High Yield Highlight-Consensus Statement on Management of Acetaminophen Poisoning in the US and Canada

The Poison Lab

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.