IV ANESTHETIC DISPOSITION IN THE AGED HEMODYNAMIC STATE

IV 老年血流动力学状态下的麻醉处置

• 批准号: 3115233
• 负责人: DONALD R STANSKI
• 金额: $ 19.13万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-01-01 至 1990-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3115233
• 关键词: aging; anesthesia complication; anesthetics; brain metabolism; dosage; drug metabolism; electroencephalography; fentanyl; general anesthesia; human middle age (35-64); human old age (65+); human subject; mathematical model; morphine; narcotics; nitrous oxide; pharmacokinetics; postoperative state; preoperative state; sedative /hypnotic; surgery; young adult human (21-34)

The narcotic analgesics have an important role in the perioperative management of surgical patients - preoperatively as hypnotics, intraoperatively as sole or adjuvant anesthetics and postoperatively for pain relief. With increasing age, there is a well demonstrated decrease of the narcotic dose requirement. Because narcotics have a narrow therapeutic index and an age-related change of dose requirement, the safe use of narcotics in the aged can become clinically difficult. This research will develop a pharmacodynamic model that relates the morphine or fentanyl plasma concentration to the degree of narcotic effect on the brain. The narcotic-induced slowing of the electroencephalogram (EEG) will be used as a noninvasive, continuous measure of the drug effect ot estimate an individual patient's brain sensitivity. The pharmacokinetics of morphine and fentanyl will be determined in surgical patients aged 20-90 years old to see if increasing age and its physiological alterations effect pharmacokinetic variables, such as the degree of protein binding, the rate or extent of narcotic distribution or the rate of elimination from the body. The pharmacodynamics of morphine and fentanyl will be determined in surgical patients, aged 20-90 years using the above indicated EEG measures of narcotic brain effect. Pharmacodynamic modelling will be used to relate the narcotic plasma concentrations to the drug induced EEG changed and to determine if aging alters the onset, degree of (brain sensitivity) and duration of morphine/fentanyl CNS effect. The above research will be used to provide better scientific guidelines for the clinical use of morphine and fentanyl in the aged surgical patient. By determining the mechanism of the altered narcotic dose requirement with increasing age in man, subsequent animal and in vivo pharmacology can more specifically be directed to obtain biochemical and molecular explanations of the effects of aging on narcotic response.

麻醉性镇痛药在围手术期中起着重要作用 手术病人的管理-手术前作为催眠药， 术中作为单一或辅助麻醉剂，术后用于 止痛药。随着年龄的增长，有很好的证据表明 麻醉剂量要求。因为麻醉剂的治疗作用很小 指数和与年龄相关的剂量需求变化，安全使用 老年人的毒品可能会成为临床上的难题。 这项研究将开发一个药效学模型，将 吗啡或芬太尼血浆浓度对麻醉效果的影响 在大脑上。麻醉剂引起的脑电减慢 (EEG)将被用作一种无创的、连续的药物效果测量 不能估计单个病人的大脑敏感度。这个 手术中将测定吗啡和芬太尼的药代动力学 年龄在20-90岁的患者是否会增加年龄及其影响 生理变化影响药代动力学变量，如 蛋白质结合的程度，麻醉剂分布的速度或程度或 从体内排出的速率。吗啡的药效学研究 芬太尼将在20-90岁的外科患者中进行检测 利用以上所示的脑电测量麻醉性脑效应。 药效学模型将被用来关联麻醉性血浆 以药物浓度变化诱发脑电变化并判断是否老化 改变(脑敏感)的发病、程度和持续时间 吗啡/芬太尼中枢神经系统效应。 上述研究将为更好的科学指导 吗啡和芬太尼在老年手术患者中的临床应用通过 确定改变麻醉药品剂量要求的机制 随着人类年龄的增长，随后的动物和体内药理学可以更多 特别是被指示获得生化和分子解释 衰老对麻醉剂反应的影响。