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Interventions for paracetamol (acetaminophen) overdoses

  • Review
  • Intervention

Authors

  • J Brok,

  • N Buckley,

  • C Gluud


Dr Jesper Brok, The Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen University Hospital, Department 7102, H:S Rigshospitalet, Blegdamsvej 9, Copenhagen, 2100 Ø, DENMARK. jbrok@ctu.rh.dk.

Abstract

Background

Self-poisoning with paracetamol (acetaminophen) is a common cause of hepatotoxicity in the Western World. Interventions for paracetamol poisoning encompass inhibition of absorption, removal from the vascular system, antidotes, and liver transplantation.

Objectives

The objective was to assess the beneficial and harmful effects of interventions or combination of interventions for paracetamol overdose.

Search strategy

The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Library, MEDLINE, EMBASE, and text searches were combined (until July 2001).

Selection criteria

Randomised clinical trials (RCTs) and observational studies as well as human volunteer randomised trials were included. The studies could be unpublished or published as an article, an abstract, or a letter and no language limitations were applied.

Data collection and analysis

All the analyses were performed according to the intention to treat. The methodological quality of the included trials was evaluated by components of methodological quality.

Main results

Nine RCTs (all small and of low methodological quality), one quasi-randomised trials, 37 observational studies, and nine randomised trials including human volunteers were identified. It was impossible to perform meta-analyses including more than two RCTs. Activated charcoal, gastric lavage, and ipecacuanha are able to reduce the absorption of paracetamol, but the clinical benefit is unclear. Of these, activated charcoal seems to have the best risk-benefit ratio. N-acetylcysteine seems preferable to placebo/supportive treatment (relative risk of mortality in patients with fulminant hepatic failure = 0.65; 95% confidence interval 0.43 to 0.99), dimercaprol, and cysteamine, but N-acetylcysteine's superiority to methionine is unproven. It is not clear which N-acetylcysteine treatment protocol offers the best efficacy. No evidence supports haemoperfusion or cimetidine for paracetamol overdose. Liver transplantation has the potential to be life saving in fulminant hepatic failure, but further refinement of selection criteria for liver transplantation and evaluation of the long-term outcome are required.

Authors' conclusions

This systematic Review has highlighted a paucity of RCTs on interventions for paracetamol overdose. Activated charcoal seems the best choice to reduce paracetamol absorption. N-acetylcysteine should be given to patients with paracetamol overdose. No N-acetylcysteine regime has been shown to be more effective than any other. It is a delicate balance when to proceed to liver transplantation, which may be life saving in patients with a poor prognosis. Interventions for paracetamol overdose need assessment in high-quality, multi-centre RCTs.

Plain language summary

Plain language summary

Evidence on interventions for paracetamol (acetaminophen) overdose patients is weak

Self-poisoning with paracetamol (acetaminophen) is a common cause of hepatic injury. The evidence for all interventions for paracetamol overdose is weak. Activated charcoal, gastric lavage, and ipecacuanha are all able to reduce absorption of paracetamol if started within two hours of paracetamol ingestion, but the clinical benefit is unclear. Of these, activated charcoal seems to be the best choice if the patient is compliant. N-acetylcysteine is superior to no intervention and seems superior to other antidotes (dimercaprol, cysteamine) and should be administered to patients at significant risk of hepatic damage. However, N-acetylcysteine superiority to methionine is unclear. Liver transplantation will clearly benefit patients with irreversible hepatic failure. However, identifying such patients early is problematic and the long-term outcomes in this group of patients have not been reported. Other interventions have not shown any clinical benefit for paracetamol overdose.

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