Episode 966: Acetaminophen Toxicity

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Jul 21, 2025

Explore the ins and outs of acetaminophen toxicity, including the critical toxic dose and the wide-ranging symptoms that emerge within the first few days. Learn about the life-saving role of activated charcoal and the importance of timing in treatment. Discover the intricacies of administering N-acetylcysteine, including dosing protocols and when to use the Rumack–Matthew nomogram. This discussion is packed with essential information for anyone in the medical field dealing with potential overdoses.

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ANECDOTE

Patient Took Dangerous Tylenol Overdose

A patient took 28 Tylenol pills, nearly double the lethal dose of 7.5 grams.
This illustrates how dangerous large acute ingestions of acetaminophen can be.

INSIGHT

Acetaminophen Toxic Dose Limits

The lethal acetaminophen dose in adults is about 7.5 grams.
The safe daily limit for adults with normal liver function is 4 grams, equivalent to fifteen 500 mg pills.

INSIGHT

Timeline of Toxicity Symptoms

Acetaminophen toxicity symptoms are nonspecific or absent in the first 24 hours.
Hepatotoxicity manifests between 24-72 hours; liver function tests peak between 72-96 hours.

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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
- If the acetaminophen level is

References

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.
Rumack BH, Matthew H. Acetaminophen poisoning and toxicity. Pediatrics. 1975 Jun;55(6):871-6. PMID: 1134886.
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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