A prospective study of multiple supratherapeutic acetaminophen doses in febrile children

Repeated doses of acetaminophen given for therapeutic reasons have been reported to cause hepatotoxicity in adults and children. We studied the effect of repeated acetaminophen (APAP) overdoses administered for therapeutic purposes in a prospective cohort of children. Forty-four children, aged 2 mo to 10 y were referred with a fever of >38.5 C for more than 48 h, and received >60 mg APAP/kg/d. In each patient AST, ALT and APAP blood levels were measured. The mean total daily dose of APAP was 92 ± 26 (63-171) mg/kg. There was a weak, but significant, negative correlation between age and daily dose of APAP where younger children received higher doses of APAP. In 4 children (9.1%) an elevation of AST and ALT was found. Three of the 4 patients with elevated liver enzymes had received >90 mg APAP/kg/day; APAP blood levels ranged from 0 to 23 mg/mL. No correlation was found between the time since last APAP dose and the serum drug level. III children receiving repeated supratherapeutic doses of acetaminophen may show abnormalities in liver function. However, severe liver injury was rare.