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Hemiarch Replacement at 28°C: An Analysis of Mild and Moderate Hypothermia in 500 Patients
Hemiarch Replacement at 28°C: An Analysis of Mild and Moderate Hypothermia in 500 Patients ADULT CARDIAC
Bradley G. Leshnower, MD, Richard J. Myung, MD, Vinod H. Thourani, MD, Michael E. Halkos, MD, Patrick D. Kilgo, MS, John D. Puskas, MD, and Edward P. Chen, MD Clinical Research Unit, Division of Cardiothoracic Surgery, Joseph B. Whitehead Department of Surgery, and the Rollins School of Public Health, Emory University School of Medicine, Atlanta, Georgia
Background. During the past decade, use has increased of moderate hypothermic circulatory arrest with antegrade cerebral perfusion for cerebral protection during aortic arch operations. This study examined the use of mild hypothermia in conjunction with unilateral selective antegrade cerebral perfusion (uSACP) for hemiarch replacement for proximal aortic arch reconstruction. Methods. A retrospective review of the Emory Aortic Database identified 708 patients who underwent aortic arch replacement between 2004 and 2011. Of these, 500 underwent hemiarch replacement at temperatures of 22°C or higher with uSACP. Outcomes were analyzed and compared between 277 patients undergoing hemiarch at a temperature of 28.6°C (mild) and 233 undergoing hemiarch at a temperature of 24.3°C (moderate). Propensity scores were generated and analyzed between the groups to adjust for confounding factors such as selection bias.
Results. Operative mortality was equivalent between mild and moderate groups in elective (4.2% vs 4.8%, p ⴝ 0.80) and emergency (7.7% vs 11.7%, p ⴝ 0.43) settings. No differences occurred in the incidence of temporary neurologic dysfunction, dialysis-dependent renal failure, or mediastinal reexploration for bleeding between mild and moderate patients. The incidence of permanent neurologic deficit was significantly reduced in mild (2.5%) vs moderate patients (7.2%, p ⴝ 0.01), which was confirmed by the propensity score analysis (adjusted odds ratio, 0.28; p ⴝ 0.02). Conclusions. Hemiarch replacement can be safely performed at 28°C with uSACP in emergency and elective settings. Mild hypothermia with uSACP offers adequate levels of neurologic protection compared with deeper levels of hypothermia. (Ann Thorac Surg 2012;93:1910 – 6) © 2012 by The Society of Thoracic Surgeons
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In a previous report, we described our initial experience of performing hemiarch and total arch reconstructions with a cerebral protection strategy of moderate hypothermic circulatory arrest (ⱖ22°C) using adjunctive unilateral selective antegrade cerebral perfusion (uSACP) through right axillary artery inflow [1]. Since that time, our technique has continued to evolve by performing aortic arch procedures at milder degrees of hypothermia, especially in the case of hemiarch reconstruction that requires brief periods of lower body circulatory arrest. This study examined the safety of performing elective and emergency hemiarch reconstructions under mild hypothermic circulatory arrest with uSACP.
uring the past decade, antegrade cerebral perfusion (ACP) with hypothermic circulatory arrest has become a preferred cerebral protection strategy for aortic arch operations in many high-volume aortic centers [1– 6]. ACP provides uninterrupted physiologic perfusion to the brain during reconstruction of the arch and has changed the paradigm from total body hypothermic circulatory arrest to isolated lower body circulatory arrest. The application of continuous, antegrade cold cerebral perfusion has led to a departure from the traditional use of deep hypothermia (18° to 22°C) for lower body protection during circulatory arrest. Many groups have moved to a strategy of moderate hypothermia with ACP for aortic arch reconstruction. The impetus for this change is to minimize the adverse effects of profound hypothermia, which include prolonged durations of cardiopulmonary bypass, leading to an increased systemic inflammatory response and subsequent increased risk of bleeding and organ dysfunction [3].
Accepted for publication Feb 23, 2012. Presented at the Fifty-eighth Annual Meeting of the Southern Thoracic Surgical Association, San Antonio, TX, Nov 9 –12, 2011. Address correspondence to Dr Chen, Division of Cardiothoracic Surgery, The Emory Clinic, 1365 Clifton Rd, Ste A2236, Atlanta, GA 30322; e-mail: [email protected].
