Postoperative Neurocognitive Dysfunction in Patients Undergoing Cardiac Surgery after Remote Ischemic Preconditioning: A Double-Blind Randomized Controlled Pilot Study

Background
Remote ischemic preconditioning (RIPC) has been shown to enhance the tolerance of remote organs to cope with a subsequent ischemic event. We hypothesized that RIPC reduces postoperative neurocognitive dysfunction (POCD) in patients undergoing complex cardiac surgery.
Methods
We conducted a prospective, randomized, double-blind, controlled trial including 180 adult patients undergoing elective cardiac surgery with cardiopulmonary bypass. Patients were randomized either to RIPC or to control group. Primary endpoint was postoperative neurocognitive dysfunction 5–7 days after surgery assessed by a comprehensive test battery. Cognitive change was assumed if the preoperative to postoperative difference in 2 or more tasks assessing different cognitive domains exceeded more than one SD (1 SD criterion) or if the combined Z score was 1.96 or greater (Z score criterion).
Results
According to 1 SD criterion, 52% of control and 46% of RIPC patients had cognitive deterioration 5–7 days after surgery (p = 0.753). The summarized Z score showed a trend to more cognitive decline in the control group (2.16±5.30) compared to the RIPC group (1.14±4.02; p = 0.228). Three months after surgery, incidence and severity of neurocognitive dysfunction did not differ between control and RIPC. RIPC tended to decrease postoperative troponin T release at both 12 hours [0.60 (0.19–1.94) µg/L vs. 0.48 (0.07–1.84) µg/L] and 24 hours after surgery [0.36 (0.14–1.89) µg/L vs. 0.26 (0.07–0.90) µg/L].
Conclusions
We failed to demonstrate efficacy of a RIPC protocol with respect to incidence and severity of POCD and secondary outcome variables in patients undergoing a wide range of cardiac surgery. Therefore, definitive large-scale multicenter trials are needed.
Trial Registration
ClinicalTrials.gov NCT00877305

背景
已有研究表明，远程缺血预处理（Remote ischemic preconditioning, RIPC）可增强远端器官对后续缺血事件的耐受能力。本研究假设，远程缺血预处理可降低接受复杂心脏手术患者的术后神经认知障碍（Postoperative neurocognitive dysfunction, POCD）发生率。
方法
本研究开展了一项前瞻性、随机、双盲对照试验，共纳入180例拟接受体外循环下择期心脏手术的成年患者。患者被随机分配至远程缺血预处理组或对照组。主要终点为术后5~7天通过综合测试组合评估的术后神经认知障碍情况。若评估不同认知域的2项及以上任务的术前-术后差值超过1个标准差（1 SD标准），或合并Z值≥1.96（Z值标准），则认定存在认知改变。
结果
按照1 SD标准，术后5~7天时对照组52%的患者及远程缺血预处理组46%的患者出现认知功能恶化（p=0.753）。合并Z值结果显示，对照组（2.16±5.30）的认知下降趋势较远程缺血预处理组（1.14±4.02）更为显著，但差异无统计学意义（p=0.228）。术后3个月时，两组患者的神经认知障碍发生率及严重程度均无显著差异。远程缺血预处理可使术后12小时[0.60（0.19~1.94）µg/L vs. 0.48（0.07~1.84）µg/L]及术后24小时[0.36（0.14~1.89）µg/L vs. 0.26（0.07~0.90）µg/L]的肌钙蛋白T释放量呈降低趋势。
结论
本研究未能证实，针对接受各类心脏手术的患者，远程缺血预处理方案可降低术后神经认知障碍的发生率与严重程度，也未改善其次要结局指标。因此，仍需开展大规模多中心的确证性试验。
试验注册
ClinicalTrials.gov NCT00877305