Cognitive Effects of Body Temperature During Hypothermic Circulatory Arrest
- Conditions
- Cognition Disorders
- Interventions
- Device: Cardiopulmonary bypass machine
- Registration Number
- NCT02834065
- Lead Sponsor
- Duke University
- Brief Summary
In this study the investigator will randomize 273 subjects to deep (\<20°C), low (20.1°C-24°C), or moderate (24.1°C-28°C) hypothermia during aortic arch surgery with circulatory arrest. The primary purpose of this study is to determine the effect of deep vs low vs moderate hypothermia on neurocognitive function, brain functional connectivity, and leukocyte SUMOylation patterns after surgical circulatory arrest in participants.
- Detailed Description
Purpose of the Study: Determine the effect of deep vs low vs moderate hypothermia on neurocognitive function, brain functional connectivity, and leukocyte SUMOylation patterns after surgical circulatory arrest.
Hypothesis: Deep hypothermia is superior to moderate hypothermia in reducing postoperative cognitive decline and preserving brain functional connectivity and that low hypothermia is non-inferior to deep hypothermia.
Design and Procedures: 273 informed and consenting patients who are scheduled for elective proximal aortic reconstructive surgery (ascending aorta + aortic valve or root) with concomitant proximal hemi- or total arch replacement via median sternotomy will be randomized to deep (\<20°C), low (20.1°C-24°C), or moderate (24.1°C-28°C) hypothermia during circulatory arrest. Cognitive testing using a standard battery will occur preoperatively (baseline), at 4 weeks, and at 1 year after surgery. Neuroimaging procedures before surgery, and at 4 weeks and 1 year after surgery will consist of high-resolution anatomic, resting-state fMRI (rs-fMRI) and magnetic resonance spectroscopy (MRS) sequences. To characterize leukocyte activation, whole blood will be drawn at 5 time points: at baseline (prior to surgery), before circulatory arrest, 10 minutes after reperfusion, 10 minutes after CPB, and 4 hours after CPB.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 273
- Patients who are scheduled for elective proximal aortic reconstructive surgery (ascending aorta + aortic valve or root) with concomitant proximal hemi- or total arch replacement via median sternotomy
- < 18 years of age
- History of symptomatic cerebrovascular disease, eg, prior stroke with residual deficit
- Alcoholism (> 2 drinks/day)
- Psychiatric illness (any clinical diagnoses requiring therapy)
- Drug abuse (any illicit drug use in the past 3 months)
- Hepatic insufficiency (liver function tests > 1.5 times the upper limit of normal)
- Severe pulmonary insufficiency (requiring home oxygen therapy)
- Renal failure (serum creatinine > 2.0 mg/dL)
- Claustrophobic fear
- Unable to read and thus unable to complete the cognitive testing
- Pregnant women
- Patients who score < 24 on a baseline Mini Mental State Examination (MMSE) or ≥ 27 on the baseline Center for Epidemiological Studies Depression (CES-D) scale
- Patients who have pre-existing unsafe implants for 3 Tesla magnetic resonance imaging (MRI).
- Patients who have received chemotherapy in the last 12 months.
- Patients with COVID-19 diagnosis within the past 12 months
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Low Hypothermia Cardiopulmonary bypass machine Initiation of circulatory arrest using the cardiopulmonary bypass machine at temperature 20.1 - 24.0 degrees Celsius Moderate Hypothermia Cardiopulmonary bypass machine Initiation of circulatory arrest using the cardiopulmonary bypass machine at temperature 24.1 - 28 degrees Celsius Deep Hypothermia Cardiopulmonary bypass machine Initiation of circulatory arrest using the cardiopulmonary bypass machine at temperature ≤20 degrees Celsius
- Primary Outcome Measures
Name Time Method Change in short-term cognition as measured by continuous cognitive score From baseline to 4 weeks post-operatively To characterize cognitive function over time while minimizing potential redundancy in the cognitive measures, a factor analysis will be performed on the cognitive test scores from baseline. A continuous change score will be calculated by subtracting the baseline cognitive index (the mean of the domain scores from factor analysis) from the follow-up cognitive index at 4 weeks.
- Secondary Outcome Measures
Name Time Method Change in neurological function as measured by NIHSS Assessed at baseline, post-op day 4, 4 weeks Change in neuronal metabolism From baseline to 4 weeks Magnetic resonance spectra (metabolic peaks) of myoinositol, creatine, choline and N-acetyl aspartate
Change in Duke Activity Status Index score From baseline to 4 weeks postoperatively Change in employment status From baseline to 1 year postoperatively Incidence of delirium Up to post-operative day 3 Confusion Assessment Method (CAM)
Change in SUMO 2/3 levels Pre-incision, before circulatory arrest, 10 minutes after reperfusion, 10 minutes after cardiopulmonary bypass, 4 hrs after cardiopulmonary bypass Change in depression score From baseline to 4 weeks postoperatively Measured by the Center for Epidemiological Studies Depression Scale (CES-D).
Change in long-term cognition as measured by continuous cognitive score From baseline to 1 year post-operatively To characterize cognitive function over time while minimizing potential redundancy in the cognitive measures, a factor analysis will be performed on the cognitive test scores from baseline. A continuous change score will be calculated by subtracting the baseline cognitive index (the mean of the domain scores from factor analysis) from the follow-up cognitive index at 1 year.
Change in resting-state functional connectivity From baseline to 4 weeks post-operatively For the rs-fMRI data, the analyses of primary interest will be the spontaneous, low-frequency fluctuations in the blood oxygen level dependent (BOLD) data of the Default Mode, Salience, and Executive Control Networks.
Change in anxiety score From baseline to 4 weeks postoperatively Measured by State Trait Anxiety Inventory (STA-I).
Change in SF-36 score From baseline to 1 year postoperatively
Trial Locations
- Locations (4)
Penn Presbyterian Medical Center
🇺🇸Philadelphia, Pennsylvania, United States
Emory Saint Joseph's Hospital
🇺🇸Atlanta, Georgia, United States
Duke University Health System
🇺🇸Durham, North Carolina, United States
Baylor Scott & White Research Institute
🇺🇸Plano, Texas, United States