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.

项目概要/摘要 母项目的目标是找到一种有效的预防性干预措施来治疗术后谵妄，这是其中之一 老年人心脏手术最常见和最有害的并发症。中心假设为 该建议是，定期预防性静脉注射 6 小时静脉注射对乙酰氨基酚可以预防术后谵妄。 老年心脏手术患者在手术后 48 小时内给药。 该提议的基本原理是，虽然存在多种病因因素， 谵妄的可改变危险因素包括炎症、疼痛治疗不足和使用阿片类药物。其中每一个都是 谵妄的独立危险因素，可通过静脉注射对乙酰氨基酚进行干预。通过 通过这种简单的干预措施，可以使用一种非常流行的无毒药物来解决一个良好的问题 已知问题。我们通过进行随机、三盲临床试验提出了三个具体目标 招募了 900 名 60 岁或以上接受心脏手术的患者。通过这次试验，我们将确定 IV 对乙酰氨基酚的影响； 1) 术后谵妄的发生率、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救援镇痛药的用量、休息和休息时的每日疼痛评分 体力消耗、在重症监护病房的停留时间以及总住院时间 3) 长期（一、 六、十二个月）手术后认知、身体和自理功能恢复。我们将追求这些目标 使用一种创新方法，按预定的每六小时间隔静脉注射常规药物 48小时，是术后二次损伤、炎症、疼痛最严重的时期。这 拟议的研究意义重大，因为它将确定是否通过 多模式镇痛方法可以降低脆弱、衰老患者术后谵妄的发生率 人口。无论研究结果如何，这项工作的预期成果将是： 确定静脉注射对乙酰氨基酚在预防谵妄和老年人疼痛管理中的作用 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 广泛采用静脉注射对乙酰氨基酚作为老年人接受重大手术的疼痛控制方式 手术，或在证明无效时提供强有力的证据以消除其使用。此外，我们将 进一步我们对疼痛管理方式和谵妄之间的关联的理解，以及其他 接受心脏手术的老年人的重要短期和长期结果。 补充目标 1：创建一个大型、多站点的脑电图记录数据库 手术采集的数据用于脑电图生物标志物的离线分析。 补充目标 2：确定可用于预测的术前/术中/术后脑电图生物标志物 心脏手术患者的 POD。 补充目标 3：探讨 POD 的脑电图生物标志物是否与静脉注射药物相互作用 对乙酰氨基酚。 影响：该应用程序需要资金来获取心脏期间记录的脑电图数据的大型数据库。 外科手术。脑电图是麻醉和手术过程中患者状态的重要指标，数据来源丰富 可以从中开发生物标志物来预测心脏手术术后谵妄。此外， 一旦我们确定了与 POD 开发一致的 EEG 特征，我们就可以测试它们如何与 IV 相互作用 服用对乙酰氨基酚。因此，拟议的补充目标增强了重要性和 父项目的创新，并与 NIH 为提高科学严谨性和 临床研究中的普遍性。