Pathophysiology of postoperative delirium in older patients

描述（由申请人提供）：由于其患病率、复杂的病因学和对患者的潜在严重影响，谵妄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、不良的功能结局和较高的医疗费用相关。被称为术后认知下降（POCD）的较轻度急性认知变化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，但尚未确定预防性治疗。患者发生老年综合征（如谵妄或POCD）的风险取决于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）。在本提案中，我们将使用一种策略，认识到基线脆弱性增加老年患者术后认知结局不良的风险，并以疾病为导向，以最大限度地减少术后谵妄和POCD的诱发因素。这一策略是由我们先前的研究结果指导的，这些研究结果表明，术后谵妄与疼痛的严重程度密切相关，并且可能与阿片类镇痛药（术后疼痛的常用治疗方法）的中枢神经系统效应有关。在我们的框架中，谵妄风险的存在，如高龄、认知障碍、抑郁和术前医疗负担，使患者更容易受到疼痛和术后阿片类药物诱发事件的不良影响。本研究的目的是确定是否干预，旨在减少已知的因素，沉淀谵妄和POCD导致术后认知功能的改善，在脆弱的老年患者。基于我们的初步研究，我们发现了一种有希望的干预措施，包括使用非阿片类药物的连续治疗来减少术后疼痛和阿片类药物的消耗，最终导致术后谵妄的发生率降低。我们将进行一项双盲、安慰剂对照研究，使用加巴喷丁作为辅助药物治疗接受非心脏手术的老年患者的术后疼痛。我们提出的研究将检验这一假设，即通过术后强化疼痛管理，可以降低那些容易经历这些结局的患者的谵妄和POCD发生率。如果我们的假设被证明是正确的，不仅有助于更好地了解谵妄和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，有望改善功能结局和生活质量。我们的建议符合国家老龄问题研究所的主要使命，即减轻老年人的疾病和残疾负担。公共卫生相关性：我们的建议旨在调查谵妄和POCD的诱发因素及其与基线脆弱性的相互作用，以便为老年手术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问题研究所的主要使命，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.