Scheduled prophylactic 6-hourly intravenous acetaminophen to prevent postoperative delirium in older cardiac surgical patients (PANDORA) - Administrative Supplement
Funded Grant
Overview
Affiliation
View All
Overview
description
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 recruit diverse patient populations that better represent the U.S. population. Supplement Aim 2: To facilitate a robust safety workflow for participants. IMPACT: This application requests funds to enable site start-up and recruitment at participating centers with more diversity including greater representation of Latinx, Asian, and Black populations. A more diverse representation of minority populations will ensure the validity and reliability of the trial’s results. Additional funds can assist with hiring bilingual research staff that can support patient engagement and recruitment. Additionally, this application requests funds for the implementation of a robust safety profile for participants who have liver function tests that are greater than three times the upper limit of normal on postoperative day two, discharge, and at 1-month postoperatively. The proposed supplementary aims are well aligned with the top priority efforts of the NIH to enhance rigor and generalizability in scientific research.
