PICU Doc On Call

Approach to Pediatric Trauma 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 today of a 7 yo M who presents to the PICU after a severe Motor Vehicle Accident.Here is the case presented by RahulA 7-year-old male child is admitted to the PICU after sustaining severe trauma. The patient was brought to the emergency department after a motor vehicle accident that involved an 18-wheeler truck & the family’s car; in this severe accident the 7 yo was noted to be restrained however upon impact was ejected from the vehicle. He was unconscious and had multiple injuries, including a laceration on the head and bruising on the chest. The EMS was activated and the patient presented to the ED for acute stabilization. Upon examination, the patient was found to have a Glasgow Coma Scale score of 8, indicating a serious head injury. He had multiple bruises and abrasions on the chest and arms, and his pulse was rapid and weak. The patient was resuscitated with colloid and blood products, intubated, and transferred to the pediatric intensive care unit for further management.Notably, a CT scan of the head showed a skull fracture and a subdural hematoma. A chest X-ray showed multiple rib fractures and bilateral pulmonary opacities with no evidence of pneumothorax. The patient was also found to have a grade 2 liver laceration and a splenic injury. Pelvic x-ray and cardiac FAST exam were unrevealing.To summarize key elements from this case, this patient has:A traumatic brain injuryPulmonary contusions and is at risk for PARDSLiver and spleen injuryAnemiaPertinent negative includes: No pelvic injuries or injuries to great vessels in the chestRahul, let's approach the PICU medical management of this case based on a culmination of various guidelines published in the Pediatric Critical Care literature. Namely, let's use this case to dive deep into guidelines for:Traumatic brain injury (TBI)****Transfusion and Anemia Expertise Initiative (****TAXI)pediatric blunt liver and spleen injury management, are also known as the ATOMAC protocol, as well as general PICU management of acute trauma.As we take the management of this pediatric trauma patient in a systems-based fashion let's first go into the Management of Pediatric Traumatic Brain Injuries, can you start us off with some key management considerations?Based on the March 2019 TBI guidelines published in Pediatric Critical Care Medicine in 2019 (PCCM20(3S):p S1-S82, March 2019)This patient should have an ICP monitor or even an EVD placed for CSF diversion in consultation with the NS and trauma team. A CPP of at least >50 in our 7 yo patient and ICP < 20 mm Hg has been shown to improve outcomes and reduce mortality.Just as a quick review, CPP stands for cerebral perfusion pressure, which is the pressure that maintains blood flow to the brain. The formula for CPP is:CPP = MAP (mean arterial pressure) - ICP (intracranial pressure)Monitoring does not affect outcomes directly; rather the information from monitoring can be used to direct treatment decisions. Treatment informed by data from monitoring may result in better outcomes than treatment informed solely by data from clinical assessment. In short, it is important to have qualitative and quantitative data to optimize your decision-making.As we talked about ICP control is so crucial for this patient, Pradip, can you talk to us about some practical points in controlling ICP?Appropriate patient position (head midline and elevated 15-30, make certain that cervical collar is not too tight but allows for venous drainage from the skull) is recommended. Control fever, treat hypoxia, and hypercarbia, and avoid hypotension.Sedation and analgesia are at the discretion of the treating physician but routine boluses must be avoided to prevent cerebral hypoperfusion. Also, continuous use of propofol for sedation or ICP management is not recommended.That's a great initial set of practical management tips, head position, temperature control to avoid hyperthermia, and avoidance of hypotension to ensure optimal CPPs. Propofol may have a deleterious effect in some patients as it can reduce the SVR and predispose patients to hypotension, especially when employed in a bolus fashion.Rahul, what about NMB?Neuromuscular blockade may be required if ICP remains elevated despite adequate sedation. Muscle relaxation can also prevent shivering, fighting against the ventilator, and