Prediction and Prevention of Postoperative Mortality and Morbidity

Real-world and Innovative Multimodal Prediction and Prevention of Postoperative Mortality and Multi-morbidities

This study will contribute to creating a prospective and automated preoperative risk assessment algorithm for predicting 30-day mortality, major adverse cardiac and cerebrovascular events (MACCE), and postoperative neurocognitive outcomes following elective cardiac and vascular surgery in older adults. It will evaluate associations between perioperative factors and longer-term neurocognitive outcomes, including postoperative neurocognitive disorder and dementia. In addition, this study will assess scalable, multimodal preoperative and intraoperative interventions to improve perioperative outcomes.

This study will explore two main hypotheses:

1. Preoperative personalized prehabilitation with proactive cognitive and behavioral interventions will improve postoperative cognitive outcomes, morbidity, and mortality in high-risk elderly surgical patients.
2. Proactive bundled intraoperative interventions are superior to reactive 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.

Study Overview

• Status: Not yet recruiting
• Conditions: Dementia; Postoperative Delirium (POD); Postoperative Cognitive Decline; Perioperative Complications; Postoperative Neurocognitive Disorder; Major Adverse Cardiac and Cerebrovascular Events
• Intervention / Treatment: Behavioral: Cognitive Training; Behavioral: Meditation; Behavioral: Daily Exercise; Procedure: Intra-operative Standard of Care; Other: Personalized CPC Prehabilitation; Behavioral: Enhanced Social Support; Procedure: Pre-operative Standard of Care; Other: Proactive Bundle Interventions

Detailed Description

This study will cover the following two specific aims:

Aim 1. A pragmatic, non-randomized study to assess the effectiveness of preoperative personalized prehabilitation with proactive cognitive and behavioral interventions versus standard of care on reducing postoperative cognitive outcomes (including postoperative delirium within 30 days, postoperative cognitive decline, and dementia), MACCE, and mortality in high-risk surgical elderly patients (≥65 years). 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 approximately 1,000 patients at high risk for 30-day mortality and MACCE who proceed to surgery for Aim 1. Participants will receive either standard of care (n=500) or CPC-guided personalized preoperative prehabilitation with proactive cognitive or behavioral interventions (physical exercise, cognitive training, enhanced social support, and depression support) (n=500), based on real-world clinical referral practices rather than randomization. Cognitive assessments will be performed at baseline, discharge, and at 1, 3, 6, and 12 months.

Aim 2 Hypothesis: Proactive bundled intraoperative interventions are superior to standard intraoperative care in reducing postoperative cognitive outcomes, MACCE, and mortality.

Expected Outcome: The refined EHR-based risk prediction algorithm will demonstrate improved accuracy for predicting MACCE, mortality, and postoperative cognitive outcomes.

• Study Type: Interventional
• Enrollment (Estimated): 1200
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Alisha Maslanka, BS, CCRC; Phone Number: 4128646779; Email: maslankaaa@upmc.edu
• Study Contact Backup: Name: Dayana Alsamsam, BSPS, MSc; Phone Number: 412-623-4147; Email: alsamsamd@upmc.edu

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • UPMC Presbyterian Hospital
      • Contact: Alisha Maslanka, BS, CCRC; Phone Number: 412-864-6779; Email: maslankaaa@upmc.edu
      • Contact: Senthilkumar Sadhasivam; Phone Number: 317-948-3845; Email: ssadhasivam@IUHealth.org
    • Pittsburgh, Pennsylvania, United States, 15219
      • UPMC Mercy Hospital
      • Contact: Senthil Sadhasivam, MD; Phone Number: 4126474484; Email: sadhasivams@upmc.edu
    • Pittsburgh, Pennsylvania, United States, 15213
      • UPMC Montefiore Hospital
      • Contact: Senthil Sadhasivam, MD; Phone Number: 4126474484; Email: sadhasivams@upmc.edu
    • Pittsburgh, Pennsylvania, United States, 15237
      • UPMC Passavant Hospital
      • Contact: Senthil Sadhasivam, MD; Phone Number: 4126474484; Email: sadhasivams@upmc.edu
    • Pittsburgh, Pennsylvania, United States, 15213
      • UPMC Shadyside Hospital
      • Contact: Senthil Sadhasivam, MD; Phone Number: 4126474484; Email: sadhasivams@upmc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Older Adult
• Accepts Healthy Volunteers: No

Description

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
• Informed consent
• English speaking patients

Part II Inclusion Criteria:

• Enrolled in Aim 1 / Part I Preoperative Intervention Trial
• Scheduled for high-risk, cardiac or vascular surgery requiring intraoperative neurophysiological monitoring (IONM)
• Moderate and high risk for mortality based on Society of Thoracic Surgery score (score >4)

Part I Exclusion Criteria:

