Paracetamol induced hepatotoxicity

Arch Dis Child. 2006 Jul;91(7):598-603. doi: 10.1136/adc.2005.076836. Epub 2006 Mar 17.

Abstract

Aim: To identify the clinical and biochemical risk factors associated with outcome of paracetamol induced significant hepatotoxicity in children.

Methods: Retrospective case notes review of those with paracetamol overdose admitted from 1992 to 2002. Patients were analysed in two groups: group I recovered after conservative treatment and group II developed progressive liver dysfunction and were listed for liver transplantation.

Results: Of 51 patients (6 males, 45 females, aged 0.8-16.1 years), 6 (aged <7 years) received cumulative multiple doses, and 45 a single large overdose (median 345 mg/kg, range 91-645). The median (range) interval to hospital at presentation post-ingestion was 24 hours (4-65) and 44 hours (24-96) respectively in groups I and II. Patients received standard supportive treatment including N-acetylcysteine. All children in group I survived. In group II, 6/11 underwent orthotopic liver transplantation (OLT) and 2/6 survived; 5/11 died awaiting OLT. Cerebral oedema was the main cause of death. Children who presented late to hospital for treatment and those with progressive hepatotoxicity with prothrombin time >100 seconds, hypoglycaemia, serum creatinine >200 micromol/l, acidosis (pH <7.3), and who developed encephalopathy grade III, had a poor prognosis or died. Although hepatic transaminase levels were markedly raised in both groups, there was no correlation with necessity for liver transplantation or death.

Conclusion: Accidental or incidental paracetamol overdose in children may be associated with toxic liver damage leading to fulminant liver failure. Delayed presentation and/or delay in treatment, and hepatic encephalopathy > or =grade III were significant risk factors, implying poor prognosis and need for OLT. Prompt identification of high risk patients, referral to a specialised unit for management, and consideration for liver transplantation is essential.

MeSH terms

  • Acetaminophen / poisoning*
  • Adolescent
  • Analgesics, Non-Narcotic / poisoning*
  • Bilirubin / metabolism
  • Blood Glucose / metabolism
  • Chemical and Drug Induced Liver Injury*
  • Child
  • Child, Preschool
  • Creatinine / metabolism
  • Drug Overdose / mortality
  • Drug Overdose / therapy
  • Female
  • Humans
  • Infant
  • Liver / metabolism
  • Liver Diseases / metabolism
  • Male
  • Prognosis
  • Retrospective Studies
  • Risk Factors
  • Transaminases / metabolism

Substances

  • Analgesics, Non-Narcotic
  • Blood Glucose
  • Acetaminophen
  • Creatinine
  • Transaminases
  • Bilirubin