permit hyperventilation if it is required. Intermittent dosing of short-acting agents (eg, vecuronium or rocuronium) is preferred.Seizure prophylaxis with levetiracetam or phenytoin to prevent post-traumatic seizures is recommended for the first 7 days. Uncontrolled seizures can increase ICP.For ICP management: Any ICP > 20 mmHg for > 5 minutes requires intervention:First-tier therapies include: CSF drainage, bolus/infusion of hypertonic saline, sedation-analgesia/NMBSecond-tier therapies used for refractory intracranial hypertension (20-40% of severe TBI cases) include Hyperventilation, surgery for decompressive craniectomy or to remove mass lesion (a repeat CT scan may be required), hyperventilation, moderate hypothermia (32-34), barbiturate coma, higher levels of osmolar therapy.I think this is a great time to incorporate an essential physiologic concept, of cerebral metabolic rate of oxygen consumption.CMRO2 refers to the cerebral metabolic rate of oxygen consumption, which is a measure of the amount of oxygen used by the brain. CMRO2 can be increased during periods of Increased neural activity, Hypercapnia, Hypoxia, increased temperature and increased ICPIt is important to note that these factors can impact the brain's oxygen consumption, and in some cases, an increase in CMRO2 can lead to a decline in brain function if the brain is not able to adequately meet its increased oxygen demand.Let's pivot to the next organ system in this patient — our patient had bilateral pulmonary contusions, about this patient meet at-risk PARDS criteria? and what would be your mechanical ventilation strategy?The patient has bilateral contusions. One study (Intensive Care Med Nov 2019, 36(7):) reported that Pediatric ARDS in children with pulmonary contusion is independently associated with lower GCS scores. This patient is at risk for PARDS based on the presence of bilateral contusions and initial GCS < 8. The incidence of PARDS in TBI is ~ 9%, and its presence is associated with significantly increased morbidity and mortality. (Nair AB, Cohen MJ, Flori HR. Pediatr Crit Care Med 2020; 21:122–128). There are no clear oxygenation/Ventilation guidelines in TBI-associated PARDS. We should avoid high positive pressures (PIP) and high positive end-expiratory pressures (PEEP) as long as oxygenation remains adequate; otherwise high PIP and PEEP may increase intrathoracic pressure and impede venous drainage. We target a PCO2 35-45 mmHg and avoid hyperventilation to prevent cerebral ischemia due to decreased cerebral blood flow.To summarize, PARDS in trauma is a heterogenous disease — it is important to pay attention to the cardiopulmonary interactions of increased positive intrathoracic pressure as this can have effects on preload to the heart as well as venous drainage of the cerebral vasculature.Pradip, What about fluid status?Additionally, we should pay close attention to fluid status: Treat hypovolemia with isotonic fluids (eg, normal saline) to achieve normal, rather than excess, volume status. We should avoid the administration of hypotonic fluids (eg, D5W). Although recent evidence from basic science research, observational research, and clinical trials suggests that using balanced crystalloids rather than saline may have beneficial effects on acid–base balance, renal physiology, and patient outcomes, we need to be careful about using balanced fluids in TBI so as to not cause iatrogenic hyponatremia. Although adult studies have reported poor outcomes with fluid overload in pediatric patients, the role of FO in pediatric TBI outcomes is not clear. Drawing from adult studies it is best to be vigilant about fluid balance and avoid fluid overload.Intensivists should pay close attention to serum electrolytes and glucose while managing Trauma patients: Serum Na should be monitored at least twice daily in TBI patients. If hyponatremia develops despite the use of NS, we should think of SIADH or CSW.Our patient in our case was noted in the PICU to become progressively hypothermic, Rahul can you highlight the effect of hypothermia in the setting of pediatric trauma?Yes, I think it is important for us to review the terrible triad of trauma. The "triad of death" in trauma refers to a combination of three physiological conditions that often occur together and significantly increase the risk of death in trauma patients. The triad of death is a dangerous state, as each component