Comparing Hypothermic Temperatures During Hemiarch Surgery

Study Overview
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Brief Summary
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Hypothermic circulatory arrest is an important surgical technique, allowing complex aortic surgeries to be performed safely. Hypothermic circulatory arrest provides protection to cerebral and visceral organs, but may result in longer cardiopulmonary bypass times during surgery, increased risks of bleeding, inflammation, and neuronal injury. To manage these consequences, a trend towards warmer core body temperatures during circulatory arrest has emerged. This trial will randomize patients to either mild (32°C) or moderate (26°C) hypothermia during aortic hemiarch surgery to determine if mild hypothermia reduces the length of cardiopulmonary bypass time and other key measures of morbidity and mortality.

Official Title
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A Randomized Controlled Trial of Mild vs. Moderate Hypothermia on Patient Outcomes in Aortic Hemiarch Surgery With Anterograde Cerebral Perfusion

Conditions
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Thoracic Aortic Disease

Intervention / Treatment
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* Procedure: Hypothermic circulatory arrest


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years Elective aortic hemiarch surgery Planned unilateral selective anterograde cardioplegia Anticipated lower body arrest time of < 20 minutes Able to provide written informed consent Exclusion Criteria: Surgery for acute aortic dissection or emergent operations Total arch replacement Inability to perform unilateral selective anterograde cerebral perfusion (uSACP) Patients with known/documented coagulopathy Patients with cold agglutinin disease or those that test positive on routine preop screening Pre-existing severe neurological impairment or inability to accurately assess neurocognitive function as determined by the operating surgeon Severe carotid disease, defined as: any patient with previously documented carotid stenosis of > 70% (via Doppler ultrasound (US), magnetic resonance angiography (MRA), or computer tomography angiography (CTA)) without neurological deficits; or carotid stenosis > 50% with neurological deficits; or previous carotid endarterectomy or stenting Patients in renal failure or currently being treated with renal replacement therapy (RRT) or estimated glomerular filtration rate (eGFR) < 30 ml/min/1.73m2 Use of an investigational drug or device at time of enrollment Participation in another clinical trial which interferes with performance of the study procedures or assessment of the outcomes

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mild Hypothermic Circulatory Arrest<br>During aortic hemiarch surgery, mild hypothermia (32°C) will be used during circulatory arrest. | Procedure: Hypothermic circulatory arrest<br>* During cardiac surgery requiring circulatory arrest, the patient's body temperature is lowered significantly to reduce the cellular metabolic rate and reduce ischemic injury.<br>|
| Active Comparator: Moderate Hypothermic Circulatory Arrest<br>During aortic hemiarch surgery, moderate hypothermia (26°C) will be used during circulatory arrest. | Procedure: Hypothermic circulatory arrest<br>* During cardiac surgery requiring circulatory arrest, the patient's body temperature is lowered significantly to reduce the cellular metabolic rate and reduce ischemic injury.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite endpoint of neurologic and acute kidney injury | The primary objective of this study is to determine whether mild hypothermia (32°C) during aortic hemiarch surgery using unilateral selective anterograde cerebral perfusion (uSACP), is superior to moderate hypothermia (26°C) in reducing the composite endpoint of neurologic and acute kidney injury. | Up to 90 days after surgery. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rates of Neurologic Injury | Comparison of mild (32°C) vs moderate (26°C) hypothermia in aortic hemiarch surgery with respect to incidence of neurologic injury, including transient ischemic attack (TIA) and permanent neurological dysfunction (PND) or stroke. | Up to 90 days after surgery. | 
| Incidence of Silent Strokes | Comparison of mild (32°C) vs moderate (26°C) hypothermia in aortic hemiarch surgery with respect to the incidence of silent strokes, defined as infarctions identified during magnetic resonance imaging (MRI) in patients without neurologic symptoms. | Up to 90 days after surgery. | 
| Incidence of Acute Kidney Injury (AKI) | Comparison of mild (32°C) vs moderate (26°C) hypothermia in aortic hemiarch surgery with respect to the incidence of acute kidney injury (AKI), defined as Stage 1 or greater using the KDIGO criteria. Using the KDIGO criteria, Stage 1 AKI is defined as an increase in serum creatinine of 1.5-1.9x the baseline or an increase >= 27umol/L with urine output <0.5mL/kg/hour for 6-12 hours. | Up to 90 days after surgery. | 
| Incidence of Delirium | Comparison of mild (32°C) vs moderate (26°C) hypothermia in aortic hemiarch surgery with respect to the incidence of delirium, using the Confusion Assessment Method (CAM). The Confusion Assessment Method defines delirium as the presence of acute changes in mental status with fluctuating course, plus inattention and the presence of either disorganized thinking OR altered level of consciousness. | Up to 90 days after surgery. | 
| Death | Comparison of mild (32°C) vs moderate (26°C) hypothermia in aortic hemiarch surgery with respect to the incidence of death | Up to 90 days after surgery. | 
| Evaluate differences in the duration of cardiopulmonary bypass used in patients who receive mild or moderate hypothermic circulatory arrest during aortic hemiarch surgery | Comparison of mild (32°C) vs moderate (26°C) hypothermia in aortic hemiarch surgery with respect to the length of time that the patient remains on cardiopulmonary bypass. | During the index procedure | 
| Rates of Mediastinal re-exploration for bleeding | Comparison of mild (32°C) vs moderate (26°C) hypothermia in aortic hemiarch surgery with respect to the rates of mediastinal re-exploration (re-operation) for bleeding. | Up to 90 days after surgery. | 
| Incidence and quantity of perioperative blood transfusions | Comparison of mild (32°C) vs moderate (26°C) hypothermia in aortic hemiarch surgery with respect to the number and quantity of perioperative blood transfusions | Up to 90 days after surgery. | 
| Incidence of prolonged Mechanical Ventilation | Comparison of mild (32°C) vs moderate (26°C) hypothermia in aortic hemiarch surgery with respect to the duration of mechanical ventilation. Mechanical ventilation will be defined as use of a mechanical ventilator ≥48 hours. | Up to 90 days after surgery. | 
| Perioperative Myocardial Infarction | Comparison of mild (32°C) vs moderate (26°C) hypothermia in aortic hemiarch surgery with respect to the incidence of perioperative myocardial infarction. This will be clinically diagnosed using a combination of electrocardiographic (new Q wave on 12 lead ECG) and/or biochemical (TnI > 45 ng/L) markers. | Up to 48 hours after surgery. | 
| Length of Stay | Comparison of mild (32°C) vs moderate (26°C) hypothermia in aortic hemiarch surgery with respect to the duration of a patient's stay in the intensive care unit and on the hospital ward. | Up to 90 days after surgery. | 
| Quality of life (SF-12) | Comparison of mild (32°C) vs moderate (26°C) hypothermia in aortic hemiarch surgery with respect to the patient's quality of life measured using the Short Form (SF) 12 questionnaire. | Up to 90 days after surgery. |