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

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)

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

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

• 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.