Original article
N-acetylcysteine in Cardiac Surgery: Do the Benefits Outweigh the Risks? A Meta-Analytic Reappraisal

https://doi.org/10.1053/j.jvca.2010.04.022Get rights and content

Objective

N-acetylcysteine (NAC) reduces proinflammatory cytokines, oxygen free-radical production, and ameliorates ischemia reperfusion injury; therefore, it may theoretically reduce postoperative complications in cardiac surgery. The aim of this study was to determine, through systematic review and meta-analysis of all relevant randomized trials, whether NAC reduces mortality, morbidity, or resource utilization in cardiac surgery.

Design

Meta-analysis.

Setting

University hospitals.

Participants

A total of 1,407 patients from 15 randomized studies were included in the analysis.

Interventions

None.

Measurements and Main Results

All randomized trials searched up to May 2009 comparing the use of NAC versus placebo during cardiac surgery in any language and reporting at least 1 predefined outcome were included. The random effect model was used to calculate odds ratios (ORs, 95% confidence intervals [CIs]) and weighted mean differences (WMD, 95% CI) for dichotomous and continuous variables, respectively. During cardiac surgery, the use of NAC did not significantly decrease acute renal failure requiring renal replacement therapy (OR = 1.05; 95% CI, 0.52-2.11; p = 0.90), new atrial fibrillation (OR = 0.67; 95% CI, 0.37-1.22; p = 0.19), or mortality (OR = 0.81; 95% CI, 0.39-1.68; p = 0.57). There were no differences in the incidence of incremental increase in serum creatinine concentration greater than 25% above baseline (OR = 0.86; 95% CI, 0.66-1.12; p = 0.26), acute myocardial infarction (OR = 0.69; 95% CI, 0.29-1.61, p =0.39), stroke (OR = 0.78; 95% CI, 0.30-2.03; p = 0.61), red blood cell transfusion requirement (OR = 0.77; 95% CI, 0.45-1.31; p = 0.33), re-exploration (OR = 1.33; 95% CI, 0.70-2.26; p = 0.29), or postoperative drainage (WMD = 33 mL; 95% CI,−125 to 191 mL; p = 0.69) between NAC and placebo.

Conclusion

Current evidence shows that the perioperative use of NAC has no proven benefit or risk on clinically important outcomes in patients undergoing cardiac surgery.

Section snippets

Methods

This meta-analysis of randomized trials was performed in accordance with Quality of Reporting of Meta-analyses and Recommendations and according to a protocol that prespecified outcomes, search strategies, inclusion criteria, and statistical analyses.21 A comprehensive search was undertaken to identify all published or unpublished randomized trials of NAC versus placebo during cardiac surgery in any language. MEDLINE, Cochrane CENTRAL, EMBASE, Current Contents, DARE (Database of Abstracts of

Results

Figure 1 outlines the search results. A total of 98 citations were screened. After reviewing the abstracts, 22 trials were retrieved for a full-text review. Of these, 7 trials were excluded because they did not meet the preset inclusion criteria. Therefore, a total of 1,407 patients in 15 original trials provided data for this meta-analysis (Table 1).3, 5, 6, 7, 8, 9, 15, 17, 18, 19, 20, 27, 28, 29, 30 Twelve studies used intravenous NAC during the perioperative period, 2 studies used an oral

Discussion

This meta-analysis of randomized trials assessed whether NAC, an inexpensive and well-tolerated medication with antioxidant and anti-inflammatory properties, reduces mortality, morbidity, and resource utilization in patients undergoing cardiac surgery. The present authors found that the perioperative use of NAC in patients undergoing cardiac surgery is not effective for the prevention of ARF, need for renal replacement therapy, new AF, mortality, or other adverse clinical outcomes.

NAC may

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