Cognitive Effects of Body Temperature During Hypothermic Circulatory Arrest

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.

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