Hypothesis: Patients with blue cerebrovascular reactivity (CVR) regional maps during a hypercapnic CO2 challenge will be at greater risk of developing post-operative delirium (POD) and stroke following major surgery. Blue CVR maps have also been recently documented with an O2 challenge. The blue CVR maps will be shown to be predictive of POD and stroke and ultimately represent a diagnostic test for patients at risk. These blue CVR maps will enable neurologic risk stratification for patients undergoing major surgery. Background: Major surgery is associated with a significant risk of postoperative morbidity and mortality. POD is a dreaded complication with such anesthesia and surgery. The prevalence of delirium after cardiac surgery has been reported to occur in up to 50% of patients. Using a definitive diagnostic tool such as the Confusion Assessment Method - Intensive Care Unit (CAM-ICU and CAM-S) results in the higher proportion reported. Delirium is a serious complication that results in prolonged length of stay, increased health care costs, and higher mortality. As much as $6.9 billion of Medicare hospital expenditures can be attributed to delirium. At such a cost, better diagnosis and treatment is urgently needed. Pre-emptive diagnosis leading to better management of delirium post-operatively is clearly one of the fundamental problems confronting modern anesthesia and peri-operative medicine.

Specific Objectives: The investigators seek to address (a) the identity of patients who have the greatest vulnerability to the surgery and (b) investigate the risks and test appropriate risk mitigations. Understanding POD is of immense import to help control a hospital's surgical and critical care costs. Patients with neurological consequences including POD often represent a choke point for optimized critical care utilization. At the very least, improved understanding and a diagnostic test to highlight patients at risk of POD would be most welcome. Such an advance would permit rational strategies to limit the problem and allow better designed therapeutic arcs for patients now known to be at risk. This is especially important for patients undergoing complicated major surgery and is the focus of this pilot project. Tighter control of ET respiratory gases may be indicated for both ET CO2 and ET O2 based on the results of this preliminary study.

Methods: Informed witnessed consent will be obtained from all participants. Patients will have a Mini Mental State Exam (MMSE) prior to their MRI studies. A battery of neurocognitive tests will be undertaken for each subject prior to surgery. This test battery will include PHQ-9, GAD-7, Trails A and WAIS-IV Digit Span, Hopkins Verbal Learning Test Revised, Rey's Complex Figure, DKEFS, F-A-S, CLOX I and II. This will take 45-60 minutes. Patients will have CVR maps with blood oxygen level dependent (BOLD-MRI) pulse sequences done with standard RespirAct (a computer-controlled gas blender) protocols in association with anatomic imaging in a 3.0 Tesla magnet. The clinical care team and patient will be blinded as to the CVR results. Patients will have standardized anesthesia and per usual approaches for their major surgery and have standard POD assessment tools (CAM-ICU and CAM-S). Storage of anesthesia hemodynamics will be to digital data acquisition systems for later collation. End-tidal CO2 will be targeted at patient baseline values +/- 2.5 mmHg during the surgical procedure and if ventilated for any period post-operatively. Inspired O2 will be targeted to 0.3 - 0.6, based on pulse oximetry of greater than 95% with adequate arterial oxygenation confirmed by ABG. Standard fast-track protocols and admission to the surgical special care unit (SSCU) will be undertaken to facilitate patient management. Any patient with obvious POD, post-op delirium or stroke will be managed per usual protocols. Multiple CVR maps (650 studies) have been done at University Health Network in Toronto. As well over 150 studies have been conducted at the Health Sciences Centre at the University of Manitoba in the past 5 years.

Significance/Importance: This study has the potential to make an important contribution in the understanding of POD for all surgical procedures and specifically a window into the problem with major surgery. A positive study based on our hypothesis can fundamentally change our understanding of cognitive dysfunction after surgery. Large follow-up multicentre trials can be constructed based on initial findings from this pilot study if the study bears fruit. At the least, further elucidation into POD for major surgery is expected with this study. tighter control of end-tidal gases may be a consequence of the findings of this study.

Inclusion Criteria:

• major surgery
• able to tolerate CO2 and O2 stress test

Exclusion Criteria:

• diagnosed dementia
• unable to have MRI
• excessive claustrophobia
• unstable angina, recent myocardial infarction (MI)
• chronic obstructive pulmonary disease (COPD)

Patients scheduled to undergo major surgery.