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

定期预防性每 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

• 批准号: 10543413
• 负责人: EDWARD R MARCANTONIO
• 金额: $ 163.32万
• 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/10543413
• 关键词: Absence of pain sensation; Acetaminophen; Acute Disease; Address; Adoption; Age Years; American; Analgesics; Anesthetics; Attention; Biological; Biological Availability; Blood; Blood brain barrier dysfunction; Breathing; Cardiac Surgery procedures; Central Nervous System; Clinical; Cognition; Cognitive; Collection; Complication; Coughing; DNA; Delirium; Development; Elderly; Etiology; Exertion; Future; Geriatrics; Hospitals; Hour; Impaired cognition; Incidence; Inflammation; Inflammation Mediators; Injury; Intensive Care Units; Intervention; Intravenous; Length of Stay; Measures; Medical; Methods; Modality; Morbidity - disease rate; Multicenter Trials; National Institute on Aging; Operative Surgical Procedures; Opioid; Opioid Analgesics; Outcome; Outcome Study; Pain; Pain management; Participant; Patients; Perioperative; Peripheral; Pharmaceutical Preparations; Physical Function; Physiological; Placebo Control; Plasma; Population; Postoperative Pain; Postoperative Period; Prevention; Property; Public Health; Randomized; Randomized, Controlled Trials; Recovery of Function; Reporting; Research; Research Personnel; Resources; Rest; Risk; Risk Factors; Role; Sampling; Schedule; Scoring Method; Sedation procedure; Self Care; Severities; Societies; Specimen; Telephone; Therapeutic Intervention; Time; Vulnerable Populations; Work; active method; aging population; bench to bedside; biobank; blind; clinical trial enrollment; cognitive function; cognitive testing; confusion assessment method; daily pain; functional decline; functional status; improved; innovation; instrumental activity of daily living; interest; intravenous administration; modifiable risk; mortality; multimodality; neuroinflammation; older patient; opioid use; pain score; patient subsets; pharmacologic; pilot trial; post intervention; post-operative cognitive dysfunction; postoperative delirium; postoperative recovery; prevent; preventive intervention; prophylactic; response; stressor; symposium; therapeutically effective; treatment arm; trial enrollment

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.

项目概要/摘要 很少有药物干预研究可以减少术后谵妄，其功效是 充其量是不确定的和有争议的。我们的目标是找到有效的预防干预措施 术后谵妄是老年人心脏手术最常见和最有害的并发症之一。 该提案的中心假设是，定期预防性注射 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 小时内给药可能导致术后谵妄。 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。其中每一个都是一个 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 通过直接干预，可以使用高度流行的无毒药物来解决众所周知的问题 问题。我们通过开展一项随机、三盲临床试验提出了三个具体目标，该试验招募了 900 名患者 60 岁或以上接受心脏手术的患者。通过这次试验，我们将确定效果 IV 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 小时内使用的其他救援镇痛药、每日休息和劳累时的疼痛评分以及时长 重症监护病房的住院时间和总住院时间 3) 长期（1、6、12 个月）认知、 手术后身体和自理功能的恢复。我们将使用创新方法来实现这些目标 定期静脉注射常规药物，每六小时一次，持续 48 小时，即 最大程度的继发性损伤、炎症和术后疼痛。拟议的研究意义重大 因为它将决定通过多模式镇痛方法针对炎症和疼痛是否可以 降低弱势、老龄化人群术后谵妄的发生率。本次活动的预期结果 无论结果如何，这项工作都会很有趣，它将确定静脉注射对乙酰氨基酚的作用 预防谵妄，以及老年心脏手术患者的疼痛管理。结果将有 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止痛药 控制接受大手术的老年人的方式，或提供有力的证据来消除其使用，如果 被证明是无效的。此外，我们将进一步了解疼痛之间的关联 管理方式和谵妄，以及老年人的其他重要的短期和长期结果 正在接受心脏手术。