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：咖啡因与术后神经认知恢复 项目概要 谵妄是一种令人痛苦的临床综合征，其特征是影响基本认知功能的失败 大约 20-50% 的老年手术患者在手术恢复期间谵妄与增加有关。 此外，还有死亡率、医疗保健支出增加以及未来认知和功能下降。 谵妄和阿尔茨海默氏病相关痴呆症患者之间的病理生理学重叠； 不幸的是，谵妄的神经生物学基础表明，未来患痴呆症的风险会增加。 仍然不完全清楚，并且没有生物学上的、有效的疗法来预防 我们的初步数据表明咖啡因可减少术后谵妄和相关并发症。 在大手术后的麻醉后监护室 (PACU) 中，通过将皮质动力学转向神经 临界性是指为满足需求而动态波动的系统状态。 认知，神经临界性是一种潜在机制，通过该机制可以将大脑的功能隔离区域 在我们的初步试验中，参与者在空间和时间上动态整合以优化认知。 手术结束时的咖啡因显示脑电图（EEG）危重标记物增加 然而，PACU 与谵妄减少同时存在，咖啡因、神经危急度、 术后神经认知恢复需要额外、严格的测试，我们的长期目标是改善。 对谵妄和相关神经认知障碍的神经生物学理解，以便有效的治疗 该提案的目标是 (1) 测试减少早期干预的措施。 术后谵妄，同时（2）识别反映认知脆弱性的动态大脑变化。 中心假设是咖啡因可以改善老年人术后神经认知恢复。 通过随机、安慰剂对照、四盲临床试验来检验这一假设，目标 1 将确定。 咖啡因是否会降低术后早期谵妄的发生率 参与者 (n=250) 将被随机分组​​。 三臂平行设计中的安慰剂、低剂量咖啡因或高剂量咖啡因。 设计还将用于测试一天与两天的咖啡因治疗，目标 2 将确定皮质动力学。 无线、高密度全头皮脑电图系统将使术后早期谵妄成为可能。 最后，目标 3 将使用相同的方法来分析神经临界性以及与咖啡因和谵妄的关联。 脑电图系统用于测试符合轻度认知障碍标准的试验参与者的基线神经临界性， 据报道，患有这种疾病以及阿尔茨海默氏病的患者偏离了危重状态。 总体而言，拟议的研究意义重大，因为结果可能提供有效的神经生物学方法 减少术后早期谵妄及相关后果的知情干预。 将为神经生物学提供对预示着谵妄的脆弱皮质动力学的洞察，并且可能， 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.

咖啡因、术后谵妄和手术后结果的变化 (CAPACHINOS)-2：随机对照试验方案。

• 发表时间: 2023-05-15
• 影响因子: 2.9
• 作者: Vlisides, Phillip E;Ragheb, Jacqueline;McKinney, Amy;Mentz, Graciela;Runstadler, Nathan;Martinez, Selena;Jewell, Elizabeth;Lee, UnCheol;Vanini, Giancarlo;Schmitt, Eva M;Inouye, Sharon K;Mashour, George A
• 通讯作者: Mashour, George A

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

入院期间谵妄筛查和管理的障碍：住院护理观点的定性分析。

• 发表时间: 2023-06-29
• 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