1. Predictors of Electrocerebral Inactivity With Deep Hypothermia Nicholas D. Andersen, MD, Michael L. James, MD, Madhav Swaminathan, MD, Aatif Husain, MD, Barbara Phillips-Bute, PhD, Jennifer M. Hanna, MD, MBA, Michael E. Barfield, MD, Syamal D. Bhattacharya, MD, Judson B. Williams, MD, MHS, Jeffrey G. Gaca, MD, and G. Chad Hughes, MD Aortic Surgery Program Duke Heart Center, Durham, North Carolina The Aortic Symposium 2012 New York City, April 26-27, 2012 Disclosures: None

2. All Rights Reserved, Duke Medicine 2007 Objective Cooling to electrocerebral inactivity (ECI) by electroencephalography (EEG) remains the gold- standard to maximize cerebral and systemic organ protection during deep hypothermic circulatory arrest (DHCA). Appearance of ECI on EEG (Stecker MM et al. Ann Thorac Surg 2001).

3. All Rights Reserved, Duke Medicine 2007 Objective In 2001, Stecker and Bavaria reported that cooling to a nasopharyngeal (NP) temperature of 12.5°C or for a duration of 50 minutes achieved ECI in 100% of patients (N = 109), however, these data have yet to be validated by another center. We sought to report the NP temperatures and cooling times required to achieve ECI at our center and determine patient- specific predictors of ECI to help guide cooling protocols when neuromonitoring is unavailable. Stecker MM et al. Ann Thorac Surg 2001

4. All Rights Reserved, Duke Medicine 2007 Query of the Duke Thoracic Aortic Surgery Database w/ IRB approval (July 2005 – July 2011). 396 patients underwent operation with DHCA; of these, 325 (82%) utilized EEG neurocerebral monitoring to guide the cooling strategy and form the basis of this report. EEG was utilized for all elective cases and when available for non-elective cases. Predictors of the nasopharyngeal (NP) temperature and cooling time required to achieve ECI were assessed by multivariable linear regression. –Candidate predictors selected a priori: age, sex, race, body surface area, prior stroke, peripheral vascular disease, baseline hemoglobin, starting NP temperature, PaCO2 during cooling. Methods

5. All Rights Reserved, Duke Medicine 2007 Variable Mean (SD) or n (%) Patient characteristics: Age (years) 58.1 (14.0) Male gender 227 (70%) White race 256 (79%) Height (cm) 175.1 (10.9) Weight (kg) 87.0 (20.8) Body mass index (kg/m 2 ) 28.3 (6.0) Body surface area (m 2) 2.0 (0.3) Variable Mean (SD) or n (%) Patient comorbidities: Hypertension 263 (81%) Hyperlipidemia 168 (52%) History of tobacco use 160 (49%) Diabetes 30 (9%) Coronary artery disease 84 (26%) History of stroke 28 (9%) COPD 50 (15%) Renal insufficiency* 29 (9%) PVD 22 (7%) Prior aortic surgery 87 (27%) COPD = chronic obstructive pulmonary disease, PVD = peripheral vascular disease, * denotes baseline creatinine > 1.5 mg/dl Clinical Features

6. All Rights Reserved, Duke Medicine 2007 Variable Mean (SD) or n (%) Case status Elective 282 (87%) Urgent 31 (10%) Emergent 12 (4%) Procedure Root/ascending aorta only 2 (1%) + Hemi-arch 256 (79%) + Total arch 33 (10%) Descending or TAAA 34 (10%) Concomitant procedure 97 (30%) Redo sternotomy 64 (20%) Variable Mean (SD) or n (%) Operative characteristics Aortic diameter (cm)5.8 (1.1) XC time (min, n=295)140.3 (43.1) CPB time (min)220.3 (52.4) Systemic DHCA time (min)26.6 (21.5) Cerebral DHCA time (min)4.7 (5.2) Antegrade CP time (min, n=259)16.1 (6.5) Retrograde CP time (min, n=34)15.5 (5.8) Cooling parameters Baseline hemoglobin (g/dl)13.3 (1.9) Starting NP temperature (ºC)35.2 (1.5) Cooling time* (min, n=228)69.3 (17.2) Cooling rate* (°C/min, n=228)0.30 (0.07) PaCO2 during cooling (mm Hg)42.6 (4.5) NP temperature at ECI (ºC)15.5 (1.9) Nadir NP temperature (ºC)14.1 (1.9) CP = cerebral perfusion, CPB = cardiopulmonary bypass, TAAA = thoracoabdominal, XC = cross-clamp. * Excludes patients undergoing concomitant procedures as cooling times may be prolonged due to performance of concomitant procedure prior to circulatory arrest. Procedural Characteristics