can contribute to the others, exacerbating the risk of death. The triad includes acidosis, hypothermia, and coagulopathy. Early recognition and aggressive management of these conditions are crucial in improving outcomes in trauma patients.Rahul, let’s wrap this section up by talking about hyperglycemia, our patient was noted to have a few blood sugars around 200 mg/dl during the first four hours of his PICU admission, can you shed some light on this?Hyperglycemia is also commonly seen in TBI patients. The optimal strategy for glucose administration or control remains controversial although it's reasonable to withhold glucose in the IVF in the first 48hrs with close monitoring to prevent hypoglycemia.The last part of this episode will cover a bit on transfusion in the critical care setting as well as the management of blunt abdominal trauma.Our patient was noted to have a Hgb of 6.8 mg/dL and an INR of 1.8. How should we tackle anemia and also balance the elevated INR?Per the Pediatric Transfusion and Anemia Expertise Initiative–Control/Avoidance of Bleeding (TAXI-CAB)guidelines published as a supplement in the January 2022 Vol 23, supplement 15 of PCCM journal, the guideline concluded that there is insufficient pediatric evidence to support specific thresholds for coagulation tests, including INR, and platelet count, and the transfusion of plasma and platelets in critically ill pediatric patients with severe trauma, moderate-to-severe TBI, or nontraumatic ICH.It is unclear if an INR of 1.8 would change much with an FFP transfusion. Some studies have reported a significant change in INR with FFP only when INR > 2.5 (Arch Surg 2010; 145:899–906). If a procedure such as an ICP monitor or EVD was being placed, the NS team would suggest FFP administration for an INR > 1.5. Similarly it's reasonable to target a platelet count > 100K during the neurosurgical procedure. Although it is not necessary to continue to maintain a platelet count of > 100K once hemostasis is achieved.What about blood transfusion?Even though there is a lack of evidence in pediatric patients, the TAXI-CAB experts concluded that a balanced resuscitation strategy/ratio for RBC/plasma/ platelet of 1:1:1 or 2:1:1 in injured children with hemorrhagic shock or with life-threatening hemorrhage might be considered. This transfusion strategy can be stopped once the hemorrhage is controlled. In our case, the patient currently has no ongoing bleeding or shock. The Hgb is 6.8. Per the September 2018 TAXI_CAB guidelines published in the PCCM supplement (Vol 19, supplement 3): In Critically ill children with acute brain injury (e.g., severe traumatic brain injury, or cerebrovascular stroke), an RBC transfusion could be considered if the Hb falls between 7 – 10 g/dL. They also recommended against the use of invasive brain oxygenation monitoring to guide RBC transfusion. Based on these guidelines, I would transfuse blood to this patient.Once hemostasis is achieved it is reasonable to watch the trend in CBC, coagulation profile every 12 hours. It is not necessary to maintain a platelet count of > 100K once hemostasis is achieved. Similarly, the routine correction of an INR below 2 with FFP is not recommended as studies show a significant change in INR with FFP only when INR > 2.5. In patients with acute brain injury, RBC transfusion must be considered if hgb falls between 7-10g/dLFinally, in our case, the patient sustained a liver and splenic injury, can you use this case to tell us more about the ATOMAC guidelines?Absolutely, so the Arizona-Texas-Oklahoma-Memphis-Arkansas Consortium (ATOMAC) consists of a group of Level I pediatric trauma centers from across the United States dedicated to performing clinical and preclinical studies aimed at optimizing management and functional outcomes for injured children. The strongly recommended guidelines include:Management of pediatric BLSI may be based on hemodynamic status, rather than injury grade.A shortened period of bed rest of 1 day or less for stable children with unchanged hemoglobin levels.A transfusion threshold of 7.0 g/dl is reasonable for children undergoing non-operative management.Unstable patients should be considered for surgery, urgent embolization, or continued non-operative management, depending on other injuries and the center's resourcesA recent study (Stewart et al Trauma Acute Care Surg. 2023 Jan 16.) reported that the ATOMAC guideline