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Risk Factors Associated With Hepatocellular Injury

Sarah W. Alander, MD; M. Denise Dowd, MD, MPH; Susan L. Bratton, MD, MPH; Gregory L. Kearns, PharmD

Arch Pediatr Adolesc Med. 2000;154:346-350.

Objectives  To characterize demographic and clinical factors associated with pediatric acetaminophen overdose and identify risk factors for hepatocellular injury.

Design  Retrospective 10-year chart review.

Setting  Two regional children's hospitals.

Materials and Methods  Records of patients examined because of acetaminophen ingestion from January 1, 1988, through December 31, 1997, were reviewed. Hepatocellular injury was defined as elevation of serum aminotransferase levels greater than 2 times the reference values. Severe hepatotoxic effect was defined as hepatotoxic effect with evidence of encephalopathy and/or coagulopathy.

Results  Data from 322 patients (208 girls and 114 boys, aged 1-17 years) were obtained. Ingestions were intentional in 140 patients (median age, 14 years) and unintentional in 172 (median age, 2 years). Another 10 cases represented dosing errors with therapeutic intent (median age, 3.5 years). Twenty-seven patients had hepatocellular injury; of these, 4 had severe hepatotoxic effects and 1 died. Hepatocellular injury occurred in 10.0% of the dosing error group, 17.9% of the intentional group, and 0.6% of the unintentional group. No patients underwent liver transplantation. Hepatocellular injury was associated with presentation longer than 24 hours after ingestion (odds ratio [OR], 335.0; 95% confidence interval [CI], 40.8-275.0), age 10 to 17 years (OR, 36.9; 95% CI, 4.9-275.4), intentional overdose (OR, 37.2; 95% CI, 5.0-278.2), dose greater than 150 mg/kg (OR, 17.9; 95% CI, 2.3-139.2), and white race (OR, 2.8; 95% CI, 1.1-7.2).

Conclusions  Intentional and unintentional acetaminophen overdoses occurred with similar frequency. Therapeutic misadventure was relatively uncommon, as was hepatocellular injury. Practitioners should have greater suspicion of acetaminophen-associated hepatocellular injury in patients who present more than 24 hours after ingestion, older children, and those who have intentional ingestion.

From the Division of Emergency Medicine, Department of Pediatrics (Drs Alander and Dowd), and Section of Pediatric Clinical Pharmacology and Experimental Therapeutics (Dr Kearns), Children's Mercy Hospital, Kansas City, Mo; Department of Anesthesiology and Pediatric Critical Care Medicine, University of Washington and Seattle Children's Hospital and Medical Center, Seattle (Dr Bratton); and Departments of Pediatrics and Pharmacology, University of Missouri–Kansas City (Dr Kearns).

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