1. Does Moderate Hypothermia Really Carry Less Bleeding Risk than Deep Hypothermia For Circulatory Arrest? A Propensity-Matched Comparison in Hemiarch Replacement
Jeffrey E. Keenan, MD; Hanghang Wang, MD; Brian C. Gulack, MD;
Asvin M. Ganapathi, MD; Nicholas D. Andersen MD; Brian R. Englum, MD; Yamini Krishnamurthy, MSIV; Jerrold H. Levy, MD;
Ian J. Welsby, MD; G. Chad Hughes, MD
American Association for Thoracic Surgery Annual Meeting
April 28, 2015
Seattle, WA

2. The authors have no conflicts of interest to report.
Disclosures
The authors have no conflicts of interest to report.
The authors have no conflicts of interest to report.

3. Background
Controversy exists over the optimal degree of hypothermia during surgery of aortic arch with circulatory arrest

4. Background
Controversy exists over the optimal degree of hypothermia during surgery of aortic arch with circulatory arrest
Deep Hypothermia
Moderate Hypothermia
Greater suppression of metabolic activity
May offer better organ protection, particularly for the brain and spinal cord which are highly susceptible to hypoxic injury
May provide adequate visceral and cerebral protection in conjunction with regional perfusion to the brain during systemic arrest
Potentially mitigates hypothermia-related complications
Vs.

5. Coagulopathic bleeding during aortic arch surgery
Background
Coagulopathic bleeding during aortic arch surgery
Multifactorial
Hypothermia-related platelet dysfunction
Coagulation factor consumption during prolonged CPB
Theoretically, milder degrees of hypothermia may reduce coagulopathy and bleeding-related complications
Lack of empirical data to support this claim

6. Objective
To determine whether moderate hypothermic circulatory arrest (MHCA) compared to deep hypothermic circulatory arrest (DHCA) reduced the risk of bleeding and the blood product transfusion in patients undergoing aortic hemiarch replacement.

7. Duke University Medical Center Aortic Surgery Database
Methods
Duke University Medical Center Aortic Surgery Database
Prospectively maintained
Contains >1500 procedures from 2005-present.
Study population
Patients who underwent replacement of aortic root or supracoronary ascending aneurysm (+/- valve) with concomitant hemiarch replacement from 7/2005 to 8/2014.

8. Methods Aortic Hemiarch Replacement Deep HCA Moderate HCA
Minimum Systemic Temperature ≤ 20°C
Moderate HCA
Minimum Systemic Temperature > 20°C

9. Methods Aortic Hemiarch Replacement Deep HCA Moderate HCA
Minimum Systemic Temperature ≤ 20°C
Moderate HCA
Minimum Systemic Temperature > 20°C
1:1 Propensity Match
age, gender, race, BMI, hypertension, tobacco use, diabetes, coronary artery disease, congestive heart failure, history of stroke, chronic renal insufficiency (baseline creatinine >1.5), connective tissue disease, ASA class, bicuspid aortic valve, acute type A aortic dissection, chronic type A aortic dissection, preoperative malperfusion or shock, aortic rupture, procedural status, concomitant root replacement, redo sternotomy, and preoperative hematologic labs

10. Methods Aortic Hemiarch Replacement Deep HCA Moderate HCA
Minimum Systemic Temperature ≤ 20°C
Moderate HCA
Minimum Systemic Temperature > 20°C
Propensity Match
Study Outcomes
Primary (bleeding-related): operative day transfusion, reoperation for bleeding, cell saver transfusion, rFVIIa utilization, 12 hour postoperative chest tube output, post-op labs
Secondary: mortality, organ-specific morbidity, intraoperative outcomes

11. Aortic Hemiarch Replacement
Results
Aortic Hemiarch Replacement
N=571
Deep HCA
N=401 (70.2%)
Min. Sys. Temp.= 17.1°C
Moderate HCA
N=170 (29.8%)
Min. Sys. Temp.= 24.0°C

