The Poison Lab

In this episode Ryan is joined by a guest panel (Dr. Grant Comstock MD, Dr. Joshua Trebach MD, Dr. Emily Kiernan DO, and Dr Frank Paloucek PharmD, DABAT) to review nine of the most interesting or clinically impactful research abstracts that were presented at the 2023 North American Congress of Clinical Toxicology (NACCT) in Montreal Canada. If you didn't get a chance to read all 363 research abstracts from some of Toxicology's best and brightest this year, tune in for a high yield review as well as clinical a break down of the studies and their relevance from the expert panel.

Check the show notes for a link to the published abstracts and the list of all studies discussed in the show

Abstracts available here

10:40- Abstract 1 (PDF #225) Methotrexate toxicity in the setting of therapeutic error, a multicenter retrospective review

• Lead author: Andrew Chambers

24:12- Abstract #2 (PDF #251) Oleander seeds in candlenut weight loss product strike again

• Lead author: Masha Yemets

31:16- Abstract #3 (PDF #2) Efficacy of sodium tetrathionate when administered intramuscularly for the treatment of acute oral cyanide toxicity in a swine model (Sus scrofa)

• Lead author: Brooke Lajeunesse

39:45- Abstract #4 (PDF #10) Is HOUR enough after out-of hospital naloxone for opioid overdose? Prospective preliminary data from real-world implementation of the modified St. Paul’s early discharge rule

• Lead author: Stephen Douglas

49:05- Abstract #5- Poster titles at NACCT 2013–2022: is NACCT experiencing a pun-demic?

• Lead author: Dayne Laskey

52:40- Rivastigmine discussion

• Lead author: none

58:40- Abstract #6 (PDF #5) Randomized controlled trial of ANEB-001 as an antidote for acute cannabinoid intoxication in healthy adults

• Lead author: Andrew Monte

1:08:00- Abstract #7 (PDF#216) Successful use of expired physostigmine to treat anticholinergic delirium in a pediatric patient

• Lead author: Bryan Hayes

01:20:00- Abstract #8 (PDF #202) Enough negativity? Clinically significant salicylism with first detectable concentration twelve hours )post-ingestion

• Lead author: Stacey Bangh

01:25:24 - Abstract #9 (PDF #267) High sensitivity troponin is frequently elevated after carbon monoxide exposure

• Lead author: Abdullatif Aloumi

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In this episode, Ryan dives into cutting-edge research on the treatment of acetaminophen (APAP) overdose, featuring interviews with authors of several key abstracts from the North American Congress of Clinical Toxicology (NACCT) in Montreal Canada (Abstracts and posters available in the show notes). We get first looks insights into research evaluating the impact of fomepizole high risk acetaminophen overdose, as well as who gets fomepizole for acetaminophen overdose and dies. Then we evaluate the effectiveness of standard N-acetylcysteine (NAC) treatment in high risk patients and high dose NAC in high risk patients. Join us for an insightful discussion on these advancements that are reshaping the management of APAP toxicity. Guests include Dr. Masha Yemets PharmD, Dr. Molly Stott PharmD, Dr. Alexandru Ulici PharmD, and Dr. Michael Moss MD.

• Link to published abstracts
• (First guest) Abstract #126 Characterizing fomepizole use in acetaminophen deaths reported to US poison centers- Dr. Yemets
• (Second guest) Abstract #125 Clinical impact of fomepizole as an adjunct therapy in massive acetaminophen overdose- Dr. Stott
• (Third guest) Abstract #131 Comparison of low-risk and high risk acetaminophen ingestions using the standard prescott protocol of intravenous N-acetylcysteine- Dr. Ulici
• (Fourth guest) Abstract #130 High-risk acetaminophen overdose outcomes after treatment with standard dose vs. increased dose N-acetylcysteine- Dr. Moss
• Other studies discussed regarding NAC dosing
• ATOM 2 Angela Chiew
• Outcomes of massive APAP treated with regular NAC (Virginia group, lead author Dr. Downes)

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In this episode, Ryan sits down with Dr. Eric Lavonas MD, a seasoned EM resuscitation guideline writer, emergency medicine physician, medical toxicologist, and lead author of the latest update to the American Heart Association's guidelines for the management of cardiac arrest and life-threatening toxicity due to poisoning. They have an in-depth discussion as they explore the key aspects of the 2023 AHA treatment recommendations and the rationale behind each decision point. A great review to discover how to effectively apply these guidelines in real-world scenarios and find out what knowledge gaps exist in the realm of toxin resuscitation. Be sure to also check out the accompanying mini-episode for a high-yield review of the major treatment recommendations.

