ANESTHESIA/ANALGESIA EFFECTS ON PERIOPERATIVE HEMOSTASIS

麻醉/镇痛对围手术期止血的影响

• 批准号: 2770994
• 负责人: BRIAN A ROSENFELD
• 金额: $ 11.73万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-09-01 至 1999-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2770994
• 关键词: analgesia; anesthesia complication; angiotensin II; arginine vasopressin; cardiovascular surgery; cortisol; electrocardiography; epidural anesthesia; epinephrine; fentanyl; fibrinogen; fibrinolysis; general anesthesia; glucagon; hemostasis; human subject; intravenous anesthesia; local anesthesia; local anesthetics; platelet aggregation; postoperative complications; postoperative state; preoperative state; prothrombin; thrombosis

Surgery causes changes in hemostatic function that are associated with postoperative arterial and venous thrombotic complications. These complications cause significant morbidity and mortality. Inasmuch as perioperative changes in coagulation, fibrinolysis and platelet function appear to be modulated by the type of intraoperative anesthesia and postoperative analgesia, the potential exists for decreasing the incidence of these complications. This investigation explores the relationship between perioperative changes in hemostatic function and postoperative arterial thrombotic complications, and seeks to define the optimal anesthetic/analgesic regimen. We propose two clinical studies to answer the specific aims. The first is a double-blind clinical trial of 240 patients undergoing abdominal aortic surgery. Subjects will be randomized to one of four groups to receive either regional supplemented general anesthesia or general anesthesia alone during surgery, and either intravenous narcotic or epidural local anesthetic patient controlled analgesia postoperatively. All aspects of perioperative management will be standardized by protocol to insure consistent clinical care. Data collection will include 96 hours of continuous holter monitoring, serial ECG's, physical examinations and measurement of cardiac isoenzymes to monitor clinically important thrombotic events. Fibrinogen, prothrombin fragment (F1.2), fibrinolysis, and platelet reactivity will be followed throughout the perioperative period to assess hemostasis. The second is a double-blind study to evaluate the modulating effects of a local anesthetic and narcotic on stress hormone-induced changes in hemostasis. Twenty normal volunteers will receive three infusions (24-hour) of an epinephrine-cortisol-glucagon-vasopressin-angiotensin-II cocktail, in combination with intravenous bupivacaine, fentanyl, or placebo. This infusion paradigm increases circulating measures of hemostatic function and will enable us to determine whether bupivacaine and fentanyl modulate hemostasis. Whole blood will be assayed at baseline, 2, 8 and 24 hours for complete blood count, fibrinogen, platelet reactivity and fibrinolysis. With completion of these two studies, we hope to 1) determine the relationship between perioperative hemostatic function and postoperative arterial thrombotic complications, 2) elucidate the modulating effects of anesthetics and analgesics on hemostatic function and the incidence of postoperative arterial thrombotic complications, and 3) define an optimal perioperative regimen.

手术引起止血功能的变化， 术后动脉和静脉血栓形成并发症。 这些 并发症导致显著的发病率和死亡率。只要 围手术期凝血、纤溶和血小板功能的变化 似乎受到术中麻醉类型的调节， 术后镇痛，存在降低发生率的潜力 这些并发症。 这项调查探讨了 围手术期止血功能变化与术后 动脉血栓并发症，并寻求确定最佳的 麻醉/镇痛方案。我们提出两项临床研究来回答 具体目标。第一个是240人的双盲临床试验 接受腹主动脉手术的患者。受试者将被随机分配 四个小组之一，接受区域补充一般 麻醉或全身麻醉，以及 静脉麻醉或硬膜外局部麻醉病人控制 术后镇痛。围手术期管理的各个方面都将 通过协议标准化，以确保一致的临床护理。 数据 采集将包括96小时的连续霍尔特监测， ECG、体格检查和心脏同工酶测量， 监测临床重要血栓形成事件。纤维蛋白原，凝血酶原 将随访F1.2片段、纤维蛋白溶解和血小板反应性 以评估止血情况。 二是 一项双盲研究，以评估局部 麻醉药及麻醉药对应激性止血作用的影响。 20名正常志愿者将接受三次（24小时）的 肾上腺素-皮质醇-胰高血糖素-血管加压素-血管紧张素-II混合物， 与静脉内布比卡因、芬太尼或安慰剂组合。这 输注模式增加了止血功能的循环指标 这将使我们能够确定布比卡因和芬太尼是否能调节 止血。将在基线、2、8和24小时测定全血， 全血细胞计数、纤维蛋白原、血小板反应性和纤维蛋白溶解。 在完成这两项研究后，我们希望1）确定 围手术期止血功能与术后 动脉血栓形成并发症，2）阐明的调节作用， 麻醉药和镇痛药对止血功能的影响以及 术后动脉血栓形成并发症，和3）定义最佳的 围手术期方案。