A single-arm clinical trial of a 48-hour intravenous N-acetylcysteine protocol for treatment of acetaminophen poisoning
- 8 April 2014
- journal article
- research article
- Published by Taylor & Francis Ltd in Clinical Toxicology
- Vol. 52 (5), 512-518
- https://doi.org/10.3109/15563650.2014.902955
Abstract
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. 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. 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. 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
This publication has 18 references indexed in Scilit:
- An Analysis ofN-Acetylcysteine Treatment for Acetaminophen Overdose Using a Systems Model of Drug-Induced Liver InjuryThe Journal of pharmacology and experimental therapeutics, 2012
- Acetaminophen and acetylcysteine dose and duration: Past, present and futureClinical Toxicology, 2012
- 2010 Annual Report of the American Association of Poison Control Centers’ National Poison Data System (NPDS): 28th Annual ReportClinical Toxicology, 2011
- Hepatic Failure Despite Early Acetylcysteine Following Large Acetaminophen-Diphenhydramine OverdosePEDIATRICS, 2011
- Comparison of the 20-Hour Intravenous and 72-Hour Oral Acetylcysteine Protocols for the Treatment of Acute Acetaminophen PoisoningAnnals of Emergency Medicine, 2009
- Development of Hepatic Failure Despite Use of Intravenous Acetylcysteine After a Massive Ingestion of Acetaminophen and DiphenhydramineAnnals of Emergency Medicine, 2009
- Hepatotoxicity Despite Early Administration of Intravenous N‐Acetylcysteine for Acute Acetaminophen OverdoseAcademic Emergency Medicine, 2008
- Safety and efficacy of intravenous N‐acetylcysteine for acetaminophen overdose: analysis of the Hunter Area Toxicology Service (HATS) databaseCurrent Medical Research and Opinion, 2007
- Efficacy of Oral N-Acetylcysteine in the Treatment of Acetaminophen OverdoseThe New England Journal of Medicine, 1988
- TREATMENT OF PARACETAMOL (ACETAMINOPHEN) POISONING WITH N-ACETYLCYSTEINEThe Lancet, 1977