal amphotericin B at 10 mg/kg IV once daily due to CNS concern and immunocompromised host status.As mentioned in the case, the patient was started on amphotericin B, let’s take a step back and review some key classes of anti-fungal medications commonly used in the PICU.As a big picture, we will be covering Poleyenes, Azoles, and EchinocandinsWhitney, do you mind highlighting our first class, the polyenes?The first class of antifungal agents we will discuss is polyenes. Within this class, there are two agents that we encounter clinically: Amphotericin B and Nystatin. These two agents bind to ergosterol in the fungal cell membrane to disrupt fungal cell permeability and cause rapid cell death.For the purposes of this podcast, we will focus our attention on amphotericin B, as this agent is a broad spectrum IV antifungal agent used clinically to treat most all fungal infections including cryptococcus, aspergillus, fusarium, and mucor.However, this medication is known for its many toxicities including electrolyte derangements, headaches, fevers, and renal impairment. There is a liposomal formulation of this medication in which most hospitals now have on formulary exclusively to help mitigate some of these adverse effects, but this formulation is also known to cause them to a lesser extent, and electrolytes should be closely monitored and aggressively replaced during therapy.Nephrotoxicity also means the use of concomitant nephrotoxic medications should be minimized as much as possible. So in our patient case, since blood cultures remained no growth to date, vancomycin, as well as meropenem, were discontinued.Returning to our case, Histopathology and debridement ended up showing evidence for mucormycosis susceptible to posaconazole and isavuconazole. Let's talk a little bit now about the Azole class.The azoles are our second group of antifungals; this class of antifungals works by preventing the formation of ergosterol, and there are five common azoles that every clinician should be familiar with, and taking into consideration our case, we will start by discussing posaconazole and isavuconazole.Posaconazole is a broad spectrum azole that covers all of your Candida as well as both Aspergillus and Mucor. It is available both IV and orally, in the form of tablets and a suspension. The oral formulations are not interchangeable since the oral suspension has erratic pharmacokinetics given that it is highly lipophilic and difficult to absorb. Therefore, it is recommended to use the tablets when able, especially given their convenience of once daily dosing.Otherwise, the drug will require therapeutic drug monitoring to ensure the patient is achieving adequate levels. The target trough concentration for adequate posaconazole prophylaxis is > 700 ng/mL and > 1,250 ng/mL for treatment drawn 5-7 days following medication initiation.Like most all of the other drugs in this class, posaconazole is a strong CYP3A4 and p-glycoprotein inhibitor; therefore, many drug interactions exist. These types of azoles are also known to prolong QTc and cause hepatotoxicity.It is important to highlight that children in the PICU may frequently be frequently on concurrent medications which also prolong the QT interval. Having close collaboration with your clinical pharmacy team and a daily discussion of the medications the patient may be on is essential in optimizing electrocardiographic monitoring for these patients.Now that we have talked about posaconazole, let’s contrast this with isavuconazole (cresemba). Whitney, do you mind highlighting some similarities & differences?Isavuconazole is the newest azole and is also available in an IV and PO formulation. Coverage is pretty similar to posaconazole; however, the additional benefits of this agent are that it does not require therapeutic drug monitoring, has QTc prolonging effects, or have as significant of drug interactions when compared to the other azoles, given that it is a moderate CYP3A4 inhibitor versus a strong one.Major side effects to be mindful of include hypersensitivity and skin reactions, hypokalemia, hepatotoxicity, peripheral edema, and cough.To summarize, Given that our patient here is an oncology patient with chemotherapy and anti-emetics on board, isavuconazole is the drug of choice for her due to the lack of QTc prolonging and minimal drug interactions. Therefore, we can then narrow her from the liposomal  amphotericin B to isavuconazole, where we would first load her with 372 mg IV Q8H x6 doses, and then continue her on a maintenance dose of 372 mg IV or PO when able for as long as she is receiving chemotherapy and is immunosuppressed.Ok, so far we have covered posaconazole, isavuconazle, let’s close out this class by highlighting voriconazole, itraconazole and fluconazole?So while our patient was growing Mucor which was susceptible to both posaconazole and isavuconazole, another agent to highlight voriconazole. While it does not cover Mucor, it is the drug of choice in the treatment of Aspergillus and has good Fusarium coverage as well.It is also available in both IV and PO which can be converted 1:1. However, it does have the most toxicities compared to any of the other azoles which can include hallucinations, visual disturbances, and phototoxicity. Therefore, therapeutic drug monitoring is essential with a goal trough level of about 2-6 mcg/mL.Absolutely, Stephanie, I want to also highlight Itraconazole. This is the azole most commonly used to treat Histoplasma and Blastomyces. It can also be used as a prophylactic agent for Aspergillus. It is only available orally as a solution and as a capsule, but they are not interchangeable. The capsules must be taken on an acidic stomach and with a full meal while the solution needs to be administered in a fasting state. This drug is also monitored via a serum trough concentration with a goal level > 0.5 mcg/mL.It is important to keep in mind, however, that this agent has two black box warnings. The first is that it may cause negative inotropic properties which may lead to heart failure, and the other is that it has the potential to lead to torsades de pointes. Therefore, it should not be used in patients with a history of heart failure and/or ventricular dysfunction.And finally, the last azole and most narrow azole we are going to discuss is fluconazole. Fluconazole is the drug of choice for Candida albicans, Cryptococcus, and Coccidia. This drug is available both IV and orally with a 1:1 conversion, and distributes everywhere in the body, including the CNS.Our final discussion today will be on echinocandins, Stephanie, how do these agents work?These agents work mechanistically by inhibiting 1,3-beta-D glucan synthase which is also involved in the synthesis of the fungal cell wall.There are three agents in this class (caspofungin, micafungin, and anidulafungin). All three are available IV only, have a similar spectrum of activity which is essentially all Candida as well as Aspergillus, and are dosed once daily.The great thing about these agents is that they have very few drug reactions and do not require therapeutic drug monitoring.To summarize our discussion today, we spoke about major classes of antifungals, polyenes, azoles, and echinocandins. While each of them has its own specific coverage, it is important to also monitor for side effects and toxicities. Working closely with your clinical pharmacist and infectious disease physicians is a high-fidelity strategy to optimize therapeutic treatment.Also, in the spirit of anti-microbials, I would like to add that if you have not checked out our prior episode number 23: PICU Bugs and Drugs, I would highly recommend you listening as it covers the: Rational Use of Antibiotics In The PICU!This concludes our episode on Approach to Anti-fungals in the PICU. We hope you found value in our short, case-based podcast. We welcome you to share your feedback, subscribe & place a review on our podcast! Please visit our website picudoconcall.org which showcases our episodes as well as our Doc on Call management cards. PICU Doc on Call is co-hosted by myself Dr. Pradip Kamat and Dr. Rahul Damania. A special thank you to Dr. Whitney Moore & Stephanie Yasechko for joining us today and sharing their expertise. Stay tuned for our next episode! Thank you!References:Antifungal Therapeutic Drug Monitoring Recommendations for Adult and Pediatric Patients. The Michigan Medicine University of Michigan. January 31, 2017.Curran, M. There’s a Fungus Among Us: A Beginner’s Guide to Antifungals. TLDRPharmcy.com. February 14, 2018.Lexi-Drugs. Hudson, OH: Lexicomp. Accessed June 5, 2022.

Welcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.I'm Pradip Kamat coming to you from Children’s Healthcare of Atlanta/Emory University School of Medicine and I'm Rahul Damania from Cleveland Clinic Children’s Hospital. We are two Pediatric ICU physicians passionate about all things MED-ED in the PICU. PICU Doc on Call focuses on interesting PICU cases & management in the acute care pediatric setting so let’s get into our episode:Welcome to our Episode about a 4-year-old girl with a chief complaint of headache and vomitingHere's the case:A 4-year-old presents to the PICU with headaches + vomiting and abnormal CT scan findings. The patient presented to the ED with h/o abdominal pain X 5 days with nonbilious, non-bloody emesis. Initial CBC, UA was normal. The patient was given some pain meds and IV fluids. Further history revealed that the patient has been having severe headaches for the last 5 days and had emesis secondary to the headaches resulting in generalized, non-specific abdominal pain. No h/o of trauma or seizures, no h/o of fever or diarrhea, no h/o toxic ingestions h/o recent travel, exposure to sick contacts, COVID test negative. No family h/o migraines, her immunizations are UTD. Besides the normal UA and CBC, her CMP was also normal.A CT scan of the head revealed right frontoparietal mass with moderate surrounding edema, 6 mm leftward midline shift, diffuse sulcal narrowing, and right cisternal narrowing. Imaging of the abdomen (US and CT w/ contrast) was unremarkable. An MRI done revealed: Right parietal diffusion restricting lesion, most compatible with abscess. Moderate surrounding vasogenic edema. Given her abdominal pain- Abdominal KUB as well as contrast CT scan of abdomen and pelvis were performed and revealed no abdominopelvic pathology.In the ED her vitals were normal and the patient was afebrile. On her PE: the patient appeared sleepy but woke up and answered questions appropriately. No focal deficits, PERRL, normal tone and strength. The rest of her physical exam was completely normal. She now is transferred to the PICU for serial neurological exams.To summarize key elements from this case, this patient has:Headache with altered mental statusNo focal deficitsVomitingsurprisingly no feverImaging showing right frontoparietal mass.All of which brings up a concern for brain abscessThis episode will be organized…Epidemiology and pathogenesisDiagnosisManagementRahul, can you inform our listeners about the epidemiology of brain abscesses?Only about 25% of brain abscesses occur in children. Incidence in developed countries is about 1-2% while in developing countries it's about 8%. Peak incidence in children is seen between the ages of 4-7 years and is more common in males. Brain abscess in the neonatal age group is rare but are associated with a higher risk of complications and mortality.Risk factors for brain abscess include Otologic infections (ear, sinus, and dental infections), Congenital heart disease (30% of patients with BA have an underlying heart defect) with intra-cardiac or intrapulmonary shunting (pulmonary AV malformations in hemorrhagic telangiectasis), immunodeficiencies (solid organ transplantation, HIV, etc), prolonged steroid use, diabetes, alcoholism neurosurgical procedures, trauma. Other rare causes can be airway foreign bodies, congenital dermal sinuses, and esophageal procedures (such as dilatations).Brain abscess typically begins with a localized area of cerebritis which evolves through various stages (typically 10-14 days) to develop into an encapsulated collection of purulent material with peripheral gliosis or fibrosis.40-50% of the spread of infection is via a contiguous site of infection such as otitis, sinusitis or mastoiditis or from head trauma or neurosurgical procedure. 30-40% is spread through the hematogenous route from endocarditis, pulmonary infections, or dental abscess.90% of brain abscesses in children are supratentorial. Mastoiditis, sphenoidal sinusitis, otitis media results in BA in the temporal lobe or cerebellum. Frontal lobe BA are due to frontal or ethmoid sinusitis or dental infections. BA from hematogenous spread results in multiple abscesses and typically follows the distribution of the middle cerebral artery including parietal and occipital lobes.Rahul, what are some of the common pathogens seen in brain abscesses?A meta-analysis reported the most common organisms in children with BA. These include streptococcus species seen in 36% (seen mostly with otologic infections, and strep viridans with endocarditis) followed by staphylococcal sp seen in 18% (head trauma, surgery, or skin infections) and gram-negative enteric bacteria seen in 16% (Proteus, Klebsiella, E. coli and Enterobacteriae. Citrobacter, E Coli, or proteus species are seen in neonates.BAs from opportunistic microorganisms are usually multiple. They can occur in HIV-positive children with a low CD4 count; the most common pathogens are Toxoplasma, Nocardia, and Mycobacterium spp. Fungal abscesses (mainly Aspergillus or Candida) typically affect solid organ transplants recipients or children treated for leukemiaTo summarize, altered mental status in a patient who is immunocompromised, think of opportunistic infections. Remember these patients can present even without a fever!Rahul, what are some of the typical clinical features seen in patients with a brain abscess?Clinical features would depend on site, size, involvement of surrounding area, patient’s immune status, and organisms involved. Fever with headache is typical. Vomiting is usually associated with headaches. Neurological manifestations include-Seizures, hemiplegia, cranial nerve palsies, and altered level of consciousness ranging from drowsiness to coma. Neonates can have bulging fontanelle and even increased head circumference.The classic triad of fever +headache +neurological deficits is clinically seen in a small percentage (~33%) of patients. Frontal abscesses may remain asymptomatic especially if they are small. Pott's Puffy tumor also called Pott's edematous tumor (PET), is a sub-periosteal abscess of the frontal bone, associated with osteomyelitis of the frontal bone. which can give rise to BA. Meningeal signs are seen in 25% of patients with BA.To summarize, Pott puffy tumor is osteomyelitis of the frontal bone with associated subperiosteal abscess causing swelling and edema over the forehead and scalp. It is a complication of frontal sinusitis or trauma.If you had to work up this patient with a brain abscess what would be your diagnostic approach?I would start with a CBC with diff, Blood Cx, ESR, CRP, and CMP. Such tests are abnormal in only 20% of pediatric patients with BA.After CT or MRI, an LP can be attempted. LP would be contraindicated if there is a non-communicating obstructive hydrocephalous and brain shift. CSF fluid analysis, gm stain, and cultures could be helpful to find an organism and tailor therapy. Although CSF studies can be normal in 30% of patients with a BA. The sudden worsening of a preexisting headache can indicate a rupture of the brain abscess into the ventricular space or impending herniation from the lesion’s mass effect. Significant alteration in mental status is an ominous clinical finding. Abscesses located within their brainstem typically present with fever, headaches, hemiparesis, and focal cranial nerve findings involving CN III, CN VI, and CN VII.MRI is considered as the gold standard (low radiation risk, better resolution, and lower toxicity of contrast compared to CT). MR imaging may require sedation and take a longer time compared to CT (which is readily available and may not require sedation due to the speed of image acquisition and can be performed quickly prior to an LP). MR has higher sensitivity and specificity in the differential diagnosis with cystic or neoplastic lesions. An MR study for bacterial BA will show a necrotic center with the low signal at the DW-MR (diffusion-weighted magnetic resonance) and a T2-hypointensity with enhancement for the peripheral capsule. Fungal abscesses show a hypointense center in the T2-weighed image with variable expression in DW-MR.CT may reveal a mass lesion but MRI will help confirm the diagnosis and characterize the abscess better. Pus obtained from the aspiration or biopsy during the operating room can be used for culture.Cultures (for aerobic and anaerobic bacteria, Mycobacterium, fungi, protozoa), Gram, and special stains (for fungi, Mycobacterium, Nocardia) and polymerase chain reaction should be performed on blood, CSF, and pus of the cerebral abscess. It is best to involve our ID colleagues in a patient with BA to guide diagnostic studies as well as therapies. The culture positivity of blood and CSF samples is low (22-28% of cases). The rate of micro-organism isolation from abscess samples is about 60–80%, with polymicrobial involvement in about 20–30% of cases.Other studies can be obtained on a case-by-case basis depending on the primary focus would include an echocardiogram, CXR, abdominal US or CT, and bone imaging.Besides infectious disease and NS experts, consults with cardiology, hematology, OMFS, and ENT experts may be required.To summarize, your approach to brain abscesses involves imaging, isolation of the lesion, and fluid/tissue diagnosis. Diagnostics such as an echo may reveal a primary source. This is definitely a coordinated effort with ID, neurosurgery, as well as neurology. These patients may also require prophylactic anti-epileptics peri-biopsy.If our history, physical, and diagnostic investigation led us to brain abscess as our diagnosis what would be your general management of framework?As we have mentioned before, A multidisciplinary team approach involving the PCCM, NS, ID, radiologists, and pharmacists are required for the successful management of patients with BA in the PICU.Again, good basic PICU care with close attention to airway patency, adequacy of oxygenation/ventilation as well as stability of hemodynamics should be the first line approach in such patients admitted to the PICU. Good access for medication administration may include the need for a PICC line. Attention to neuro-status by frequent physical exams including attention to the patient's handling of oral secretions should be a priority. Continuous EEG may be required depending on the site, size, and involvement of the surrounding area.Long-term antibiotics are the mainstay of therapy: A combination of vancomycin+ceftriaxone and metronidazole for 4-6 weeks if surgically drained vs 8 weeks for those without surgical drainage. Along the same lines, it is important to anticipate PICC lines or stable central lines for the long-term abx therapy.Non-operative approach can be considered in patient with multiple small abscess or a single abscess which is < 2.5cm. Non surgical approach is also considered in patients with surgically inaccessible lesions, early cerebritis, or medical comorbidities that puts patient at high surgical risk.What about operative approach?Operative approach involves aspiration (typically CT guided), or excision. Aspiration results in removal of infected nidus (source control) as well as provision of material for gm stain/Cx. Excision of the abscess cavity may be useful when it is located in a periventricular or posterior fossa distribution, is loculated, or contains a foreign body. Excision should also be considered for abscesses that enlarge after 2 weeks of antibiotic therapy or that fail to shrink after 3 to 4 weeks of antibiotics. Primary excision may be the procedure of choice for lesions located in the cerebellum. Compared to aspiration, excision of BA in nonvital areas of brain had a lower rate of re-operation, a higher rate of postoperative abscess clearance, and better neurologic improvement after 1 month with no difference in long-term neurological outcomes or mortality.Rahul, what are some of the prognostic features of BA?BA from a contiguous focus of infection and those developing after a traumatic injury tend to have a better prognosis. Poorer prognosis is associated with delayed diagnosis, immunocompromised status, rupture of the abscess into the ventricular space, fungal etiology, and pretreatment neurologic compromise.Let’s summarizeThe classic triad of diagnosis of BA- headache +fever+ neurological deficit is seen in only 1/3rd of the patients with BA. Therefore a high index of suspicion is required based on patients risk factors such as immunosuppression, cyanotic heart disease etc.Early imaging with CT/MRI is necessary to diagnosisAntibiotic therapy should not be delayed. Triple therapy with vancomycin +ceftriaxone and metronidazole is typically initiated at diagnosis.This concludes our episode on brain abscesses. 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!ReferencesFuhrman & Zimmerman - Textbook of Pediatric Critical Care Chapter 67 Central nervous system infections and related conditions (Havlin KM et al.)Reference 1: Mameli, C., Genoni, T., Madia, C. et al. Brain abscess in pediatric age: a review. Childs Nerv Syst 35, 1117–1128 (2019).Reference 2: Panda PK, Natarajan V, Vigneshwar NKV, Sharawat IK. Clinical Presentation and Outcome of Children with Brain Abscess. Ann Indian Acad Neurol. 2021 Nov-Dec;24(6):951-952. doi: 10.4103/aian.AIAN_794_20. Epub 2021 Jan 19. PMID: 35359509; PMCID: PMC8965945.

In this episode, the hosts discuss a case of an 18-year-old female with multiple symptoms including fever, neck pain, and chest pain. They explore the possibility of Lemierre's Syndrome, a condition characterized by bacteremia and vein thromboflobitis. They provide a comprehensive overview of the syndrome including causative organisms, pathophysiology, and diagnostic approach. They also discuss the importance of prompt admission to the pediatric ICU, multidisciplinary approaches, and complications to watch out for.

Welcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.Welcome to our Episode a 16-year-old who is coughing up blood.Here's the case:A 16-year-old female with h/o SLE was transferred to the PICU due to hypoxia requiring increasing FIO2. A few hours prior to admission to the PICU patient also started coughing up blood and had difficulty breathing. The patient was admitted to the general pediatric floor 2 days earlier for pneumonia requiring an IV antibiotic and O2 via NC. Once transferred to the PICU, she had a rapid deterioration with progressive hematemesis, worsening respiratory distress, and saturations in the low 70s requiring escalating FIO2. The patient was emergently intubated using ketamine + fentanyl and rocuronium. Chest radiograph showed: Worsening bibasilar alveolar and interstitial airspace disease concerning pulmonary hemorrhage. The patient was initially placed on HFOV Paw 26, FIO2 70%, Hz 8, Dp 70, and later transitioned to airway pressure release ventilation or APRV. The patient was also started on inhaled tranexamic acid or TXA and high-dose pulse steroids. The patient initially continued to have some blood coming out from the ETT with suctioning but secretions became clear in ~24 hours.The mother reported that the patient has never had hematemesis/hemoptysis before, or bleeding from any site in the past. Denied history of frequent respiratory infections or recent URI symptoms. The patient has been vaccinated/boosted x3 vs covid. Her COVID PCR is negative. The mother states that she does not engage in tobacco products or alcohol.A physical exam revealed a well-developed teenage girl laying supine in bed deeply sedated and mechanically ventilated. There was decreased AE at lung bases and coarse breath sounds throughout. There was no hepatosplenomegaly and exams of the heart, abdomen and other systems were normal. There was no skin rash and extremities were well perfused with no clubbing in the fingers. The pulmonary team was consulted and a workup was started for pulmonary hemorrhage.To summarize key elements from this case, this patient has:Autoimmune disease: Systemic lupus erythematosusRespiratory Failure warranting MV 2/2 Pulmonary hemorrhageHer presentation and deterioration bring up a concern for diffuse alveolar hemorrhage our topic of discussion for today.This episode will be organized…DefinitionEtiologyPathophysiologyDiagnosisManagementRahul: How do we define pulmonary hemorrhage (PH):PH is defined as the extravasation of blood into airways and/or lung parenchyma. Blood in the airways produces a diffusion barrier resulting in hypoxemia. Due to the reduction of airway diameter from accumulated blood, there is increased airway resistance and even airway obstruction. Subsequently, ventilation can be impaired leading to increased WOB as well as myocardial work required for O2 delivery. Repeated episodes of PH can result in interstitial fibrosis thus changing lung compliance. Hemoptysis by definition is any bleeding from below the vocal cords. PH can be classified as focal or diffuse. Diffuse is further classified as diffuse immune or diffuse nonimmune.Loss of 10% of a patient’s circulating blood volume into the lungs, regardless of age, causes a significant alteration in cardiorespiratory function and should be considered massive. In adults, massive pulmonary hemorrhage is defined as blood loss of 600mL or more in 24 hours. In infants, the involvement of at least two pulmonary lobes by confluent foci of extravasated RBCs constitutes as massive PH. “Enough bleeding to make one nervous is probably massive.”Let's pivot and talk about etiologies.Pradip, What are some of the causes of pulmonary hemorrhage in the PICU?Non-immune diffuse PH is usually seen in patients with congenital heart disease (TAPVR, pulmonary atresia, mitral stenosis, hypoplastic left heart syndrome to name a few) neonates (secondary to sepsis, HIE, BW < 1500 gms, persistent pulmonary hypertension) and due to coagulopathy. bronchiectasis, infections such as TB, mycetomas are also important causes of PH. Cocaineas and vaping (typically adulterated with other substances) are also important toxic causes of DAH.Diffuse PH due to immune causes includes pulmonary-renal syndromes (good pastures, Wegener granulomatosis, SLE, anti-phospholipid syndrome PAN, HSP), drug-induced vasculitis (PTU, methimazole, hydralazine, and minocycline) and infections such as hantavirus, CMV, legionella, etc. Lupus and PAN account for the majority of the vasculitis resulting in PH.Focal PH: FB aspiration with chronic retention, pulmonary sequestration, AV fistula, thrombus or embolus, and neoplasms.Idiopathic pulmonary hemosiderosis a diagnosis of exclusion presents with the triad of hemoptysis, microcytic hypochromic anemia, and diffuse alveolar-filling opacities. Nonspecific lung injury not attributed to vasculitis or immune deposits is noted on microscopic examination.Alright to summarize diffuse pulmonary hemorrhage — think about non-immune causes secondary to heart disease and immune causes secondary to rheumatologic conditions. Our patient in our case likely had immune-mediated PH.Let's conclude our episode by going through diagnostics and management.If you had to work up this patient with PH, what would be your diagnostic approach?We can start with a chest radiograph. Typically in PH, you can see ground-glass diffuse opacities or consolidations; sometimes a mosaic-type perfusion pattern can indicate a true arteriolar vasculitis. In some patients, the chest radiograph can be normal. High Resolution Computed tomography(HRCT) has higher sensitivity and the classic features include ground-glass opacities in a random distribution.Bronchoscopy and bronchoalveolar lavage (BAL) are other diagnostic tools. In bronchoalveolar lavage, the pathologist must search for hemosiderin-laden macrophages, which usually appear 24–48 h after the DAH has started. The presence of >5% of hemosiderin-laden macrophages highly suggests the presence of blood from DAH.EchocardiogramLabs: Blood gas, CMP, CBC, Coagulation panel, ESR, CRP, specific auto-antibodies (consult with renal or rheumatology colleagues). Urine analysis, In some rare cases a biopsy (skin, lung, or kidney) may be needed in pulmonary-renal syndromes.I would also highly recommend a collaborative approach with pulmonary specialists, rheumatologists, intensivists, and hematology.If our history, physical, and diagnostic investigation led us to PH as our diagnosis what would be your general management framework?Initially, we must focus on basic PICU care with maintenance of airway and oxygenation/ventilation as well as hemodynamic stability. O2 supplementation EVEN mechanical ventilation may be required; Prior to intubation placement of the patient in Trendelenburg position (which helps clots exit the airway) may be helpful. PEEP should be increased on conventional ventilation for tamponade effect as well as help with hypoxemia. We typically use HFOV with deep sedation +/- chemical paralysis or APRV mode on a conventional ventilator. It is important to correct any coagulation factor deficiency as well as transfuse platelets or pRBCs as needed.Increased PEEP, HFOV, and APRV all create increased mean airway pressure which not only has a local tamponade but increases intrathoracic pressure to decrease preload and downstream pulmonary hydrostatic pressure. What are some other modalities used in DAH?Endobronchial tamponade (Fogarty catheter, cuffed endotracheal tube) can be tried if bleeding is restricted to a segment of a particular lung. Right upper lobe bleeding is best managed by intubating the left main stem bronchus with a cuffed endotracheal tube and inflating the cuff of the tube. Utilization of a double-lumen or Carlens-type endotracheal tube may also be helpful in isolating the bleeding segment. Consult with anesthesia colleagues may be helpful in the management of such patients.There may be a role for rigid bronchoscopy to identify the source and type of bleeding. Rigid Bronchoscopy can also be used for large volume lavage as well as suctioning of blood and even control the source of bleeding. The help of general or cardiothoracic surgery colleagues is invaluable in such patients. For focal PH- surgical resection of the involved segment or selective embolization of bronchial vessels may be needed.What about medical management?Specific pulmonary-renal syndromes can be treated using corticosteroids and other immunosuppressive agents. Plasmapheresis is an option for Good Pastures syndrome. High-dose methylprednisolone (30mg/kg or 1gm daily X 3 days followed by slow taper) is typically used in diffuse immune-mediated PH. Cyclophosphamide is the drug of choice for the treatment of patients with Wegener granulomatosisAre there any therapeutics on the horizon?One study by O’Neil et al in Crit Care Explor 2020 reported the use of Inhaled Tranexamic Acid As a Novel Treatment for Pulmonary Hemorrhage in Critically Ill Pediatric Patients-Cessation of pulmonary hemorrhage was achieved in 18 of 19 patients (95%) with inhaled tranexamic acid with no major adverse events recorded. The study also reported that other variables such as oxygenation and coagulation were not affected by the use of inhaled TXA in our study. Additionally, they reported that the patients received significantly less blood product after receiving inhaled TXA.How does TXA work and what are the applications clinically?Tranexamic acid (TXA) is a lysine analog that blocks the conversion of plasminogen to plasmin and inhibits binding of plasmin to fibrin which stabilizes the fibrin matrix, thereby reducing bleeding. Systemic TXA, however, may be associated with serious complications including venous thromboembolism, neurotoxicity, and seizures. In our patients, we use inhaled or endotracheally instilled TXA (250-500mg of 100mg/ml solution) every 6 hours. Nebulization is done over 15-20minutes and can be delivered in line during mechanical ventilation. Dosing frequency was subsequently decreased based on patients’ responses.Rahul, can you summarize today's episode on DAH:Diffuse alveolar hemorrhage is a medical emergency. 33% can present without hemoptysis. Along with clinical findings of cough, hemoptysis, and dyspnea the presence of hemosiderin-laden macrophages confirms the diagnosis of pulmonary hemorrhage. Protecting the airway and optimizing oxygenation/ventilation is the most important part of management. Then identify and stop the offending agent if possible and administer treatments accordingly.This concludes our episode on a pulmonary hemorrhage. 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!ReferencesFuhrman & Zimmerman - Textbook of Pediatric Critical Care 6th edition. Chapter 52: Pneumonitis and interstitial Disease. Parakininkas D. Pages 603-607Reference 1: Martínez-Martínez MU, Oostdam DAH, Abud-Mendoza C. Diffuse Alveolar Hemorrhage in Autoimmune Diseases. Curr Rheumatol Rep. 2017 May;19(5):27. doi: 10.1007/s11926-017-0651-y. PMID: 28397125.Reference 2: States LJ, Fields JM. Pulmonary hemorrhage in children. Semin Roentgenol. 1998 Apr;33(2):174-86. doi: 10.1016/s0037-198x(98)80021-7. PMID: 9583112.

The podcast discusses a case of a 12-year-old male ingesting iron pills, resulting in severe symptoms and a medical emergency. Topics include exploring acid-base disorders, interpreting blood gas results, managing anion gap metabolic acidosis, and understanding compensation mechanisms in acid-base disorders.

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 3rd-year pediatric critical care fellow and we are coming to you from Children’s Healthcare of Atlanta Emory University School of MedicineToday's episode is dedicated to the transition between NICU & PICU. We will focus on the ventilation of the ex-premature infant who graduated from NICU care and transitioned to the PICU.I will turn it over to Rahul to start with our patient case.Case: A 4-month-old ex-27 week baby boy is transferred to our PICU after an echo at an outside hospital showed elevated pulmonary pressures. The infant was born via a stat C-section due to maternal complications during pregnancy. His birth weight was 560 g. The patient was intubated shortly after delivery and had a protracted course in the NICU which included a sepsis rule out, increased ventilator settings, and a few weeks on inhaled nitric oxide (iNO).The intubation course was complicated pulmonary hemorrhage on day 1 after intubation. After such an extensive NICU course, thankfully, the infant survived & was sent home on 1/2 LPM NC, diuretics, albuterol, inhaled corticosteroids, Synthroid, multivitamin with iron as well as Vitamin D. The patient was able to tolerate breast milk via NG tube and had a home apnea monitor with pulse oximetry.After about a week’s stay at home, the mother noted that the patient’s SPO2 was in the low 80s. The mother took the patient to the local hospital, where the patient was started on HFNC which improved his saturations. An echo done at the OSH showed elevated RV pressures (higher than the prior echo). The patient was subsequently transferred to our hospital for further management. At our hospital, the patient presented hypoxemic, tachycardic, and tachypneic. On physical exam: Baby appeared well developed, had a systolic murmur heard throughout the precordium, and there was increased WOB with significant intercostal retraction. There was no hepatosplenomegaly.Due to worsening respiratory distress, and increasing FIO2 requirement despite maximum RAM cannula, the patient was intubated and placed on conventional MV. A blood gas prior to intubation revealed a pH of 7.1/PCO2 of 100. An arterial line and a central venous line were also placed for better access and monitoring. Initial vent settings post intubation PRVC ventilation: TV 32cc, (25/10), 0.7 time, rate 0 (patient sedated/paralyzed).To summarize, What are some of the features in H&P that are concerning for you in this case:Ex-27 week prematurity with a birth weight of 560 gmsProlonged MV in the NICUHome O2 requirementAbnormal echo showing high pulmonary pressureshypercarbia despite the use of RAM cannulaAs mentioned, our patient was intubated, can you tell us pertinent diagnostics which were obtained?CXR revealed: Hazy airspace opacification in the right upper lung concerning developing pneumonia. Streaky airspace opacity in the left lung base medially may represent atelectasis.I do want to highlight that the intubation of an ex-premie especially with elevated RV pressures is a high-risk scenario, it is best managed by a provider with experience, in a very controlled setting with optimal team dynamics. Adequate preparation to optimize the patient prior to the intubation as well as the knowledge to manage the post intubation cardiopulmonary interactions are essential. I would highly advise you to re-visit our previous podcast on intubation of the high-risk PICU patient by Dr. Heather Viamonte. Like many Peds ICU conditions, the management of the EX-NICU graduate in the PICU is a multidisciplinary team sport.Our patient likely has the diagnosis of Bronchopulmonary Dysplasia or BPD, Pradip, can you comment on the evolving definition of this diagnosis?Let me first define BPD — Clinically, BPD is defined by a requirement of oxygen supplementation either at 28 days postnatal age or 36 weeks postmenstrual age. The literature stratifies the difference between old vs. new BPD definitions. In the old BPD, seen before the 1980s and in usually more mature infants - the pathogenesis is related to damage caused to the lungs from mechanical ventilation and/or oxygen resulting in inflammation/fibrosis. It can occur in premature as well as term infants. We see less of the old BPD due to the use of surfactant and HFOV use. In old BPD, we have e/o hyperinflation and diffuse parenchymal infiltrate -lung histology dilated distal airspace, fibrosis throughout the interstitium, and significant pulmonary arterial fibroproliferative diseaseWhat about the new BPD?New BPD: Refers to abnormal or arrest in lung development (fewer and larger alveoli) and decreased microvascular development in extremely low birth weight infants. In new BPD, we see more evidence of dilated distal lung, less evidence of fibrosis, more typically have an arrest of distal lung development, and still have vascular beds are abnormal. The key here is impaired lung surface area, decreased alveoli, and decreased vascular growth.It is important to note that In severely affected infants, fibrosis, bronchial smooth muscle hypertrophy, and interstitial edema (“old” BPD) may be superimposed on the characteristic reduced numbers of alveoli and capillariesLet's transition and speak about the pathogenesis of BPD, Rahul, what are the key risk factors?The important concept here is to understand the maternal fetal interface that can lead to premature birth. Determinants of disease include-Prenatal factors such as chorio-amniotic, fetal infection, IUGR, preeclampsia, maternal smoking/drug use with interplay from epigenetic/genetic factors, hyperoxia, inflammation, infection, ventilator induced lung injury can cause disruption of growth factor signaling pathways leading to changes in vascular growth, alveolar growth, and lung function.There is a 43% incidence (unchanged in the last 50 years) of BPD born < 29 weeks of age. The earlier one is born, the more severe is the BPD. At autopsy, one can see Regions of Hyperinflation, areas of atelectatic/edema and have pseudo-fissures between them, and dilated distal airways with little septae (”alveolar simplification).Pradip, as it seems the histological architecture of the lung is altered, can you comment on the persistent respiratory disease seen in BPD?Patients with BPD can have persistent respiratory disease, which can be seen as prolonged respiratory support/NICU hospitalization, chronic respiratory distress, recurrent exacerbations, re-hospitalizations, exercise intolerance, wheezing, and increased susceptibility to chronic lung disease in adulthood. These patients may require long-term ventilatory support via an ETT or tracheostomy.To highlight epidemiology, did you know that 58% of preterm infants are readmitted to the hospital within the first year of life. 20% of these were admitted to the PICU and 12% ended up on MV.Pradip, we mentioned the use of mechanical ventilation in BPD. Let’s pivot today’s episode and focus on management, understanding how to invasively ventilate a patient with BPD. How can we use our understanding of ARDS (say in an adolescent) to understand the ventilation strategies in BPD?If we look at the lungs of a teenager with ARDS and hypoxemia, we may see diffuse parenchymal infiltrates. In these patients, the CT is will show a heterogeneous disease. There is a portion of the lung which may be susceptible to atelectasis, gravity dependent, and is edematous. It is this baby lung that we want to ventilate and recruit without overstretching. It’s balance. This is why we use the ARDSnet protocol which involves low tidal volumes, typically 6-8 mL/kg. We use prone positioning and increased PEEP to help recruit the lungs.Great, let's contrast this with BPD, what are the radiographic and physiologic considerations in our patient who is now intubated in the PICU?In BPD, the CT may show hyperinflation, diffuse infiltrates, peri-bronchial lesions, ground glass lesions, cystic lesions, etc. This is a stark contrast with ARDS. They can have large central airway diseases like tracheobronchomalacia, or subglottic or bronchial stenosis, and even granulomas. Patients with severe BPD can have small airway structural remodeling such as mucus gland hyperplasia and clinically we will see more secretions that are not cleared well due to ciliary dysfunction. These airways have an epithelial injury, edema, smooth muscle proliferation, broncho-constriction, and hyper-reactivity. The patients with BPD also have decreased alveolarization, decreased vascular growth (i.e. fewer vessels), abnormal vascular remodeling, tone, and reactivity as well as impaired lymphatic function. As these infants age, they can have sleep-disordered breathing, diaphragm dysfunction, and chest-wall instability. In summary, BPD affects not only the lung parenchyma, but the whole respiratory unit — pulmonary vessels, lymphatics, chest wall, and diaphragm!Yes, it seems the take home is that the patient with severe BPD who is intubated in the PICU has vastly different physiologic and radiographic lesions compared to the run-of-the-mill teenager with acute ARDS. Hence a different ventilation and oxygenation strategy is required for the intubated BPD patient in the PICU. BPD subtypes include those with parenchymal lung disease, those with vascular disease (pulmonary arterial hypertension-evaluated at least initially with an echo), and those with airways disease (tracheo-bronchomalacia-evaluated by bronchoscopy). Additionally, a single patient may have more than one BPD subtype for example 28% can have all the above 3 subtypes. (Wu K et al. AJRCC Med 2020).Before we dive deep into management how do you evaluate the underlying lung disease in patients with severe BPD?We typically get CXR, blood gas, +/-Chest CT scan (may not require acutely), target SPO2 and PCO2, evaluate for chronic aspiration (ph probe, barium swallow, swallow study, etc.), sleep study, flexible bronchoscopy to evaluate structural airway disease as well as EKG, echocardiography, cardiac catheterization, etc may be required.In terms of labs, lactates, BNP, and NT-pro BNP may be required on a case-by-case basis. Additionally, an Interstitial lung disease panel may also be required on a case-by-case basis. The management of the patient with severe BPD in the PICU is really a team sport, which involves the intensivist, the cardiologist, the pulmonologist, gastroenterologists, and support staff such as the speech therapist and the rehabilitation team. It also involves open discussions with family as these patients are hospitalized long term not infrequently. Family conferences at periodic intervals in collaboration with social workers can help optimize decision making, set goals of care, and allow for facilitation amongst teams.Absolutely, it is a team sport!Now Pradip, you mentioned the radiographic and lab evaluation of these patients who have chronic lung disease. As we think about continuous monitoring in the PICU, do you have some management pearls?It is important to prevent hyperoxia by targeting an SPO2 of 92-94%. We also should avoid accepting an SPO2 of 90% as that can cause pulmonary hyper-vascular reactivity and these children can have marked vasospasm. We allow for permissive hypercapnia but avoid marked spikes or swings in PCO2 as long as pH is buffered. If PCO2 is chronically elevated its effect on PHTN is unclear. Elevated PCO2 may be a biomarker for severe parenchymal lung disease.Rahul, we mentioned in the pathogenesis the abnormal vascular development in the pulmonary circuit, can you comment on the cardiopulmonary interactions seen in a patient with BPD?In patients with severe BPD, we have High pulmonary artery pressures due to lung disease. Remember these children will have hyperinflation in some areas, atelectasis, and fluctuations in O2 and CO2. This can create chronic heart disease as well. Particularly RV dysfunction. Patients downstream can have issues with LV contractility as we have at times an exaggerated systolic interdependence which can affect LV contractility. The LV diastolic dysfunction may be due to persistent pulmonary edema. As these children are premature, it is also important to assess for abnormalities in cardiac development. These children will frequently have shunts. ASD, VSD, PDAs for example. The L to R shunting may create over-circulation, and in times of crises, these shunts may reverse leading to hypoxemia. Fortunately, when children have these shunts, they serve as “pop-offs” during times of increased pulmonary pressure. As we mentioned cath as one of our diagnostics it is important to assess for pulmonary vein stenosis as this fixed anatomic defect can further contribute to high pulmonary artery pressures.In a summary, remember that the RV is relatively afterload sensitive and the LV is more sensitive to changes in preload!As we set titrate the ventilator in our patient with BPD, Pradip, what strategies are you going to use for effective oxygenation and ventilation?The biggest point before we go into the specific ventilator strategies is the heterogeneity of lung disease. This is not a two-compartment model as seen in ARDS. There is marked variability of regional time constants, and as mentioned, airway secretions, and pulmonary hypertension in many cases. Some areas of the lung may have normal compliance and resistance, whereas others may have poor compliance and high resistance. In this heterogeneous disease, there are also significant areas of high compliance and low resistance. So if we ventilate these patients with BPD with low tidal volumes, rapid rates, and low iTimes (similar to ARDS), we run the risk of having worse distribution of gas, increased dead space ventilation, hypercarbia, the need for higher FiO2 and radiographically progressive atelectasis.As such, it is important for users to manage the patient with severe, chronic BPD with high TV. This allows for more gas to fill the lungs. Couple this high tidal volume, usually 8-10 mL/kg with higher iTimes and low rates to decrease the risk of atelectasis.Ok, to summarize here, BPD patients, in general, have higher iTimes, higher tidal volumes, and low rates. This is to especially account for the areas of the lungs with higher time constants.Rahul, real quick what is the definition of a time constant?The time constant is the time required for inflation of alveoli up to 63% of the final volume, or deflation by 63%. It is the product of resistance and compliance. For a normal set of lungs as a whole, the normal time constant is 0.1-0.2 seconds. In BPD, these children have varied, heterogenous time constants.Rahul what about PEEP use in the intubated BPD patient?These patients in general require higher PEEP. It opens the airways and along with larger lung volumes has a tethering effect. This stretching effect with high peep may favor airflow and improves gas exchange. Like you frequently preach on rounds Pradip, PEEP is your friend! High PEEP with high rates can lead to air trapping and dynamic hyperinflation, so continue to reassess your patient, serial gas, x-rays, and ventilator scalars to determine the optimal rate to set on the ventilator in addition to the PEEP.Let's take a holistic picture now, Pradip, beyond the ventilator, what do we have to consider?Don't rush towards extubation, but work to reduce distress, retractions, and “dyspnea”; at times growth with optimal nutrition is very beneficial. We need to optimize therapies such as OT and PT. but also consider the desaturations/increased PVR which may ensue during this hands-on care. We should focus on weaning sedation and NMB as tolerated.These children are in the PICU at times for long periods, so optimize day night cycles, sleep hygiene, lab schedules, and most importantly bonding with family & caregivers. Don’t forget to catch up on immunizations and ROP care. Remember Rahul, we are pediatricians first!!I love these points, it is really a team effort. As we conclude this episode, in your opinion what does successful care of the BPD patient in the PICU look like?Successful treatment with BPD is synonymous with good supportive care — we want to do no harm. In this setting, we want ”minimal impact respiratory support”. Prevention of harm, prevention of infection, prevention of right heart failure, excellent nutrition for growth and repair as well as developmental assistance. You will frequently be coordinating care with your NICU or PICU...

