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

Brok J, Buckley N, Gluud C

Published Online:

January 21, 2009

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 able to reduce absorption of paracetamol if started within one to two hours of paracetamol ingestion, but the clinical benefit is unclear. Activated charcoal seems to be the best choice if the patient is compliant. N-acetylcysteine seems superior to no intervention and 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.

Abstract (click to read)

Background:

Poisoning with paracetamol (acetaminophen) is a common cause of hepatotoxicity in the Western World. Inhibition of absorption, removal from the vascular system, antidotes, and liver transplantation are interventions for paracetamol poisoning.

Objectives:

To assess the benefits and harms of interventions for paracetamol overdose.

Search strategy:

We identified trials through electronic databases, manual searches of bibliographies and journals, authors of trials, and pharmaceutical companies until December 2005.

Selection criteria:

Randomised clinical trials and observational studies were included.

Data collection and analysis:

The primary outcome measure was all-cause mortality plus liver transplantation. Secondary outcome measures were clinical symptoms, (eg, hepatic encephalopathy, fulminant hepatic failure), hepatotoxicity, adverse events, and plasma paracetamol concentration. We used Peto odds ratios and odds ratios with 95% confidence intervals (CI) for analysis of outcomes. Random- and fixed-effects meta-analyses were performed.

Main results:

Ten small and low-methodological quality randomised trials, one quasi-randomised study, and 48 observational studies were identified. It was not possible to perform relevant meta-analyses of randomised trials that have addressed our outcome measures. 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, 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 strong evidence supports other interventions for paracetamol overdose. N-acetylcysteine may reduce mortality in patients with fulminant hepatic failure (Peto OR 0.26, 95% CI 0.09 to 0.94, one trial). Liver transplantation has the potential to be life saving in fulminant hepatic failure, but refinement of selection criteria for transplantation and long-term outcome reporting are required.

Authors' conclusions:

Our results highlight a paucity of randomised trials on interventions for paracetamol overdose. Activated charcoal seems the best choice to reduce absorption. N-acetylcysteine should be given to patients with overdose but the selection criteria are not clear. 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 for patients with poor prognosis.

This record should be cited as:

Brok J, Buckley N, Gluud C. Interventions for paracetamol (acetaminophen) overdose. Cochrane Database of Systematic Reviews 2006, Issue 2. Art. No.: CD003328. DOI: 10.1002/14651858.CD003328.pub2

Assessed as up to date:

February 22, 2006

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Primary Review Group:

Hepato-Biliary Group

Cochrane Summaries^beta

Independent high-quality evidence for health care decision making

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

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