Estradiol For Neurocognitive Dysfunction After CABG

与男性相比，接受冠状动脉旁路移植(CABG)手术的女性具有更高的手术死亡率、更长的住院时间和更高的住院费用。女性外科手术的高发病率和高死亡率很大一部分是由于围手术期的神经损伤。在各种体外和动物实验性中风模型中，雌激素一直被证明可以减少神经损伤的程度。这些数据有力地表明，老年女性围手术期神经系统并发症的风险较高可能与她们的雌激素缺乏状态有关。在这项随机的安慰剂对照研究中，我们将检验这样一个假设，即绝经后妇女围手术期补充雌激素可降低CABG术后神经损伤的风险。334名接受冠脉搭桥手术的女性将被前瞻性地随机分配，从手术前一天开始，以双盲方式服用17β-雌二醇或安慰剂，手术后持续5天。患者将接受神经认知功能障碍的评估，这是心脏手术中神经损伤的最常见表现。分别于术前1~2天、术后4~6周、术后6个月进行神经认知测试。与安慰剂相比，接受17β-雌二醇术后4至6周的女性的主要终点将是神经认知功能。我们还将评估术后6个月认知功能和生活质量指标中认知功能下降的重要性，以及围手术期17β-雌二醇治疗是否改善了这些结果。这项研究的结果将评估一种易于实施的疗法在改善绝经后妇女冠状动脉旁路移植术后神经学结果和生活质量方面的有效性和安全性。

Women undergoing coronary artery bypass graft (CABG) surgery have a higher operative mortality rate, longer hospitalizations, and higher hospital cost compared with men. A large proportion of this excess morbidity and mortality of surgery for women is due to perioperative neurologic injury. Estrogens have been consistently shown to reduce the extent of neurologic injury in a variety of in vitro and animal experimental stroke models. These data together strongly suggest that the higher risk for perioperative neurologic complications for elderly women may relate to their estrogen deficient state. In this randomized, placebo controlled study, we will test the hypothesis that perioperative estrogen replacement in postmenopausal women reduces the risk for neurologic injury after CABG surgery. Three hundred thirty four women undergoing CABG surgery will be prospectively randomized to receive either 17beta-estradiol or placebo in a double-blind fashion beginning the day before surgery and continued for 5 days after surgery. Patients will be assessed for neurocognitive dysfunction, the most common manifestation of neurologic injury from cardiac surgery. Neurocognitive testing will be performed 1-2 days before surgery, 4 to 6 weeks postoperatively, and 6- months after surgery. The primary endpoint will be neurocognitive function 4 to 6 weeks after surgery for women who received 17beta- estradiol compared with placebo perioperatively. We will also evaluate for the importance of postoperative cognitive decline on measures of cognitive function and quality of life 6 months after surgery and whether perioperative 17beta-estradiol treatment improves these latter outcomes. The results of this study will evaluate the efficacy and safety of an easily implemented therapy for improving neurologic outcome and quality of life after CABG surgery for postmenopausal women.