Burton Deborah A, Nicholson Grainne, Hall George M
Department of Anaesthesia, St George's Hospital Medical School, London, England.
Drugs Aging. 2004;21(4):229-42. doi: 10.2165/00002512-200421040-00002.
Neurodegenerative diseases are increasingly common in elderly patients, who present a particular anaesthetic challenge. The majority of people over the age of 70 years have some degree of cerebral atrophy. The pathogenesis of neurodegenerative diseases is due to alterations in the transport, degradation and aggregation of proteins. Alterations in physiology that occur with advancing age affect both the pharmacokinetics and pharmacodynamics of drugs used in the elderly. Changes in pharmacokinetics result in either increased or reduced drug concentrations depending on the variable contributions of absorption, metabolism and elimination. The distribution of a drug depends on its protein binding, cardiac output and blood volume, which are all altered in the elderly. Metabolism and excretion of drugs are also affected due to changes in hepatic and renal mass and blood flow in the elderly. A number of drugs are used in neurodegenerative disorders including antidepressants, benzodiazepines, antipsychotics, acetylcholinesterase inhibitors and levodopa. Polypharmacy is a common problem, which can lead to adverse drug interactions and an exacerbation of dementia. Levodopa, bromocriptine and tricyclic antidepressants are known to cause orthostatic hypotension in patients with neurodegenerative disease. Elderly patients are liable to excessive sedation from benzodiazepines in both the pre- and postoperative period; therefore these drugs should be prescribed in low doses. For induction of general anaesthesia propofol is a suitable agent in patients with neurodegenerative disease due to its rapid metabolism, but may not be suitable in patients with Parkinson's disease as it can induce spontaneous involuntary movements. Volatile inhalational agents should be administered carefully in the elderly, as they are more sensitive to the depressant cerebral and cardiovascular effects. Levodopa should be avoided in conjunction with halothane, which sensitises the heart to catecholamines. Co-administration of monoamine oxidase inhibitors and opioids should be avoided as it can cause agitation, muscular rigidity, sweating and hyperpyrexia. If an anticholinergic agent is required, then glycopyrronium bromide is the drug of choice in this group of patients, as it does not cross the blood brain barrier. Patients should continue to take their usual medications in hospital and do not let the change in routine alter the times at which treatments are administered. This is particularly relevant to the timing of levodopa in Parkinson's disease, as missed treatment can be detrimental. Regional anaesthesia may, however, have significant advantages in patients with Parkinson's disease, who can continue to take oral levodopa preoperatively, during surgery, if required, and early in the postoperative period. Anti-emetic drugs such as phenothiazines, butyrophenones and metoclopramide should be used carefully in the postoperative period in these patients as their antidopaminergic effects may induce or exacerbate parkinsonian effects.
神经退行性疾病在老年患者中越来越常见,这给麻醉带来了特殊挑战。大多数70岁以上的人都有一定程度的脑萎缩。神经退行性疾病的发病机制是由于蛋白质的运输、降解和聚集发生改变。随着年龄增长而出现的生理变化会影响老年人所用药物的药代动力学和药效学。药代动力学的变化会导致药物浓度升高或降低,这取决于吸收、代谢和排泄的不同作用。药物的分布取决于其蛋白结合、心输出量和血容量,而这些在老年人中都会发生改变。由于老年人肝脏和肾脏质量及血流量的变化,药物的代谢和排泄也会受到影响。神经退行性疾病会使用多种药物,包括抗抑郁药、苯二氮䓬类药物、抗精神病药、乙酰胆碱酯酶抑制剂和左旋多巴。多重用药是一个常见问题,可能导致药物不良反应相互作用并加重痴呆。已知左旋多巴、溴隐亭和三环类抗抑郁药会使神经退行性疾病患者发生体位性低血压。老年患者在术前和术后都容易因苯二氮䓬类药物而出现过度镇静;因此,这些药物应低剂量使用。对于全身麻醉诱导,丙泊酚因其代谢迅速,是神经退行性疾病患者的合适药物,但可能不适用于帕金森病患者,因为它可诱发自发性不自主运动。挥发性吸入麻醉剂在老年人中应谨慎使用,因为他们对其对大脑和心血管的抑制作用更敏感。应避免左旋多巴与氟烷合用,因为氟烷会使心脏对儿茶酚胺敏感。应避免单胺氧化酶抑制剂与阿片类药物合用,因为这可能导致激动、肌肉强直、出汗和高热。如果需要使用抗胆碱能药物,那么溴化格隆溴铵是这类患者的首选药物,因为它不会穿过血脑屏障。患者在住院期间应继续服用常用药物,不要因日常安排的改变而改变治疗给药时间。这对于帕金森病患者服用左旋多巴的时间尤为重要,因为漏服治疗可能有害。然而,区域麻醉对帕金森病患者可能具有显著优势,这类患者在术前、手术期间(如有需要)以及术后早期都可以继续口服左旋多巴。在这些患者术后应谨慎使用吩噻嗪类、丁酰苯类和甲氧氯普胺等止吐药物,因为它们的抗多巴胺能作用可能诱发或加重帕金森症状。