A single-arm clinical trial of a 48-hour intravenous N-acetylcysteine protocol for treatment of acetaminophen poisoning

Clin Toxicol (Phila). 2014 Jun;52(5):512-8. doi: 10.3109/15563650.2014.902955. Epub 2014 Apr 8.


Introduction: Acetylcysteine prevents hepatic injury when administered soon after acetaminophen overdose. The most commonly used treatment protocols are a 72-hour oral and a 21-hour intravenous (IV) protocol. Between 1984 and 1994, 409 patients were enrolled in a study to describe the outcomes of patients who were treated using a 48-hour IV protocol. In 1991, an interim analysis reported the first 223 patients. The objective of this manuscript is to report the rates of hepatotoxicity and adverse events occurring during a 48-hour IV acetylcysteine protocol in the entire 409 patient cohort.

Methods: This was a multicenter, single-arm, open-label clinical trial enrolling patients who presented with a toxic serum acetaminophen concentration within 24 h of acute acetaminophen ingestion. Patients were treated with 140 mg/kg loading dose followed by 70 mg/kg every 4 h for 12 doses. Serum aminotransferase activities were measured every 8 h during the protocol, and adverse events were recorded. The primary outcome was the percentage of subjects who developed hepatotoxicity defined as a peak serum aminotransferase greater than 1000 IU/L.

Results: Four hundred and nine patients were enrolled, and 309 met inclusion for the outcome analysis. The overall percentage of patients developing hepatotoxicity was 18.1%, and 3.4% of patients treated within 10 h developed hepatotoxicity. One acetaminophen-related death occurred in a patient treated at 22 h. Adverse events occurred in 28.9% of enrolled subjects; the most common adverse events were nausea, vomiting, and flushing, and no events were rated as serious by the investigator.

Conclusions: Acetaminophen-overdosed patients treated with IV acetylcysteine administered as 140 mg/kg loading dose followed by 70 mg/kg every 4 h for 12 doses had a low rate of hepatotoxicity and few adverse events. This protocol delivers a higher dose of acetylcysteine which may be useful in selected cases involving very large overdoses.

Keywords: Acetaminophen; Acetylcysteine; Antidote; Liver injury; Poisoning.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetaminophen / blood
  • Acetaminophen / poisoning*
  • Acetylcysteine / administration & dosage
  • Acetylcysteine / adverse effects
  • Acetylcysteine / therapeutic use*
  • Administration, Intravenous
  • Adolescent
  • Adult
  • Antidotes / administration & dosage
  • Antidotes / adverse effects
  • Antidotes / therapeutic use*
  • Chemical and Drug Induced Liver Injury / epidemiology
  • Chemical and Drug Induced Liver Injury / etiology
  • Chemical and Drug Induced Liver Injury / prevention & control*
  • Child
  • Child, Preschool
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Drug Overdose
  • Female
  • Humans
  • Male
  • Prospective Studies
  • Time Factors
  • Transaminases / blood
  • Treatment Outcome
  • Young Adult


  • Antidotes
  • Acetaminophen
  • Transaminases
  • Acetylcysteine