Cognitive Effects of Body Temperature During Hypothermic Circulatory Arrest

Duke University

Status: Completed

Conditions: Cognition Disorders

Treatments: Device: Cardiopulmonary bypass machine

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT02834065

Pro00064962

1R01HL130443-01A1 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 273 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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273 participants in 3 patient groups

Deep Hypothermia

Active Comparator group

Description:

Initiation of circulatory arrest using the cardiopulmonary bypass machine at temperature ≤20 degrees Celsius

Treatment:

Device: Cardiopulmonary bypass machine

Low Hypothermia

Active Comparator group

Description:

Initiation of circulatory arrest using the cardiopulmonary bypass machine at temperature 20.1 - 24.0 degrees Celsius

Treatment:

Device: Cardiopulmonary bypass machine

Moderate Hypothermia

Active Comparator group

Description:

Initiation of circulatory arrest using the cardiopulmonary bypass machine at temperature 24.1 - 28 degrees Celsius

Treatment:

Device: Cardiopulmonary bypass machine