Accidental paracetamol overdosing and fulminant hepatic failure in children

Abstract

Objective To delineate clinical characteristics useful for identifying children with liver failure due to accidental paracetamol overdose. Design Retrospective review of medical records of all patients admitted from 1985 to 1998 with fulminant hepatic failure. Setting Royal Alexandra Hospital for Children, a tertiary referral centre for paediatric liver transplantation. Main outcome measures Contribution of paracetamol to liver failure; other risk factors for liver failure; comparison of clinical features of paracetamol group and others. Results 18 patients were identified. Eight were considered to have accidental paracetamol hepatotoxicity. In a further three, other risk factors were present but paracetamol was considered a major contributor to liver failure. The seven remaining patients had other risk factors for liver failure. Patients with paracetamol‐induced liver failure usually had an acute prodromal illness with prolonged fasting and, at presentation, had encephalopathy, coagulopathy, very high transaminase levels, but disproportionately low total bilirubin levels. Five patients had hypoglycaemia. End‐stage liver failure occurred in 4/11 of the paracetamol group compared with 7/7 of the others. Conclusion Accidental paracetamol overdose is associated with fulminant hepatic failure in infants and children. Patients present with high transaminase levels and liver synthetic failure out of proportion to the level of serum bilirubin. Prompt identification of such patients is important as many recover with supportive therapy.

Evaluation of drug utilization and prescribing errors in infants: A primary care prescription-based study

“…Paracetamol is generally considered to be safe and pediatric dosage varies between 10 and 15 mg/kg every 4 h as a safe maximal dose [14]. Although toxicity is the likely outcome if more than 150 mg/kg of paracetamol is ingested [15], a dose as low as 20 mg/kg/day over several days can result in liver failure [14,16].…”

Comparison of Oral Versus Normal and High-Dose Rectal Acetaminophen in the Treatment of Febrile Children

“…[25][26][27][28][29] In the largest series quoted, which describes liver failure associated with acetaminophen ingestion, the details are not given regarding dosage, route, or duration for all of the patients. Thus, caution must be exercised in widespread adoption of any repeated dosing recommendations that use higher doses of acetaminophen.…”

Chronic Acetaminophen Exposure in Pediatric Acute Liver Failure

“…5,8,9 These and other studies suggest that risk factors for developing severe hepatotoxicity include concomitant use of multiple APAPcontaining products or other medicines that alter hepatic metabolism, delays in getting appropriate medical care, younger age, and a prodromal illness associated with periods of fasting. 4,5,8 Although the magnitude of this clinical problem in children is not well defined, 48% of APAP-induced ALF in adults in the United States is due to unintentional overdoses of APAP, often with the chronic use of ethanol or concomitant use of opioids or other potentially hepatotoxic medications, reinforcing the concept that accidental misuse of this medication leading to serious liver injury is a significant problem.…”