Effect of intravenous n-acetylcysteine in acute respiratory distress syndrome: A systematic review and meta-analysis

Abstract

INTRODUCTION. Oxidative stress plays an important role in the development of acute respiratory distress syndrome(ARDS) (1). There are several clinical trials investigating the efficacy of the free radical scavenger N-acetylcysteine (NAC) in ARDS, but its advantage remains uncertain. OBJECTIVES. Critically appraise and summarize all randomized clinical trials involving intravenous NAC administration in adult patients suffering from ARDS. METHODS. We included trials involving participants with ARDS according to the American- European Consensus Conference Criteria (2) regardless of the underlying cause, and where one of the groups was treated with intravenous N-acetylcysteine in bolus intravenous doses or as continuous infusion, or combination of the two, and the other group was given placebo or standard treatment. The following databases were searched: Cochrane Central Register of Clinical Trials (CENTRAL) (The Cochrane Library); MEDLINE (January 1950 to March 2010); EMBASE (January 1980 to March 2010); CINAHL (1982 to March 2010); the NHS Trusts Clinical Trials Register and Current Controlled Trials (http://www.controlledtrials. com); LILAC; KoreaMED; MEDCARIB; INDMED; PANTELEIMON; Ingenta; ISI Web of Knowledge and the National Trials Register to identify all relevant randomized controlled trials available for review. RESULTS. 15 fully published studies (including 583 patients)met the study inclusion criteria. 12 out of the 15 studies reported mortality. Using the longest reported follow-up data mortality was similar in the NAC group: 97/244 (37.75%) and in the placebo group: 92/258 (35.65%) (RR 1.12 95% CI 0.90-1.40). Neither had NAC any significant effect on length of stay or duration of mechanical ventilation. Excluding those studies with high risk of bias, did not affect risk of mortality (RR 1.25, 95% CI 0.99 to 1.59 Analysis 1.4).Early NAC treatment did not affect outcome, however late administration ofNAC(after 24 h of initial presentation of symptoms)was associated with increased mortality (RR 1.38, 95% CI 1.05 to 1.81, 285 patients, 7 trials). CONCLUSIONS. The main finding of this meta-analysis is that intravenous NAC is ineffective in reducing mortality, length of stay or duration of mechanical ventilation in ARDS. We also found that late administration of NAC may be associated with adverse outcome. The mechanism of this potentially deleterious effect remains unclear, but dosing and timing of NAC appear to be critical issues.