NARCOTICS AND THE AGED SURGICAL PATIENT

麻醉品与老年手术患者

• 批准号: 3115236
• 负责人: DONALD R STANSKI
• 金额: $ 8.47万
• 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 1986-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3115236
• 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.

麻醉镇痛药在围手术期中具有重要作用 手术患者的管理 - 术前为催眠药， 术中为唯一或辅助麻醉剂，并在术后进行 缓解疼痛。 随着年龄的增长，有很好的证明减少了 麻醉剂量要求。 因为麻醉品具有狭窄的治疗方法 索引和与年龄相关的剂量需求变化，安全使用 老年人的麻醉品在临床上可能会变得困难。 这项研究将开发一个与 吗啡或芬太尼血浆浓度达到麻醉效果的程度 在大脑上。 麻醉诱导的脑电图减慢 （EEG）将用作药物效应的无创，连续测量 OT估计患者的大脑敏感性。 这 吗啡和芬太尼的药代动力学将在手术中确定 年龄在20-90岁之间的患者，以查看年龄的增长及其 生理改变会影响药代动力学变量，例如 蛋白质结合程度，麻醉分布的速率或程度 从身体中消除的速度。 吗啡的药效学 芬太尼将在20-90岁的手术患者中确定 使用上面指示的麻醉脑作用的脑电图指标。 药效学建模将用于关联麻醉血浆 药物诱导的脑电图的浓度发生了变化，以确定是否衰老 改变（大脑灵敏度）的发作，程度和持续时间 吗啡/芬太尼CNS效应。 上述研究将用于为更好的科学指南提供 老年手术患者中吗啡和芬太尼的临床使用。 经过 确定改变的麻醉剂量要求的机制 人类的年龄增加，随后的动物和体内药理学可以更多 专门针对获得生化和分子解释 衰老对麻醉反应的影响。