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

点击翻译按钮获取中文摘要

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.