Delirium is common after cardiac surgery, occurring in 45-55% of patients, and is
independently associated with increased postoperative complications, reduced functional
capacity, cognitive decline, and increased mortality. Although the pathophysiology of
delirium is unclear, a leading hypothesis is that delirium results from unrecognized cerebral
ischemia during surgery. In preliminary data from the investigators group, delirium was
reduced in patients randomized to optimal blood pressure control during cardiopulmonary
bypass, using novel technology that determines an individual patient's lower limit of
cerebral autoregulation. Thus, patients undergoing cardiac surgery may suffer from
unrecognized cerebral ischemia that contributes to delirium, and strategies to attenuate the
effects of cerebral ischemia may reduce the incidence of delirium.
Ischemic preconditioning represents a novel strategy to attenuate the effects of cerebral
ischemia during cardiac surgery. Exposure to a brief period of ischemia, below the threshold
for tissue injury, has been demonstrated to protect against the harmful effects of a
subsequent more severe ischemic insult, in both animal and human studies. The protection
provided by ischemic preconditioning may also be effective when the preconditioning is
applied to a location remote from the organ of interest (i.e. a limb). Recently, a large
randomized trial in patients undergoing cardiac surgery demonstrated a survival benefit among
patients randomized to remote ischemic preconditioning vs. placebo. Remote ischemic
preconditioning was achieved by simple inflation of a blood pressure cuff to supra-systolic
pressures for 5 minutes, repeated for 3 cycles. However, neurological outcomes were not
assessed in this trial, although animal models support potential neurological protection
following remote ischemic preconditioning.
In this study the investigator will examine whether remote ischemic preconditioning can
reduce delirium, functional decline, and biomarkers of cerebral injury after cardiac surgery.
The investigator will explore the mechanism of preconditioning by examining proteomic
analyses in a subset of patients. These results will provide data to support an NIH trial to
examine the protective effects of remote ischemic preconditioning in cardiac surgery,
identify potential mechanisms of action and potential targets for therapeutic pharmacologic
interventions.