• Link to guidelines
• Link to high yield review
• Cyanide paper mentioned in the show
• Adult calcium channel blocker toxicity guidelines

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In this episode Ryan does a high yield "just the facts" break down of the recently released "2023 American Heart Association Focused Update on the Management of Patients With Cardiac Arrest or Life-Threatening Toxicity Due to Poisoning: An Update to the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care". Tune in to learn about the most recent treatment recommendations made by AHA via a panel of toxicology experts. This was released alongside a full interview with the lead author Dr. Eric Lavonas MD. Be sure to check out the full interview to hear it straight from the source! (link in show notes).

• Link to guidelines
• Link to full in depth interview

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In this enlightening episode, Ryan engages in a deep conversation with Dr. Paul Hutson, PharmD, a renowned researcher in the field of psilocybin and director of the Transdisciplinary Center for Research in Psychoactive Substances at the University of Wisconsin Madison. Dr. Hutson shares his extensive knowledge and insights into the promising role of psilocybin in the treatment of depression and substance use disorder.

Throughout the discussion, they delve into the research that supports the use of psilocybin in medical therapy, shedding light on the rigorous processes involved in conducting such studies. Dr. Hutson elucidates the efficacy and safety findings that have emerged from his and others research, offering listeners a glimpse into the potential future of psilocybin in mainstream medical practices. Listeners will gain a deeper understanding of the meticulous approach to research that ensures both safety and effectiveness. Dr. Hutson shares firsthand experiences and observations, providing a rich and detailed perspective on the current state of psilocybin research. Moreover, the conversation ventures into the practical aspects of integrating psilocybin into contemporary medical practices, discussing the potential frameworks and guidelines that would govern its use. They explore what the future might hold for patients and practitioners alike as they stand on the cusp of a revolutionary shift in mental health treatment.

Whether you're a healthcare professional keen on the latest developments in medical research or someone interested in the evolving landscape of mental health treatment, this episode promises to be a rich source of information and insight. Tune in to be informed and to foster a deeper understanding of the promising horizon that psilocybin research is unveiling in the medical community.

• Biography for Dr. Paul Hutson PharmD
• Transdisciplinary Center for Research in Psychoactive Substances
• Dr Hutson's Publications
• Single Dose Psilocybin for Major Depression- JAMA 2023
• Psilocybin and QTc in healthy volunteers
• Meta-Analysis of research supporting Psilocybin use in anxiety and depression
• Pharmacokinetics of Psilocybin
• Subjective effects of high dose Psilocybin
• Other referenced studies
• Single dose psilocybin for treatment resistant depression
• Psilocybin for alcohol use disorder
• Psilocybin for For tobacco cessation

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New Art and New Tox Trinkets. If you want to share your tox joy in the real world, find some trinkets here: https://www.etsy.com/shop/thepoisonlab

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• Mini episode- High-yield over view of Management of Acetaminophen Poisoning in the US and Canada Consensus Statement

In this Ryan sits down with Dr. Richard Dart MD, PhD. He is the lead author of the recently released "Management of Acetaminophen Poisoning in the US and Canada Consensus Statement" from the American Academy of Clinical Toxicology, American College of Medical Toxicology, Americans Poisons Centers, and the Canadian Association of Poison Centers. Listen to be informed on the most recent treatment recommendations. They dive in to the definitions established by the guideline and notable treatment recommendations, dissecting the ratinonale for each desiscion point and how to apply the guidelines. A mini episode was released along side this episode that is a high yield review of major treatment recommendations and definitions estabilished by the consensus statement.

