Scheduled Prophylactic 6-hourly IV Acetaminophen to Prevent Postoperative Delirium in Older Cardiac Surgical Patients (PANDORA) - EEG Administrative Supplement

预定预防性每 6 小时静脉注射对乙酰氨基酚可预防老年心脏外科患者术后谵妄 (PANDORA) - 脑电图行政补充

• 批准号: 10672573
• 负责人: KESTUTIS KVERAGA
• 金额: $ 21.85万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-30 至 2024-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10672573
• 关键词: Acetaminophen; Address; Administrative Supplement; Adoption; Age-Years; Analgesics; Anesthesia procedures; Biological Markers; Cardiac; Cardiac Surgery procedures; Clinical Research; Clinical Trials; Cognitive; Data; Databases; Delirium; Development; Elderly; Electroencephalography; Enrollment; Etiology; Exertion; Funding; Harvest; Hour; Incidence; Inflammation; Injury; Intensive Care Units; Intervention; Intravenous; Length of Stay; Methods; Modality; Operative Surgical Procedures; Opioid; Outcome; Pain; Pain management; Patients; Pharmaceutical Preparations; Postoperative Pain; Postoperative Period; Prevention; Randomized; Recovery of Function; Request for Applications; Research; Rest; Risk Factors; Role; Schedule; Self Care; Severities; Site; Source; Testing; United States National Institutes of Health; Work; aging population; blind; daily pain; indexing; innovation; modifiable risk; multimodality; pain relief; pain score; parent project; postoperative delirium; postoperative recovery; prevent; prophylactic; racial and ethnic

Project Summary / Abstract The parent project’s objective is to find an effective prophylactic intervention for postoperative delirium, one of the most common and detrimental complications of cardiac surgery in older adults. The central hypothesis of this proposal is that scheduled prophylactic 6-hourly IV acetaminophen can prevent postoperative delirium in older cardiac surgical patients when administered in the first 48 hours following surgery. The rationale underlying this proposal is that while multiple etiological factors exist for the development of delirium, modifiable risk factors include inflammation, undertreated pain, and use of opioids. Each of these is an independent risk factor for delirium that is amenable to intervention with use of IV acetaminophen. Through this straightforward intervention, it is possible to use a highly prevalent, non-toxic medication to address a well- known problem. We propose three specific aims by conducting a randomized, triple blind clinical trial that enrolls 900 patients 60 years of age or older undergoing cardiac surgery. Through this trial, we will determine the effect of IV acetaminophen on; 1) the incidence, duration, and severity of postoperative delirium, 2) the use of opioids and other rescue analgesics in the first 48 postoperative hours, daily pain scores at rest and exertion, and length of stay in the Intensive Care Unit and overall hospital length of stay 3) longer-term (one, six, 12 months) cognitive,physical, and self-care functional recovery after surgery. We will pursue these aims using an innovative method of administering a routine drug intravenously in scheduled, six hourly intervals for 48 hours, which is the period of maximum secondary injury, inflammation, and pain postoperatively. The proposed research is significant because it will determine whether targeting inflammation and pain through a multimodal analgesic approach can reduce the incidence of postoperative delirium in a vulnerable, aging population. The expected outcome of this work, which will be interesting regardless of the findings, will be to determine the role of IV acetaminophen in the prevention of delirium, and in pain management for older cardiac surgery patients. The results will have an important positive impact as they will facilitate either widespread adoption of IV acetaminophen as a pain control modality for older adults undergoing major surgery, or to provide strong evidence to eliminate its use if it is proven to be ineffective. Additionally, we will further our understanding of the association between pain management modalities and delirium, and other important short and long term outcomes of older adults undergoing cardiac surgery. Supplement Aim 1: To create a large, multi-site database of EEG recordings obtained during cardiac surgery to be harvested for offline analysis of EEG biomarkers. Supplement Aim 2: To identify pre/intra/postoperative EEG biomarkers that can be useful in predicting POD in cardiac surgery patients. Supplement Aim 3: To explore whether EEG biomarkers for POD interact with IV administration of acetaminophen. IMPACT: This application requests funds to acquire a large database of EEG data recorded during cardiac surgery. EEG is an important index of patient state during anesthesia and surgery and a rich source of data from which biomarkers can be developed to predict postoperative delirium in cardiac surgery. Furthermore, once we identify EEG signatures consistent with POD developed, we can test how they interact with IV administration of acetaminophen. The proposed supplementary aims thus augment the significance and innovation of the parent project and are congruent with the efforts of the NIH to enhance scientific rigor and generalizability in clinical research.

项目摘要 /摘要 母公司项目的目标是为术后del妄寻找有效的预防干预措施， 老年人心脏手术最常见和有害的并发症。中心假设 该建议是计划的预防性6小时IV乙酰氨基酚可以防止术后del妄 在手术后的头48小时内服用年长的心脏手术患者。 该提议的基本原理是，尽管存在多个病因因素 del妄，可修改的危险因素包括注射，疼痛不足和使用阿片类药物。这些都是 使用IV对乙酰氨基酚的独立风险因素，可以进行干预。通过 这种直接的干预措施，可以使用高度普遍的无毒药物来解决 已知问题。我们通过进行一项随机的三重盲临床试验提出了三个特定目标， 参加心脏手术60岁或以上的900例患者。通过此试验，我们将确定 静脉对乙酰氨基酚的作用； 1）术后del妄的事件，持续时间和严重程度，2）使用 术后48个小时内阿片类药物和其他救援镇痛药，静止和 重症监护室的劳累，住院时间和整体住院时间3）长期（一 六，12个月）手术后的认知，身体和自我保健功能恢复。我们将追求这些目标 使用一种创新的方法，用于在计划的六个小时静脉内静脉注射常规药物 48小时，这是最大继发​​性损伤，感染和疼痛的时期。 拟议的研究很重要，因为它将决定是否通过 多模式的镇痛方法可以减少脆弱的老龄化术后del妄的发生率 人口。这项工作的预期结果，无论发现如何，这都会很有趣，将是 确定静脉对乙酰氨基酚在预防ir妄中的作用，以及在老年人的疼痛管理中 心脏手术患者。结果将产生重要的积极影响，因为它们将促进 宽度采用静脉对乙酰氨基酚作为接受主要成年人的疼痛控制方式 手术，或提供有力的证据以消除其用途，如果被证明是无效的。此外，我们会的 进一步，我们对疼痛管理方式与ir妄之间的关联以及其他 老年人接受心脏手术的重要短期和长期结局。 补充目标1：创建一个在心脏中获得的大型脑电图记录的大型多站点数据库 要收集的手术以进行脑电图生物标志物的离线分析。 补充目的2：确定可以在预测的情况 心脏手术患者的豆荚。 补充目的3：探索POD的EEG生物标志物是否与IV施用相互作用 对乙酰氨基酚。 影响：本申请要求资金获取心脏记录的大量脑电图数据库 外科手术。脑电图是麻醉和手术期间患者状态的重要指数，并且是丰富的数据来源 可以从中开发出生物标志物来预测心脏手术术后del妄。此外， 一旦我们确定了与开发的POD一致的EEG特征，我们就可以测试它们与IV的相互作用 对乙酰氨基酚的给药。拟议的补充目的因此增加了重要性和 母公司项目的创新，并与NIH的努力一致，以增强科学严谨性和 临床研究中的普遍性。