Cognition Disorders
Conditions
Keywords
Postoperative Cognitive Decline, Deep Hypothermic Circulatory Arrest, Cardiovascular Surgical Procedures, Functional Magnetic Resonance Imaging, Small Ubiquitin-Related Modifier Proteins
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.
Interventions
DEVICECardiopulmonary bypass machine
Routinely used cardiopulmonary bypass machine (standard of care) will be used to initiate circulatory arrest
Sponsors
Emory Healthcare
University of Pennsylvania
National Institutes of Health (NIH)
Baylor Scott and White Health
National Heart, Lung, and Blood Institute (NHLBI)
Duke University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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
Exclusion criteria
* \< 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| Incidence of delirium | Up to post-operative day 3 | Confusion Assessment Method (CAM) |
| 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 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 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 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 | — |
| Change in employment status | From baseline to 1 year postoperatively | — |
| Change in Duke Activity Status Index score | From baseline to 4 weeks postoperatively | — |
Countries
United States
Outcome results
None listed