1,226
Views
27
CrossRef citations to date
0
Altmetric
Research Article

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

, , , , , & show all
Pages 512-518 | Received 28 Oct 2013, Accepted 02 Mar 2014, Published online: 08 Apr 2014
 

Abstract

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.

Acknowledgements

The authors wish to thank the investigators who enrolled subjects in this study and the research staff at Rocky Mountain Poison and Drug Center who re-entered and validated the study data. We would also like to thank Dr. Martin Smilkstein for his work on the project. This study was funded by Bristol-Meyers-Squib. The sponsor had no role in the analysis or manuscript preparation. Dr. Heard was supported by Award Number K08DA020573 from the National Institute On Drug Abuse. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute On Drug Abuse or the National Institutes of Health.

Declaration of interest

KH, JG, RCD, ACB, BBB, and SH were employees of Denver Health while working on this manuscript, and BR was an employee of Denver Health while the study was conducted. Denver Health has research and consulting contracts with McNeil Consumer Healthcare, Cumberland Pharmaceuticals and Cadence Pharmaceuticals. The authors received only their salaries for work performed on this project. Dr. Rumack provides consulting services to McNeil Consumer Healthcare on behalf of the Denver Health and Hospital Authority. In addition, Dr. Rumack has testified on behalf of McNeil Consumer Healthcare in litigation.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.