Prediction and Prevention of Postoperative Mortality and Morbidity

Official title

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

Overview

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.

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.

Interventions

• 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 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 volunte
• 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 co
• 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 add
• 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 per
• Procedure Pre-operative Standard of Care
  Participants will receive routine preoperative clinical care per institutional standard practice.
• 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.

Primary outcome measures

• Postoperative Delirium (POD) [Time frame: At baseline screening, then up to 30 days post-operatively]

Secondary outcome measures (8)

• Depression [Time frame: at pre-operative baseline screening, and then at post-operative months of 1, 3, 6, and 12.]
• Dementia [Time frame: Post-operative months 6 and 12.]
• Postoperative Cognitive Decline (POCD) [Time frame: Post-operative months 1, 3, 6, and 12.]
• Postoperative Neurocognitive Disorder (PND) [Time frame: Post-operative months 1 and 3.]
• 30-day Major Adverse Cardiac and Cerebrovascular Events (MACCE) [Time frame: Within 30 days post-surgery.]
• Acute Kidney Injury (AKI) [Time frame: During index hospitalization, up to 30 days post-operatively.]
• Major Adverse Limb Events (MALE) [Time frame: Post-operative months 1, 3, 6, and 12.]
• Postoperative Stroke [Time frame: Within 30 days post-surgery.]

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
• 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Prevention

Study locations

United States · 5 centers

• UPMC Montefiore Hospital — Pittsburgh
• UPMC Presbyterian Hospital — Pittsburgh
• UPMC Shadyside Hospital — Pittsburgh
• UPMC Mercy Hospital — Pittsburgh
• UPMC Passavant Hospital — Pittsburgh

Identifiers

NCT: NCT06042413 · STUDY25110125

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