• Children (<18 years)
• Patients unable to provide consent
• Participants undergoing same day procedures or operations (discharged same day)
• Patients with severe preoperative medical diseases such as blindness or significant visual impairment, unresolved motor weakness, or any other perioperative events or complications that would have a bearing on the patient's 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CPC Preoperative Intervention (Aim 1); Participants referred to the Center for Perioperative Care (CPC) by their surgical team will receive preoperative prehabilitation and proactive cognitive and behavioral interventions prior to surgery. Assignment to this group is not randomized and reflects real world clinical practice. Participants will receive standard intraoperative monitoring during surgery.	Behavioral: Cognitive Training; Participants will be provided with access to the Lumosity (Lumos Labs) software for installation on a home device. They will be trained to navigate the touchscreen tablet and guided through an introductory series of brain exercise games focused on 5 main categories: memory, speed, attention, flexibility, and problem-solving. Patients will be asked to complete a cognitive exercise dosage of a minimum of 20 minutes a day for ≥5 days prior to their date of surgery. Research coordinators and volunteers from UPMC's Hospital Elder Life Program (HELP) will reach out to participants daily for a quick social check-in and to remind them to perform their training. Compliance data will be retrieved from the Lumosity app.; Behavioral: Meditation; A single guided meditation session with instructions will be provided using a smart device. The meditation session will last for at least 10 minutes daily starting at least 1-week prior to surgery. If the subject does not own a smart device, one will be provided or meditation will be completed in-person or over the phone.; Behavioral: Daily Exercise; Participants in the intervention group will meet with an occupational or physical therapist approximately 1-6 weeks before surgery who will discuss the potential benefits of exercise and give directions for an easy strength training exercise. Participants will then be provided with a video link for a guided exercise and encouraged to walk or perform a seated strength exercise for ≥ 5 minutes each day for at least 1 week before surgery and after surgery. Patient reported frequency, fitness app compliance and exercise duration with REDCap email or mobile link or over telephone will be collected before and after surgery. Patients will be cleared by an occupational or physical therapist to perform the upper-extremity exercises and will confirm the exercises are not contraindicated after surgery. An occupational or physical therapist will see subject again post-surgery to mitigate risk of injury.; Procedure: Intra-operative Standard of Care; This includes routine intraoperative SSEP and EEG monitoring. Physician oversight and interpretation of real-time neuromonitoring data will be performed using a combined on-site and remote model at UPMC. In the event that changes in EEG or SSEP are considered significant by the oversight neurophysiologists, the surgical team will be immediately informed so that immediate appropriate action can be taken to reverse the change.; Other: Personalized CPC Prehabilitation; Patients referred for elective surgery will be scheduled for a preoperative evaluation (3 to 6 weeks prior to surgery) and will receive standardized and personalized assessment and prehabilitation according to UPMC disease specific algorithms; Behavioral: Enhanced Social Support; Research coordinators and volunteers from the Hospital Elder Life Program (HELP) will contact participants prior to surgery to discuss concerns, provide regular social support, and remind participants to complete assigned cognitive exercises. The role of family members and caregivers in supporting the participant will also be discussed, and their involvement will be encouraged when appropriate. Participants in the CPC preoperative intervention group may receive preoperative interventions to address depressive symptoms as part of CPC-guided prehabilitation, when clinically indicated.
Active Comparator: Preoperative Standard of Care (Aim 1); Participants who do not receive CPC referral will receive standard preoperative care prior to surgery. Assignment to this group is not randomized. Participants will receive standard intraoperative monitoring during surgery.	Procedure: Intra-operative Standard of Care; This includes routine intraoperative SSEP and EEG monitoring. Physician oversight and interpretation of real-time neuromonitoring data will be performed using a combined on-site and remote model at UPMC. In the event that changes in EEG or SSEP are considered significant by the oversight neurophysiologists, the surgical team will be immediately informed so that immediate appropriate action can be taken to reverse the change.; Procedure: Pre-operative Standard of Care; Participants will receive routine preoperative clinical care per institutional standard practice.
Experimental: Proactive Bundled Intraoperative Interventions (Aim 2); Participants in Aim 2 are drawn from Aim 1 participants who meet IONM eligibility. Participants requiring intraoperative neurophysiological monitoring will be randomized on the day of surgery to receive proactive bundled intraoperative interventions in addition to standard intraoperative monitoring.	Procedure: Intra-operative Standard of Care; This includes routine intraoperative SSEP and EEG monitoring. Physician oversight and interpretation of real-time neuromonitoring data will be performed using a combined on-site and remote model at UPMC. In the event that changes in EEG or SSEP are considered significant by the oversight neurophysiologists, the surgical team will be immediately informed so that immediate appropriate action can be taken to reverse the change.; Other: Proactive Bundle Interventions; Participants randomized to the proactive bundled intervention group (Group D) will receive routine intraoperative SSEP and EEG monitoring and proactive optimization of intraoperative physiology, including maintaining mean arterial pressure ≥65 mmHg, adequate oxygenation, opioid sparing analgesia, and avoidance of deep anesthesia and benzodiazepines. If persistent focal changes in SSEP and EEG (i.e., changes in one hemisphere) occur, reactive measures will be implemented to increase cerebral perfusion, including ensuring hematocrit >30, maintaining anesthetic BIS >50-60, and initiating stroke management and thrombectomy if clinically indicated
Active Comparator: Reactive Intraoperative Standard of Care (Aim 2); Participants in Aim 2 are drawn from Aim 1 participants who meet IONM eligibility. Participants requiring intraoperative neurophysiological monitoring will be randomized on the day of surgery to receive reactive standard of care intraoperative management with routine SSEP and EEG monitoring.	Procedure: Intra-operative Standard of Care; This includes routine intraoperative SSEP and EEG monitoring. Physician oversight and interpretation of real-time neuromonitoring data will be performed using a combined on-site and remote model at UPMC. In the event that changes in EEG or SSEP are considered significant by the oversight neurophysiologists, the surgical team will be immediately informed so that immediate appropriate action can be taken to reverse the change.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative Delirium (POD)	Postoperative delirium will be assessed using the Confusion Assessment Method (CAM). Participants will be classified as having delirium or not having delirium based on standard CAM criteria. A positive CAM indicates the presence of delirium.	At baseline screening, then up to 30 days post-operatively

