Clinical course of repeated supratherapeutic ingestion of acetaminophen

Repeated supratherapeutic ingestion (RSTI) of acetaminophen (APAP) is recognized as an important cause of APAP-related morbidity and mortality. This study describes the characteristics and clinical course of patients with RSTI, and identifies the risk factors for developing hepatotoxicity and death.

This secondary analysis of a multicenter retrospective chart review studied patients treated with IV and/or oral N-acetylcysteine for acetaminophen poisoning. For this analysis, we included all subjects coded as RSTIs, defined as ingestions of greater than 4 g of APAP per 24 h over a period longer than 8 h. Data collected include demographics, coingestants, comorbidities, presenting laboratory data, and outcomes. The analysis includes descriptive statistics and associations of demographic and clinical factors with patient outcome.

Of the 503 patients enrolled, 119 (23.7%) were RSTI. The mean age was 39.6 years (SD ± 15); 63.9% of the patients were females, 60.5% Caucasians, 27.7% alcoholics, 5% malnourished, 10.9% had viral hepatitis, and 3.4% had other liver diseases. Coingestants included ethanol, opioids, and antihistamines (17.6, 48.7, and 19.3%, respectively). Among this group, 44 patients developed hepatotoxicity, two received liver transplants, and four died (37.0, 1.7, and 3.4%, respectively). The risk for hepatotoxicity increased with a history of alcoholism, viral hepatitis, and other liver diseases. A history of alcoholism and an elevated presenting serum creatinine were associated with increased risk for death/transplant. The lowest presenting ALT levels in a subject who developed hepatotoxicity and who died were 252 and 426 IU/l, respectively.

RSTI-induced hepatotoxicity and poor outcomes can be predicted at the patient's presentation. All patients with RSTI who developed hepatotoxicity presented with an abnormal ALT. A history of alcoholism and an elevated creatinine at presentation are markers of increased risk for hepatotoxicity and death.