Welcome to PICU Doc On Call, a podcast dedicated to current and aspiring intensivists. I am Pradip Kamat.I am Rahul Damania, a current 3rd year pediatric critical care fellow.I am Kate Phelps- a second year pediatric critical care medicine. We come to you from Children's Healthcare of Atlanta Emory University School of Medicine.We are delighted to be joined by guest expert Dr Stephanie Jernigan Assistant Professor of Pediatric-Pediatric nephrology, Medical Director of the Pediatric Dialysis Program at Children’s Healthcare of Atlanta. She is the Chief of Medicine and Campus Medical Director at Children’s Healthcare of Atlanta, Egleston Campus. Her research interests include chronic kidney disease, and dialysis. She is on twitter @stephaniejern13I will turn it over to Rahul to start with our patient case...A 3 year old previously healthy male presents with periorbital edema. Patient was initially seen by a pediatrician who prescribed anti-histamines for allergy. After no improvement in the eye swelling after a two week anti-histamine course, the patient was given a short course of steroids, which also did not improve his periorbital edema. The patient progressed to having abdominal distention and was prescribed miralax for constipation. Grandparents subsequently noticed worsening edema in his face, eyes, and feet. The patient subsequently had low urine output, low appetite and lack of energy patient was subsequently brought to an ED and labs were obtained. Grandparents denied any illness prior to presentation, fever, congestion, sore throat, cough, nausea, vomiting, gross hematuria, or diarrhea. In ED patient was noted to be hypertensive (Average systolic 135-highest 159mm HG), tachycardic (HR 130s-140s), breathing ~20-30 times per minute on RA with SpO2 92%. Admission weight was recorded at 16.5Kg. Physical exam showed periorbital edema, edema of ankles, there was mild abdominal distention (no tenderness and no hepatosplenomegaly), heart and lung exams were normal. There were no rashes on extremities.Labs at the time of transfer to the PICU: WBC 10 (62% neutrophils, 26% lymphocytes) Hgb 7.2, Hct 21, Platelets 276. BMP: Na 142/K 8.4/Cl 102/HCO3 19/BUN 173/creatinine 5.8. Serum phosphorus was 10.5, Total Ca 6.4 (ionized Ca= 3.4), Mag 2.0, albumin 2.6, AST/ALT were normal. An urine analysis showed: 1015, ph 7.5, urine protein 300 and rest negative. Chest radiograph revealed small bilateral pleural effusions. After initial stabilization of his hyperkalemia-patient was admitted to the PICU. PTH intact 295 (range 8.5-22pg/mL). Respiratory viral panel including for SARS-COV-2 was negative. C3 and C4 were normal. A nephrotic syndrome/FSGS genetic panel was sent. A renal US showed: bilateral echogenic kidneys and ascites (small volume).Pradip: Dr Phelps what are the salient features of the above case presented?Kate Phelps: This patient has a subacute illness characterized by edema, anemia, and proteinuria. His labs show that he has severe acute kidney injury with significantly elevated BUN and Creatinine, hyperkalemia, hyperphosphatemia, and hypocalemia.Rahul: Dr Jernigan welcome to PICU Doc on Call Podcast.Thanks Kate, Rahul and Pradip for inviting me to your podcast. This is a such a great way to provide education and it is my pleasure to come today to speak about one of my favorite topics, pediatric dialysis. I have no financial disclosures or conflicts of interest and am ready to get started.Rahul: Dr Jernigan as you get that call from the ED and then subsequently from the PCCM docs, as a nephrologists whats going on in your mind ?When I get the call from the outside hospital my first job is to make sure the patient is safe and stable for transfer to a tertiary care center. This includes concern about airway, breathing and level of alertness. From a renal standpoint, I am worried about elevated blood pressure, electrolyte abnormalities, in this case primarily the hyperkalemia, and fluid overload, especially given the low oxygen saturation. It is important that children are transported to an appropriate center early, but still safely, to allow for diagnostic work up and intervention. This is particularly true in the case of renal replacement therapy which most community hospitals are reticent or unable to offer to our pediatric patients.Our episode today will be divided into a few broad categories: INDICATIONS/PRINCIPLES of KIDNEY REPLACEMENT, TECHNICAL ASPECTS of RRT, Anticoagulation, and a comparison of various types of RRT and their complications.Let’s start with INDICATIONS/PRINCIPLES of KIDNEY REPLACEMENTKate Phelps: What are in general indications for renal replacement in pediatric patients?Indications for renal replacement therapy are similar for acute vs chronic dialysis however differ in their urgency. As we know, our kidneys are important for waste product elimination, a primary measurement of this is blood urea nitrogen, acid base and electrolyte balance and of course maintaining fluid balance. When these functions fail acutely so as to be dangerous to a patient or when they are chronically inadequate despite medical management, then renal replacement is indicated. Acute indications tend to be significant uremia which can have consequences on multiple systems (CNS, heart, coagulation), symptomatic fluid overload (affecting breathing and cardiac function), and/or hyperkalemia and intractable acidosis not responsive to medical intervention. Medical management includes for fluid overload the use of diuretics and the use of bicarb in order to correct acidosis and shift potassium intracellularly. Additional therapy for hyperkalemia – membrane stabilization with calcium, further increase of uptake of potassium by cells with glucose, insulin and Beta agonists and elimination of potassium in the gut with ion exchange resin (kayexlate). Not related to the kidney directly, dialysis may also be needed in toxic overdose (salicylates and acetaminophen, lithium, metformin to name a few) or inborn errors of metabolism resulting in hyperammonemia.This has led to the mnemonic AEIOU – acidosis, electrolytes, ingestions, overload and uremia.Uremia with a BUN of greater than 100 and symptomatic or greater than 150 even without current symptoms are concerning and in most cases indication for dialysis.Less acute indication but no less important is need for dialysis when treatment and caloric nutrition are impeded by fluid issues and dialysis allows for these to be maximized without regard the secondary consequences of fluid imbalance.Of note, while creatinine gives us a stable measurement of glomerular filtration rate, it’s value is not in and of itself an indicator for renal replacement therapy.🎯 Just to summarize, acidosis – metabolic acidosis with a pH <7.1; electrolyte refractory hyperkalemia with a serum potassium >6.5 mEq/L or rapidly rising potassium levels; Intoxications – use the mnemonic SLIME to remember the drugs and toxins that can be removed with dialysis: salicylates, lithium, isopropyl alcohol, methanol, ethylene glycol; Overload – volume overload refractory to diuresis; Uremia – elevated BUN with signs or symptoms of uremia, including pericarditis, neuropathy, uremic bleeding, or an otherwise unexplained decline in mental statusRahul: Dr Jernigan what physical principles are used in dialysis and what are the properties of the substances we can dialyze?Let’s start with the principles of dialysis. Important here is understanding the laws governing movement of molecules between solutions and across a semipermeable membrane.First is diffusion which is movement of molecules from a solution of higher concentration to lower concentration. This is much like “tea” where tea in the bag diffuses out into the water based on a concentration gradient. In diffusion, equilibrium will eventually occur and all things equal diffusion will slow and then stop. Smaller molecules will diffuse faster than larger molecules so this modality does better with smaller molecules.Next is convection. Convection is movement across the membrane due to a pressure gradient, sometimes called solute drag. This can be compared to the making of coffee where water passed through the coffee grounds “pulling” or “dragging” the coffee (flavor and caffeine thank goodness) with it. This can be a pressure gradient (CVVH) or an osmotic gradient (PD)Convective therapies are better for larger molecular weight substances but removes small molecules as well.Hemofiltration is movement of fluid across the membrane due to a gradient.I believe we will talk more specifically about the different types of dialysis later however in brief, Hemodialysis utilizes primarily diffusion with the blood flow rate and the dialyzer being the factors that increases or decreases clearance.PD uses both diffusion and convection equally but is not the most common modality seen in the ICU setting.CVVH (continuous veno-venous hemofiltration) in its classic form uses primarily convection but has different modes which also allows for convection , diffusion and a combination of both.So for best clearance molecules are smaller <10000 Daltons have high water solubility and small volume of distribution and low protein binding (most are greater than 10K Dalton, albumin is 66K Dalton)To summarize, dialysis systems operate either via diffusion (i.e movement of molecules across a semipermeable membrane using a concentration gradient OR