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.
