Prediction and Prevention of Postoperative Mortality and Morbidity

This study will contribute to creating a prospective and robust automated preoperative risk assessment algorithm for 30-day mortality, major adverse cardiac and cerebrovascular events (MACCE) and perioperative neurocognitive disorders (PND) outcomes following elective general, orthopedic, cardiac, or vascular surgery. It will help to identify correlations between perioperative factors and Alzheimer's Disease (AD) or AD-related dementias (ADRD). Lastly, this study will create effective, validated multi-modal interventions to improve perioperative health. This study will explore two main hypotheses: 1. Preoperative prehabilitation and proactive cognitive/behavioral interventions will effectively improve postoperative cognitive outcomes, morbidities, and mortality, and; 2. The proactive bundled interventions are superior to current standard of care in reducing postoperative cognitive outcomes, MACCE and mortality. Expected Outcome: Improved EHR algorithm will have higher predictive accuracy for MACCE and mortality while predicting postoperative cognitive outcomes.

This study will cover the following two specific aims:

Aim 1. A randomized controlled trial (RCT) to assess the effectiveness of pre-operative personalized prehabilitation with proactive cognitive and behavioral interventions versus standard of care on reducing postoperative cognitive outcomes (POD, POCD, dementia), MACCE, and mortality in high-risk surgical elderly patients (≥65y). Our Electronic Health Record (EHR)-based automated machine-learning risk prediction algorithm for postoperative mortality and MACCE has been developed using \>1.25 million surgical patients' data and implemented with superior performance to comparators. This EHR algorithm will identify 1000 patients at high risk for 30-day mortality and MACCE for Aim 1. Patients will be stratified by baseline cognition status and randomly assigned to standard of care (n=500) or personalized preoperative prehabilitation with proactive cognitive/behavioral interventions (physical exercise, cognitive training, enhanced social support, and proactive depression treatment) (n=500). Cognitive assessments will be performed at baseline, at discharge, 1-, 3-, 6-, and 12- months.

Aim 1 Hypothesis: Preoperative prehabilitation and proactive cognitive/behavioral interventions will effectively improve postoperative cognitive outcomes, morbidities, and mortality.

Aim 2: An RCT to examine the effectiveness of proactive intra-operative bundled interventions versus reactive standard of care to improve postoperative cognitive outcomes, MACCE, and mortality in high-risk surgical elderly patients scheduled for cardiac surgery with IONM. Intraoperative factors are associated with mortality, morbidity, and stroke. Intraoperative triple-low events (mean arterial pressure \<75 mmHg, Bispectral Index \<45, and minimum alveolar fraction \<0.8) are associated with postoperative cognitive outcomes. Eligible patients scheduled for IONM from Aim 1 (n=500) will be stratified based on Aim 1 intervention groups and randomized to either reactive standard of care intervention (n=250) or proactive bundled interventions to determine if optimizing intraoperative physiology reduces postoperative cognitive outcomes and 30-day MACCE and mortality. Both groups will receive reactive response to shifts in electroencephalography (EEG) and somatosensory evoked potential (SSEP). Proactive bundled interventions91 include maintaining normal blood pressure, oxygen levels, opioid sparing analgesia92-94, avoiding deep anesthesia95 and benzodiazepines.

Aim 2 Hypothesis: The proactive bundled interventions are superior to current standard of care in reducing postoperative cognitive outcomes, MACCE and mortality. Expected Outcome: Improved EHR algorithm will have higher predictive accuracy for MACCE and mortality while predicting postoperative cognitive outcomes

Eligibility Criteria:
Part I Inclusion Criteria:

* 65 years of age and older
* Identified as higher risk (≥2.5%) for 30-day mortality and MACCE based on the UPMC's Perioperative Model (EHR risk prediction algorithm)
* Scheduled for major cardiac surgeries including coronary artery bypass and valvular repair and/or vascular surgeries including carotid endarterectomy, aortic aneurysm repair, and major vascular surgeries
* RAI score ≥ 30
* PHQ-9 score ≥ 5
* Anticipated length of stay \> 3 days
* Informed consent
* English speaking patients
* All races and ethnicities
* Diverse background (education, area deprivation index)

Part II Inclusion Criteria:

* Patients undergoing high-risk cardiac and vascular surgery, such as intraoperative bypass for cardiac surgeries and carotid endarterectomy/ aortic aneurysm vascular surgeries.
* History of fully resolved stroke and TIA without any residual weakness
* Significant carotid artery stenosis (defined as \>70% unilateral or bilateral stenosis)
* Moderate and high risk for mortality based on Society of Thoracic Surgery score (score \>4)
* Enrolled in Part 1, "Randomized controlled clinical trial to assess the effectiveness of preoperative personalized prehabilitation as well as cognitive and behavioral interventions on reducing postoperative delirium (POD), postoperative cognitive dysfunction (POCD), dementia, 30-day major adverse cardiac and cerebrovascular events (MACCE) and mortality in high-risk surgical patients (≥65y)."

Part I Exclusion Criteria:

* Children (\<18 years)
* Patients unable to provide consent
* MoCA score \<23
* Persistent weakness from prior cerebrovascular accident
* Patients with severe preoperative medical diseases, blindness or significant visual impairment, unresolved motor weakness, or any other perioperative events or complications that would have a bearing on the patients' ability to perform study tasks, neuropsychological tests and proposed interventions

Part II Exclusion Criteria:

* Pregnant women
* Patients do not provide consent.
* Patients are unable to participate in cognitive and other behavioral assessment due to physical limitations
* Patients refuse any blood transfusions during surgery