fostered high rates of non-operative management with low ICU utilization and LOS, while demonstrating safety in implementation, irrespective of injury grade.In this patient, I would recommend serial CBC monitoring every 4 to 6 hours!To summarize, the most commonly injured abdominal organ in blunt trauma is the spleen followed by the liver. Intra-abdominal solid organ injuries are graded by the appearance on the computed tomography scans. Higher the grade, the more injury. Most intra-abdominal blunt trauma injuries are managed non-operatively provided the patient is hemodynamically stable. Pay close attention to, localized tenderness, ecchymosis, abrasion, flank tenderness, and flank or abdominal mass along with elevation of liver enzymes or drops in hgb.For any trainees out there, we would highly recommend familiarizing yourself with TBI guidelines TAXI guidelines and the ATOMAC protocols as these will provide a framework for the management of Pediatric Trauma.Pediatric trauma like many diagnoses in the PICU involves a multidisciplinary approach with close communication. The approach sense outside of the pediatric ICU as many of these patients undergo long-term rehab in inpatient and outpatient facilities.This concludes our episode on the PICU management of the patient with trauma. 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 117 Evaluation, Stabilization, and initial management after trauma (Naiditch JA et al) pages 1363-1374. Also Chapter 118 Traumatic Brain Injury(Kochanek PM et al.) page 1375-1399. Also Chapter 119 Pediatric Thoracic Trauma (Fitzgerald et al) pages 1401-1407. Also Chapter 120. Pediatric Abdominal trauma (Vogel AM et al) pages 1408-1416Kochanek, Patrick M.; Tasker, Robert C.; Carney, Nancy; Totten, Annette M.; Adelson, P. David; Selden, Nathan R.; Davis-O’Reilly, Cynthia; Hart, Erica L.; Bell, Michael J.; Bratton, Susan L.; Grant, Gerald A.; Kissoon, Niranjan; Reuter-Rice, Karin E.; Vavilala, Monica S.; Wainwright, Mark S. Guidelines for the Management of Pediatric Severe Traumatic Brain Injury, Third Edition: Update of the Brain Trauma Foundation Guidelines. Pediatric Critical Care Medicine. 20(3S):S1-S82, March 2019Emeriaud, Guillaume, Khemani R et al. on behalf of the Second Pediatric Acute Lung Injury Consensus Conference (PALICC-2) Group on behalf of the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network Executive Summary of the Second International Guidelines for the Diagnosis and Management of Pediatric Acute Respiratory Distress Syndrome (PALICC-2). Pediatric Critical Care Medicine. 24(2):143-168, February 2023Nellis ME, Karam O, Valentine SL, Bateman ST, Remy KE, Lacroix J, Cholette JM, Bembea MM, Russell RT, Steiner ME, Goobie SM, Tucci M, Stricker PA, Stanworth SJ, Delaney M, Lieberman L, Muszynski JA, Bauer DF, Steffen K, Nishijima D, Ibla J, Emani S, Vogel AM, Haas T, Goel R, Crighton G, Delgado D, Demetres M, Parker RI; Pediatric Critical Care Transfusion and Anemia EXpertise Initiative—Control/Avoidance of Bleeding (TAXI-CAB), in collaboration with the Pediatric Critical Care Blood Research Network (BloodNet), and the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network. Executive Summary of Recommendations and Expert Consensus for Plasma and Platelet Transfusion Practice in Critically Ill Children: From the Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding (TAXI-CAB). Pediatr Crit Care Med. 2022 Jan 1;23(1):34-51. doi: 10.1097/PCC.0000000000002851. PMID: 34989711; PMCID: PMC8820267.Tasker, Robert C. MA, MBBS, MD, FRCP1,2, Turgeon, Alexis F. MD, MSc, FRCPC3; Spinella, Philip C. MD, FCCM4; for the Pediatric Critical Care Transfusion and Anemia Expertise Initiative (TAXI), in collaboration with Pediatric Critical Care Blood Research Network (BloodNet), and the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network. Recommendations on RBC Transfusion in Critically Ill Children With Acute Brain Injury From the Pediatric Critical Care Transfusion and Anemia Expertise Initiative. Pediatric Critical Care Medicine 19(9S):p S133-S136, September 2018. | DOI: 10.1097/PCC.0000000000001589Stewart S, Fraser JA, Shah N, Rentea RM, Aguayo P, Juang D, Fraser JD, Snyder CL, Hendrickson RJ, St Peter SD, Oyetunji TA. INSTITUTIONAL OUTCOMES OF BLUNT LIVER & SPLENIC INJURY IN THE ATOMAC ERA. J Trauma Acute Care Surg. 2023 Jan 16. doi: 10.1097/TA.0000000000003870. Epub ahead of print. PMID: 36649594.

