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

项目总结/摘要 母项目的目标是找到一种有效的预防术后谵妄的干预措施， 老年人心脏手术最常见和最有害的并发症。的中心假设 这一建议是，预定的预防性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。 这一建议的基本原理是，虽然存在多种病因因素， 谵妄，可改变的风险因素包括炎症，治疗不足的疼痛和使用阿片类药物。这些中的每一者 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 这种直接的干预，有可能使用一种非常普遍的，无毒的药物来解决一个很好的， 已知的问题。我们提出了三个具体的目标，通过进行随机，三盲临床试验， 招募了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 IV对乙酰氨基酚对以下方面的影响：1）术后谵妄的发生率、持续时间和严重程度，2）使用 术后前48小时内阿片类药物和其他补救镇痛药的使用率，休息时的每日疼痛评分， 劳累、在重症监护室的停留时间和总的住院时间3）长期（1， 术后6个月、12个月）认知、身体和自理功能恢复。我们将努力实现这些目标 使用一种创新的方法，在预定的六小时间隔内静脉注射常规药物， 48小时，这是术后继发性损伤、炎症和疼痛最严重的时期。的 拟议的研究是重要的，因为它将确定是否通过靶向炎症和疼痛， 多模式镇痛方法可以减少脆弱的老年患者术后谵妄的发生率， 人口这项工作的预期成果将是有趣的，无论结果如何， 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。 心脏手术病人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，或提供有力的证据，以消除其使用，如果它被证明是无效的。此外，我们将 进一步了解疼痛管理方式和谵妄之间的联系，以及其他 接受心脏手术的老年人的重要短期和长期结局。 补充目标1：创建一个大型的、多中心的心电图记录数据库， 手术以用于EEG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EEG生物标志物 心脏手术患者的POD。 补充目的3：探索POD的EEG生物标志物是否与IV给予 对乙酰氨基酚 影响：该申请要求获得资金，以获取心脏手术期间记录的EEG数据的大型数据库。 手术脑电是麻醉和手术期间病人状态的重要指标，是丰富的数据来源 由此可以开发生物标志物来预测心脏手术中的术后谵妄。此外，委员会认为， 一旦我们识别出与POD一致的EEG信号，我们就可以测试它们如何与IV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， 创新的母项目，并与美国国立卫生研究院的努力，以提高科学的严谨性， 临床研究的普遍性。

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.