Caffeine and Postoperative Neurocognitive Recovery

咖啡因与术后神经认知恢复

• 批准号: 10674966
• 负责人: Phillip Eleas Vlisides
• 金额: $ 52.36万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-02 至 2027-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10674966
• 关键词: Acetylcholine; Acute; Affect; Alzheimer' s Disease; Alzheimer' s disease related dementia; Anesthesia procedures; Anesthetics; Area; Arousal; Awareness; Blinded; Brain; Caffeine; Caring; Characteristics; Clinical; Clinical Trials; Cognition; Cognitive; Consumption; Data; Delirium; Dementia; Diagnostic; Distress; Dose; Elderly; Electroencephalography; Failure; Family; Future; Goals; Health Expenditures; Hospitalization; Hour; Impaired cognition; Incidence; Intervention; Intravenous; Length of Stay; Measures; Memory; Neurobiology; Neurocognitive; Operative Surgical Procedures; Outcome; Participant; Patients; Placebo Control; Placebos; Postoperative Period; Process; Public Health; Purinergic P1 Receptors; Randomized; Recovery; Reporting; Research; Risk; Risk Reduction; Scalp structure; Severities; Subgroup; Surgical complication; Syndrome; System; Techniques; Testing; Therapeutic; Time; Wakefulness; antagonist; arm; cognitive function; cognitive testing; density; design; effective intervention; effective therapy; experience; falls; flexibility; functional decline; improved; insight; meetings; mild cognitive impairment; mortality; neural; neurocognitive disorder; novel; pharmacologic; postoperative delirium; prevent; primary outcome; public health relevance; randomized placebo controlled trial; randomized, clinical trials; recruit; secondary analysis; secondary outcome; segregation; wireless

TITLE: CAFFEINE AND POSTOPERATIVE NEUROCOGNITIVE RECOVERY PROJECT SUMMARY Delirium is a distressing clinical syndrome characterized by failure of basic cognitive functions that affects approximately 20-50% of older surgical patients. Delirium during surgical recovery is associated with increased mortality, increased healthcare expenditures, and future cognitive and functional decline. Moreover, there is pathophysiologic overlap between delirium and Alzheimer’s Disease-Related Dementias; patients experiencing delirium demonstrate increased risk of future dementia. Unfortunately, the underlying neurobiology of delirium remains incompletely understood, and there are no biologically informed, effective therapies for preventing postoperative delirium and related complications. Our preliminary data suggest that caffeine reduces delirium in the postanesthesia care unit (PACU) after major surgery by shifting cortical dynamics towards neural criticality. Criticality refers to a system state that is poised to dynamically fluctuate to meet demands. For cognition, neural criticality is a potential mechanism by which functionally segregated areas of the brain can be dynamically integrated over space and time to optimize cognition. In our preliminary trial, participants receiving caffeine at the end of surgery demonstrated increased electroencephalographic (EEG) markers of criticality in the PACU concurrent with delirium reduction. Nonetheless, the relationships among caffeine, neural criticality, and postoperative neurocognitive recovery require additional, rigorous testing. Our long-term goal is to improve neurobiological understanding of delirium and related neurocognitive disorders, such that effective therapies can be developed. The objectives of this proposal are to (1) test an intervention for reducing early postoperative delirium while (2) identifying dynamic brain changes that reflect cognitive vulnerability. The central hypothesis is that caffeine will improve postoperative neurocognitive recovery in older adults. We will test this hypothesis via a randomized, placebo-controlled, quadruple-blinded clinical trial. Aim 1 will determine whether caffeine reduces the incidence of early postoperative delirium. Participants (n=250) will be randomized to placebo, low-dose caffeine, or high-dose caffeine in a three-arm parallel design. A sequential randomization design will also be used to test one vs. two days of caffeine therapy. Aim 2 will identify cortical dynamics underlying early postoperative delirium. A wireless, high-density whole-scalp EEG system will enable the analysis of neural criticality and the associations with caffeine and delirium. Lastly, Aim 3 will use the same EEG system to test baseline neural criticality in trial participants meeting criteria for Mild Cognitive Impairment, as deviations from criticality have been reported in patients with this condition as well as Alzheimer’s Disease. Overall, the proposed research is significant because results may provide an effective, neurobiologically informed intervention for reducing early postoperative delirium and related consequences. Additionally, results will provide neurobiological insight into vulnerable cortical dynamics that portend delirium and, possibly, subsequent neurocognitive disorders.

