Psychoactive Medications: Associations with Delirium Persistance vs Resolution

描述（由申请人提供）：谵妄（急性精神错乱）是老年人急性疾病的常见并发症，对健康造成短期和长期的不良影响。近年来，在定义和评估谵妄，描述其发病率和患病率在几个临床人群，确定其危险因素，甚至制定其预防策略方面取得了实质性进展。然而，一旦出现谵妄，人们对最佳管理仍然知之甚少。争议最大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，要么用于谵妄本身的治疗，要么用于合并症，如睡眠障碍和疼痛。虽然在确定药物作为偶发性谵妄的危险因素方面取得了进展，但在已建立的谵妄中药物的使用及其在其持续与消退中的作用尚不清楚。我们的提案涉及对PI最近完成的两项由美国国立卫生研究院资助的谵妄研究收集的数据进行二次分析。第一项，减少老年急性后患者谵妄的试验，招募了8个急性后护理机构新入院的457名谵妄受试者。第二项研究，心脏手术后的思考和恢复（TRACS），招募了247名60岁及以上的受试者在三个医疗中心接受心脏手术，其中111人出现谵妄。他们共同代表了有史以来参与研究的两个最大的谵妄受试者的前瞻性队列。除了在这些研究中进行一系列谵妄评估外，我们还完成了正式的医疗记录审查，包括有关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型的精神活性药物在谵妄持续与消退中的作用。我们提出以下两个具体目标和四个假设：目标1：使用急性后数据集，检查暴露于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)阿片类镇痛药，谵妄持续超过一个月的时间。目的2：使用心脏手术数据集中出现谵妄的患者，检查在术后立即暴露于相同的四类精神活性药物与谵妄持续之间的关系。我们假设镇静催眠和抗胆碱能药物将与谵妄持续有关，而抗精神病药物和阿片类镇痛药将与谵妄消退有关。我们提出的目标是利用已经投入的资源，对两个包含数百名谵妄患者的大型队列进行集结和纵向随访。我们的研究结果将为谵妄的药物管理提供信息，并能够设计特定的循证干预措施来治疗谵妄，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：谵妄（急性精神错乱）经常使老年人急性疾病复杂化，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谵妄患者，或用于谵妄本身的管理，或用于合并症，如睡眠障碍和疼痛；然而，这些药物是否有助于清除谵妄或延长谵妄仍不确定。我们的建议包括对PI最近完成的两项由nih资助的谵妄研究收集的数据进行二次分析，以评估四大类精神活性药物在谵妄延长和消退中的作用。我们的研究结果将为谵妄的药物管理和设计特定的循证干预措施提供信息，以治疗谵妄，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.