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Acetaminophen overdose is one of the few toxicological emergencies with a specific antidote; however, acetylcysteine administration regimens can be complicated, time-consuming, and costly. In a randomized, double-blind study at 3 U.K. hospitals, 222 patients who presented within 8 hours of acute acetaminophen overdose received either the standard U.K. acetylcysteine treatment regimen or a shorter, modified regimen (). In addition, patients were randomized to pretreatment with ondansetron or placebo.
Vomiting, retching, or need for rescue antiemetics within 2 hours after initiation of acetylcysteine was less frequent in patients randomized to the shorter regimen (36% vs. 65%; adjusted odds ratio, 0.26) and in those randomized to ondansetron (41% vs. 63%; adjusted OR, 0.41). Anaphylactoid reactions occurred in 28% of those in the standard-treatment group, but only 5% of those in the shorter-regimen group. The proportion of patients with a 50% increase in alanine aminotransferase activity did not differ between acetylcysteine-regimen groups, but was higher in ondansetron recipients than placebo recipients.
Bateman DN et al. Reduction of adverse effects from intravenous acetylcysteine treatment for paracetamol poisoning: A randomised controlled trial. Lancet 2013 Nov 28; [e-pub ahead of print]. (http://dx.doi.org/10.1016/S0140-6736(13)62062-0)
Comment
This well-designed study performed in the U.K., where acetaminophen overdose is more common than in the U.S., provides strong evidence that an abbreviated, 12-hour acetylcysteine regimen is better tolerated and has fewer side effects than currently recommended regimens. We may soon see a reduction in treatment times to the point that we can fully manage acetaminophen-overdose patients in emergency department observation units, thereby decreasing hospital admissions.