Perioperative n-acetylcysteine to prevent renal dysfunction in high-risk patients undergoing CABG surgery - A randomized controlled trial
Perioperative n-acetylcysteine to prevent renal dysfunction in high-risk patients undergoing CABG surgery - A randomized controlled trial
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DOI：
10.1001/jama.294.3.342
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发表时间：
2005-07-20
影响因子：
120.7
通讯作者：
Moist, L
中科院分区：
文献类型：
--
作者：
Burns, KEA;Chu, MWA;Moist, L
肾功能不全是冠状动脉旁路移植术（CABG）和体外循环（CPB）手术的并发症，与发病率和死亡率增加有关。N-乙酰半胱氨酸是一种抗氧化剂和血管扩张剂，可对抗肾缺血和缺氧。目的确定与安慰剂相比，围手术期静脉注射（IV）N-乙酰半胱氨酸是否可保护接受CPB CABG手术的高危患者的肾功能。一项安慰剂对照试验（2003年10月至2004年9月），在安大略三级护理中心的手术室和普通重症监护室（ICU）进行。295例患者需要择期或紧急CABG，并且至少有以下1项：既存肾功能不全，年龄至少70岁，糖尿病，左心室功能受损，或同时接受瓣膜或再次手术的患者接受了4次干预（2次术中和2次术后）在24小时内静脉注射N-乙酰半胱氨酸（600 mg）（n = 148）或安慰剂（n = 147）。主要结果测量主要结果是发生术后肾功能不全的患者比例，定义为术后前5天内血清肌酐水平升高大于0.5 mg/dL（44 μ mol/L）或较基线升高25%。次要结局包括术后干预和并发症、肾脏替代治疗（RRT）的需求、不良事件、住院死亡率、ICU和住院时间。（29.7% vs 29.0%，P= 0.89;相对风险[RR]，1.03 [95%置信区间{CI}，0.72-1.46]）。我们注意到N-乙酰半胱氨酸组和安慰剂组在术后干预和并发症、RRT需求（0.7% vs 2.1%; P=37）、总不良事件（6.1% vs 9.6%; P= 0.26）和严重不良事件、住院死亡率（3.4% vs 2.7%; P>39）以及ICU和住院时间方面无显著差异。患者的事后亚组分析（基线肌酐水平>1.4 mg/dL [120 μ mol/L]）显示，与安慰剂组相比，N-乙酰半胱氨酸组发生术后肾功能不全的患者较少，（25.0%对37.1%;结论N-乙酰半胱氨酸不能预防接受CPB CABG手术的高危患者术后肾功能不全、干预、并发症或死亡率。需要进一步的研究来识别有术后肾脏事件风险的冠状动脉旁路移植术患者、肾功能不全的有效标志物，并建立与重要临床结果相关的肾脏阈值。
Context Renal dysfunction is a complication of coronary artery bypass graft (CABG) surgery performed with cardiopulmonary bypass (CPB) that is associated with increased morbidity and mortality. N-acetylcysteine, an antioxidant and vasodilator, counteracts renal ischemia and hypoxia.Objective To determine whether perioperative intravenous (IV) N-acetylcysteine preserves renal function in high-risk patients undergoing CABG surgery with CPB compared with placebo.Design, Setting, and Patients Randomized, quadruple blind, placebo-controlled trial (October 2003-September 2004) in operating rooms and general intensive care units (ICUs) of 2 Ontario tertiary care centers. The 295 patients required elective or urgent CABG and had at least 1 of the following: preexisting renal dysfunction, at least 70 years old, diabetes mellitus, impaired left ventricular function, or undergoing concomitant valve or redo surgeryInterventions Patients received 4 (2 intraoperative and 2 postoperative) doses of IV N-acetylcysteine (600 mg) (n = 148) or placebo (n = 147) over 24 hours.Main Outcome Measures The primary outcome was the proportion of patients developing postoperative renal dysfunction, defined by an increase in serum creatinine level greater than 0.5 mg/dL (44 mu mol/L) or a 25% increase from baseline within the first 5 postoperative days. Secondary outcomes included postoperative interventions and complications, the requirement for renal replacement therapy (RRT), adverse events, hospital mortality, and ICU and hospital length of stay.Results There was no difference in the proportion of patients with postoperative renal dysfunction (29.7% vs 29.0%, P=.89; relative risk [RR], 1.03 [95% confidence interval {CI}, 0.72-1.46]) in the N-acetylcysteine and placebo groups, respectively. We noted nonsignificant differences in postoperative interventions and complications, the need for RRT (0.7% vs 2.1 %; P=37), total (6.1% vs 9.6%; P=.26) and serious adverse events, hospital mortality (3.4% vs 2.7%; P>39), and ICU and hospital length of stay between the N-acetylcysteine and placebo groups. A post hoc subgroup analysis of patients (baseline creatinine level >1.4 mg/dL [120 mu mol/L]) showed a nonsignificant trend toward fewer patients experiencing postoperative renal dysfunction in the N-acetylcysteine group compared with the placebo group (25.0% vs 37.1 %; P=.29).Conclusions N-acetylcysteine did not prevent postoperative renal dysfunction, interventions, complications, or mortality in high-risk patients undergoing CABG surgery with CPB. Further research is required to identify CABG patients at risk for postoperative renal events, valid markers of renal dysfunction, and to establish renal thresholds associated with important clinical outcomes.