Effects of N-acetylcysteine treatment in acute respiratory distress syndrome: A meta-analysis

Abstract

Acute respiratory distress syndrome (ARDS) is a serious complication of acute lung injury. Severe systemic inflammation is the main cause of multiple organ dysfunction and high mortality. Removal of reactive oxygen species by anti-oxidants has been applied in clinical practice. N-acetylcysteine (NAC) is the most commonly used anti-oxidant. However, the benefit of anti-oxidant therapy was not consistently demonstrated by previous studies. In the present study, a meta-analysis was performed to evaluate the effects of NAC for adult patients with ARDS. The PubMed, Cochrane and EMBASE databases were searched to retrieve all of the available randomized controlled trials (RCTs) published until October 2015. Quality evaluation of included studies was performed according to the modified Jadad scale score. The Cochrane Collaboration Review Manager 5.3 software was used to perform the meta-analysis. Five RCTs comprising 183 patients were found to be eligible for inclusion in the meta-analysis. Pooled analysis showed that NAC did not contribute to reduce short-term mortality [risk ratio (RR)=0.73; 95% confidence interval (CI): 0.50-1.07; P=0.10] or 30-day mortality (RR=0.72; 95% CI: 0.44-1.19; P=0.20) when compared with those in the control group. However, duration of intensive care unit (ICU) stay in the NAC group was shortened [weighted mean difference (WMD), -4.56; 95% CI: (-7.32 to -1.80); P=0.001]. There was no significant difference in the ratio of partial arterial oxygen pressure to the fraction of inspired oxygen between the two groups [WMD, 54.34; 95% CI: (-30.50 to 139.17); P=0.21]. No severe adverse reactions were observed in the patients included. Although the duration of ICU stay was shortened, the clinical benefits of NAC were limited for ARDS based on the present meta-analysis. As the number of included trials and patients was small, additional trials are required to provide sufficient evidence for the efficacy of NAC in ARDS.

Keywords: N-acetylcysteine; acute respiratory distress syndrome; mortality; randomized controlled trials; systematic review.

Figure 1.

Flow chart of the meta-analysis.

Figure 2.

Publication bias evaluated by Begg's funnel plot. Each empty spot represents one publication. RR, relative risk; SE, standard error.

Figure 3.

Forest plots for short-term mortality. M-H, Mantel-Haetszel; df, degrees of freedom; CI, confidence interval; NAC, N-acetylcysteine.

Figure 4.

Forest plots for 30-day mortality. M-H, Mantel-Haetszel; df, degrees of freedom; CI, confidence interval; NAC, N-acetylcysteine.

Figure 5.

Forest plots for duration of Intensive Care Unit stay. IV, inverse variance; df, degrees of freedom; CI, confidence interval; NAC, N-acetylcysteine; SD, standard deviation.

Figure 6.

Forest plots for ratio of arterial partial pressure of oxygen/fraction of inspired oxygen using the random-effects model. IV, inverse variance; df, degrees of freedom; CI, confidence interval; NAC, N-acetylcysteine; SD, standard deviation.