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A prospective study of multiple supratherapeutic acetaminophen doses in febrile children
Eran Kozer1, Joseph Barr, Mordechai Bulkowstein
1Department of Pediatric Emergency Medicine, Assaf Harofeh Medical Center, Tel-Aviv University, Israel.
Insights
Repeated acetaminophen (APAP) overdoses in children can cause liver enzyme elevations. While severe liver injury was rare, monitoring is advised for ill children receiving high APAP doses.
Area of Science:
- Pediatric Medicine
- Pharmacology
- Toxicology
Background:
- Acetaminophen (APAP) is commonly used for fever in children.
- Therapeutic overuse of APAP can lead to hepatotoxicity.
- Data on APAP overdose effects in pediatric populations is limited.
Purpose of the Study:
- To investigate the impact of repeated supratherapeutic acetaminophen doses on liver function in children.
- To assess the correlation between APAP dosage, age, and liver enzyme levels.
Main Methods:
- Prospective cohort study of 44 children (2 months to 10 years) with fever receiving >60 mg APAP/kg/day.
- Measurement of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and APAP blood levels.
- Analysis of dose-response relationship and correlation with age and time since last dose.
Main Results:
- Mean APAP dose was 92+/-26 mg/kg/day; younger children received higher doses.
- Four children (9.1%) exhibited elevated AST and ALT levels.
- Elevated liver enzymes were associated with doses >90 mg APAP/kg/day; APAP levels ranged from 0-23 mg/mL.
Conclusions:
- Repeated supratherapeutic acetaminophen doses in children can lead to transient liver function abnormalities.
- Severe hepatotoxicity appears rare even with significant overdoses.
- Close monitoring of liver function is recommended for children receiving high-dose acetaminophen therapy.
Abstract:
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. Ill children receiving repeated supratherapeutic doses of acetaminophen may show abnormalities in liver function. However, severe liver injury was rare.