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. 2013 May;14(3):218-26.
doi: 10.5811/westjem.2012.4.6885.

Oral and Intravenous Acetylcysteine for Treatment of Acetaminophen Toxicity: A Systematic Review and Meta-analysis

Jody L Green  1 , Kennon J Heard, Kate M Reynolds, Donald Albert
Affiliations

Oral and Intravenous Acetylcysteine for Treatment of Acetaminophen Toxicity: A Systematic Review and Meta-analysis

Jody L Green et al. West J Emerg Med. 2013 May.

Abstract

Introduction: There are few reports summarizing the effectiveness of oral and intravenous (IV) acetylcysteine. We determined the proportion of acetaminophen poisoned patients who develop hepatotoxicity (serum transaminase > 1000 IU/L) when treated with oral and IV acetylcysteine.

Methods: Studies were double abstracted by trained researchers. We determined the proportions of patients who developed hepatotoxicity for each route using a random effects model. Studies were further stratified by early and late treatment.

Results: We screened 4,416 abstracts; 16 articles, including 5,164 patients, were included in the meta-analysis. The overall rate of hepatotoxicity for the oral and IV routes were 12.6% and 13.2%, respectively. Treatment delays are associated with a higher rate of hepatotoxicity.

Conclusion: Studies report similar rates of hepatotoxicity for oral and IV acetylcysteine, but direct comparisons are lacking. While it is difficult to disentangle the effects of dose and duration from route, our findings suggest that the rates of hepatotoxicity are similar for oral and IV administration.

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Conflict of interest statement

Conflicts of Interest: By the WestJEM article submission agreement, all authors are required to disclose all affiliations, funding sources and financial or management relationships that could be perceived as potential sources of bias. This study was supported by Cumberland Pharmaceuticals (a manufacturer of IV acetylcysteine). All authors are employees of Denver Health. Denver Health has clinical, consulting and research contracts with Cumberland Pharmaceuticals (a manufacturer of IV acetylcysteine), Cadence Pharmaceuticals (a manufacturer of acetaminophen products) and McNeil Consumer Healthcare (a manufacturer of acetaminophen products). The investigators received only their salaries for work performed on this project. The sponsors had no role in the study design, performance, analysis or authorship of the article. The sponsor reviewed the final manuscript, but the authors are responsible for the final content. KH was also 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.

Figures

Figure 1.
Figure 1.
PRISMA diagram of articles identified during the article search and abstraction process.
Figure 2.
Figure 2.
Forest plot showing proportion of patients with acetaminophen poisoning who developed hepatoxicity for intravenous and oral acetylcysteine treatment.
Figure 3.
Figure 3.
Forest plot showing proportion of patients with acetaminophen poisoning who developed hepatotoxicity for intravenous and oral acetylcysteine treatment when acetylcysteine was administered early (within 10 hours or as defined by author).
Figure 4.
Figure 4.
Forest plot showing proportion of patients with acetaminophen poisoning who developed hepatotoxicity for intravenous and oral acetylcysteine treatment when acetylcysteine was administered late (more than 10 hours or as defined by author).
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