Episode 966: Acetaminophen Toxicity

Contributor: Jorge Chalit-Hernandez, OMS4

Educational Pearls:

• What is the toxic dose of acetaminophen?
  • 7.5 grams, in an adult. The safe daily limit is 4 grams in an adult with a normally functioning liver.
  • This is equivalent to fifteen 500mg pills.
• What are the symptoms of acetaminophen toxicity?
  • First 24 hours, symptoms are non-specific e.g. nausea, vomiting, lack of appetite. Can also be asymptomatic.
  • 24-72 hours, hepatotoxicity occurs (causing yellow skin, pruritus, abdominal pain, bleeding, and confusion)
  • Fulminant liver failure at 72-96 hours
  • Liver function tests (LFTs) peak at 72-96 hours.
• When would you give activated charcoal?
  • Within 4 hours of ingestion.
  • The risk of activated charcoal is that it can be very dangerous if aspirated so use with caution with a poorly mentating patient
• When would you give N-acetylcysteine (NAC)?
  • The peak absorption of acetaminophen occurs at about 4 hours with acute ingestions
  • Use the Rumack–Matthew nomogram to plot the serum level of acetaminophen versus the time since ingestion to see if you are above the treatment line.
  • If the ingestion time is unknown then just give it.
• How do you dose NAC?
  • 3 bag system: First, a 150 mg/kg bolus is administered IV over 15-60 minutes (Bag 1), then a 50 mg/kg drip is administered over 4 hours (Bag 2), then a 100 mg/kg drip is administered over the following 16 hours (Bag 3).
    • This is the Prescott Protocol that requires three bag of IV fluids
  • 2 bag system: There is a simplified protocol that only requires 2 bags, 200mg/kg IV over 4 hours (Bag 1) followed by 100mg/kg over 16 hours (Bag 2)
    • Less risk of anaphylactoid reactions with a 2-bag system due to the high rate of IV NAC given in the 3 bag system.
• What are the endpoints for stopping NAC?
  • If the INR is <1.5
  • If the acetaminophen level is < 10 mcg/mL or undetectable

References

1. Hodgman MJ, Garrard AR. A review of acetaminophen poisoning. Crit Care Clin. 2012 Oct;28(4):499-516. doi: 10.1016/j.ccc.2012.07.006. PMID: 22998987.
2. Rumack BH, Matthew H. Acetaminophen poisoning and toxicity. Pediatrics. 1975 Jun;55(6):871-6. PMID: 1134886.
3. Sudanagunta S, Camarena-Michel A, Pennington S, Leonard J, Hoyte C, Wang GS. Comparison of Two-Bag Versus Three-Bag N-Acetylcysteine Regimens for Pediatric Acetaminophen Toxicity. Ann Pharmacother. 2023 Jan;57(1):36-43. doi: 10.1177/10600280221097700. Epub 2022 May 19. PMID: 35587124.

Summarized by Jeffrey Olson, MS4 | Edited by Jeffrey Olson and Jorge Chalit, OMS4

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