Dear Listeners & Peds ICU community, WE are back on air!Welcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.I'm Pradip Kamat coming BACK to you from Children’s Healthcare of Atlanta/Emory University School of Medicineand 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.As we turn into a new year, we would like to introduce Season 2 of PICU Doc on Call. Yes Pradip, I am super excited for this year & I want to take this moment to thank YOU all, our listener community for making PICU Doc on Call such a success as we share our passion for medical education thru this forum!This episode will give you a quick layout of how we will be organizing each episode of PICU doc on call this year. We will also highlight some tips and tricks on how to best learn from a medical podcast. Our goal in this episode is to provide you a framework on some best practices in medical podcasting and how to retain information from a podcast. Especially for our past & future episodes, we hope you can use this audio learning platform to assist you in applying the knowledge at the bedside when you are working in the acute care setting.Let’s get into our first learning objective,Rahul, did you know that learning via podcasts can actually benefit your brain & change the neural chemistry.In fact, a 2016 med ed study published  out of UC Berkeley concluded that listening to narrative stories from podcasts can stimulate multiple parts of your brain such as the limbic system and can enhance mood as it modulates dopamine and serotonin driven neural pathways. Think about listening to your favorite true-crime podcast  — the suspense actually allows for you to stimulate centers in your medulla that increase the amount of endorphines, dopamine and serotonin that keep you on the edge of your seat.That is so unique, so based on this, I do want to highlight some of the key elements which will make our podcast or any medical podcast you listen to beneficial. These pearls will also help you if you are developing a medical podcast of your own!The first concept here is that many podcasts provide narratives.When it comes to medical podcasts, narratives are in the form of medical cases which allow for you to retain content knowledge as a patient case invokes emotion and this can help you remember information more robustly.When listening to a podcast, you have to use your imagination to picture what’s going on. For example, if I painted a 2 yo M with a history of rhinorrhea at home for about a week who now presents to the ED with subcostal & intercostal retractions that then progresses to intubation in the PICU, you not only are envisioning a patient in front of you, but also are shifting your mind across settings. Our brain has to work at the pace of the audio, so hopefully your mind doesn’t wander off like it does when reading a textbook page. And because you have to actively think, you can retain much more.The second advantage of audio learning is that it provides flexibility and accessibilityWhen it comes to incorporating a podcast into your daily learning, it is easy, at any time of the day, you can open up your smart phone and access your Apple podcast or Spotify app and listen to a short episode on a certain topic. I would really encourage you to have a portion of the day, whether it is your commute, during chores, or even during a workout to incorporate listening to a podcast in your daily learning. Especially for PICU DOC ON CALL, our episodes are on average around 20 minutes to really capture your attention span.In fact, a very interesting study published in 2022 by Wolpaw et al. looking at knowledge retention from a podcast showed thattrainees preferred podcast learning over reading for many topics.When compared to textbook reading, podcast learning (seated or on a treadmill) produced significantly better learning gain, and equivalent retention for two of the three topics which they piloted in the study. This study even hooked the resident & med student participants to an EEG to highlight increased attention when using an audiobased tool.Finally, a good medical podcast follows a consistent outline or organization & is rooted in principles of multi-media learning.Multi-media learning theory specifically comes from Dr. Richard Mayer from UC Santa Barbara. His lab focuses on learning science and use of ed technologies.Some of the key multi-media principles which make podcasts such a unique form of learning involve:Dual channel processing — the fact that we can utilize both visual and audio representations.WE are really passionate about this theory on PICU Doc on Call, so make sure you check out our chalk talk infographic & show notes which are paried with each episode; they will help you garner a visual representation of the content we cover!That’s great, I think another unique multi-media principle is to have a minimization of extraneous load, i.e. the fact is that effective podcasts cut out redudancy, have optimal length of segments, & have user controls like double speed, etc.The key summary which we would like to impart on you:Utilize medical podcasts to actively learn — try to identify relevant material which is new to you and create a schema so that you are able to connect the information to your prior knolwedge. This idea of knowledge construction where you can integrate new information with prior experience is crucial in creating long-term memory with podcasts. Podcasts are unique