Patients undergoing thoracic aortic surgery at Duke University Medical Center (DUMC) requiring hypothermic circulatory arrest (HCA) and neurophysiologic monitoring (NIOM) will give written informed consent and be enrolled into the study. Exclusion criteria will include previously documented allergy to nicardipine and age less than 18 years. Patients will then be randomized to one of two study groups: general anesthesia with or without nicardipine. Pre-operatively they will undergo clinical evaluation determined by the attending surgeon and anesthesiologist. During the pre-induction time period, all usual monitors and intravenous devices will be placed at the discretion of the attending anesthesiologist. In addition to the standard anesthetic monitors (Bispectral Index \[BIS\] and cerebral oximetry), transcranial Doppler (TCD) will be placed. Furthermore, the neurophysiology technician will place both standard EEG and somatosensory evoked potential (SSEP) electrode configurations. During the pre-induction time period, midazolam use will be at the discretion of the anesthesiologist but will be limited to a maximum dose of 0.1 mg/kg; other benzodiazepines will not be allowed. Opioid (fentanyl) administration will be at the discretion of the anesthesiologist. Total benzodiazepine and opioid doses will be recorded and converted to midazolam and fentanyl equivalents for subsequent analysis.

When ready, patients will be transported into the operating room and anesthesia will be induced. Induction will consist of propofol (1 - 5 mg/kg single intravenous bolus), fentanyl and vecuronium for neuromuscular blockade. Other drugs and dosages of opioids and neuromuscular blockers are at the discretion of the anesthesiologist. After induction and tracheal intubation, patients will receive maintenance anesthesia of 0.5 minimal alveolar concentration (MAC) isoflurane in a 50% air/oxygen balanced mixture supplemented with fentanyl at the discretion of the anesthesiologist. At the onset of cardiopulmonary bypass (CPB), study drug (nicardipine or equivalent volume of placebo - 0.9% saline) infusion at 5 mg/hr will be initiated, and patients will receive 0.5 MAC isoflurane in the CPB circuit sweep gas. Bolus doses of 100mcg phenylephrine will be administered to both groups in order to maintain a constant mean arterial pressure of at least 50 mmHg. Cooling will occur primarily through the CPB machine. When the patient's brain temperature reaches 28o C, isoflurane (via the pump) will be reduced to 0.25 MAC. When ECS on EEG and ablation of cortical responses on SSEP have both occurred, CPB and study drug infusion will be halted, and thoracic aortic surgery will be commenced. After aortic repair has occurred, CPB and study drug infusion at 5 mg/hr will be reinstated, anesthesia administration resumed, and the patient actively rewarmed. When the patient's brain temperature reaches 28o C (as recorded by nasopharyngeal temperature), patients will receive 0.5 MAC isoflurane. After the patient has been fully re-warmed and is ready for separation from CPB, study drug infusion will be halted. At this point, but not before, commercially available nicardipine may be infused if so desired. 10 ml blood samples will be drawn from the pump at baseline and 15 minute intervals thereafter until HCA is achieved. When the pump is restarted, further samples will be drawn at 15 minute intervals until the patient separates from CPB after which no further samples will be taken. One sample of 10 ml will be drawn from the retrograde cardioplegia line immediately after placement (baseline) and one sample will be drawn immediately prior to separation from CPB. In total, approximately 100 ml of blood will be drawn from the patient for research purposes. This volume represents a tiny percentage of the excess volume associated with the pump prime, and is insignificant in terms of its effect on hemodynamics.

Baseline patient characteristics will be collected in the pre-operative period and will include age, sex, weight, height, blood pressure, heart rate, temperature, comorbidities, type of aortic disease, and American Society of Anesthesiologists (ASA) grade. Prior to initiation of CPB, several factors will be recorded including arterial blood pressure, heart rate, cerebral oximetry, bispectral index score (BIS), latency \& amplitude of SSEP, frequency of EEG background, cerebral blood flow assessed by middle cerebral artery (MCA) velocity on TCD, and nasopharyngeal temperature. During cooling, BIS scores, cerebral oximetry, and MCA velocity by TCD will be noted for each 0.5o C decrement in nasopharyngeal temperature; the duration from CPB initiation to 3 characteristic EEG changes (1. rhythmic delta, 2. Generalized periodic epileptiform discharge (GPED), 3. burst suppression) as defined by the neurophysiologist, the duration from CPB initiation to 2 characteristic SSEP changes (1. latency increase of \>10%, 2. amplitude decrease of 50% from baseline), and hemodynamics at each 1o C nasopharyngeal temperature drop will also be recorded. At the time of HCA, several factors will be documented including nasopharyngeal temperature, duration from CPB initiation (the primary endpoint measure), total opioid doses, cerebral oximetry, BIS score, MCA velocity by TCD, hemodynamics. During rewarming, factors will be documented in the same fashion and at the same intervals as during cooling. At the first attempt at separation from CPB, documented factors will include BIS score, cerebral oximetry, MCA velocity by TCD, duration from CPB reinstitution to first attempt at separation, total dose of study drug, nasopharyngeal temperature, and hemodynamics. Finally, in addition to any Adverse Events (AEs) that may have occurred, data relating to length of ICU stay, length of hospital stay, in-hospital mortality, in-hospital acute kidney injury (defined as a 50% rise from baseline in serum creatinine, and of at least 0.3 mg/dl or need for dialysis), in-hospital stroke, in-hospital myocardial infarction, and discharge disposition from hospital (home, skilled nursing facility, other institution) will be recorded postoperatively.

With the exception of the on-pump blood draws, in this protocol there are no additional procedures or safety measures indicated or necessary for the purpose of research only. All anesthetic regimens and monitoring techniques are currently standard of care. Nicardipine infusion is currently widely used during cardiac anesthesia and post-operative cardiac recovery.