Today we discuss massive acetaminophen ingestion. I nabbed an amazing toxicologist for the discussion…
Emily Austin, MD
Emily Austin is a toxicologist at the Ontario Poison Centre. She completed her training at the U of T Clinical Pharmacology and Toxicology Royal College sub-specialty program. She is also an emergency medicine physician at St. Michael's Hospital in Toronto, Ontario.
Massive Ingestion is Defined By
- 1 tablet or 500 mg/kg
- 30 gms in the presence of co-ingestants
- Over 250-500 APAP level
- Signs of Mitochondrial Toxicity
Presentation
- Altered mental status within ~4 hours of ingestion
- Elevated Lactate
- Signs of Liver injury at ~12 hour mark
Labs for Suspected Massive
- Send VBG, Lactate, LFTs, PT/PTT, and Phosphate in addition to standard APAP/ASA
Repeat the APAP level at least every 4 hours
Intial INR elevation may not be from liver failure simply from an interaction to NAPQI (to below 2)
From EM Cases: In the setting of a single acute acetaminophen ingestion such as this case, an early rise in INR is not actually indicative of hepatotoxicity. Both acetaminophen and its toxic metabolite NAPQI interfere with Vitamin K dependent coagulation factors and therefore lead to a transiently elevated INR (typically under 2). This will resolve without any specific management and does not affect the standard indications for starting NAC. Additionally, high levels of circulating acetaminophen may also interfere with the INR lab assay leading to falsely elevated INR.
Both of these reasons for elevated INR are distinct from a case where acetaminophen toxicity leads to fulminant hepatic failure and there is subsequent INR elevation. In cases of acetaminophen and fulminant hepatic failure, INR will rise 2-3 days after the acute ingestion and be accompanied by elevated transaminases and other markers that fit a clinical picture of fulminant hepatic failure.
Higher Doses of NAC in Severe Toxicity
Hendrickson RG advocates there should be higher doses at 300, 450, and 600 on the nomogram [2019 Clin Tox 10.1080/15563650.2019.1579914]
Fomepizole for Massive APAP
- Fomepizole inhibits the CYP2E1 pathway, thus preventing conversion of APAP into NAPQI
- Still at the level of case series
- 15 mg/kg
- Talk to your toxicologist
- Link et al. Fomepizole as an adjunct in acetylcysteine treated acetaminophen overdose patients: a case series, Clinical Toxicology, 2022;60:4, 472-477, DOI: 10.1080/15563650.2021.1996591
RRT for Massive APAP
Extrip Guidelines (Full Publication as of 6/23)
Indications
ECTR is recommended:
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If the [APAP] more than 1000 mg/L (6620 μmol/L) and NAC is NOT administered (1D)
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If the patient presents with altered mental status, metabolic acidosis, with an elevated lactate, and an [APAP] is more than 700 mg/L (4630 μmol/L) and NAC is NOT administered (1D)
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If the patient presents with an altered mental status, metabolic acidosis, an elevated lactate, and an [APAP] is more than 900 mg/L (5960 μmol/L) even if NAC is administered (1D)
Choice of ECTR
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Intermittent hemodialysis is the preferred ECTR in patients with APAP poisoning (1D)
Miscellaneous
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NAC therapy should be continued during ECTR at an increased rate (1D)
Plasma Exchange for Hepatic Failure from APAP?
- Super Interesting, would love to hear more from all of you. There are some data.
See comment below from Matt Welles on the combination of PLEX and CVVHD at their shop.
Who Needs to be Transferred to Liver Xplant Center
- Modified Kings Criteria
- need to add lactate > 3.5 after initial resuscitation
Acetaminophen Basics for Your Review
- Anton Helman did an amazing EM Cases episode including Emily
- and he did a write-up for ACEP Now
Additional New Information
More on EMCrit
Additional Resources
- EMCrit 373 – Mike Weinstock with another Critical Care Bounceback: “Asymptomatic Hypertension” - April 18, 2024
- EMCrit Wee – Ross Prager on 10 Heuristics for the New ICU Attending - April 13, 2024
- EMCrit 372 – FoundStab Intubation SOP - April 5, 2024
In our abdominal transplant ICU we use plasma exchange combined with CVVHD regularly for acute liver failure patients including acetaminophen overdose. The goal being 1) drug clearance 2) toxic metabolite clearance 3) Ammonia clearance and prevention of cerebral edema. Our typical protocol is 1 session of large volume PLEX 3 days in a row, with high flow CVVHD running in between sessions and continuing until NH3 is below ~150. We start this very early on, usually on ICU admission. There seems to be some evidence for PLEX: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6962432/ Anecdotally from people in this unit for decades it has reduced the… Read more »
Matt–fantastic additions. thanks for giving us the viewpoint from your institution!
Thanks for for sharing knowledge,
At the right time i found this blog, with the satisfaction i’ve learnt some new today, hoping to get more valuable writing in future too.
Regards
Raghu
Analyst at 3VJ MCCB
Interesting discussion on PLEX. It would help clear larger molecules and some protein bound things missed in HD or CRRT, but I can’t really say why this would be helpful. All depends on what we want to clear. Will be logistically easier to clear small molecules with CRRT, but PLEX is the only way to clear big stuff (>50kda). I think there’s a bit of physician directed placebo here, but it deserves an actual study. Would be very interesting to see what’s in that effluent if PLEX does indeed help.
Russell Allan
Great episode and discussion.
I had a recent case where it stuck me that although I was doubling my usual rate of NAC I was also on high rate CVVHD so wondered if that would be clearing NAC and reducing effect. Our national toxicology experts advised increasing NAC even further. Any thoughts on this? Our guy did great with this eventually.
Also even once recovered he was was noted to have severe LV dysfunction with Takotsubo appearance. Seemed odd for a 22 year old. Is this common in massive paracetamol OD?
Hi People, I’m a fairly old Australian ED physician, and i was just listening to this podcast on paracetamol where gastric lavage was mentioned, and it reminded me about something. My first ED training was in at Gosford District Hospital (Central Coast of NSW) that some of us consider to be the birthplace of emergency medicine). At the time it was a little country hospital. We didn’t even have a CT scanner, and the only way we could get a CT was to take the patient’s down the road to a private place, and they wouldn’t accept our patients unless… Read more »
Lavage is still recommended for life threatening ODs without antidote. Anyone using standard NGT has no idea what they are doing. The red rubber tube you describe is an Ewald tube in the States and still works, but the commercial kits are dramatically easier to use. This is the one we use