Abstract
BACKGROUND: Aortic arch surgery remains the only viable life-saving treatment for aortic arch disease. However, the necessity for cessation of systemic blood flow with hypothermic cardiac arrest carries substantial risk of morbidity and mortality, including poor neurological outcomes and kidney failure. While uncontrolled studies have suggested the safety of operating at warmer temperatures, significant variables remain un-investigated, supporting the need for a randomized clinical trial (RCT) to produce evidence-based guidelines for perfusion strategies in aortic surgery. This study proposes a multi-center RCT in order to compare outcomes of warmer hypothermic strategies during aortic hemiarch surgery on a composite endpoint of neurologic and acute kidney injury (AKI). METHODS/DESIGN: This is a prospective multi-center, single-blind two-arm RCT comparing mild (32 °C) versus moderate (26 °C) hypothermic cardiac arrest in patients (n = 282) undergoing hemiarch surgery with antegrade cerebral perfusion (ACP). The primary endpoint is a composite of neurological injury (incidence of transient ischemic attack and/or stroke) and Kidney Disease Improving Global Outcomes (KDIGO) stage 1 or higher AKI. Secondary outcomes include death, cardiopulmonary bypass time, bleeding, transfusion rates, prolonged mechanical ventilation, myocardial infarction, length of stay, and quality of life measures. Patients will undergo 1:1 block randomization to each treatment arm on day of surgery. Sequence of operation will be at the surgeon's discretion with mandatory guidelines for temperature and ACP administration. Perioperative management will occur as per enrolling center standard of care. Neurocognitive function will be assessed for neurological injury using validated neurological screening tests: NIHSS, MOCA, BI, and MRS throughout patient follow-up. Diagnosis and classification of AKI will be based on rising creatinine values as per the KDIGO criteria. Study duration for each patient will be 60 ± 14 days. DISCUSSION: It is hoped that performing hemiarch surgery using mild hypothermia (32 °C) and selective ACP will result in a 15% absolute risk reduction in the composite outcomes. The potential of this risk reduction will translate into improved patient outcomes, survival, and long-term financial savings to the health care system. In addition, the results of this trial will be used to create the first-ever guidelines for temperature management strategy during aortic surgery. TRIAL REGISTRATION: This trial is registered on ClinicalTrials.gov with the registration number NCT02860364. Registration date August 9th, 2016.