NARCOTICS AND THE AGED SURGICAL PATIENT

麻醉性镇痛药在围手术期有重要作用 手术患者的管理-术前作为催眠药， 术中作为唯一或辅助麻醉剂，术后形成 缓解疼痛。 随着年龄的增长， 麻醉剂剂量要求。 因为麻醉剂的治疗范围很窄 指数和年龄相关的剂量需求变化，安全使用 老年人使用麻醉剂在临床上可能会变得困难。 本研究将开发一种药效学模型， 吗啡或芬太尼血浆浓度与麻醉作用程度 在大脑上。 麻醉剂引起的脑电图减慢 (EEG)将作为一种非侵入性的，连续的药物效果的测量方法， 无法估计单个病人的大脑敏感度 的 吗啡和芬太尼的药代动力学将在外科手术中测定。 年龄在20-90岁之间的患者，看看年龄的增加及其 生理改变影响药代动力学变量，例如 蛋白质结合的程度，麻醉剂分布的速率或程度，或 从体内排出的速度 吗啡的药效学 芬太尼将在20-90岁的手术患者中测定 使用上述麻醉剂脑效应的EEG测量。 药效学建模将用于将麻醉药血浆 药物诱导的EEG浓度改变，并确定是否老化 改变（大脑敏感性）的发作、程度和持续时间， 吗啡/芬太尼CNS效应。 上述研究将用于提供更好的科学指导方针， 吗啡和芬太尼在老年外科病人中的临床应用 通过 确定改变的麻醉剂剂量需求的机制， 随着人类年龄的增长，随后的动物和体内药理学可以更多地 特别是为了获得生物化学和分子学解释 衰老对麻醉反应的影响

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.