The Australasian Clinical Toxicology Investigators Collaboration randomized trial of different loading infusion rates of N-acetylcysteine

Ann Emerg Med. 2005 Apr;45(4):402-8. doi: 10.1016/j.annemergmed.2004.08.040.

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.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Acetaminophen / blood
  • Acetaminophen / poisoning*
  • Acetylcysteine / administration & dosage*
  • Acetylcysteine / adverse effects*
  • Adult
  • Alanine Transaminase / blood
  • Anaphylaxis / chemically induced
  • Aspartate Aminotransferases / blood
  • Chemical and Drug Induced Liver Injury
  • Drug Administration Schedule
  • Female
  • Humans
  • Infusions, Intravenous
  • International Normalized Ratio
  • Liver Diseases / diagnosis
  • Liver Diseases / prevention & control*
  • Male
  • Nausea / chemically induced

Substances

  • Acetaminophen
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Acetylcysteine