to Adult Learning theory because they are a great self directed way to enhance your learning. Imagine this, you see a patient with ARDS in the PICU or on transport, you can easily direct your learning to a podcast to help solidify what you see & optimize your management decisions.This is great, Pradip, do you have other tips on how we can effectively learn from a medical podcast?Yes, I like to hit the pause button often during an in-depth podcast. It helps me stop for a moment and digest the information so I can link it to my clinical experience or knowledge which I have read in the past.I also try to keep a small notebook in my pocket which I can write out anything that resonates with me — writing it down helps me remember & I can have an area which acts as my second brain as I develop lectures or even teach on rounds.Such great advice, I also think listening to a podcast and discussing the contents with a colleague or your learner group is so essential. This principle comes from a highly recommended book on learning science called Make it Stick by Peter Brown and colleagues out of their research lab in St Louis and one of the quotes which really resonate with me is:“Learning is deeper and more durable when it’s effortful. Learning that’s easy is like writing in sand, here today and gone tomorrow.”Taking that extra effort to construct a mini-chalk talk for your learner group after you listen to the podcast or incorporate it into your next fellow didactics may be helpful for you to retain the new information!To wrap up this episode, Rahul do you mind sharing with our listeners on how each of our upcoming podcasts in Season 2 will be organized?Start with a case to highlight the PICU topic at handWe will provide you a case summary highlighting the pertinent positives and negativesGo into a board style multiple choice question to help assess your knowledgeProvide diagnostic and management frameworks highlighting relevant literature which surround the topic.We aim to make this season’s podcasts very dynamic, engaging, & practical. We hope to have you listen to our podcast and actually garner some content that you can incorporate in your practice as well as even utilize to teach your learners/colleaguesJust a quick anecdote, I recently gave a lecture to the EM residency at Cleveland Clinic & before the didactic session, I did assign a podcast to listen to! I see this flipping the class room idea in the undergraduate medical school realm & I really think leveraging this model in the graduate med ed realm is on the horizon.This concludes our first Season 2 episode on How to Learn & Retain Knowledge from a Medical Podcast. We hope you found value in our short podcast. We really would like to 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 infographics. 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:Wolpaw J, Ozsoy S, Berenholtz S, Wright S, Bowen K, Gogula S, Lee S, Toy S. A Multimodal Evaluation of Podcast Learning, Retention, and Electroencephalographically Measured Attention in Medical Trainees. Cureus. 2022 Nov 9;14(11):e31289. doi: 10.7759/cureus.31289. PMID: 36514626; PMCID: PMC9733582.Brown, Peter C. Make It Stick : the Science of Successful Learning. Cambridge, Massachusetts :The Belknap Press of Harvard University Press, 2014.

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 Medicineand 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 a three-year-old girl with altered mental status and acute respiratory failureHere's the case presented by Rahul—A three-year-old presents to the PICU with altered mental status and difficulty breathing.Per the mother, the patient was in the usual state of health on the day prior to admission when the mother left her in the care of her maternal grandmother. When mom arrived home later in the afternoon, mom was unable to wake her and reported that she seemed "stiff". She did not have any abnormal movements or shaking episodes. Mom called 911 and the patient was brought to our ED. No known head trauma, though the patient is in the care of MGM throughout the day. No emesis. No recent sick symptoms. No witnessed ingestion, however, the patient's mother reports that MGM is on multiple medications (Xarelto, zolpidem, Buspar, gabapentin, and acetaminophen) and uses THC-containing products specifically THC gummies. In the ED: The patient had waxing and waning mentation with decreased respiratory effort. GCS was recorded at 7. Arterial blood gas was performed showing an initial pH of 7.26/61/31/0. The patient was intubated for airway protection in the setting of likely ingestion. The patient has no allergies, immunizations are UTD.BP 112/52 (67) | Pulse 106 | Temp 36.2 °C (Tympanic) | Resp (!) 