7. All Rights Reserved, Duke Medicine 2007 ComplicationNumber (%) Acute renal failure (Cr > 2.0 and > 2x baseline) 25 (7.7%) New onset dialysis 7 (2.2%) Prolonged ventilation (> 24 hours) 22 (6.8%) Tracheostomy 9 (2.8%) Stroke (neurologic deficit lasting > 72 hours) 13 (4.0%) - Embolic stroke 6 (1.8%) - Ischemic stroke 5 (1.5%) - Intracerebral hemorrhage 2 (0.6%) Permanent paraparesis/paraplegia 5 (1.5%) 30-day / In-hospital death 14 (4.3%) Cr = creatinine Outcomes

8. All Rights Reserved, Duke Medicine 2007 Cooling to a NP temperature of 12.7ºC was required to achieve ECI in > 95% of patients (range 10.4ºC – 24.9ºC). Only 7% of patients achieved ECI by 18ºC. NP Temperature Required to Achieve ECI

9. All Rights Reserved, Duke Medicine 2007 Cooling for a duration of 97 minutes was required to achieve ECI in > 95% of patients (range 29 – 136 minutes). Only 11% of patients achieved ECI after 50 minutes of cooling. Cooling Time Required to Achieve ECI

10. All Rights Reserved, Duke Medicine 2007 Variable Parameter estimate Standard errorT valueP value Age (years)-0.010.01 -1.720.09 Male gender0.380.28 1.330.19 White race-0.080.28 -0.280.78 Body surface area (m 2 )-0.0030.46 -0.010.99 History of stroke-0.010.38 -0.020.98 Peripheral vascular disease0.500.43 1.180.24 Baseline hemoglobin (g/dl)0.010.07 0.210.83 Starting NP temperature (ºC)0.050.07 0.730.47 PaCO2 during cooling (mm Hg)0.040.02 1.740.08 Multivariable linear regression model, r 2 = 0.04 Predictors of NP Temperature at ECI No independent predictors of NP temperature at ECI were identified.

11. All Rights Reserved, Duke Medicine 2007 Variable Parameter estimate Standard errorT valueP value Age (years)0.050.08 0.600.55 Male gender3.572.82 1.260.21 White race7.212.89 2.500.01 Body surface area (m 2 )18.464.52 4.09< 0.0001 History of stroke-5.933.79 -1.570.12 Peripheral vascular disease-1.645.23 -0.310.75 Baseline hemoglobin (g/dl)-0.870.72 -1.210.23 Starting NP temperature (ºC)2.771.08 2.570.01 PaCO2 during cooling (mm Hg)-0.280.24 -1.170.24 Multivariable linear regression model, r 2 = 0.21 Predictors of Cooling Time to ECI Independent predictors of cooling time included body surface area (+18 minutes/m 2 ), white race (+7 minutes), and starting NP temperature (+3 minutes/ o C).

12. All Rights Reserved, Duke Medicine 2007 Cooling to ECI with DHCA affords excellent neurologic and visceral protection. Our data validates in a large contemporary series that cooling to a NP temperature between 12-13 o C achieves ECI in nearly all patients. The cooling time required to achieve ECI appears highly variable between patients and centers and should not be used to predict ECI. Patient-specific factors were poorly predictive of the temperature or cooling time required to achieve ECI, necessitating EEG neurocerebral monitoring for reliable ECI detection. When EEG neurocerebral monitoring is unavailable, cooling below 13 o C NP may be the ideal method to ensure ECI. Conclusions