via convection where solutes move across a semipermeable membrane using a pressure gradient. In some modalities ultrafiltration occurs due to an osmotic pressure gradient. Lets transition to the next portion of our podcast which will cover vascular access & anticoagulationVASCULAR ACCESSRahul: Dr Jernigan before we go into each modality, should we discuss the access required for RRT in the PICU?Before we can begin dialysis we need access to the vasculature (HD and CRRT) and the peritoneal cavity (PD). Vascular access can be placed by you, our ICU colleagues, as well as interventional radiologists and surgeons. In general, we need a large gage vascular catheter. The smallest catheter utilized is 8 gage up to 14 gage. It is best placed in the internal jugular. The subclavian (the location of old) has been changed as complications during placement and vessel stenosis are problematic. This is especially true if future need of arteriovenous fistulas. If there is urgency of placement and especially in larger individuals (greater than 28 BMI) then femoral access may be needed but this has a higher infection risk and we worry about future vascular access for renal transplantation.While old terminology included vas cath (temporary) and permcath (longer term), we have a system move to terminology that better describes the type of catheter placed. This includes single vs double lumen, low flow vs high flow, tunneled and cuffed (permanent) vs non tunneled. For dialysis we require double lumen and high flow. For long term, the catheter is tunneled and cuffed to allow for lesser infection and movement risk.Peritoneal catheters are placed by surgeons. These are silicone or polyurethane and in best practice are double cuffed. The first cuff is placed under the skin and then the catheter is tunneled with the second cuff in the rectus muscle. The catheter then enters the peritoneal cavity where the coiled tip is placed in the pericolic gutter or pelvis. While they can be used urgently, the preference is to allow them to sit and heal for two weeks to avoid leakage and infection. The exception is in infants where this is the best option for many situations due to patient size.ANTICOAGULATIONKate: Dr Jernigan can you shed some light on the type of anticoagulation required during RRT?Any time blood is circulated outside the body, it is at risk for clotting which leads to blood loss. For this reason, anticoagulation is required.This original anticoagulation for blood dialysis is heparin and this is still the mainstay in hemodialysis. This is given as a bolus and thin continuous infusion until some point before discontinuation of dialysis as this is systemic anticoagulation (turned off sooner for fistula’s due to bleeding) Monitoring is through ACT’s however standard dosing is fairly well established and act’s used less often and not in the chronic unit. Starting bolus 20-50 units/kg and infusion of 10-30 units/kg/hr over remaining time.Side effects are HIT (heparin induced thrombocytopenia) and bleeding risk due to systemic anticoagulation.Citrate: This is used as regional anticoagulation meaning it only anticoagulates the circuit and not the patient. Citrate binds to calcium in the circuit and prevents activation of both coagulation cascades and platelet aggregation. The majority of the calcium–citrate complex is moves across the membrane by diffusion during dialysis and is lost in the ultrafiltrate. A systemic calcium infusion is necessary post filter to replace the calcium lost with citrate. Any calcium–citrate complex is not filtered and returns to the patient has a very short half life and is metabolized to bicarb by the liver, kidney and skeletal muscle. This citrate is titrated to blood flow to maintain low iCa in the circuit. The Calcium infusion is adjusted to keep iCa normal in the patient.There are several advantages to citrate. First and foremost is the regional anticoagulation and less systemic bleeding, especially for those at high risk. It can be used in patients with HIT and in some patients, the additional bicarb from the citrate metabolism is helpful. The disadvantages are that in some patients the additional bicarb is not helpful and there can be other metabolic complications related to acid/base and calcium loss. In addition, with citrate there are the more complex protocols for the varying infusion rates and frequent calcium measurements. Citrate is relatively contraindicated in patient with hepatic failure and inborn errors of metabolism related to mitochondrial disorders.Flolan: Epoprostenol, a naturally occurring prostaglandin with potent vasodilatory activity and inhibitory activity of platelet aggregation and thrombus generation which is it’s mechanism to prevent clotting. For this reason it is avoided in patients with thrombocytopenia and should be used with caution in patients with hypotension. It has a short half-life and like other anticoagulants for CVVH is a continuous infusion of 2-8 ng/kg/min. Monitoring is simple and in addition to the above is circuit longevity.🎯 Summary time — citrate binds calcium, be careful in patients with liver failure. With Flolan, watch for thrombocytopenia.MEMBRANEPradip: Dr Jernigan what are the types of dialyzers used during RRT?Hemodialysis dialyzers are primarily made of synthetic material. (polysulfone , poly mix) Synthetic membranes have less complement activation and systemic “allergic” reaction. They are made of multiple hollow semi permeable membrane fibers through which blood is flows with dialysate moving counter current outside the fibers. The effectiveness of the dialyzer is based on the thinness of the material and the number and size of the pores. There is a large surface area which in HD should approximate the patients BSA.For prismaflex/CVVH we use two synthetic catheters the HF 20 and the HF1000 which are determined by patient size and clearance capability. HF 20 allows CRRT more safely on the small child weighing 8-20 kg.The volume of the dialyzer and tubing is important as in there is limit to the volume of blood that can be in the extracorporeal circuit. This is less than 10% of estimated blood volume and if more needs a blood prime. Keeping in mind that the extracorporeal tubing is also part of this calculation.Although vascular access for dialysis in the PICU is easily attained by the intensivists, we have to be cautious about infants < 1 year of age. Due to fluid overload, platelet dysfunction (from uremia) etc., these are best done by the surgeon or interventional colleagues in a controlled setting. Pediatric Intensivists should be well versed with anti-coagulation choices during RRT.RENAL REPLACEMENT MODALITIESDr. Phelps: Dr Jernigan what are modalities of renal replacement therapies typically used in children?In children we can used peritoneal dialysis, hemodialysis, and continuous veno-venous hemofiltration (CVVH), CVVHD, or CVVHDF.Rahul: Dr. Jernigan Lets start with peritoneal dialysisAfter placement of the catheter, Peritoneal dialysis takes advantage of the large surface area of the peritoneal lining, a semi permeable bidirectional membrane to do dialysis by diffusion and convection.PD is perfomed by instilling fluid, dianeal, into the peritoneal cavity which is then allowed to dwell for a prescribed amount of time (allowing solute movement via diffusion) and then drained. This is repeated for a prescribed number of cycles or time. Dianeal contains calcium, magnesium, sodium chloride and sodium lactate as a buffer. The variable in dianeal is dextrose which creates the osmolarity to allow for fluid removal and secondary solute drag (convection). The dextrose concentrations include 1.5%, 2.5% and 4.25% with higher dextrose pulling more fluid. As the peritoneal membrane is bidirectional, equilibration will occur so the fine art is to find the right dwell time to remove waste and fluid and drain before equilibration happens. Volumes range from 10-40 ml/kg and dialysis improves with increased volume and thus more membrane exposure to dianeal and by increasing time on dialysis.In general PD is well tolerated and is the best dialysis for young babies with catheters being able to be placed in children weighing as little as 1.8 to 2kg without needing blood exposure as in hemodialysis. While inpatient, PD can be done with a manual exchange set for very small volumes and once appropriate volumes obtained transitioned to an automated cycler.In addition to its advantage in the smallest patients, other advantages of PD include less need for specialized equipment and highly trained extracorporeal personnel. It does not require vascular access or anticoagulation. Electrolyte shifts are gentle and slow. In the outpatient world, PD is done at home and daily so has advantages to quality of life. Concerns include that waste and fluid removal are variable and may not be acute or aggressive enough for some ill children (fluid overload or hyperkalemia) and PD is not great acute therapy due to concerns for leakage with a fresh catheter. Instilling fluid into the abdomen may impinge on respiratory excursion could be an issue for some patients and as this modality does rely on adequate blood pressure to perfuse the peritoneum, it hypotension present, if may be less effective. Recent or impending abdominal surgery or gastroschisis /omphalocele are contraindications however VP shunts, ostomies and Eagle Barret...

Welcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.I'm Pradip KamatI'm Rahul Damania, a third-year PICU fellow.I’m Kate Phelps, a second-year PICU fellow and we are all coming to you from Children's Healthcare of Atlanta - Emory University School of Medicine, joining Pradip and Rahul today. Welcome to our episode, where will be discussing gastrointestinal bleeding.Kate: Let’s start with a case:A 4-year-old, previously healthy male presents to the emergency room after a large, bloody stool at home. He notably had an episode of dark emesis and an episode of blood-tinged emesis on the day prior. In triage, he is altered and unable to answer questions coherently. Initial vital signs are temperature 36.1 C, RR 24, HR 146, BP 110/54. Point-of-care labs show hemoglobin to be 5.1 with hematocrit 15. His venous blood gas is reassuring against respiratory disease, and he is in no respiratory distress. Further labs are sent and a massive transfusion protocol is initiated before transfer to the PICU. Before arrival in the PICU, he receives two aliquots of RBCs, 1 aliquot of FFP, and 1 aliquot of platelets. Additional labs are sent from the PICU, post-transfusion. His post-transfusion hemoglobin is 8.8. Other labs are notable for normal MCV, elevated total bilirubin to 4.1 (with direct component 3.4), and elevated AST and ALT to 309 and 495 respectively.Rahul: To summarize key elements from this case, this patient has:An undifferentiated gastrointestinal bleed with both hematemesis and hematochezia.He has symptomatic anemia, as evidenced by tachycardiaAltered mental status.He is initially stabilized via transfusion of several blood products and liver function labs are shown to be very abnormal — which we will get more into later!PK: Let’s get into important parts of the history and physical. Kate, can you tell me what some key history items in this patient are — and what are some areas to make sure to touch on when a patient has a GI bleed?Kate: Yeah! I’d love to.First - in our patient, some important elements are his rather acute onset. His parents mention he has had one day of bleeding symptoms - first with emesis yesterday, with components of old, partially digested blood, as well as some fresh blood. Second, he has a frankly bloody stool at home. Given his clinical instability, history taking was probably limited at first, so it’s important to ask follow-up questions and really dig into the case after stabilization!I like to put my questions about gastrointestinal bleeding into buckets based on the questions I need to answer. I need to answer: is this active bleeding or old blood? Is this slow, insidious bleeding or fast, life-threatening bleeding? Is this an upper GI bleed or a lower GI bleed? Bright red blood in emesis tells us that bleeding is active, whereas coffee-ground or dark emesis tells us that, while recent, the blood has been partially digested in the stomach and may not be ongoing. Similarly, melena (dark, tarry stool), tells us blood has come through the colon. While coffee-ground emesis and melena don’t rule out an active bleed, they do tell us the bleeding may be slower, as large volume, active bleedy is irritating to the stomach and gastrointestinal tracks and moves through the system quickly.The next question I want to answer is: what is the cause of this bleed? Easy bruising, petechiae and mucosal bleeding may point to a coagulation disorder. Abdominal cramping, frequent stooling, and weight loss may point to inflammatory bowel disease. Past medical history, family history, and a thorough review of systems are key here.Rahul: Yeah, that’s great! Let’s talk about your question of upper GI vs lower GI bleed.First, a definition: an upper GI bleed is bleeding that occurs above the ligament of Treitz — which is ligamentous tissue that supports the end of the duodenum and beginning of the jejunum at their junction. While not 100% specific, some symptoms that point to an upper GI bleed are: hematemesis, coffee-ground or dark emesis, and melena. Symptoms that lend themselves to the diagnosis of a lower GI bleed are hematochezia (bright red blood in the stool) and melena (which may represent a more bleed more proximal to Treitz). However, with a brisk, heavy upper GI bleed — say from the duodenum — patients can also have hematochezia.OK to summarize, when we think of GI bleeding, first stratify your patient into slow vs. fast bleeding, identify whether it is upper or lower GI bleeding, and dive deeper into an underlying cause after your patient is stabilized.Pradip: Relatively little data exists about the prevalence of GI bleeds in the PICU. In a study by Chaibou, et al., they reported that approx 10% of PICU children have upper GI bleeding with only 1/5 of those with UGIB having clinically relevant bleeding (characterized by significant hemoglobin drop, need for transfusion, hypotension, multi-organ failure, or death). Incidence of lower GI bleeding is even less well characterized in current available evidence.Kate: Thanks, Pradip. Given our patient’s symptoms, I would be most concerned for an upper GI bleed, given the bloody emesis — but a significant one if it’s leading to hematochezia.Rahul: Yeah, that’s exactly what I was thinking, KP. Pradip, in the literature we see they mention that NG saline lavage can be used diagnostically to help confirm if bleeding is occurring in the upper GI tract vs a pulmonary source. Further, NG lavage has been advocated as a therapeutic practices, however, this may be outdated now as we push for more timely endoscopy. In fact, studies show: ice water lavage is not recommended; this older practice does not slow bleeding and may induce iatrogenic hypothermia, particularly in infants and small children.Kate: Ok, let’s back up for a second — let’s talk about red flag symptoms! ABCs should always come first for every patient who arrives anywhere in the hospital. In this patient, concerning symptoms in this scenario, are his tachycardia and his altered mental status. These symptoms tell us that anemia is symptomatic and likely more acute. Hypotension and tachycardia indicate that bleeding is significant enough to cause hypovolemia. Altered mental status indicates that the brain is hypoxic, in this case, due to inadequate hemoglobin. Other red flags symptoms in GI bleeding include: orthostatic changes, delayed capillary refill and other signs of poor perfusion, currant jelly stools (which may indicate bowel ischemia), and of course anything that points to a large volume of blood in emesis or stool (for example, “the whole toilet bowl was red”) — as these may precede hypotension. Rahul will fill us in later about how to treat patients with red flag symptoms!Absolutely, the identification of hypovolemic shock is essential in GI bleeding. Notice subtle data trends and optimize O2 delivery. Please check out our prior episode entitled Oxygen Content & Delivery.Pradip: To switch gears, tell me how you think about the differential in patients with bleeding?Kate: Sure, the differential will be different for upper vs lower but will also be relevant to the age of the patient. The differential for clinically relevant GI bleeding in an infant includes hemorrhagic disease of the newborn (in those who did not receive Vit K at birth), necrotizing enterocolitis, and Hirschprung’s enterocolitis (which interestingly can occur after repair), and volvulus. For children >1 year, the differential includes esophageal varices, gastric or duodenal ulcers, volvulus, intussusception, Meckel’s diverticulum, Mallory Weiss tears, IgA vasculitis, hemolytic uremic syndrome, and several infectious etiologies. Adolescents and young adults have a similar differential but now we begin to think more about inflammatory bowel disease and NSAIDs. Of course, there is a lot of overlap between school-age children and adolescents. In the oncology population, we have to think about graft-versus-host disease and typhlitis.Rahul: So really — the differential is broad. Let’s talk about initial and ongoing work up to narrow our differential.Initial labs should include a complete blood count, a comprehensive metabolic panel with a fractionated bilirubin, coagulation studies, and — perhaps most importantly — a type & screen! Initial imaging might include a two-view abdominal X-ray to evaluate for obstruction or perforation. Ultrasound can help rule in intussusception. Later imaging might include CT with angiography or even MRI.Remember when it comes to liver function tests: alkaline phosphatase and GGT give us info about the biliary ducts, AST and ALT tell us about hepatocellular function, and albumin and PT/INR give us info about hepatic synthetic function.Pradip: Great — now let’s get into treatment.Rahul: As Kate eluded to earlier, if any red flag symptoms are present, we need to think about resuscitation and stabilization. Initial stabilization for patients should include attention to the airway, breathing, and circulation. For serious upper GI bleeds, intubation should be considered for repeated bloody emesis, to control the airway and prevent aspiration. Hypotension can be initially managed with judicious fluid resuscitation to temporize but should be followed by blood products as soon as possible. Most hospital centers have a massive transfusion protocol, so consider this in hemorrhage states before you have signs of end-organ hypo-perfusion! Kate, can you touch on additional specific treatment for ongoing bleeding?Kate: Yeah - we really have two avenues for intervention: medical and surgical. Medical treatment can be tailored to the etiology but can include an IV proton pump inhibitor (or PPI) as first like during workup, followed by an octreotide infusion. Rahul, can you tell us about octreotide before I continue?Rahul:Octreotide is a Long-acting somatostatin-analog: that reduces splanchnic blood flow and inhibits gastric acid secretion.Dosing: an initial bonus of 1 mcg/kg followed by a maximum infusion of 10 mcg/kg/hr, which can be titrated down as bleeding improves and resolves.Side effect: hyperglycemia as we inhibit the effects of insulin.Kate: Perfect- thanks! An additional medication sometimes used in GI bleeding is vasopressin, though octreotide has been shown to be as efficacious and does not carry the same daunting side effect profile. Most management strategies have shifted to using octreotide over vasopressin. If intermittent PPI dosing plus octreotide doesn’t control bleeding, a continuous infusion of a proton pump inhibitor can be considered though no data has shown this.Let’s summarize the medical therapies, PPI, octreotide, and in some cases vasopressin.Pradip: For surgical intervention, we’re first talking about upper endoscopy (esophagogastroduodenoscopy) or a colonoscopy — which can be both diagnostic and therapeutic. Endoscopy should ideally occur after hemodynamic stabilization but within 12 hours of admission for variceal bleeding and within 24 hours of admission for non-variceal bleeding in the case of upper gastrointestinal sources. Endoscopic interventions may include: adhesive cyanoacrylate applied to the bleeding lesion, band ligation applied to varix, injection sclerotherapy, and epinephrine injection, among other things. Interventional radiology may be able to perform arterial embolization.Kate: I think this is the perfect point to follow up with our case, initial labs point toward normocytic anemia biliary duct obstruction without coagulopathy. During the hospital admission, bleeding stabilized after the initial massive transfusion. EGD showed acute clot formation near the ampulla of Vater in the duodenum. The eventual MRI showed a choledochal cyst with arterial erosion leading to the acute hemorrhage. An angiogram and percutaneous biliary drain placement were accomplished with IR.OK Kate, do you mind summarizing our takeaways for today?Kate: Key objective takeaways:Clinical relevant GI bleeds are uncommon in the PICU, but the skills to stabilize are crucial in the setting of a life-threatening hemorrhage.The differential for a GI bleed is broad but can be narrowed through careful and thorough history taking, physical examination, laboratory data, and imaging.Endoscopy should occur in a timely fashion in the setting of clinically significant upper GI bleeding.For more reading, information can be found in:Pediatrics in Review, “Gastrointestinal Bleeds” by Baker, et. al in the October 2021 edition.Chapter 95 of the most recent edition of Fuhrman & Zimmerman’s Pediatric Critical Care, with sections on many of the differential diagnoses, included today.This concludes our episode on GI hemorrhage. 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 Dr. Pradip Kamat, and my dream cohosts Dr. Rahul Damania and Dr. Kate Phelps. Stay tuned for our next episode! Thank you!

Welcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.I'm Pradip Kama and I'm Rahul Damania, a third-year PICU fellow. I’m Kate Phelps, a second-year PICU fellow and we are all coming to you from Children's Healthcare of Atlanta, Emory University School of Medicine, joining Pradip and Rahul today. Welcome to our episode, where will be discussing rhabdomyolysis and associated acute kidney injury in the ICU.Rahul: Here's the case, a 7-year-old female presents to the ED with three days of fever, poor PO, and diffuse myalgia. In the ED, her vital signs are T 39.1C, HR 139, BP 82/44, RR 32. She is pale and diaphoretic, complaining weakly about how much her legs hurt. Her parents note that she has not been peeing very well since yesterday, and when she does pee it is “very concentrated, almost brown.” She’s also been spending all her time on the couch and has asked to be carried to the bathroom when she does need to go.An IV is placed by the emergency room team, and she is given a fluid bolus, acetaminophen, and initial labs are drawn (CMP, CBC, RSV/Flu swab) before she is admitted to the PICU. In the PICU, her fever is better and her vitals have improved to T 37.7, HR 119, BP 115/70, and RR 25. Her respiratory swab has just resulted positive for Influenza A. Further labs are sent, including creatine kinase (CK), coagulation studies, and a urinalysis. Labs are notable for K 3.9, Bicarb 22, BUN 15, Cr 0.8, and CK 5768 IU/L. Her urinalysis is notable for 1 WBC, 2 RBC, +3 blood, negative nitrites, and leukocyte esterase.Kate: To summarize key elements from this case, this patient has:Influenza A, as evidenced by her respiratory swab, as well as her clinical prodrome.She has diffuse myalgias, as well as fevers, diaphoresis, and hypotension.Labs are most notable for elevated creatinine and elevated creatine kinase, as well as an abnormal urinalysis.All of which brings up a concern for rhabdomyolysis and myoglobin-induced acute kidney injury.Before we get into this episode — let's create a mental framework for this episode — we will dissect our case by highlighting key H&P components, visit a differential diagnosis, pivot to speaking about pathophysiology, and finally, speak about management!Rahul: Let's transition into some history and physical exam components of this case.The classic presentation of rhabdomyolysis is myalgias, muscle weakness, and tea-colored urine, all of which our patient has. Decreased urinary output can also accompany, a variety of reasons, but most notably if the patient has myoglobin-induced acute kidney injury. In our patient, poor PO is also probably contributing to her decrease in urine output. Red flag signs or symptoms will include anuria, hypotension, and altered mental status (which is rare but may indicate severe acidemia and deterioration)Pradip: As we think about our case, what other disease processes might be in our differential? As we dive in a bit more, we’ll come up with ways to distinguish between rhabdo and other things!Viral myositis - inflammation in the muscles in the setting of a viral illness, which can definitely happen with influenza and other common virusesSome other things which may cause reddish-brown urine, including hematuria, hemoglobinuria, porphyria, some specific foods or drugs (like rifampin, beets, food coloring — even ibuprofen)We also have to investigate a bit more to convince ourselves that our patient’s AKI is due to rhabdomyolysis, as it could be from dehydration, sepsis, NSAIDS, etc.Kate: Let’s dive further into rhabdomyolysis!Rhabdomyolysis affects over 25,000 adults and children every year. While toxins (including prescription drugs, alcohol, and illicit drugs) and trauma are two common causes of rhabdo in adults (and teens), infections, especially viruses, are the most common cause in young children. Influenza, EBV, and CMV are three most commonly reported.What’s the pathophysiology of Rhabdomyolysis?Rhabdomyolysis is the injury of skeletal muscle, which leads to cellular damage, apoptosis, and necrosis. As a result, skeletal muscle cells lyse and release their intracellular contents. Insult directly to the cell membrane and ATP-depletion are two mechanisms that can start the chain reaction leading to this cell death.When the cell membrane itself is injured (as may happen in trauma or crush injury, metabolic conditions, or toxins), ionized calcium can freely enter the cell, leading to activation of proteases and phospholipases, which further injure the cell membrane, as well as mitochondria. As a result, the cell undergoes apoptosis and necrosis. When there is an ATP-depletion, pumps on the cell membrane important for maintaining sodium and calcium homeostasis between the intracellular and extracellular components become compromised. Intracellular calcium levels build, and the same process of cell and mitochondrial injury leads to apoptosis and necrosis.To summarize, Rhabdomyolysis is an index example of cell adaptations, injury, and death. The key here is cell membrane damage which leads to downstream apoptosis.Absolutely Rahul, the danger of this is that other intracellular contents are released into the extracellular space, including myoglobin, potassium, uric acid, intracellular enzymes, and many other things. Creatine kinase, or CK, released from cells is relatively indicative of rhabdo. Though no consensus criteria for rhabdo exist, most experts agree that serum CK level >1000 IU/L combined with the history and physical findings we will discuss is consistent with rhabdomyolysis.This is especially important as there is are a multitude of pathologies that can cause a mild, transient increase in CK levels usually < 1000.Pradip: One of the most common and most dangerous complications of rhabdomyolysis is acute kidney injury. While more common in adults, AKI occurs in ~5% of children with rhabdomyolysis. Let’s take a brief moment to discuss rhabdomyolysis-induced, or more specifically myoglobin-induced, acute kidney injury. While the mechanisms for myoglobin injury to the nephron aren’t entirely clear, most experts believe one of three things or, more likely, a combination of three things occur. Rahul, can you walk us through those?Rahul: Sure, I’d love to!First, myoglobin is directly nephrotoxic, though notably only in an acidic environment!Second, it causes oxidation of ferrous oxide, leading to free radicals and reactive oxygen species, unregulated by usual intracellular processes.Third, myoglobin, through protein-binding, can precipitate in the tubule, leading to obstructive nephropathy.Kate: Whew! That is a lot! Let’s take a break and review what we just learned:Rhabdomyolysis is the injury of skeletal muscle leading to calcium influx into cells, which cascades into eventual apoptosis and necrosis. This leads to a massive release of intracellular components that upsets the overall homeostasis of the intra- and extracellular spaces. Myoglobin released from cells can directly injure the kidneys, leading to AKI. Potassium and hydrogen proton leakage, combined with AKI, can lead to life-threatening hyperkalemia and acidosis. CK is a serum measurement that can help confirm the diagnosis of rhabdomyolysis.Rahul: Fun Fact Myoglobinuria usually only occurs in rhabdomyolysis (BUT not all rhabdomyolysis has myoglobinuria as it only spills out in urine above certain serum concentrations). Myoglobinuria can be inferred from a urine dipstick when there is moderate or large blood but few or no red blood cells. This is because the dipstick test for blood is non-specific for hemoglobin vs myoglobin! Myoglobin is also the reason the urine turns reddish-brown or “tea-colored.”Pradip: Let’s change gears and talk about management. Kate, can you tell us about the management of rhabdomyolysis?Kate: With this patient, our first step should be resuscitation — always ABCs first! After initial fluid resuscitation and stabilization, we can begin to think about further workup and screening. Labs should include a comprehensive metabolic panel (CMP), urinalysis with dipstick, complete blood count, and creatine kinase. Depending on the severity of clinical illness, coagulation studies can be sent, as DIC is a rare complication of rhabdomyolysis, as well as sepsis, which is on our differential! In rhabdo, labs will show an elevated CK, possible hyperkalemia, acidosis, hyperphosphatemia, and hyperuricemia. If kidney injury is present, hyperkalemia is more likely, in addition to elevated creatinine.Once rhabdomyolysis is confirmed, treatment should focus on hydration, hydration, hydration! Additionally any complications of abnormal electrolytes, etc, should be monitored for and addressed. This includes telemetry monitoring or EKG in the setting of hyperkalemia.Rahul: Remember, symptomatic hyperkalemia as evidenced by EKG changes, including wide QRS, absent P waves, or arrhythmias, including ventricular fibrillation, should be treated immediately. IV calcium administration will stabilize the cardiac membrane. Bicarbonate, insulin + glucose, and albuterol can quickly but only temporarily shift potassium into cells. Kayexalate and diuretics can remove potassium from the body.Pradip: Hydration is the most important treatment in rhabdomyolysis. There is a paucity of data, but most expert consensus suggests targeting a urine output of 3-4 ml/kg/hr while administering 2x maintenance fluids for children with rhabdo. Which fluid is the right fluid is still an area for more research, as studies have shown conflicting data about the benefits of NS vs LR vs bicarb-fluids. Normal saline without potassium can be used. Bicarbonate-containing fluids can be considered to buffer the urine on a case-by-case basis.Kate: And treatment of AKI should include avoidance of nephrotoxic medications and treatment of the underlying etiology. Renal replacement therapy should be considered for refractory fluid overload in the setting of oliguria or anuria, refractory acidosis (with pH<7.1), and refractory or life-threatening hyperkalemia. Remember those AEIOU reasons for RRT!With the resolution of the underlying cause, CK should peak in 3-5 days and then start to down-trend. Patients can be considered safe for discharge with the return of kidney function, normalization of electrolytes, and resolution of myoglobinuria.We should note here that underlying metabolic myopathies can cause recurrent, mild rhabdomyolysis, though these children do not usually need critical care unless the cause for an exacerbation is sepsis or other potentially life-threatening illness!Kate: To wrap up, here are some take-away points:The key is hydration, hydration, hydration for the treatment and prevention of life-threatening electrolyte abnormalities and acute kidney injury in the setting of rhabdomyolysisIf present, myoglobinuria indicates rhabdomyolysis.In children, viral illness is the most common cause of rhabdomyolysis, while toxins and trauma are more common in older teens and adults.Rahul: More information can be found“Rhabdomyolysis and acute kidney injury” from Bosch, et al, in the July 2009 issue of the New England Journal of Medicine and,“Pediatric rhabdomyolysis” in the June 2020 Pediatrics in ReviewReferences: (don't read these)Szugye HS. Pediatric Rhabdomyolysis. Pediatr Rev. 2020 Jun;41(6):265-275. doi: 10.1542/pir.2018-0300. PMID: 32482689.Nance JR, Mammen AL. Diagnostic evaluation of rhabdomyolysis. Muscle Nerve. 2015 un;51(6):793-810. doi: 10.1002/mus.24606. Epub 2015 Mar 14. PMID: 25678154; PMCID: PMC4437836.Bosch X, Poch E, Grau JM. Rhabdomyolysis and acute kidney injury. N Engl J Med. 2009 Jul 2;361(1):62-72. doi: 10.1056/NEJMra0801327. Erratum in: N Engl J Med. 2011 May 19;364(20):1982. PMID: 19571284.Pradip: This concludes our episode on rhabdomyolysis. 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 — with special guest Kate Phelps today. Stay tuned for our next episode! Thank you!