Potentially life-threatening emergency
Acetaminophen poisoning
Alerts and Notices
Synopsis
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.
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.
Related topic: acute liver failure
Codes
ICD10CM:T39.1X4A – Poisoning by 4-Aminophenol derivatives, undetermined, initial encounter
SNOMEDCT:
70273001 – Poisoning caused by acetaminophen
Look For
Subscription Required
Diagnostic Pearls
Subscription Required
Differential Diagnosis & Pitfalls
- Acute alcoholic hepatitis – Serum aminotransferase elevations usually do not reach as high a peak as seen in acetaminophen toxicity.
- Hepatotoxicity induced by other drugs or substances (drug-induced hepatotoxicity) may present similarly, but history and serum acetaminophen levels can help distinguish. In rare cases, a liver biopsy may be needed to confirm the pattern of injury is consistent with acetaminophen toxicity.
- Ischemic hepatitis – More likely with history of hypotension, unconsciousness, and/or prolonged immobilization secondary to incapacitation.
- Rhabdomyolysis – Will often have elevations in serum transaminases in a pattern similar to acetaminophen (aspartate transaminase [AST] > alanine transaminase [ALT]); obtaining a creatinine kinase (CK) concentration can be helpful in distinguishing between these.
Best Tests
Subscription Required
Management Pearls
Subscription Required
Therapy
Subscription Required
Drug Reaction Data
Below is a list of drugs with literature evidence indicating an adverse association with this diagnosis. The list is continually updated through ongoing research and new medication approvals. Click on Citations to sort by number of citations or click on Medication to sort the medications alphabetically.Subscription Required
References
Subscription Required
Last Reviewed:08/03/2022
Last Updated:01/26/2023
Last Updated:01/26/2023
Potentially life-threatening emergency
Acetaminophen poisoning