12. Results: Frequency of DHCA and MHCA

13. Aortic Hemiarch Replacement
Methods
Aortic Hemiarch Replacement
Deep HCA
N=401
Min. Sys. Temp.= 17.1°C
Moderate HCA
N=170
Min. Sys. Temp.= 24.0°C
Propensity Matching
Deep HCA
N=155
Min. Sys. Temp.= 17.0°C
Moderate HCA
N=155
Min. Sys. Temp.= 24.0°C

14. Results: Matched Baseline Characteristics
Variable
Deep HCA
(N=155)
Moderate HCA
P-value
Age
60 (47, 69)
58 (51.5, 68)
0.82
Female
50 (32.3%)
49 (31.6%)
0.99
White Race
108 (69.7%)
114 (73.5%)
0.53
Body Mass Index
28.4 (25.0, 31.8)
28.4 (25.3, 32.3)
0.66
Hypertension
124 (80.0%)
123 (79.4%)
Hyperlipidemia
78 (50.3%)
86 (55.5%)
0.43
Smoker
62 (40.0%)
55 (35.5%)
0.48
Diabetes
12 (7.7%)
13 (8.4%)
Coronary Artery Disease
38 (24.5%)
History of MI
10 (6.5%)
16 (10.3%)
0.31
CHF (NYHA ≥2)
52 (33.5%)
43 (27.7%)
0.32
History of Stroke/TIA
11 (7.1%)
COPD
17 (11.0%)
0.57
Chronic Kidney Disease
24 (15.5%)
23 (14.8%)
Peripheral Artery Disease
6 (3.9%)

15. Results: Matched Aortic Characteristics
Variable
Deep HCA
(N=155)
Moderate HCA
P-value
Connective Tissue Disease
4 (2.6%)
5 (3.2%)
0.99
Bicuspid Aortic Valve
58 (37.4%)
56 (36.1%)
0.91
Ascending Aortic Dissection
45 (29.0%)
48 (31.0%)
0.80
Acute
35 (77.8%)
42 (87.5%)
0.28
Chronic
10 (22.2%)
7 (14.6%)
0.42
Acute Dissection with Malperfusion or Shock
10 (6.5%)
12 (7.7%)
0.83
Max Aortic Diameter
5.4 (5.0, 5.8)
5.3 (5.0, 5.8)
0.53
Aortic Rupture
8 (5.2%)
9 (5.8%)

16. Results: Matched Procedural Characteristics
Variable
Deep HCA
(N=155)
Moderate HCA
P-value
ASA class
0.28 2
18 (11.6%)
27 (17.4%) 3
94 (60.6%)
83 (53.5%) 4
43 (27.7%)
45 (29.0%)
Procedural Status
0.45
Elective
111 (71.6%)
104 (67.1%)
Urgent
16 (10.3%)
14 (9.0%)
Emergent
28 (18.1%)
37 (23.9%)
Previous Aortic Surgery
25 (16.1%)
22 (14.2%)
0.75
Redo Sternotomy
0.76
Root Replacement
49 (31.6%)
0.99

17. Results: Preoperative Hematologic Labs
Variable
Deep HCA
(N=155)
Moderate HCA
P-value
Hemoglobin (g/dL)
13.3 (11.9, 14.7)
13.5 (12.1, 14.7)
0.28
INR
1.0 (1.0, 1.1)
0.47
Platelets (109/L)
204 (170.5, 249)
197 (165, 242)
0.26
PTT
30.1 (27.8, 32.7)
30.5 (28.0, 32.7)
0.70
Creatinine
1.0 (0.9, 1.2)
0.58

18. Results: Bleeding-Related Outcomes
Deep HCA
(N=155)
Moderate HCA
P-value
Operative Day Transfusion
PRBC (units)
2 (0, 4)
0.86
Plasma (units)
6 (4, 8)
4 (4, 8)
0.1
Platelets (units)
2 (1, 3)
2 (1.5, 3)
0.45
Cryoprecipitate (units)
0 (0, 1)
0.02
≥1 unit Cryoprecipitate
60 (36.1%)
70 (44.5%)
0.003
Cell Saver (mL)
500 (250, 744)
472 (250, 700)
< 0.001
Intraoperative rFVIIa
35 (22.6%)
52 (33.5%)
0.04
Postoperative rFVIIa
8 (5.2%)
5 (3.2%)
0.57
12hr Chest Tube Output (mL)
405 (262, 740)
360 (230, 633)
Reoperation for Bleeding 1

