ORIGINAL ARTICLE

Paracetamol induced hepatotoxicity

S B K Mahadevan, P J McKiernan, P Davies, D A Kelly

The Liver Unit, Birmingham Children’s Hospital, Birmingham, UK

Correspondence to:
Dr S B K Mahadevan
The Liver Unit, Birmingham Children’s Hospital NHS Trust, Steelhouse Lane, Birmingham B4 6NH, UK; bkmsubra{at}yahoo.co.uk

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 µmol/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 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.

Abbreviations: ALT, alanine transaminase; AST, aspartate transaminase; KCH, King’s College Hospital; OLT, orthotopic liver transplantation; PT, prothrombin time

Keywords: paracetamol; fulminant liver failure; orthotopic liver transplantation; hepatotoxicity

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

Relevant Article

A brief digest of the July issue
Arch. Dis. Child. 2006 91: e1. [Extract] [Full Text] [PDF]

This article has been cited by other articles:

• Megarbane, B., Deye, N., Baud, F. J., Farmer, B. M., Hoffman, R. S., Dear, J. W., Waring, W. S., Bateman, D. N., Nogue-Xarau, S., Castanyer-Puig, B., Barcelo-Martin, B., Goldberg, J. B., Leiner, S., Heard, K. J. (2008). Acetaminophen Poisoning. NEJM 359: 1962-1965 [Full Text]  
• Waring, W.S., Stephen, A.F.L., Robinson, O.D.G., Dow, M.A., Pettie, J.M. (2008). Serum urea concentration and the risk of hepatotoxicity after paracetamol overdose. QJM 101: 359-363 [Abstract] [Full Text]  
• Owen, R., Sammons, H. M (2007). More blood tests in paracetamol overdose?. Arch. Dis. Child. 92: 278-278 [Full Text]