© 2012 by The Society of Thoracic Surgeons Published by Elsevier Inc
Patients and Methods A retrospective review of the Emory Aortic Surgery Database identified 708 patients who underwent aortic arch operations at the 3 primary hospitals within the Emory Healthcare system between January 2004 and October 2011. Inclusion criteria were all patients undergoing hemiarch reconstruction with right axillary artery cannulation, moderate hypothermic circulatory arrest (ⱖ 22°C), and uSACP. Exclusion criteria were femoral or ascending aortic cannulation, deep hypothermic circula0003-4975/$36.00 doi:10.1016/j.athoracsur.2012.02.069
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Operative Technique Technical details of our operative technique have been published [1]. We used a Foley catheter with a temperature probe to measure core body temperature. Transcutaneous cerebral oximetry (INVOS 3100-SD, Troy, Mich) and continuous electroencephalogram monitoring were routinely performed. Intraoperative transesophageal echocardiography was used in all patients. The goal core body temperature was determined by each surgeon and depended on several factors, including age, preoperative renal function, aortic pathology, and the complexity of the planned hemiarch reconstruction. Upon reaching the goal core body temperature, the innominate artery was occluded proximally. Cerebral perfusion was initiated at 16°C at a rate of 10 mL/kg/min and adjusted to maintain cerebral perfusion pressures of 60 to 70 mm Hg. If cerebral oximetry saturations dropped below 10% below baseline values after lower body circulatory arrest was initiated, the left common carotid artery was isolated and occluded. Upon completion of the circulatory arrest period, vigorous maneuvers were performed to remove air before reinstitution of full flow cardiopulmonary bypass and rewarming was initiated. Proximal aortic procedures and any coronary or valve interventions were typically performed during the rewarming period.
Statistical Analysis Univariate (unadjusted) associations between preoperative and intraoperative variables and clinical outcomes were determined using t tests and 2 tests. To adjust for potential selection bias, propensity scores (PS) were generated for each patient that represented the probability of being assigned to mild hypothermia. The PS was estimated from 19 preoperative variables (variables from Table 1 and also year of operation). The PS was relatively balanced between the mild and moderate groups, indicating that the covariate patterns of the two groups were similar. Once the PSs were generated, analyses were performed in quintile strata of PSs (which represent homog-
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Table 1. Preoperative Demographics in Mild or Moderate Hypothermia Patients Risk Factora Age, years BMI, kg/m2 Male sex History of CVA NYHA class III/IV Diabetes mellitus Hypertension Renal failure Myocardial infarction COPD None Mild Moderate Severe Ejection fraction Aneurysm size, cm
Moderate (n ⫽ 223)
Mild (n ⫽ 277)
57.9 ⫾ 14.1 28.6 ⫾ 6.9 160 (73.4) 11 (2.3) 52 (32.5) 25 (11.5) 47 (21.6) 30 (13.8) 23 (10.6)
57.7 ⫾ 14.1 28.8 ⫾ 6.0 181 (70.4) 19 (7.4) 74 (42.1) 28 (10.9) 49 (19.1) 21 (8.2) 27 (10.5)
176 (81.9) 30 (14.0) 3 (1.4) 6 (2.8) 0.545 ⫾ 0.118 5.6 ⫾ 1.1
210 (82.0) 31 (12.1) 9 (3.5) 6 (2.3) 0.547 ⫾ 0.113 5.5 ⫾ 1.1
p Value 0.88 0.69 0.47 0.29 0.07 0.84 0.50 0.05b 0.99 0.48
0.88 0.11
a Continuous data are presented as mean ⫾ standard deviation and b categoric data are number (%). Statistically significant (p ⱕ 0.05). BMI ⫽ body mass index; COPD ⫽ chronic obstructive pulmonary disease; CVA ⫽ cerebrovascular accident; NYHA ⫽ New York Heart Association.
enous groups of patients) and outcomes analyzed by mild vs moderate hypothermia. In addition, to take advantage of the strength of the full sample, a logistic regression model was constructed that modeled each outcome as a function of temperature (mild vs moderate), adjusted for the PS. Adjusted odds ratios and 95% confidence intervals (CI) were computed. The data were analyzed with SAS 9.2 software (SAS Institute, Cary, NC). All data are presented as means ⫾ standard deviation. Statistical tests were evaluated at the ␣ ⫽ 0.05 level. All comparisons and model terms were preplanned.
