OBJECTIVE To investigate whether remote ischaemic preconditioning (RIPC) prevents myocardial injury in patients undergoing hip fracture surgery. DESIGN Phase II, multicentre, randomised, observer blinded, clinical trial. SETTING Three Danish university hospitals, 2015-17. PARTICIPANTS 648 patients with cardiovascular risk factors undergoing hip fracture surgery. 286 patients were assigned to RIPC and 287 were assigned to standard practice (control group). INTERVENTION The RIPC procedure was initiated before surgery with a tourniquet applied to the upper arm and consisted of four cycles of forearm ischaemia for five minutes followed by reperfusion for five minutes. MAIN OUTCOME MEASURES The original primary outcome was myocardial injury within four days of surgery, defined as a peak plasma cardiac troponin I concentration of 45 ng/L or more caused by ischaemia. The revised primary outcome was myocardial injury within four days of surgery, defined as a peak plasma cardiac troponin I concentration of 45 ng/L or more or high sensitive troponin I greater than 24 ng/L (the primary outcome was changed owing to availability of testing). Secondary outcomes were peak plasma troponin I and total troponin I release during the first four days after surgery (cardiac and high sensitive troponin I), perioperative myocardial infarction, major adverse cardiovascular events, and all cause mortality within 30 days of surgery, length of postoperative stay, and length of stay in the intensive care unit. Several planned secondary outcomes will be reported elsewhere. RESULTS 573 of the 648 randomised patients were included in the intention-to-treat analysis (mean age 79 (SD 10) years; 399 (70%) women). The primary outcome occurred in 25 of 168 (15%) patients in the RIPC group and 45 of 158 (28%) in the control group (odds ratio 0.44, 95% confidence interval 0.25 to 0.76; P=0.003). The revised primary outcome occurred in 57 of 286 patients (20%) in the RIPC group and 90 of 287 (31%) in the control group (0.55, 0.37 to 0.80; P=0.002). Myocardial infarction occurred in 10 patients (3%) in the RIPC group and 21 patients (7%) in the control group (0.46, 0.21 to 0.99; P=0.04). Statistical power was insufficient to draw firm conclusions on differences between groups for the other clinical secondary outcomes (major adverse cardiovascular events, 30 day all cause mortality, length of postoperative stay, and length of stay in the intensive care unit). CONCLUSIONS RIPC reduced the risk of myocardial injury and infarction after emergency hip fracture surgery. It cannot be concluded that RIPC overall prevents major adverse cardiovascular events after surgery. The findings support larger scale clinical trials to assess longer term clinical outcomes and mortality. TRIAL REGISTRATION ClinicalTrials.gov NCT02344797.

中文翻译：

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远程缺血预处理对紧急髋部骨折手术中心肌损伤的影响（PIXIE试验）：II期随机临床试验。

目的探讨远端缺血预处理（RIPC）是否可以预防髋部骨折手术患者的心肌损伤。设计第二阶段，多中心，随机，观察者不知情，临床试验。设置三所丹麦大学医院，2015-17年。参与者648名患有心血管危险因素的患者正在接受髋部骨折手术。286名患者被分配到RIPC，287名患者被分配到标准实践（对照组）。干预RIPC手术在手术前开始，将止血带套在上臂，包括前四个周期的前肢缺血5分钟，然后再灌注5分钟。主要观察指标最初的主要观察指标是手术后四天内的心肌损伤，定义为缺血导致的血浆心肌肌钙蛋白I峰值浓度为45 ng / L或更高。修改后的主要结局是手术后四天内的心肌损伤，定义为血浆肌钙蛋白I峰值浓度为45 ng / L或更高或高敏感性肌钙蛋白I高于24 ng / L（主要结局因可使用测试）。次要结果是术后头四天血浆心肌肌钙蛋白I和总肌钙蛋白I释放高峰（心脏和高敏感性肌钙蛋白I），围手术期心肌梗塞，重大不良心血管事件，并在手术后30天内引起死亡率，术后时间长短。住院时间以及在重症监护室的住院时间。几个计划的次要结果将在其他地方报告。结果648名随机分组的患者中有573名被纳入意向性治疗分析（平均年龄79岁（SD 10）岁； 399名女性（70％））。主要结果发生在RIPC组的168名患者中的25名（15％）和对照组的158名患者中的45名（28％）中（赔率比0.44，95％置信区间0.25至0.76； P = 0.003）。修订后的主要结局发生在RIPC组的286例患者中的57例（20％）和对照组的287例中的90例（31％）中（0.55，0.37至0.80; P = 0.002）。RIPC组有10例患者（3％）发生心肌梗塞，而对照组为21例（7％）（0.46，0.21至0.99; P = 0.04）。统计能力不足以就其他临床次要结局（主要不良心血管事件，30天均导致死亡率，术后住院时间，和在重症监护室的停留时间）。结论RIPC减少了紧急髋部骨折手术后发生心肌损伤和梗塞的风险。不能得出结论，RIPC总体上可以预防术后严重的不良心血管事件。这些发现支持更大规模的临床试验，以评估长期的临床结果和死亡率。试验注册ClinicalTrials.gov NCT02344797。