Interventions for paracetamol (acetaminophen) overdose.
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.


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


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


METHODS
Randomised clinical trials and observational studies were included.


METHODS
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.


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.


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.
Brok
J
J
Copenhagen University Hospital, Copenhagen Trial Unit, Dept. 7102, H:S Rigshospitalet, Blegdamsvej 9, Copenhagen Ø, Denmark, 2100 KBH Ø. jbrok@ctu.rh.dk
Buckley
N
N
Gluud
C
C
D000082:Acetaminophen / Q000493:pharmacokinetics / Q000506:poisoning*; D018712:Analgesics, Non-Narcotic / Q000493:pharmacokinetics / Q000506:poisoning*; D000931:Antidotes / Q000627:therapeutic use; D002606:Charcoal / Q000627:therapeutic use; D062787:Drug Overdose / Q000628:therapy; D005751:Gastric Lavage; D006801:Humans; D007408:Intestinal Absorption; D017114:Liver Failure, Acute / Q000139:chemically induced / Q000601:surgery; D016031:Liver Transplantation
D018712:Analgesics, Non-Narcotic; D000931:Antidotes; D002606:Charcoal; D000082:Acetaminophen