Cerebral Autoregulation in the Cardiac Surgery Intensive Care Unit: Associations with Postoperative Delirium, Cognitive Change, and Biomarkers of Brain Injury

PROJECT SUMMARY/ABSTRACT
Delirium occurs in up to 50% of patients after cardiac surgery and is associated with cognitive decline and
Alzheimer’s disease and related dementias (ADRD). However, the underlying mechanisms for these
complications are elusive. Further, the extent to which events in the early postoperative period increase risk
for delirium, cognitive decline, and ADRD is unclear. The goal of this proposal is to examine cerebrovascular
contributions to delirium / cognitive decline, with a focus on cerebral perfusion in the cardiac surgery intensive
care unit (ICU). Given the wide variations in blood pressure in the ICU, coupled with the high prevalence of
cerebrovascular disease, cerebral malperfusion in the ICU may contribute to delirium and cognitive decline.
Current practice of targeting empiric mean arterial pressure (MAP) goals in the perioperative period may be
inadequate for individual patients. Our group has championed a more personalized method based on cerebral
autoregulation monitoring. Through the process of cerebral autoregulation, the brain is regulated to maintain a
constant cerebral blood flow across a range of MAP. However, when MAP exceeds limits of autoregulation or
when autoregulation is impaired, compensatory mechanisms fail and inadequate or excessive cerebral blood
flow results. Our work in the cardiac surgery operating room has shown several results that emphasize the
importance of individualizing blood pressure goals. First, the MAPs at the limits of autoregulation vary widely
in patients, and both impaired autoregulation and MAP outside the limits of autoregulation are associated with
organ injury. Second, in a recent trial, targeting MAP to be >lower limit of autoregulation during cardio-
pulmonary bypass vs. usual care reduced delirium by 28% and improved memory scores at 1- and 12-months.
To date, the majority of research has been conducted in the operating room during cardiopulmonary bypass.
However, our preliminary data suggests that the early phase of ICU care may be equally important. In a small
pilot study, we found that in the ICU, the extent of MAP outside the limits of autoregulation, as well as impaired
autoregulation, were associated with delirium. Importantly, cognitive change was not assessed in this pilot and
mechanisms for these findings are unclear. These results motivate the proposed observational study, which
will examine whether (a) MAP outside the limits of autoregulation and (b) impaired autoregulation in the ICU
are associated with delirium after cardiac surgery (Aim 1) and cognitive change from baseline at 1- and 12-
months (Aim 2). In an exploratory mechanistic aim (Aim 3), we will characterize whether perioperative brain
injury mediates or baseline neurodegeneration moderates the association of cerebral autoregulation
characteristics and delirium and cognitive decline.
The results of this study will more precisely characterize the role of cerebral malperfusion in the ICU with
delirium and will identify mechanisms through which brain injury occurs. Promising results would also support
a trial to target MAP in the ICU based on these methods. Although the cohort is only followed for one year,
these results may also provide insight into potential mechanisms for longer-term cognitive decline and ADRD.

Grant Number: 4R01AG072387-02
NIH Institute/Center: NIH
Principal Investigator: Charles Brown