Silent acetaminophen-induced hepatotoxicity in febrile children: does this entity exist?

Acta Paediatr. 2004 May;93(5):618-22. doi: 10.1111/j.1651-2227.2004.tb18256.x.


Several descriptions of acetaminophen-associated liver injury caused by therapeutic or a dosage slightly above the recommended dosage have been described. Our hypothesis is that in sick febrile infants and children, who may also be calorie depleted, there might be an increased hepatic vulnerability to acetaminophen.

Aim: (1) To correlate serum acetaminophen levels in febrile infants and children with the following parameters: aspartate aminotransferase (AST) levels, fever, vomiting and/or decreased caloric intake; and (2) to assess parental knowledge regarding the medication dosage and hazards of acetaminophen.

Methods: Healthy children with an acute febrile illness, who had received acetaminophen, were eligible to participate in the study. AST and acetaminophen levels were drawn, and a detailed questionnaire was completed for every child.

Results: 107 children participated in the study; 50 girls and 57 boys with ages ranging from 1 mo to 16 y (mean 33 mo). All serum acetaminophen levels were within the safety range. Although 32% of parents administered a single acetaminophen dose above 15 mg/kg and 46% gave a daily dose above 60 mg/kg/d, no significant differences were observed in the serum acetaminophen and AST levels compared to those who received the appropriate dose. In about 60% of cases, the high doses were recommended by a physician. Young age and high fever were associated with significantly higher acetaminophen levels. We could not find an association between acetaminophen levels and vomiting, decreased caloric intake and AST levels. Only 24 parents (22%) were aware of the possible toxicity of acetaminophen.

Conclusions: No evidence of increased hepatic vulnerability to acetaminophen was noted in a cohort of febrile infants and children. Furthermore, significant numbers of parents and physicians were unaware of acetaminophen dangers.

MeSH terms

  • Acetaminophen / adverse effects*
  • Acetaminophen / blood
  • Acetaminophen / therapeutic use
  • Alanine Transaminase / blood
  • Analgesics, Non-Narcotic / administration & dosage
  • Analgesics, Non-Narcotic / adverse effects*
  • Analgesics, Non-Narcotic / therapeutic use
  • Aspartate Aminotransferases / blood
  • Chemical and Drug Induced Liver Injury*
  • Dose-Response Relationship, Drug
  • Humans
  • Infant
  • Liver / drug effects
  • Liver / pathology
  • Liver / physiopathology
  • Liver Function Tests
  • Pilot Projects
  • Seizures, Febrile / drug therapy*


  • Analgesics, Non-Narcotic
  • Acetaminophen
  • Aspartate Aminotransferases
  • Alanine Transaminase