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Depression	Patient Health Questionnaire (PHQ-9) will be used to assess depression symptoms. Scores range from 0 to 27, with higher scores indicating more severe depression. Scoring is as follows: 1 to 4 minimal, 5 to 9 mild, 10 to 14 moderate, 15 to 19 moderately severe, and 20 to 27 severe depression.	at pre-operative baseline screening, and then at post-operative months of 1, 3, 6, and 12.
Dementia	Dementia severity will be assessed using the Clinical Dementia Rating scale (CDR). Scores range from 0 (none) to 3 (severe).	Post-operative months 6 and 12.
Postoperative Cognitive Decline (POCD)	Cognitive function will be assessed using the Montreal Cognitive Assessment (MoCA). Scores range from 0 to 30, with higher scores indicating better cognitive function. Postoperative cognitive decline will be defined as a decline in MoCA score compared with the preoperative baseline.	Post-operative months 1, 3, 6, and 12.
Postoperative Neurocognitive Disorder (PND)	Postoperative neurocognitive disorder will be assessed based on changes from preoperative baseline in standardized cognitive assessments, including the Montreal Cognitive Assessment (MoCA). Declines in cognitive performance relative to baseline will be used to identify postoperative neurocognitive disorder.	Post-operative months 1 and 3.
30-day Major Adverse Cardiac and Cerebrovascular Events (MACCE)	This outcome measures whether a participant experiences any major adverse cardiac or cerebrovascular event within 30 days after surgery. Events included in this composite outcome are death from any cause, myocardial infarction (heart attack), stroke, or cardiac arrest. Participants will be counted once if they experience one or more of these events during the 30 day postoperative period.	Within 30 days post-surgery.
Acute Kidney Injury (AKI)	Incidence of postoperative acute kidney injury based on changes in serum creatinine during the index hospitalization, consistent with standard clinical criteria.	During index hospitalization, up to 30 days post-operatively.
Major Adverse Limb Events (MALE)	Incidence of major adverse limb events including surgical or catheter-based revascularization or amputation. MALE includes any open surgical revascularization procedure (i.e., femoral endarterectomy, bypass surgery, thrombectomy or embolectomy, etc), catheter directed lysis to the lower extremities, and above ankle amputation.	Post-operative months 1, 3, 6, and 12.
Postoperative Stroke	Incidence of postoperative stroke confirmed by clinical diagnosis.	Within 30 days post-surgery.

Collaborators and Investigators

• Sponsor: University of Pittsburgh
• Collaborators: National Institute on Aging (NIA)
• Investigators: Study Director: Amy Monroe, MPH, MBA, University of Pittsburgh; Principal Investigator: Senthilkumar Sadhasivam, MD, MPH, MBA, University of Pittsburgh

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: September 6, 2023
• First Submitted That Met QC Criteria: September 13, 2023
• First Posted (Actual): September 18, 2023

Study Record Updates

• Last Update Posted (Actual): June 4, 2026
• Last Update Submitted That Met QC Criteria: June 2, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Cognitive decline; Postoperative delirium; Neurocognitive disorder; MACCE; Perioperative brain health
• Additional Relevant MeSH Terms: Neurologic Manifestations; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Postoperative Complications; Pathologic Processes; Confusion; Neurobehavioral Manifestations; Cognition Disorders; Delirium; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Postoperative Cognitive Complications; Emergence Delirium; Cognitive Dysfunction; Dementia; Neurocognitive Disorders; Therapeutics; Mind-Body Therapies; Complementary Therapies; Spiritual Therapies; Patient Care; Health Services; Health Care Facilities Workforce and Services; Behavior Therapy; Psychotherapy; Behavioral Disciplines and Activities; Rehabilitation; Aftercare; Continuity of Patient Care; Neurological Rehabilitation; Relaxation Therapy; Cognitive Training; Meditation
• Other Study ID Numbers: STUDY25110125; R01AG085115 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No