Pharmacological Management of Delirium

描述（由申请人提供）：大约有270万65岁及以上的美国人在重症监护室（ICU）至少呆了一天，医疗费用总计275亿美元。高达80%的老年ICU患者在住院期间发生谵妄，这对他们的医院相关健康结局产生了负面和独立的影响。患有谵妄的老年人接受潜在有害的药物治疗，如抗胆碱能药物和苯二氮卓类药物，并且比没有谵妄的老年人更容易发生福尔斯、受伤、压疮和束缚。这些并发症导致ICU和住院时间延长、死亡率升高、功能状态较差、康复受限、机构化增加和医疗保健费用增加。目前，没有FDA批准的药物化合物来降低与谵妄相关的死亡率和发病率。几种神经递质的紊乱，如乙酰胆碱、多巴胺、谷氨酸、5-羟色胺、去甲肾上腺素和γ-氨基丁酸（GABA），已被认为参与了谵妄的病理生理学。这些神经递质被提出作为发展谵妄药物治疗的潜在靶点。然而，最有力的数据支持乙酰胆碱增强、GABA减少和多巴胺减少的关键治疗作用。药物流行病学研究和分散的随机临床试验表明，老年人谵妄的药物治疗是复杂的，可能需要减少苯二氮卓类药物和抗胆碱能药物的使用，沿着使用低剂量精神抑制剂，如氟哌啶醇。然而，还没有随机对照试验评价这种药物治疗对减少谵妄严重程度、持续时间及其相关并发症的疗效。该提案正在寻求资金，以进行一项随机对照试验，该试验将评价谵妄药理学方案的疗效，包括1）减少抗胆碱能药物的暴露; 2）减少苯二氮卓类药物的暴露; 3）每日使用低剂量氟哌啶醇。该研究的主要结局是谵妄严重程度（通过谵妄评定量表（DRS-R-98）测量）和谵妄持续时间（通过ICU混乱评估方法（CAM-ICU）测量）。

DESCRIPTION (provided by applicant): Approximately 2.7 million Americans aged 65 and older spent at least one day in the intensive care unit (ICU) costing MEDICARE a total of $27.5 billion. Up to 80% of these older ICU patients had delirium during their hospital stay that affects negatively and independently their hospital related health outcomes. Older adults with delirium receive potentially harmful medications such as anticholinergics and benzodiazepines and are more prone to falls, injuries, pressure ulcers and restraints than their counterparts with no delirium. These complications contribute to prolonged ICU and hospital length of stay, higher mortality rates, poorer functional status, limited rehabilitation, increased institutionalization, and higher health care costs. Currently, there is no FDA-approved pharmacological compound to reduce mortality and morbidity related to delirium. Disturbances in several neurotransmitters, such as acetylcholine, dopamine, glutamate, serotonin, norepinephrine, and gamma-aminobutyric acid (GABA), have been suggested to be involved in the pathophysiology of delirium. These neurotransmitters are put forward as potential targets for the development of pharmacological therapeutics for delirium. However, the strongest data supports a critical therapeutic role for acetylcholine enhancement, GABA reduction, and dopamine reduction. Pharmaco-epidemiological studies and scattered randomized clinical trials have demonstrated that the pharmacological management of delirium among older adults is complicated and may need to include a combination of a reduction in the use of benzodiazepines and anticholinergics, along with the use of low dose neuroleptics such as haloperidol. However, there have been no randomized controlled trials evaluating the efficacy of such a pharmacological management on reducing delirium severity, duration, and its related complications. This proposal is seeking funding to conduct a randomized controlled trial that would evaluate the efficacy of a pharmacological protocol for delirium that includes 1) a reduction of exposure to anticholinergic medications; 2) a reduction of exposure to benzodiazepines; and 3) daily use of a low dose of haloperidol. The primary outcomes of the study are delirium severity, as measured by the Delirium Rating Scale (DRS-R-98); and delirium duration as measured by the Confusion Assessment Method in the ICU (CAM-ICU).