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
T39.1X4A – Poisoning by 4-Aminophenol derivatives, undetermined, initial encounter
70273001 – Poisoning caused by acetaminophen
- 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.