19. Results: Bleeding-Related Outcomes
Deep HCA
(N=155)
Moderate HCA
P-value
Operative Day Transfusion
PRBC (units)
2 (0, 4)
0.86
Plasma (units)
6 (4, 8)
4 (4, 8)
0.1
Platelets (units)
2 (1, 3)
2 (1.5, 3)
0.45
Cryoprecipitate (units)
0 (0, 1)
0.02
≥1 unit Cryoprecipitate
60 (36.1%)
70 (44.5%)
0.003
Cell Saver (mL)
500 (250, 744)
472 (250, 700)
< 0.001
Intraoperative rFVIIa
35 (22.6%)
52 (33.5%)
0.04
Postoperative rFVIIa
8 (5.2%)
5 (3.2%)
0.57
12hr Chest Tube Output (mL)
405 (262, 740)
360 (230, 633)
Reoperation for Bleeding 1

20. Results: Bleeding-Related Outcomes
Deep HCA
(N=155)
Moderate HCA
P-value
Operative Day Transfusion
PRBC (units)
2 (0, 4)
0.86
Plasma (units)
6 (4, 8)
4 (4, 8)
0.10
Platelets (units)
2 (1, 3)
2 (1.5, 3)
0.45
Cryoprecipitate (units)
0 (0, 1)
0.02
≥1 unit Cryoprecipitate
60 (36.1%)
70 (44.5%)
0.003
Cell Saver (mL)
500 (250, 744)
472 (250, 700)
< 0.001
Intraoperative rFVIIa
35 (22.6%)
52 (33.5%)
0.04
Postoperative rFVIIa
8 (5.2%)
5 (3.2%)
0.57
12hr Chest Tube Output (mL)
405 (262, 740)
360 (230, 633)
Reoperation for Bleeding 1

21. Results: Bleeding-Related Outcomes
Deep HCA
(N=155)
Moderate HCA
P-value
Operative Day Transfusion
PRBC (units)
2 (0, 4)
0.86
Plasma (units)
6 (4, 8)
4 (4, 8)
0.1
Platelets (units)
2 (1, 3)
2 (1.5, 3)
0.45
Cryoprecipitate (units)
0 (0, 1)
0.02
≥1 unit Cryoprecipitate
60 (36.1%)
70 (44.5%)
0.003
Cell Saver (mL)
500 (250, 744)
472 (250, 700)
< 0.001
Intraoperative rFVIIa
35 (22.6%)
52 (33.5%)
0.04
Postoperative rFVIIa
8 (5.2%)
5 (3.2%)
0.57
12hr Chest Tube Output (mL)
405 (262, 740)
360 (230, 633)
Reoperation for Bleeding 1
A total of 50,010 patients received a lobectomy during the study period of which 3.9% were found to have positive margins following surgery.
Patients with positive margins were more likely to be male (CLICK) and black (CLICK) than patients with negative margins.
They were also less likely to be treated at an academic center (CLICK).

22. Results: Bleeding-Related Outcomes
Deep HCA
(N=155)
Moderate HCA
P-value
Operative Day Transfusion
PRBC (units)
2 (0, 4)
0.86
Plasma (units)
6 (4, 8)
4 (4, 8)
0.1
Platelets (units)
2 (1, 3)
2 (1.5, 3)
0.45
Cryoprecipitate (units)
0 (0, 1)
0.02
≥1 unit Cryoprecipitate
60 (36.1%)
70 (44.5%)
0.003
Cell Saver (mL)
500 (250, 744)
472 (250, 700)
< 0.001
Intraoperative rFVIIa
35 (22.6%)
52 (33.5%)
0.04
Postoperative rFVIIa
8 (5.2%)
5 (3.2%)
0.57
12hr Chest Tube Output (mL)
405 (262, 740)
360 (230, 633)
Reoperation for Bleeding 1

