Scheduled Prophylactic 6-hourly IV Acetaminophen to Prevent Postoperative Delirium in Older Cardiac Surgical Patients

项目摘要/摘要 很少有药物干预被研究来减少术后精神错乱，它们的疗效是 不确定，充其量也是有争议的。我们的目标是找到一种有效的预防干预措施 术后精神错乱是老年人心脏手术最常见和最有害的并发症之一。 这项建议的中心假设是，定期预防性注射6小时一次的对乙酰氨基酚可以预防 老年心脏手术患者术后48小时内用药时出现的术后精神错乱。 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。其中的每一个都是 易使用对乙酰氨基酚进行干预的独立的精神障碍危险因素。通过这件事 直接干预，有可能使用一种高度流行的、无毒的药物来解决众所周知的 有问题。我们通过进行一项随机的三盲临床试验提出了三个具体的目标，该试验有900人参加。 60岁或以上正在接受心脏手术的患者。通过这次试验，我们将确定 静脉注射对乙酰氨基酚；1)术后精神分裂症的发生率、持续时间和严重程度；2)阿片类药物的使用 以及术后前48小时内的其他抢救止痛药，每天休息和用力时的疼痛评分，以及疼痛持续时间 在重症监护病房的住院时间和总住院时间3)较长的(1、6、12个月)认知， 术后身体、自理功能恢复。我们将以创新的方式实现这些目标。 定期静脉注射常规药物，每小时六次，持续48小时，这是一个时期 术后最大程度的继发性损伤、炎症和疼痛。这项拟议的研究具有重要意义 因为它将确定通过多模式止痛方法靶向炎症和疼痛是否可以 减少脆弱、老龄化人群术后精神错乱的发生率。这样做的预期结果是 无论结果如何，确定静脉注射对乙酰氨基酚的作用都将是一项有趣的工作 在预防精神错乱和老年心脏手术患者的疼痛管理方面。结果将会有 一个重要的积极影响，因为它们将促进静脉注射对乙酰氨基酚作为疼痛的广泛采用 用于接受大手术的老年人的控制方式，或提供强有力的证据以消除其使用，如果它 已经被证明是无效的。此外，我们还将加深对疼痛之间联系的理解 老年人的管理模式和精神错乱以及其他重要的短期和长期结果 正在接受心脏手术。

Project Summary / Abstract Few pharmacological interventions have been studied to reduce postoperative delirium, and their efficacy is inconclusive and controversial at best. Our 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.