Paracetamol induced hepatotoxicity.
OBJECTIVE
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.


CONCLUSIONS
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.
Mahadevan
S B K
SB
The Liver Unit, Birmingham Children's Hospital, Birmingham, UK. bkmsubra@yahoo.co.uk
McKiernan
P J
PJ
Davies
P
P
Kelly
D A
DA
D000082:Acetaminophen / Q000506:poisoning*; D000293:Adolescent; D018712:Analgesics, Non-Narcotic / Q000506:poisoning*; D001663:Bilirubin / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury; D002648:Child; D002675:Child, Preschool; D003404:Creatinine / Q000378:metabolism; D062787:Drug Overdose / Q000401:mortality / Q000628:therapy; D005260:Female; D006801:Humans; D007223:Infant; D008099:Liver / Q000378:metabolism; D008107:Liver Diseases / Q000378:metabolism; D008297:Male; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D000637:Transaminases / Q000378:metabolism
D018712:Analgesics, Non-Narcotic; D001786:Blood Glucose; D000082:Acetaminophen; D003404:Creatinine; D000637:Transaminases; D001663:Bilirubin