标题：咖啡因和术后神经认知恢复 项目摘要 ir妄是一种令人痛苦的临床综合征，其特征是影响影响的基本认知功能的失败 大约20-50％的老年手术患者。手术恢复期间的ir妄与增加有关 死亡率，增加医疗支出以及未来的认知和功能下降。而且，有 del妄与阿尔茨海默氏病与疾病相关的痴呆症之间的病理生理重叠；患者经历 ir妄表现出来未来痴呆症的风险增加。不幸的是，ir妄的基本神经生物学 仍然不完全理解，并且没有生物学知情，有效的疗法 术后del妄和相关并发症。我们的初步数据表明咖啡因减少了del妄 大手术后，在麻醉后护理单元（PACU）中，将皮质动力转向神经 批判性。批判性是指被中毒以动态波动以满足需求的系统状态。为了 认知，神经政治性是一种潜在的机制，大脑的功能隔离区域可以是 在空间和时间上动态整合以优化认知。在我们的初步试验中，参与者接受 咖啡因在手术结束时表明，脑脑摄影（EEG）的关键标记增加了 PACU同时减少了ir妄。尽管如此，咖啡馆之间的关系，神经批判性， 术后神经认知恢复需要进行额外的严格测试。我们的长期目标是改善 神经生物学对del妄和相关神经认知障碍的理解，使得有效疗法 可以开发。该提案的目标是（1）测试提早减少的干预措施 术后del妄，而（2）识别反映认知脆弱性的动态大脑变化。这 中心假设是咖啡因将改善老年人的术后神经认知恢复。我们将 通过一项随机，安慰剂对照，四倍盲临床试验检验该假设。 AIM 1将确定 咖啡因是否会降低术后早期del妄的发生率。参与者（n = 250）将被随机分配 安慰剂，低剂量咖啡因或三臂平行设计中的高剂量咖啡因。顺序随机化 设计还将用于测试与两天的咖啡馆治疗。 AIM 2将识别皮质动态 潜在的术后早期del妄。无线，高密度的全量表脑电图系统将使 神经关键性的分析以及与咖啡因和del妄的关联。最后，AIM 3将使用相同的 在试验参与者中测试基线神经关键性的脑电图系统符合轻度认知障碍标准， 由于有这种疾病和阿尔茨海默氏病的患者的差异已经报道。 总体而言，拟议的研究很重要，因为结果可能会提供有效的神经生物学 知情的干预措施减少了早期术后del妄和相关后果。另外，结果 将提供对脆弱的皮质动态的神经生物学见解，这些动态预示着del妄和可能 随后的神经认知障碍。

项目成果

Caffeine, Postoperative Delirium And Change In Outcomes after Surgery (CAPACHINOS)-2: protocol for a randomised controlled trial.

• DOI: 10.1136/bmjopen-2023-073945
• 发表时间: 2023-05-15
• 期刊: BMJ open
• 影响因子: 2.9

Barriers to delirium screening and management during hospital admission: a qualitative analysis of inpatient nursing perspectives.

• DOI: 10.1186/s12913-023-09681-4
• 发表时间: 2023-06-29
• 期刊: BMC HEALTH SERVICES RESEARCH
• 影响因子: 2.8
• 作者: Ragheb, Jacqueline;Norcott, Alexandra;Benn, Lakeshia;Shah, Nirav;McKinney, Amy;Min, Lillian;Vlisides, Phillip E.
• 通讯作者: Vlisides, Phillip E.