The Australasian clinical toxicology investigators collaboration randomized trial of different loading infusion rates of N-acetylcysteine

Fergus Kerr, Andrew Dawson, Ian Whyte, Nick Buckley, Lindsay Murray, Andis Graudins, Betty Chan, Barbara Trudinger

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109 Citations (Scopus)

Abstract

Study objective: We determine whether the incidence of adverse events caused by intravenous N-acetylcysteine is significantly less when the initial dose is infused over a 60-minute period compared with the standard infusion period of 15 minutes. A secondary objective is to assess the efficacy of the 2 treatment arms. Methods: This was a multicenter, randomized, prospective trial of patients who presented with acetaminophen poisoning and who were treated with N-acetylcysteine and had no history of hypersensitivity to N-acetylcysteine. Patients were randomly assigned to receive the initial dose of N-acetylcysteine over a 15-minute or 60-minute period. Baseline signs and symptoms and adverse events were serially evaluated before and during administration of N-acetylcysteine. Tests of liver injury and coagulation were collected at baseline and then at 12-hour intervals. Results: The study was designed with an 80 power to detect a halving of the incidence of adverse events. Of 180 evaluable patients, 109 patients were randomized to the 15-minute group and 71 patients were randomized to the 60-minute group. The incidence of drug-related adverse events was 45 in the 15-minute group and 38 in the 60-minute group (95 confidence interval -8 to 22 ). The study did not demonstrate a reduction of drug-related adverse outcomes with the 60-minute infusion. Incidence of maximum alanine aminotransferase levels indicating hepatotoxicity (serum level >1,000 IU/L) was 6.8 (5.6 for 15-minute, 8.7 for 60-minute). The difference did not attain statistical significance. Conclusion: This study did not demonstrate a reduction of drug-related adverse outcomes with the 60-minute infusion. The study also confirmed that early treatment with N-acetylcysteine (within 8 hours of ingestion) is more effective than later treatment. Copyright A? 2005 by the American College of Emergency Physicians.
Original languageEnglish
Pages (from-to)402 - 408
Number of pages7
JournalAnnals of Emergency Medicine
Volume45
Issue number4
DOIs
Publication statusPublished - 2005
Externally publishedYes

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