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: 10023255
• 负责人: EDWARD R MARCANTONIO
• 金额: $ 141.64万
• 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/10023255
• 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 anatomy; Breathing; Cardiac; Cardiac Surgery procedures; Clinical; Clinical Trials; Cognition; Cognitive; Collection; Complication; Coughing; DNA; Delirium; Development; Elderly; Enrollment; Etiology; Exertion; Functional disorder; Future; Geriatrics; Hospitals; Hour; Impaired cognition; Incidence; Inflammation; Inflammation Mediators; Injury; Intensive Care Units; Intervention; Intravenous; Lead; Length of Stay; Measures; Medical; Methods; Modality; Multicenter Trials; National Institute on Aging; Neuraxis; Operative Surgical Procedures; Opioid; Opioid Analgesics; Outcome; Outcome Study; Pain; Pain management; Participant; Patients; Perioperative; Peripheral; Pharmaceutical Preparations; Pharmacology; Physical Function; Physiological; Placebos; 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; Sedation procedure; Self Care; Severities; Societies; Specimen; Telephone; Therapeutic Intervention; Time; Vulnerable Populations; Work; active method; aging population; bench to bedside; biobank; blind; cognitive function; cognitive testing; confusion assessment method; daily pain; functional decline; functional status; improved; innovation; instrumental activity of daily living; interest; modifiable risk; mortality; multimodality; neuroinflammation; older patient; opioid use; pain score; patient subsets; pilot trial; post-operative cognitive dysfunction; postoperative delirium; postoperative recovery; prevent; preventive intervention; prophylactic; response; stressor; symposium; therapeutically effective; treatment arm; Absence of pain sensation; Acetaminophen; Acute Disease; Address; Adoption; Age-Years; American; Analgesics; Anesthetics; Attention; Biological; Biological Availability; Blood; Blood - brain barrier anatomy; Breathing; Cardiac; Cardiac Surgery procedures; Clinical; Clinical Trials; Cognition; Cognitive; Collection; Complication; Coughing; DNA; Delirium; Development; Elderly; Enrollment; Etiology; Exertion; Functional disorder; Future; Geriatrics; Hospitals; Hour; Impaired cognition; Incidence; Inflammation; Inflammation Mediators; Injury; Intensive Care Units; Intervention; Intravenous; Lead; Length of Stay; Measures; Medical; Methods; Modality; Multicenter Trials; National Institute on Aging; Neuraxis; Operative Surgical Procedures; Opioid; Opioid Analgesics; Outcome; Outcome Study; Pain; Pain management; Participant; Patients; Perioperative; Peripheral; Pharmaceutical Preparations; Pharmacology; Physical Function; Physiological; Placebos; 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; Sedation procedure; Self Care; Severities; Societies; Specimen; Telephone; Therapeutic Intervention; Time; Vulnerable Populations; Work; active method; aging population; bench to bedside; biobank; blind; cognitive function; cognitive testing; confusion assessment method; daily pain; functional decline; functional status; improved; innovation; instrumental activity of daily living; interest; modifiable risk; mortality; multimodality; neuroinflammation; older patient; opioid use; pain score; patient subsets; pilot trial; post-operative cognitive dysfunction; postoperative delirium; postoperative recovery; prevent; preventive intervention; prophylactic; response; stressor; symposium; therapeutically effective; treatment arm

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.

项目摘要 /摘要 很少研究药理干预措施以减少术后del妄，其功效是 充其量没有定论和有争议。我们的目标是找到有效的预防干预措施 术后del妄，这是老年人心脏手术最常见和有害的并发症之一。 该提议的中心假设是预定的预防性6小时IV乙酰氨基酚可以预防 在手术后的前48小时内服用，旧心外科手术患者的术后del妄。 该提议的基本原理是，尽管存在多个病因因素 del妄，可修改的危险因素包括炎症，治疗不足的疼痛以及阿片类药物的使用。这些都是 使用静脉注射对乙酰氨基酚的独立风险因素可容纳干预。通过这个 直接干预，可以使用高度普遍的无毒药物来解决众所周知的 问题。我们提出了三个特定目标，通过进行随机的三重盲临床试验，该试验注册900 60岁或以上的患者接受心脏手术。通过此试验，我们将确定 IV对乙酰氨基酚； 1）术后del妄的发病率，持续时间和严重程度，2）使用阿片类药物 以及其他术后48个小时的救援镇痛药，静止和劳累的每日疼痛评分以及长度 在重症监护室住宿和整体住院时间3）长期（一个，六个，12个月）认知， 手术后的身体和自我保健功能恢复。我们将使用创新方法追求这些目标 在预定的六个小时间隔48小时内静脉内静脉注射常规药物，这是该期间 术后最大的继发损伤，炎症和疼痛。拟议的研究很重要 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 在脆弱的，老龄化的人群中减少术后del妄的发生率。预期的结果 无论发现如何，工作都会很有趣，将是确定IV对乙酰氨基酚的作用 在预防del妄的预防和较早心脏手术患者的疼痛管理中。结果将有 重要的积极影响，因为它们将有助于广泛采用静脉注射乙酰氨基酚作为痛苦 对接受大手术的老年人的控制方式，或提供有力的证据以消除其使用 被证明是无效的。此外，我们将进一步理解疼痛之间的关联 管理方式和del妄，以及其他重要的老年人的短期和长期结局 接受心脏手术。