Comparison of the 20-Hour Intravenous and 72-Hour Oral Acetylcysteine Protocols for the Treatment of Acute Acetaminophen Poisoning
Study objective
To compare outcomes after acute acetaminophen poisoning in 2 large cohorts of patients treated with either the 20-hour intravenous or 72-hour oral acetylcysteine protocol.
Methods
We conducted a retrospective cohort study with historical control comparing patients treated with one of 2 acetylcysteine regimens. Data for the 20-hour group were obtained from a medical record review of patients on whom the 20-hour intravenous protocol was initiated in Canadian hospitals from 1980 to 2005. The 72-hour group consisted of a historical cohort of patients treated in US hospitals with the 72-hour oral protocol from 1976 to 1985. The primary outcome was hepatotoxicity (aminotransferase levels >1,000 IU/L).
Results
Of the 4,048 patients analyzed, 2,086 were in the 20-hour group and 1,962 were in the 72-hour group. The incidence of hepatotoxicity was 13.9% in the 20-hour group and 15.8% in the 72-hour group (–1.9% absolute difference; 95% confidence interval [CI] -4.2 to 0.3). The relative risk of hepatotoxicity was lower in the 20-hour group when acetylcysteine was initiated within 12 hours of ingestion. The relative risk was lower in the 72-hour group when acetylcysteine was initiated later than 18 hours after ingestion. There was no significant risk difference between groups when acetylcysteine treatment was started 12 to 18 hours after ingestion. One patient in the 20-hour group received a liver transplant and died because of acetaminophen toxicity compared with no liver transplants and 3 deaths in the 72-hour group. Anaphylactoid reactions to intravenous acetylcysteine were reported in 148 of 2,086 patients (7.1%; 95% CI 6.1% to 8.3%). This study is limited by comparison of 2 separate data sets from different countries and study years.
Conclusion
The risk of hepatotoxicity differed between the 20-hour and 72-hour protocols according to the time to initiation of acetylcysteine. It favored the 20-hour protocol for patients presenting early and favored the 72-hour protocol for patients presenting late after acute acetaminophen overdose.
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Supervising editors: E. Martin Caravati, MD, MPH; Michael L. Callaham, MD
Dr. Caravati and Dr. Callaham were the supervising editors on this article. Dr. Dart did not participate in the editorial review or decision to publish this article.
Author contributions: RJB had the original idea for the study. MCY drafted the study protocol. DWJ, RJB, MLAS, and RFB revised the study protocol. MCY, DWJ, RJB, MLAS, and RAP obtained funding for the Canadian medical record review. BHR obtained funding for the United States National Multicenter Study. AN-A, RFB, and DAS performed the statistical analysis, and all authors contributed to the interpretation of the findings. MCY drafted the article, and all authors contributed substantially to its revision. All authors approved the final version to be published. MCY takes responsibility for the paper as a whole.
Funding and support: By Annals policy, all authors are required to disclose any and all commercial, financial, and other relationships in any way related to the subject of this article that might create any potential conflict of interest. See the Manuscript Submission Agreement in this issue for examples of specific conflicts covered by this statement. The authors disclose that unrestricted financial support for this study was received from Cumberland Pharmaceuticals, the Physicians of Ontario through the Physicians Services Incorporated Foundation, Calgary Health Region Adult Research Committee, Canadian Institutes of Health Research, Alberta Heritage Foundation for Medical Research, Canadian Association of Emergency Physicians, and the University of British Columbia Summer Student Research Program. Dr. Rumack has received honoraria and consulting fees from McNeil Consumer Products Company (Johnson & Johnson), which funded the United States National Multicenter Study on the effectiveness of oral acetylcysteine in the treatment of acute acetaminophen overdose. Dr. Dart is the Director of the Rocky Mountain Poison and Drug Center, which has received financial support from McNeil Consumer Products Company (Johnson & Johnson) and Cumberland Pharmaceuticals.
Reprints not available from the authors.
Publication date: Available online June 25, 2009.
PII: S0196-0644(09)00495-8
doi:10.1016/j.annemergmed.2009.05.010
© 2009 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.
Refers to article:
- Is the Oral Acetylcysteine Protocol the Best Treatment for Late-Presenting Acetaminophen Poisoning? , 21 August 2009
