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 母项目的目标是找到一种有效的预防术后精神错乱的干预措施，其中之一 老年人心脏手术最常见和最有害的并发症。的中心假说 这项建议是，定期预防性6小时静脉注射对乙酰氨基酚可以预防儿童术后精神错乱 老年心脏手术患者在手术后48小时内给药。 这一建议的基本原理是，尽管存在多种病因，但 精神错乱，可改变的危险因素包括炎症、治疗不足的疼痛和阿片类药物的使用。其中每一项都是 使用对乙酰氨基酚进行干预是导致神志不清的独立危险因素。穿过 这种直接的干预，有可能使用一种高度流行的、无毒的药物来解决井- 已知问题。我们通过进行一项随机、三盲临床试验提出了三个具体目标 招募900名60岁或以上接受心脏手术的患者。通过这次审判，我们将确定 静脉注射对乙酰氨基酚对以下方面的影响：1)术后妄想的发生率、持续时间和严重程度；2)使用 术后48小时内阿片类药物和其他抢救止痛剂的使用情况，每天休息和休息时的疼痛评分 工作量、在重症监护病房的住院时间和总住院时间3)较长的时间(1) 6个月、12个月)术后认知、身体和自理功能恢复。我们将追求这些目标 使用一种创新的方法，按计划每隔六小时静脉注射常规药物，以治疗 48小时，这是术后继发性损伤、炎症和疼痛的最大时期。这个 拟议的研究具有重要意义，因为它将确定是否通过 多模式止痛方法可以减少易受伤害的老年患者术后精神分裂症的发生率 人口。这项工作的预期结果将是，无论发现什么，都将是有趣的 确定静脉注射对乙酰氨基酚在预防精神错乱和老年人疼痛控制中的作用 心脏手术患者。这些结果将产生重要的积极影响，因为它们将促进 广泛采用对乙酰氨基酚静脉注射作为老年人手术后的疼痛控制方式 手术，或提供强有力的证据，以消除其使用，如果被证明是无效的。此外，我们还将 进一步了解疼痛管理方式和精神错乱之间的联系，以及其他 老年人接受心脏手术的重要短期和长期结果。 补充目标1：为心脏手术期间获得的脑电记录创建一个大型、多站点数据库 手术将用于脑电生物标记物的离线分析。 补充目标2：确定可用于预测的脑电生物标志物 心脏手术患者的POD。 补充目标3：探讨POD的脑电生物标志物是否与静脉注射 对乙酰氨基酚。 影响：此应用程序请求资金以获取心脏手术期间记录的脑电数据的大型数据库 做手术。脑电是麻醉和手术中患者状态的重要指标，也是丰富的数据来源 这些生物标记物可以用来预测心脏手术后的精神错乱。此外， 一旦我们识别出与开发出的POD一致的脑电信号，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。因此，拟议的补充目标增加了重要性和 母项目的创新，并与美国国立卫生研究院提高科学严谨性和 临床研究中的概括性。