Pathophysiology of postoperative delirium in older patients

描述（由申请人提供）：谵妄由于其普遍性、复杂的病因和对患者潜在的严重影响，是老年医学实践面临的主要挑战。术后谵妄与较长的住院时间、较差的功能预后和较高的医疗费用有关。一种较轻的急性认知变化称为术后认知衰退（POCD），与日常功能的长期下降有关。尽管术后谵妄和POCD的患病率和临床重要性，预防治疗尚未确定。患者发生老年综合征（如谵妄或POCD）的风险是由易患基线脆弱性和暴露于导致患者预后不良的因素（如疼痛或与手术相关的新药物）决定的。在本提案中，我们将采用一种策略，认识到基线脆弱性会增加老年患者术后认知结果不良的风险，并结合以疾病为导向的重点，最大限度地减少术后谵妄和POCD的诱发因素。我们之前的研究结果表明，术后谵妄与疼痛的严重程度密切相关，可能与阿片类镇痛药的中枢神经系统作用有关，阿片类镇痛药是术后疼痛的常用治疗方法。在我们的研究框架中，高龄、认知障碍、抑郁和术前医疗负担等谵妄风险的存在使患者更容易遭受疼痛和术后阿片类药物的不良反应。本研究的目的是确定旨在减少导致谵妄和POCD的已知因素的干预是否会改善易感老年患者的术后认知结果。根据我们的初步研究，我们发现了一种有希望的干预措施，包括使用辅助的非阿片类药物治疗来减少术后疼痛和阿片类药物的消耗，最终减少了术后谵妄的发生率。我们将进行一项双盲、安慰剂对照研究，使用加巴喷丁作为治疗非心脏手术老年患者术后疼痛的附加药物。我们提出的研究将检验这样一种假设，即在那些容易经历这些结果的患者中，通过术后强化疼痛管理可以降低谵妄和POCD的发生率。我们的假设如果被证明是正确的，不仅有助于更好地理解谵妄和POCD的诱发因素及其与基线脆弱性的相互作用，而且还将为老年手术患者的管理提供新的方向，希望能改善功能结果和生活质量。我们的建议符合国家老龄研究所的主要使命，即减轻老年人的疾病和残疾负担。公共卫生相关性：我们的建议旨在探讨谵妄和POCD的诱发因素及其与基线脆弱性的相互作用，为老年外科患者的管理提供新的方向。我们的研究结果有望改善这些患者的功能结局和生活质量。我们的建议符合国家老龄研究所的主要使命，即减轻老年人的疾病和残疾负担。

DESCRIPTION (provided by applicant): Delirium is a major challenge facing geriatric practice due to its prevalence, complex etiology, and potential severe impact on patients. Postoperative delirium is associated with longer hospital stays, poor functional outcomes, and higher healthcare costs. A milder form of acute cognitive change known as postoperative cognitive decline (POCD) is associated with long term declines in daily functioning. Despite the prevalence and clinical importance of postoperative delirium and POCD, a preventive therapy has not been identified. Patients' risk for the development of geriatric syndromes (such as delirium or POCD) is determined by predisposing baseline vulnerabilities and exposure to factors that precipitate poor patient outcomes (such as pain or new medications associated with surgery). In this proposal, we will use a strategy recognizing that baseline vulnerabilities increase geriatric patients risk for poor postoperative cognitive outcomes in conjunction with a disease-oriented focus to minimize the precipitating factors of postoperative delirium and POCD. This strategy is guided by our previous findings demonstrating that postoperative delirium is strongly related to the severity of pain, and probably to the central nervous system effects of opioid analgesics, the usual therapy for postoperative pain. In our framework, the presence of risks for delirium such as advanced age, cognitive impairment, depression, and preoperative medical burden make patients more vulnerable to experiencing adverse effects from the precipitating events of pain and postoperative opioids. The goal of this research is to determine whether an intervention aimed at reducing factors known to precipitate delirium and POCD leads to improvement in postoperative cognitive outcomes in the vulnerable geriatric patients. Based on our pilot study, we found a promising intervention involving the use of an adjunctive non-opioid therapy to reduce postoperative pain and the consumption of opioids, which ultimately resulted in a reduction of the incidence of postoperative delirium. We will conduct a double blind, placebo-controlled study using gabapentin, as an add-on agent in the treatment of postoperative pain in elderly patients undergoing non-cardiac surgery. Our proposed study will test the hypothesis that rates of delirium and POCD can be reduced in those who are vulnerable to experiencing these outcomes through intensive pain management after surgery. Our hypothesis if proven true will contribute not only to a better understanding of the precipitating factors of delirium and POCD and their interactions with baseline vulnerabilities, but will also provide new directions for management of the older surgical patients, hopefully leading to improved functional outcomes and quality of life. Our proposal meets with the major mission of the National Institute of Aging to reduce the burdens of illness and disability in the elderly. PUBLIC HEALTH RELEVANCE: Our proposal aims to investigate the precipitating factors of delirium and POCD and their interactions with baseline vulnerabilities, in order to provide new directions for management of the older surgical patients. Our results will hopefully lead to improved functional outcomes and quality of life of these patients. Our proposal meets with the major mission of the National Institute of Aging to reduce the burden of illness and disability in the elderly.