Links :

• Mini episode- High-yield over view of Management of Acetaminophen Poisoning in the US and Canada Consensus Statement
• Guidelines https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2808062

Definitions made by the guideline

• Acute ingestion
• Any overdose taken with 24 hours period
• Overdose "dose" not defined
• >7.5 g in 24 h was criteria for Rumack Matthew nomogram
• Consensus statement
• Adult overdose at 10g/d or 200 mg/kg/d in <24 hours= potentially toxic
• Pediatric <6 year at 150 mg/kg/d in <24 h = potentially toxic
• Repeated Supra Therapeutic Ingestion (RSTI)
• Overdose "dose"
• Repeated dosing totaling
• 6g/d or 150 mg/kg/day x 24-48 h = potential toxic
• 4g/d or 100 mg/kg/day x >48 h = potential toxic (Recognize this means some people could be toxic at therapeutic dosing, but if they do not have symptoms not likely)
• High risk ingestion
• Reported dose >30 grams OR
• [APAP] 2 x Rummack-Matthew nomogram treatment line
• NAC stopping criteria
• APAP<10
• INR<2
• AST/ALT Normal for patient or decreased by 25-50%
• Patient clinically well

Notable treatment recommendations

• RSTI
• If patient has history of RSTI (>6 g x 24-48 h, >4 g x >48 hours) AND signs of APAP toxicity (vomiting, RUQ abd pain, AMS)
• Treat if APAP >20 ug/ml OR AST/ALT elevated
• Acute
• Non-detectable [APAP] between 2 and 4 hours excludes ingestion
• Give SDAC w/in 4 hours (something I’ve been a proponent of since ATOM2)
• Treat
• Start treatment with NAC if unable to plot on nomogram by 8 hours
• NAC dose
• “Higher dose” NAC (undefined) for high risk ingestion
• Minimum NAC regimen should include 300 mg/kg orally or within 20-24 hours
• CAP NAC dose at 100 kg (this was known with PO, but IV there was always some question since it delivers less overall)
• Unique scenarios
• Line crossers
• APAP with anticholinergic or opioid
• If 1st concentration below treatment line repeat in 4-6 hours
• APAP Extended release
• If 1st concentration below treatment line @ 4-12 hours, repeat in 4-6 hours
• Dialysis-
• Dialyze If APAP >900 w/ AMS or acidosis.
• NAC IV rate during HD 12.5 mg/kg/hr minimum. No dose change for PO (not new but good reminders)
• Consult liver transplant for rapid AST/ALT inc w/ coagulopathy, AMS, or mulistytem organ failure
• The addition of fomepizole to acetylcysteine in the treatment of serious acetaminophen ingestions has been proposed. The panel concluded that the data available did not support a standard recommendation. As for any complicated or serious acetaminophen poisoning, a PC or clinical toxicologist should be consulted.

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This episode is a a high yield "just the facts" break down of the recently released "Management of Acetaminophen Poisoning in the US and Canada Consensus Statement" from the American Academy of Clinical Toxicology, American College of Medical Toxicology, Americans Poisons Centers, and the Canadian Association of Poison Centers. Listen to be informed on the most recent treatment recommendations. This was released alongside a full interview with the consensus statement corresponding author Dr. Richard Dart MD, PhD. Be sure to check out the full interview to hear it straight from the source! (link in show notes).

Link to the guidelines:

• Full interview with consensus statement author Dr. Richard Dart
• https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2808062

Definitions made by the guideline

• Acute ingestion
• >7.5 g in 24 h per Rummack Matthew initial studies
• 10 g/d or 200 mg/kg/day in <24 h also suggested
• Repeated Supra Therapeutic Ingestion (RSTI)
• Repeated dosing totaling
• 10g or 200 mg/kg in 24 hour
• 6g/d or 150 mg/kg/day x 48 h
• 4g/d or 100 mg/kg/day x >48 h
• High risk ingestion
• Reported dose >30 grams OR
• [APAP] 2 x Rummack-Matthew nomogram treatment line
• NAC stopping criteria
• APAP<10
• INR<2
• AST/ALT Normal for patient or decreased by 25-50%
• Patient clinically well