14 | Ht 68.5 cm | Wt 14.2 kg | SpO2 100% | BMI 30.26 kg/m²Physical exam was unremarkable-pupils were 4-5mm and sluggish. There was no rash, no e/o of traumaInitial CMP was normal with AG of 12, CBC was unremarkable, and Respiratory viral panel was negative. Serum toxicology was negative for acetaminophen, salicylates, and alcohol.Basic Urine drug screen was positive for THCTo summarize key elements from this case, this patient has:Altered mental status: - waxing and waning with GCS less than 8 suggestive of decreased ventilatory effort pre-intubationimpending acute respiratory failureDilated but reactive pupilsAll of which brings up a concern for possible ingestion such as THC (but cannot rule out other ingestion)This episode will be organized…Pharmacology of CannabisClinical presentation of Cannabis toxicityWorkup & management of Cannabis toxicityThe Cannabis sativa plant contains over 500 chemical components called cannabinoids, which exert their psychoactive effect on specific receptors in the central nervous system and immune system. The 2 best-described cannabinoids are THC and cannabidiol (CBD)—and are the most commonly used for medical purposes. Patients with intractable epilepsy or chronic cancer pain may be using these drugs. THC is the active ingredient of the cannabis plant that is responsible for most symptoms of central nervous system intoxication. The term cannabis and the common name, marijuana, are often used interchangeably).Rahul, can you shed some light on the pharmacokinetics/pharmacodynamics of cannabis?Cannabis exists in various forms: marijuana (dried, crushed flower heads, and leaves), hashish (resin), and hash oil (concentrated resin extract), which can be smoked, inhaled, or ingested. THC is the active ingredient of the cannabis plant that is responsible for most symptoms of central nervous system intoxication, in contrast to CBD, the main non-psychoactive component of cannabis. The potency of cannabis is usually based on the THC content of the preparation. The THC is lipid soluble and highly protein bound and has a volume of distribution of 2.5 to 3.5 L/kg. The THC binds to brain cannabinoid receptors, producing dose- and time-dependent stimulant, hallucinogenic, or sedative effects. Cannabis can be consumed through inhalation (smoking or vaporization) and oral ingestion, as well as via transcutaneous, rectal, and vaginal routes. On inhalation of cannabis, due to rapid delivery to the brain, the THC serum concentrations peak within 15 to 30 minutes and have a duration of up to 4 hours. Approximately 2 to 3 mg of inhaled THC is sufficient to produce drug effects in a naive user.In contrast to oral consumption, due to poor bioavailability, cannabis has a delayed onset of psychoactive effects that ranges from 30 minutes to 3 hours, lasting up to 12 hours. Because of enterohepatic circulation and slow release from lipid storage compartments, the elimination half-life of THC after oral intake ranges from 25 to 36 hours. In naive users, psychotropic effects occur with 5 to 20 mg of ingested THC.Pradip, what's the mechanism of action of THC?**There are 2 known cannabinoid receptors: CB-1 and CB-2. The CB-1 is a G-protein coupled receptor that provides inhibitory modulation of neurotransmitters, including norepinephrine, dopamine, serotonin, γ-aminobutyric acid, and acetylcholine. The CB-1 receptors are found in high densities in the cerebellum, basal ganglia, cerebral cortex, and hippocampus. The action of cannabinoids at these locations is thought to contribute to cannabis' ability to produce the cognitive and motor impairment of cannabinoid toxidromeTHC can produce wide-ranging symptoms and signs involving the neurological (euphoria, disorientation, impaired memory, ataxia, stupor or coma), ophthalmological (dilated and sluggish pupils with injected conjunctiva), cardiovascular (tachycardia), and gastrointestinal (nausea, vomiting, increased appetite, or thirst) systems.Rahul, what are the manifestations of Cannabis toxicity in children?Unintentional Cannabis poisoning in children may be a consequence of legalizing cannabis for adult use. Edible gummies, chocolates, and baked goods with THCannabinol are now available in most parts of the US & Canada. A recent NEJM study (Myran et al NEJM Aug 2022) reported that the legalization of cannabis products was associated with an increased incidence in hospitalizations for children with cannabis poisoning in certain provinces of Canada. The potency of cannabis in a single product can be variable and potentially high. A single food item can contain 400 mg or more of THC (10–20 times the typical oral dose of THC). In some instances, a single chocolate bar or brownie can contain 10 to 50 adult doses of THC, a toxic dose for a young child. Among children under 10 years presenting to a children's hospital with THC exposure, 50% are related to an edible cannabis product, with cases attributed to poor child supervision or lack of adequate storage or child-resistant packagingMore recently, Canna-vaping or the use of the vaporized form of THC is common amongst teenagers. The THC can also be extracted by lipophilic volatile organic solvents (eg, butane or propane) into a highly concentrated waxy resin (commonly referred to as “dab,” “shatter,” or “butane hash oil”) with a THC content often exceeding 70% by weight.The manifestations of cannabis intoxication among infants are primarily related to changes in the sensorium, from encephalopathy to frank coma. Older children and adults with marijuana intoxication typically present with diverse symptoms, ranging from cardiovascular (tachycardia, hypertension), ophthalmological (conjunctival injection, nystagmus), respiratory (tachypnea, bradypnea), and gastrointestinal (dry mouth, increased appetite) to neurological (sleepiness, somnolence, ataxia, slurred speech) abnormalitiesThe term “edibles” is commonly used to refer to food products containing cannabis. Edibles are available in numerous forms including baked goods, candies, gummies, lozenges, butter, oils, and beverages. Typically, edibles are sought out for recreational use due to their greater concentration of