An Intervention to Reduce Delirium After Cardiac Surgery

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.