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

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.