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Potentially life-threatening emergency
Acetaminophen poisoning
Other Resources UpToDate PubMed
Potentially life-threatening emergency

Acetaminophen poisoning

Contributors: Marielle Brenner MD, Kristine Nanagas MD, Blake A. Froberg MD, Gerald F. O'Malley DO
Other Resources UpToDate PubMed

Synopsis

Emergent Care / Stabilization:
In the United States, the American Association of Poison Control Centers at 800-222-1222 is available 24 hours a day to connect callers directly to their region's poison center. They are also available online.

Be prepared to provide emergent supportive therapy. This may include airway protection or administration of vasopressors, intravenous (IV) fluid, or renal replacement therapy. N-acetyl cysteine (NAC) works as an antidote to prevent liver failure when used within a timely manner. It can be used for acute and chronic cases and works best if administered within 8 hours of acute ingestion. See N-acetyl cysteine administration for dosage / administration, indications, contraindications, monitoring, adverse effects, toxicity, and mechanism of action information. Fomepizole may be considered an adjunctive treatment in high-risk APAP overdose patients, particularly when time of ingestion is unknown. Consult a toxicologist.

About Acetaminophen and Acetaminophen Poisoning:
Acetaminophen, also known as paracetamol and N-acetyl-p-aminophenol (APAP), is one of the most widely used over-the-counter analgesics. APAP is also in many prescription pain relievers. When taken at supratherapeutic doses, it can cause significant liver toxicity due to increased production of its toxic metabolite N-acetyl-p-benzoquinone imine (NAPQI) via the cytochrome P450 enzyme CYP2E1. NAPQI is a free radical molecule that causes hepatocellular damage.

Acetaminophen toxicity may occur with acute ingestion or chronic ingestions. In general, acute ingestions involve the consumption of acetaminophen as a single dose that results in a toxic concentration on the Rumack-Matthew nomogram. This typically correlates to an ingestion of 200 mg/kg of APAP in children and 150 mg/kg in adults.

Repeated ingestion of supratherapeutic doses of APAP (or even therapeutic doses taken too frequently) are more difficult to evaluate, as the Rumack-Matthew nomogram cannot be applied to these situations. History of recent acetaminophen use and elevated serum aminotransferases can be helpful in making this diagnosis. A detectable acetaminophen concentration can be helpful but is not necessary with a history of supratherapeutic acetaminophen use and elevated transaminase concentrations.

The natural history of acetaminophen toxicity occurs in 4 stages.
  • Stage 1 occurs within 24 hours of ingestion. Patients may have nausea, vomiting, lethargy, and diaphoresis, or they may be asymptomatic.
  • Stage 2 occurs between 24 and 72 hours after ingestion and is associated with elevated aminotransferases and right upper quadrant tenderness.
  • Stage 3 occurs between 72 and 96 hours after ingestion and can present as hepatic encephalopathy, jaundice, coagulopathy, and acidosis.
  • Stage 4 is the recovery phase and occurs between 96 hours and 2 weeks after ingestion; laboratory values may take longer to normalize.
The presence of concurrent acute kidney injury, metabolic acidosis, significant coagulopathy, hyperammonemia, or encephalopathy is associated with more severe toxicity. The acute kidney injury is likely due to the acetaminophen toxicity itself, as the kidney also contains CYP2E1 and can directly generate NAPQI, leading to free radical damage and acute tubular necrosis. The metabolic acidosis could be secondary to liver failure or from 5-oxoproline due to acetaminophen use, which directly contributes to metabolic acidosis. The rate of rise of ammonia concentrations in critically ill acetaminophen-poisoned patients is concerning for the development of cerebral edema and cerebellar herniation.

Related topic: acute liver failure

Codes

ICD10CM:
T39.1X4A – Poisoning by 4-Aminophenol derivatives, undetermined, initial encounter

SNOMEDCT:
70273001 – Poisoning caused by acetaminophen

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Last Reviewed:08/03/2022
Last Updated:07/29/2024
Copyright © 2024 VisualDx®. All rights reserved.
Potentially life-threatening emergency
Acetaminophen poisoning
A medical illustration showing key findings of Acetaminophen poisoning (Stage 1) : Nausea, Vomiting
Copyright © 2024 VisualDx®. All rights reserved.