23. Results: Bleeding-Related Outcomes
Deep HCA
(N=155)
Moderate HCA
P-value
Operative Day Transfusion
PRBC (units)
2 (0, 4)
0.86
Plasma (units)
6 (4, 8)
4 (4, 8)
0.1
Platelets (units)
2 (1, 3)
2 (1.5, 3)
0.45
Cryoprecipitate (units)
0 (0, 1)
0.02
≥1 unit Cryoprecipitate
60 (36.1%)
70 (44.5%)
0.003
Cell Saver (mL)
500 (250, 744)
472 (250, 700)
< 0.001
Intraoperative rFVIIa
35 (22.6%)
52 (33.5%)
0.04
Postoperative rFVIIa
8 (5.2%)
5 (3.2%)
0.57
12hr Chest Tube Output (mL)
405 (262, 740)
360 (230, 633)
Reoperation for Bleeding 1

24. Results: Bleeding-Related Outcomes
Deep HCA
(N=155)
Moderate HCA
P-value
Hemoglobin (g/dL)
9.9 (9.25, 10.5)
10.0 (9.4, 10.55)
0.23
Platelets (109/L)
140 (115, 176.5)
147 (127, 173)
0.08
INR
1.1 (1.0, 1.2)
1.1 (0.9, 1.2)
0.03
INR ≥ 1.2
72 (46.8%)
53 (35.6%)
0.048
PTT (sec)
28.7 (25.95, 37.0)
28.6 (21.3, 31.4)
0.26

25. Results: Secondary Outcomes - Intraoperative
Variable
Deep HCA
(N=155)
Moderate HCA
P-value
Cardiopulmonary Bypass Time
204 (182, 232)
182 (150, 215)
< 0.001
Crossclamp Time
126 (107, 154)
117 (95, 147)
0.07
Circulatory Arrest Time
17 (15, 22)
16.5 (13, 20)
0.04
Operative Time
329 (297, 378)
320 (281, 367)
0.27

26. Results: Secondary Outcomes - Intraoperative
Variable
Deep HCA
(N=155)
Moderate HCA
P-value
Cardiopulmonary Bypass Time
204 (182, 232)
182 (150, 215)
< 0.001
Crossclamp Time
127 (107, 154)
117 (95, 147)
0.07
Circulatory Arrest Time
17 (15, 22)
16.5 (13, 20)
0.04
Operative Time
329 (297, 378)
320 (281, 367)
0.27

27. Results: Secondary Outcomes - Clinical
Deep HCA
(N=155)
Moderate HCA
P-value
30-Day/Inpatient Mortality
3 (1.9%)
5 (3.2%)
0.72
AKI ( Creatinine > 2.0 & 2x baseline)
11 (7.1%)
16 (10.3%)
0.42
New Onset Dialysis
1 (0.6%)
7 (4.5%)
0.07
Stroke
2 (1.3%)
0.99
Transient Ischemic Attack
Paraparesis
Paraplegia
Prolonged Ventilation (>24 hours)
19 (12.3%)
13 (8.4%)
0.35
30-Day Readmission
20 (12.9%)
0.60
Discharge to location other than home

28. Summary
MHCA compared to DHCA may have led to a slight statistical decrease in perioperative bleeding (decreased cell saver transfusion, post-operative output)
However, this did not translate to clinically apparent benefit such as reduced rate of transfusion or reoperation for bleeding
Mortality and morbidity did not appear to differ between patients managed with MHCA vs. DHCA

29. Potential for unobserved confounding
Limitations
Potential for unobserved confounding
Non-standardization of transfusion and surgical practice over the entire course of the study
Lack of functional coagulation assessments

30. Conclusions
Although perioperative bleeding may be slightly lower in MHCA patients, this difference does not correspond to a change in the rate of blood product transfusion or the need for reoperation due to bleeding.
The comparable mortality and morbidity observed between the DHCA and MHCA groups confirm the current clinical equipoise between these two strategies and supports the need for prospective study to better elucidate the optimal degree of hypothermia during aortic reconstruction with circulatory arrest.