Clinical Pathology: Clinical Chemistry

• In cases of acetaminophen intoxication, liver function tests should be monitored over time to evaluate hepatotoxicity. Hepatic necrosis typically begins 24 to 36 hours after a toxic ingestion and becomes severe by 72 to 96 hours after ingestion.

• Acetaminophen levels can be monitored to evaluate clearance of the drug (or indicate possible continuing absorption). The half-life of acetaminophen can also be a predictor of outcome, with hepatotoxicity being more probable when the half-life is more than 4 hours and hepatic coma more probable when the half-life is more than 12 hours.

• Gas chromatography–mass spectrometry (GC-MS), liquid chromatography–mass spectrometry (LC-MS), and/or liquid chromatography–mass spectrometry/mass spectrometry (LC-MS/MS) can be used to confirm that acetaminophen was the cause of the overdose. Depending on the assay used, various analytical interferences may occur.

• N-acetylcysteine therapy (intravenous and oral) has relatively minor side effects, so therapy can be initiated easily.

• In this case, the acetaminophen serum concentration is higher than 200 mg/L, and it is very likely that the tablets were taken more than 4 hours before collecting the sample. Therefore, according to the Rumack-Matthew nomogram (see figure), it is very probable that hepatotoxicity will occur despite normal initial liver function tests. Hepatic necrosis typically begins 24 to 36 hours after a toxic ingestion and becomes severe by 72 to 96 hours after ingestion. Initiation of treatment with N-acetylcysteine is indicated. This therapy is most effective when administered well before hepatic injury occurs, as signified by elevations of serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT).