Prediction and Prevention of Postoperative Mortality and Morbidity
- Conditions
- Alzheimer Disease Related DementiasAlzheimer Disease
- Interventions
- Other: Personalized CPC PrehabilitationOther: Proactive Bundle InterventionsBehavioral: Cognitive TrainingBehavioral: MeditationBehavioral: Daily ExerciseBehavioral: Enhanced Social SupportProcedure: Pre-operative Standard of CareProcedure: Intra-operative Standard of Care
- Registration Number
- NCT06042413
- Lead Sponsor
- University of Pittsburgh
- Brief Summary
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.
- Detailed Description
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
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 1200
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group A/C (intervention) Personalized CPC Prehabilitation Participants randomized to this intervention group will receive the following interventions: * Personalized CPC Prehabilitation * Cognitive Training * Meditation * Daily Exercise * Enhanced Social Support Additionally, they will undergo standard of care routine intraoperative SSEP and EEG monitoring during the scheduled surgery. Group A/D (intervention + SOC) Intra-operative Standard of Care Participants randomized to this intervention group will receive the following interventions for study Part I: * Personalized CPC Prehabilitation * Cognitive Training * Meditation * Daily Exercise * Enhanced Social Support If eligible to continue to Study Part 2, participants who received the Part I intervention will receive standard of care monitoring that includes: Routine intraoperative SSEP and EEG monitoring. Group B/D (SOC + proactive bundle interventions) Intra-operative Standard of Care Participants randomized to the control group in study Part I will receive standard of care pre-operative treatment, which may or may not include a visit to the CPC. If eligible to continue to Study Part 2, participants who received standard of care pre-operatively, will receive Proactive Bundle Interventions during surgery that includes: Participants randomized to the proactive bundled intervention group (Group D) will receive a routine intraoperative SSEP and EEG monitoring as well as optimization of intraoperative physiology by maintaining normal blood pressure, oxygen levels, opioid sparing analgesia, avoiding deep anesthesia and benzodiazepines. Group A/D (intervention + SOC) Pre-operative Standard of Care Participants randomized to this intervention group will receive the following interventions for study Part I: * Personalized CPC Prehabilitation * Cognitive Training * Meditation * Daily Exercise * Enhanced Social Support If eligible to continue to Study Part 2, participants who received the Part I intervention will receive standard of care monitoring that includes: Routine intraoperative SSEP and EEG monitoring. Group A/C (intervention) Meditation Participants randomized to this intervention group will receive the following interventions: * Personalized CPC Prehabilitation * Cognitive Training * Meditation * Daily Exercise * Enhanced Social Support Additionally, they will undergo standard of care routine intraoperative SSEP and EEG monitoring during the scheduled surgery. Group B/C (SOC control) Pre-operative Standard of Care Participants randomized to the control group will receive standard of care pre-operative treatment, which may or may not include a visit to the CPC. Participants will receive standard of care routine intraoperative SSEP and EEG monitoring during the scheduled surgery. Group A/D (intervention + SOC) Meditation Participants randomized to this intervention group will receive the following interventions for study Part I: * Personalized CPC Prehabilitation * Cognitive Training * Meditation * Daily Exercise * Enhanced Social Support If eligible to continue to Study Part 2, participants who received the Part I intervention will receive standard of care monitoring that includes: Routine intraoperative SSEP and EEG monitoring. Group A/C (intervention) Daily Exercise Participants randomized to this intervention group will receive the following interventions: * Personalized CPC Prehabilitation * Cognitive Training * Meditation * Daily Exercise * Enhanced Social Support Additionally, they will undergo standard of care routine intraoperative SSEP and EEG monitoring during the scheduled surgery. Group A/C (intervention) Pre-operative Standard of Care Participants randomized to this intervention group will receive the following interventions: * Personalized CPC Prehabilitation * Cognitive Training * Meditation * Daily Exercise * Enhanced Social Support Additionally, they will undergo standard of care routine intraoperative SSEP and EEG monitoring during the scheduled surgery. Group A/C (intervention) Cognitive Training Participants randomized to this intervention group will receive the following interventions: * Personalized CPC Prehabilitation * Cognitive Training * Meditation * Daily Exercise * Enhanced Social Support Additionally, they will undergo standard of care routine intraoperative SSEP and EEG monitoring during the scheduled surgery. Group A/C (intervention) Intra-operative Standard of Care Participants randomized to this intervention group will receive the following interventions: * Personalized CPC Prehabilitation * Cognitive Training * Meditation * Daily Exercise * Enhanced Social Support Additionally, they will undergo standard of care routine intraoperative SSEP and EEG monitoring during the scheduled surgery. Group A/D (intervention + SOC) Cognitive Training Participants randomized to this intervention group will receive the following interventions for study Part I: * Personalized CPC Prehabilitation * Cognitive Training * Meditation * Daily Exercise * Enhanced Social Support If eligible to continue to Study Part 2, participants who received the Part I intervention will receive standard of care monitoring that includes: Routine intraoperative SSEP and EEG monitoring. Group B/D (SOC + proactive bundle interventions) Proactive Bundle Interventions Participants randomized to the control group in study Part I will receive standard of care pre-operative treatment, which may or may not include a visit to the CPC. If eligible to continue to Study Part 2, participants who received standard of care pre-operatively, will receive Proactive Bundle Interventions during surgery that includes: Participants randomized to the proactive bundled intervention group (Group D) will receive a routine intraoperative SSEP and EEG monitoring as well as optimization of intraoperative physiology by maintaining normal blood pressure, oxygen levels, opioid sparing analgesia, avoiding deep anesthesia and benzodiazepines. Group A/C (intervention) Enhanced Social Support Participants randomized to this intervention group will receive the following interventions: * Personalized CPC Prehabilitation * Cognitive Training * Meditation * Daily Exercise * Enhanced Social Support Additionally, they will undergo standard of care routine intraoperative SSEP and EEG monitoring during the scheduled surgery. Group B/C (SOC control) Intra-operative Standard of Care Participants randomized to the control group will receive standard of care pre-operative treatment, which may or may not include a visit to the CPC. Participants will receive standard of care routine intraoperative SSEP and EEG monitoring during the scheduled surgery. Group A/D (intervention + SOC) Daily Exercise Participants randomized to this intervention group will receive the following interventions for study Part I: * Personalized CPC Prehabilitation * Cognitive Training * Meditation * Daily Exercise * Enhanced Social Support If eligible to continue to Study Part 2, participants who received the Part I intervention will receive standard of care monitoring that includes: Routine intraoperative SSEP and EEG monitoring. Group A/D (intervention + SOC) Proactive Bundle Interventions Participants randomized to this intervention group will receive the following interventions for study Part I: * Personalized CPC Prehabilitation * Cognitive Training * Meditation * Daily Exercise * Enhanced Social Support If eligible to continue to Study Part 2, participants who received the Part I intervention will receive standard of care monitoring that includes: Routine intraoperative SSEP and EEG monitoring. Group A/D (intervention + SOC) Personalized CPC Prehabilitation Participants randomized to this intervention group will receive the following interventions for study Part I: * Personalized CPC Prehabilitation * Cognitive Training * Meditation * Daily Exercise * Enhanced Social Support If eligible to continue to Study Part 2, participants who received the Part I intervention will receive standard of care monitoring that includes: Routine intraoperative SSEP and EEG monitoring. Group A/D (intervention + SOC) Enhanced Social Support Participants randomized to this intervention group will receive the following interventions for study Part I: * Personalized CPC Prehabilitation * Cognitive Training * Meditation * Daily Exercise * Enhanced Social Support If eligible to continue to Study Part 2, participants who received the Part I intervention will receive standard of care monitoring that includes: Routine intraoperative SSEP and EEG monitoring. Group B/D (SOC + proactive bundle interventions) Pre-operative Standard of Care Participants randomized to the control group in study Part I will receive standard of care pre-operative treatment, which may or may not include a visit to the CPC. If eligible to continue to Study Part 2, participants who received standard of care pre-operatively, will receive Proactive Bundle Interventions during surgery that includes: Participants randomized to the proactive bundled intervention group (Group D) will receive a routine intraoperative SSEP and EEG monitoring as well as optimization of intraoperative physiology by maintaining normal blood pressure, oxygen levels, opioid sparing analgesia, avoiding deep anesthesia and benzodiazepines.
- Primary Outcome Measures
Name Time Method Cognitive Outcomes - Cognitive Function Postoperative 12-months The Montreal Cognitive Assessment (MoCA) will be used to assess cognitive functioning. A normal score is considered \>/= 26 out of 30 total points.
Cognitive Outcomes - Dementia Postoperative 12-months Clinical Dementia Rating Instrument (CDR) will be used to assess dementia. Ratings are as follows: 0 = none, 0.5 = questionable, 1 = mild, 2 = moderate, 3 = severe
Cognitive Outcomes - Delirium Postoperative 12-months The long CAM-Severity will be used to assess delirium. For a diagnosis of delirium by CAM, the subject must display: 1. Presence of acute onset and fluctuating discourse AND 2. Inattention AND EITHER 3. Disorganized thinking OR 4. Altered level of consciousness. Subjects will be reported as yes/no for delirium.
- Secondary Outcome Measures
Name Time Method Cognitive Outcomes - Depression Postoperative 12-months Patient Health Questionnaire (PHQ-9) will be used to assess depression. Scoring is as follows: 1-4 = minimal depression, 5-9 = mild depression, 10-14 = moderate depression, 15-19 = moderately severe depression, and 20-27 = severe depression
Trial Locations
- Locations (1)
UPMC Presbyterian Hospital
🇺🇸Pittsburgh, Pennsylvania, United States