N-乙酰半胱氨酸对心脏手术患者术后临床结局的影响：随机试验系统评价及Meta分析
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N-acetylcysteine use among patients undergoing cardiac surgery: A systematic review and meta-analysis of randomized trials
背景与目的
心脏手术是旨在重建冠状动脉血流和换瓣膜等的复杂手术，由手术相关炎症和缺血再灌注损伤引起的氧化应激增加了不良后果发生的风险。N-乙酰半胱氨酸（NAC）通过补充谷胱甘肽储备来作为抗氧化剂，新近研究发现NAC可降低围手术期不良结局。本研究进行了一项系统回顾和Meta分析，分析NAC对心脏手术成年患者术后结局的影响。
方 法
检索了从建库开始到2018年10月的四个数据库（PubMed、Embase、Central、Lilac）获取研究NAC对包括死亡率在内的术后结局影响的随机对照试验（RCT）： 急性肾功能不全（ARI）、急性心功能不全（ACI）、住院时间（HLOS）、重症监护病房住院时间（ICULOS）、心律失常和急性心肌梗死（AMI）等。审核员独立筛选质量合格的文章，提取数据并评估质量合格文章之间的偏差风险。使用GRADE法对每个结果总体确定性进行评价。
结 果
共纳入29项随机对照试验（包括2486名参与者）。数据表明，添加NAC对降低死亡率无统计学意义（RR：0.71；95% CI0.40-1.25）、ARI（RR：0.92；95% CI：0.79-1.09）、ACI（RR：0.77；95% CI：0.44-1.38）、HLOS（MD:0.21；95% CI:0.64-0.23）、ICULOS（MD：-0.04；95% CI：0.29-0.20）、心律失（RR=0.79；95% CI：0.52-1.20），AMI（RR：0.84；95% CI：0.48-1.48）。在符合条件的试验中，我们观察了人群和干预措施的异质性，包括有或没有肾功能不全的患者，以及在给药途径、剂量和干预措施上存在差异的干预措施。 治疗持续时间，但我们的亚组分析不能解释这种观察到的异质性。
结 论
心脏手术期间中使用NAC并不能显著降低患者术后临床结局。
原始文献摘要
Jose Eduardo G. Pereira, Regina El Dib, Leandro G. Braz1,etal;N-acetylcysteine use among patients undergoing cardiac surgery: A systematic review and meta-analysis of randomized trials;PLoS ONE 14(5): e0213862.
Background
Cardiac surgeries are complex procedures aiming to re-establish coronary flow and correct valvular defects. Oxidative stress, caused by inflammation and ischemia- reperfusion injury, is associated with these procedures, increasing the risk of adverse outcomes. N-acetylcysteine (NAC) acts as an antioxidant by replenishing the glutathione stores, and emerging evidence suggests that NAC may reduce the risk of adverse perioperative outcomes. We conducted a systematic review and meta-analysis to investigate the addition of NAC to a standard of care among adult patients
undergoing cardiac surgery.
Methods
We searched four databases (PubMed, EMBASE, CENTRAL, LILACS) from inception to October 2018 and the grey literaure for randomized controlled trials (RCTs) investigating the effect of NAC on pre-defined outcomes including mortality, acute renal insufficiency (ARI), acute cardiac insufficiency (ACI), hospital length of stay (HLoS), intensive care unit length of stay (ICULoS), arrhythmia and acute myocardial infarction (AMI). Reviewers independently screened potentially eligible articles, extracted data and assessed the risk of bias among eligible articles. We used the GRADE approach to rate the overall certainty of evidence for each outcome.
Results
Twenty-nine RCTs including 2,486 participants proved eligible. Low to moderate certainty evidence demonstrated that the addition of NAC resulted in a non- statistically significant reduction in mortality (Risk Ratio (RR) 0.71; 95% Confidence Interval (CI) 0.40 to 1.25), ARI (RR 0.92; 95% CI 0.79 to 1.09), ACI (RR 0.77; 95% CI 0.44 to 1.38), HLoS (Mean Difference (MD) 0.21; 95% CI -0.64 to 0.23), ICULoS (MD -0.04; 95% CI -0.29 to 0.20), arrhythmia (RR 0.79; 95% CI 0.52 to 1.20), and AMI (RR 0.84; 95% CI 0.48 to 1.48).
Limitations
Among eligible trials, we observed heterogeneity in the population and interventions including patients with and without kidney dysfunction and interventions that differed in route of administration, dosage, and duration of treatment. This observed heterogeneity was not explained by our subgroup analyses.
Conclusions
The addition of NAC during cardiac surgery did not result in a statistically significant reduction in clinical outcomes. A large randomized placebo-controlled multi-centre trial is needed to determine whether NAC reduces mortality.
麻醉学文献进展分享
贵州医科大学高鸿教授课题组
翻译：王贵龙 编辑：何幼芹 审校：王贵龙