Notable treatment recommendations

• RSTI
• If patient has history of RSTI (>6 g x 24-48 h, >4 g x >48 hours) AND signs of APAP toxicity (vomiting, RUQ abd pain, AMS)
• Treat if APAP >20 ug/ml OR AST/ALT elevated
• Acute
• Non-detectable [APAP] between 2 and 4 hours excludes ingestion
• Give SDAC w/in 4 hours (something I’ve been a proponent of since ATOM2)
• Start treatment with NAC if unable to plot on nomogram by 8 hours
• NAC dose
• “Higher dose” NAC (undefined) for high risk ingestion
• Minimum NAC regimen should include 300 mg/kg orally or within 20-24 hours
• CAP NAC dose at 100 kg (this was known with PO, but IV there was always some question since it delivers less overall)
• Unique scenarios
• Line crossers
• APAP with anticholinergic or opioid
• If 1st concentration below treatment line repeat in 4-6 hours
• APAP Extended release
• If 1st concentration below treatment line @ 4-12 hours, repeat in 4-6 hours
• Dialysis-
• Dialyze If APAP >900 w/ AMS or acidosis.
• NAC IV rate during HD 12.5 mg/kg/hr minimum. No dose change for PO (not new but good reminders)
• Consult liver transplant for rapid AST/ALT inc w/ coagulopathy, AMS, or mulistytem organ failure
• The addition of fomepizole to acetylcysteine in the treatment of serious acetaminophen ingestions has been proposed. The panel concluded that the data available did not support a standard recommendation. As for any complicated or serious acetaminophen poisoning, a PC or clinical toxicologist should be consulted.

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• Full book reading (6 minutes!)

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Dr. Frank Paloucek, PharmD, DABAT (@itsalltox) joins the show. He was one of the very first emergency medicine pharmacists and one of the original board-certified clinical toxicologists (DABAT). He is now a proudly retired professor emeritus at The Univeristy of Illinois at Chicago. In his tenure there he spent nearly 20 years as the program director for their clinical pharmacy residency, was an integral part of the Toxikon Consortium toxicology fellowship, and coauthored the text book "Poisoning and Toxicology Handbook (Poisoning and Toxicology Handbook (Leiken & Paloucek's)) 4th Edition. Frank and Ryan kick off the show hearing about Frank's fledgling years working in an emergency department without EM attendings. Then they bust some toxicology myths (do you REALLY need BAL before Calcium disodium edetate in severe lead poisoning? Frank thinks no...) before jumping into solving some toxic cases. Finally, the episode ends with Frank and Ryan solving a case of poisoned AI. They ask GPT to take on the role of a poisoned patient and work together to identify the culprit. Enjoy and don't forget to leave a review.

Introduction

• Chisolm lead 1
• Chisolm lead papers 2
• Cory-Slechta lead redistribution paper
• Tylenol murders suspect dies
• Franks book
• Toxikon fellowship

Stump the toxicologist

Case 1

• CDC article
• NEJM Article

Case 2

• A review paper written by the Frank Paloucek himself on toxin #2

Case 3

• Case report
• Case where toxin was found in stomach on autopsy published by colleagues Dr. Amy Zosel and Dr. Matt Stanton

Case 4

• A very SIMILAR case to case 4

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In this episode Ryan explores the concept of brain death and the implications of drug overdoses causing false positive diagnosis of brain death. He is joined by an author of the ACMT Position statement on brain death in overdose (Dr. Andrew Stolbach MD) as well as authors of two case reports (neuro critical care physician Dr. Ranier Reyes and emergency physician Dr. Doug Stranges) involving bupropion where patients had absent brain stem reflexes after overdose but made a full neurologic recovery. We delve into the criteria used to determine brain death and the challenges faced by families and healthcare professionals when dealing with this sensitive topic.

• 00:00-19:00 Introduction to brain death guidelines
• 19:00-28:00 Introduction to limitations in guidelines regarding overdose
• 28:30-38:00 Interview with ACMT Position statement author
• 39:00- End- Interview with Bupropion brain death mimic authors and summary

Links references in show

• American Academy of Neurology Bran death guidance
• ACMT Position statement on brain death in overdose
• Brain death mimics with cerebral edema
• Case report of “hypoxic patient with diffuses cerebral edema” who recovered in 48 hour
• Carbamazepine with diffuse cerebral edema who recovered
• Cases taking >2 months to recover brain stem reflexes
• https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(02)07577-3/fulltext
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4543058/
• Attempts to withdraw care in as little as 48 hours
• Dr. Stranges case report
• Dr. Reyes case report
• Narrative review of brain death mimics
• Introductory cases
• Caroline Burns- Patient who woke up on operating table
• Paul Maturo- Patient woke up in a morgue

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• Full book reading (6 minutes!)

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• Email: [email protected]

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