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

项目总结/摘要 很少有药物干预研究，以减少术后谵妄，其疗效是 最多也就是不确定和有争议我们的目标是找到一种有效的预防性干预措施， 术后谵妄是老年人心脏手术中最常见和最有害的并发症之一。 该建议的中心假设是，预定的预防性6小时静脉注射对乙酰氨基酚可以预防 老年心脏手术患者在术后48小时内给药时出现术后谵妄。 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。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。通过这个 简单的干预，有可能使用一种高度流行的无毒药物来解决众所周知的 问题.我们提出了三个具体的目标，进行随机，三盲临床试验，招募900 接受心脏手术的60岁或以上患者。通过这次试验，我们将确定 静脉注射对乙酰氨基酚; 1）术后谵妄的发生率、持续时间和严重程度，2）阿片类药物的使用 术后48小时内使用其他急救镇痛药，休息和活动时的每日疼痛评分， 3）长期（1个月、6个月、12个月）认知， 术后身体及自理功能恢复。我们将采用创新方法实现这些目标 在预定的时间内，每隔六小时静脉注射一种常规药物，持续48小时， 最大程度的继发性损伤炎症和术后疼痛所提出的研究是有意义的 因为它将确定通过多模式镇痛方法靶向炎症和疼痛是否可以 降低脆弱老龄人群术后谵妄的发生率。预期的结果是， 无论结果如何，这项工作都将是有趣的，它将确定静脉注射对乙酰氨基酚的作用 在预防谵妄和老年心脏手术患者的疼痛管理方面。结果会有 一个重要的积极影响，因为它们将促进广泛采用静脉注射对乙酰氨基酚作为疼痛 控制方式为老年人接受大手术，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与 管理方式和谵妄，以及其他重要的短期和长期结果的老年人 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.