THC. Also newer synthetic versions of THC are constantly being developed and may remain undetected on drug testing.If you had to work up this patient with cannabis toxicity, what would be your diagnostic approach?Acute cannabis intoxication is a clinical diagnosis especially with a clear h/o of an adult using THC gummies with unintentional ingestion by the toddler is highly suggestive of acute cannabis intoxication. Cannabis intoxication should be suspected when an afebrile child with no prior medical history presents with neurological impairment, such as drowsiness, lethargy, or coma with no focal neurological signs.Labs include: Blood gas, basic metabolic panel (to check serum glucose and electrolytes), serum toxicology panel, urine drug screen, etc. may be sent.EKG, and chest radiograph is warranted based on clinical manifestation such as chest pain.cEEG may be required if a comatose patient is intubated.We need to be aware of co-investments such as cocaine, opioids, acetaminophen, etc, and expand the workup accordingly.If our history, physical, and diagnostic investigation led us to acute cannabis toxicity as our diagnosis what would be your general management of framework?PICU care of the infant or older child with acute cannabis intoxication is largely supportive with a focus on airway, breathing, and hemodynamics. Naloxone will not reverse coma, apnea, or hypoventilation associated with cannabis and intubation may be needed.Provide IV fluids to correct hypovolemia, and correct any electrolyte abnormalities, especially hypoglycemia.Most adolescents and adults presenting with acute cannabis toxicity have mild intoxication, with dysphoria that can be managed supportively in a dimly lit room, decreased stimulation, and, for patients with marked anxiety or agitation, benzodiazepines. Chest pain in adolescents and adults may arise from a pneumothorax (prolonged breath holding during cannabis use), exacerbation of underlying pulmonary disease (eg, asthma), or, rarely, myocardial ischemia or infarction.Patient may complain of cannabis hyperemesis syndrome, which consists of abdominal pain, vomiting, or nausea relieved by hot showers. Although cannabis hyperemesis syndrome is seen with chronic ingestion, it may be seen with acute on chronic use. Acute treatment consists of symptomatic care, including intravenous fluid hydration, antiemetics (eg, ondansetron), benzodiazepines, and cessation of cannabis use.Pradip, what are some clinical pearls regarding Cannabis for pediatric critical care medicine folks?Pearl # 1: Acute cannabis intoxication can result in altered mental status & acute respiratory failure in infants and children.Pearl # 2: Cannabis intoxication should be suspected when an afebrile child with no prior medical history presents with neurological impairment, such as drowsiness, lethargy, or coma with no focal neurological signs.Pearl # 3: Studies have reported that daily cannabis : Studies have reported exposure was associated with a significantly higher propofol dose to achieve adequate sedation compared to those without cannabis exposure. However, there was not an increased incidence of adverse events in these patients. Similarly, studies report an increased need for fentanyl and midazolam in patients with daily cannabis exposure. It is hypothesized that propofol may impart a portion of its sedative effect via the endocannabinoid system. In patients with daily cannabis exposure, down-regulation of the cannabinoid (CB)-1 receptor in chronic cannabis users versus partial agonism/antagonism at the CB-1 receptor by other phytocannabinoids in marijuana products that may compete with propofol, increasing the required dose.This concludes our episode on acute cannabis 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!ReferencesFuhrman & Zimmerman - Textbook of Pediatric Critical Care Chapter 132- Sedation and Analgesia Heard C. et al. page1599-1600Reference 1: Barrus DG, Capogrossi KL, Cates SC, et al. Tasty THC: promises and challenges of cannabis edibles. Methods Rep RTI Press. 2016;2016. doi:10.3768/rtipress.2016.op.0035.1611.Reference 2: Wong K, Baum C. Acute Cannabis toxicity. Pediatric Emergency Care. November 2019, Volume 35 (11), p 799–804.Reference 3: Boadu O, Gombolay GY, Caviness VS, et al. Intoxication from accidental marijuana ingestion in pediatric patients: what may lie ahead. Pediatr Emerg Care. 2018Blohm E, Sell P, Neavyn M. Cannabinoid toxicity in pediatrics. Curr Opin Pediatr. 2019;31:256–261.Imasogie N, Rose RV, Wilson A. High quantities: Evaluating the association between cannabis use and propofol anesthesia during endoscopy. PLoS One. 2021 Mar 4;16(3):e0248062.

In this podcast, the hosts discuss the case of a somnolent toddler who presented to the PICU. They explore the toxicity and effects of beta blockers in toddlers, as well as the management framework for severe bradycardia and hypotension. They also cover the topics of chlonidine and diazepam ingestions in children, and discuss the presence of toxic substances commonly found in grandma's purses.

Pediatric ICU physicians discuss a case of a 4-day-old with jaundice, vomiting, and dehydration. They explore the clinical and biochemical aspects of galactosemia, including diagnostic procedures and management strategies. The podcast emphasizes the importance of early detection and treatment for optimal patient outcomes.

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.