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.
Kerr, F., Dawson, A., Whyte, I., Buckley, N., Murray, L., Graudins, A., Chan, B., & Trudinger, B. (2005). The Australasian clinical toxicology investigators collaboration randomized trial of different loading infusion rates of N-acetylcysteine. Annals of Emergency Medicine, 45(4), 402 - 408. https://doi.org/10.1016/j.annemergmed.2004.08.040