Psychoactive Medications: Associations with Delirium Persistance vs Resolution

描述(申请人提供)：精神错乱(急性精神错乱)经常使老年人的急性疾病复杂化，对健康造成短期和长期的不利影响。近年来，在定义和评估妄想，描述其在几个临床人群中的发病率和流行率，确定其危险因素，甚至制定预防策略方面，都取得了实质性的进展。然而，一旦出现精神错乱，人们对最佳管理仍知之甚少。最具争议的领域之一是在精神错乱患者中使用精神活性药物。精神活性药物在这一人群中经常使用，要么是为了治疗精神错乱本身，要么是为了治疗睡眠障碍和疼痛等并发症。虽然在确定药物是偶发性精神错乱的危险因素方面取得了进展，但药物在已建立的精神错乱中的使用及其在其持久性与解决性方面的作用还不太清楚。我们的建议涉及对PI最近完成的两项由NIH资助的精神错乱研究中收集的数据进行二次分析。第一项名为减少老年急性后遗症患者妄想的试验，招募了457名新入院的急性后护理机构的神志不清患者。第二项是心脏手术后的思考和恢复(TRACS)，招募了247名年龄在60岁及以上的在三个医疗中心接受心脏手术的患者，其中111人出现了精神错乱。加在一起，他们代表了有史以来参与研究的两个最大的精神错乱受试者的预期队列。除了在这些研究中进行系列精神错乱评估外，我们还完成了正式的医疗记录审查，包括精神活性药物管理的详细信息。我们现在建议使用这些数据来评估主要类别的精神活性药物在精神错乱的持久性和消退性方面的作用。我们提出了以下两个具体目标和四个假设：目标1：使用急性后数据集，检查接触四类精神活性药物之间的关系：1)镇静催眠药，2)抗精神病药，3)抗胆碱能药，4)阿片类止痛药，持续一个月的精神错乱。目的：使用心脏外科数据集中出现妄想的患者，研究在术后即刻期间接触相同的四类精神活性药物与妄想持续之间的关系。我们假设镇静催眠药和抗胆碱能药物将与精神错乱的持续性有关，而抗精神病药物和阿片类止痛药将与精神错乱的消退有关。我们建议的目标是利用已投入的资源，对包含数百名精神错乱患者的两个大队列进行纵向随访。我们的研究结果将为治疗精神错乱的药物管理提供信息，并使基于证据的具体干预措施的设计成为可能，以治疗精神错乱并改善急性和急性后护理环境中的功能恢复。公共卫生相关性：精神错乱(急性精神错乱)经常使老年人的急性疾病复杂化，对健康造成短期和长期的不利影响。精神活性药物经常用于精神错乱患者，要么用于治疗精神错乱本身，要么用于治疗睡眠障碍和疼痛等共病；然而，这些药物是否有助于消除精神错乱或延长精神错乱的时间仍不确定。我们的建议包括对PI最近完成的两项由NIH资助的精神分裂症研究中收集的数据进行二次分析，以评估四种主要类别的精神活性药物在延长和解决精神错乱方面的作用。我们的研究结果将为治疗精神错乱的药物管理和设计特定的循证干预措施提供参考，以治疗精神错乱并改善急性和急性后护理环境中的功能恢复。

DESCRIPTION (provided by applicant): Delirium (acute confusion) frequently complicates the acute illness of elders, resulting in both short- and long- term adverse impacts on health. In recent years, there has been substantial progress in defining and assessing delirium, describing its incidence and prevalence in several clinical populations, identifying its risk factors, and even developing strategies for its prevention. Yet, once delirium occurs, optimal management remains poorly understood. One of the areas of greatest controversy is the use of psychoactive medications in delirious patients. Psychoactive medications are used frequently in this population, either for the management of delirium itself, or for comorbid conditions, such as sleep disorders and pain. While there has been progress in identifying medications as risk factors for incident delirium, the use of medications in established delirium, and their role in its persistence vs. resolution are less well understood. Our proposal involves secondary analysis of data collected in two of the PI's recently completed, NIH-funded studies of delirium. The first, A Trial to Reduce Delirium in Aged Post-acute Patients, enrolled 457 delirious subjects newly admitted to 8 post-acute care facilities. The second, Thinking and Recovery after Cardiac Surgery (TRACS), enrolled 247 subjects aged 60 and older undergoing cardiac surgery at three medical centers, 111 of whom developed delirium. Together, they represent two of the largest prospective cohorts of delirious subjects ever enrolled in research. In addition to performing serial delirium assessments in these studies, we have also completed formal medical record reviews including detailed information on the administration of psychoactive medications. We now propose to use these data to assess the role of major classes of psychoactive medications in the persistence vs. resolution of delirium. We propose the following two Specific Aims and four hypotheses: Aim 1: Using the post-acute dataset, to examine the relationship between exposure to four classes of psychoactive medications: 1) sedative-hypnotics, 2) antipsychotics, 3) anticholinergics, and 4) opioid analgesics, with delirium persistence over a one-month time period. Aim 2: Using patients who developed delirium in the cardiac surgery dataset, to examine the relationship between exposure to the same four classes of psychoactive medications with delirium persistence in the immediate postoperative period. We hypothesize that sedative-hypnotic and anticholinergic medications will be associated with delirium persistence, while antipsychotic medications and opioid analgesics will be associated with delirium resolution. Our proposed aims leverage the resources already invested in assembling and performing longitudinal follow-up on two large cohorts containing hundreds of delirious patients. Our results will inform the medication management of delirium and enable the design of specific evidence-based interventions to treat delirium and improve functional recovery in both acute and post-acute care settings. PUBLIC HEALTH RELEVANCE: Delirium (acute confusion) frequently complicates the acute illness of elders, resulting in both short- and long- term adverse impacts on health. Psychoactive medications are used frequently in delirious patients, either for the management of delirium itself, or for comorbid conditions, such as sleep disorders and pain; yet, whether these medications help to clear delirium or prolong it remains uncertain. Our proposal involves secondary analysis of data collected in two of the PI's recently completed, NIH-funded studies of delirium to assess the role of four major classes of psychoactive medications in the prolongation vs. resolution of delirium. Our results will inform the medication management of delirium and the design of specific evidence-based interventions to treat delirium and improve functional recovery in both acute and post-acute care settings.