Results Entire Series A total of 500 patients underwent hemiarch replacement under mild or moderate hypothermic circulatory arrest with uSACP. Of these, 142 patients (28%) received emergency hemiarch replacement for acute type A aortic dissection, and the remaining 358 (72%) underwent elective ascending aortic and hemiarch replacement for aneurysmal disease (91%), chronic type A dissection (6%), or other etiologies. Concomitant procedures in 380 patients (80%) included root replacement, aortic valve replacement, mitral valve replacement, and coronary artery bypass grafting. A total of 240 (48%) patients required concomitant aortic root replacement, including 80 patients (16%) who received a David V valve-sparing procedure. The series included 78 patients (15.6%) who required redo sternotomy for their aortic operation. The mean core body temperature at the initiation of circulatory arrest for the entire series was 26.7° ⫾ 2.5°C. Permanent neurologic dysfunction (PND) occurred in
ADULT CARDIAC
tory arrest (⬍22°C), retrograde cerebral perfusion, and total arch replacement. The analysis is based on data from 500 patients who met these strict criteria. The median core body temperature at the initiation of circulatory arrest for these 500 patients was 27°C. Patients were divided into two groups according to this median temperature, and a comparative analysis was performed: 223 received hemiarch replacement using moderate hypothermic circulatory arrest with core temperatures of 22° to 26°C (moderate group), and 277 received hemiarch replacement using mild hypothermic circulatory arrest with core temperatures of 27° to 34°C (mild group). Medical records were reviewed for preoperative, intraoperative, and postoperative variables. This study was approved by the Institutional Review Board at Emory University in compliance with Health Insurance Portability and Accountability Act regulations and the Declaration of Helsinki. The Institutional Review Board waived the need for individual patient consent.
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Table 2. Procedures in Mild or Moderate Hypothermia Patients
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Proceduresa
Moderate (n ⫽ 223)
Mild (n ⫽ 277)
p Value
Elective Emergency type A Reoperative Aortic root replacement David V Artic valve replacement CABG
156 (65.5) 77 (34.5) 39 (17) 109 (49) 35 (16) 36 (16) 41 (18)
212 (76.5) 65 (23.5) 39 (14) 131 (47) 45 (16) 51 (18) 36 (13)
0.45 ⬍0.01b 0.34 0.65 0.75 0.72 0.24
a All data are presented as number (%). 0.05).
b
Statistically significant (p ⱕ
CABG ⫽ coronary artery bypass grafting.
4.6% and temporary neurologic dysfunction (TND) in 5.2%. The incidence of dialysis-dependent renal failure (DDRF) was 4.0%. Thirty-six patients (7.2%) required mediastinal re-exploration for bleeding. No paraplegia occurred in the series. Operative mortality for the entire series was 6% (30 of 500). Mortality was 4.5% for elective procedures and 9.9% for emergency type A dissection repairs.
Preoperative Demographics Table 1 lists the preoperative demographics for mild and moderate group patients. Both groups were a mean age of 58 ⫾ 14 years and were similar with respect to body mass Table 3. Overall Outcomes in Mild or Moderate Hypothermia Patients Mild (n ⫽ 277)
index, sex, and the preoperative risk factors of prior cerebrovascular accident, diabetes mellitus, hypertension, chronic obstructive pulmonary disease, and myocardial infarction. Moderate group patients had a higher incidence of preoperative renal failure (13.8%) than the mild group (8.2%, p ⫽ 0.05). Both cohorts had normal preoperative left ventricular function and similar aneurysm sizes.
Analysis 1: Overall Mild vs Moderate Group Table 2 lists the operative procedures performed in each group. The moderate cohort contained a significantly higher percentage of patients who received emergency operations for acute type A dissection (35%) vs the mild group (24%; p ⬍ 0.01). The incidence of redo sternotomy, aortic root replacement, aortic valve replacement, and coronary artery bypass grafting were similar between the two groups. Circulatory arrest was initiated at a significantly warmer core body temperature in the mild group (28.6° ⫾ 1.2°C) vs the moderate group (24.3° ⫾ 1.3°C, p ⬍ 0.001) Cardiopulmonary bypass times (minutes) were reduced in the mild patients (184 ⫾ 57) vs the moderate group (197 ⫾ 60; p ⫽ 0.01), but cross-clamp and circulatory arrest times were equivalent. Operative mortality did not differ significantly between mild (5.1%) and moderate (7.2%) patients. The incidence of PND was significantly less in the mild group (2.5%) vs the moderate group (7.2%, p ⫽ 0.01); however, there was no difference in TND, DDRF, or mediastinal reexploration for bleeding between the two groups. Mild patients required significantly less postoperative ventilator support (46 ⫾ 104 hours) compared with moderate patients (69 ⫾ 123 hours; p ⫽ 0.03) and had shorter intensive care unit (ICU) stays. This translated into a trend toward a shorter hospital length of stay of 9.5 ⫾ 8.1 days for mild patients vs 10.5 ⫾ 7.0 days for moderate patients (p ⫽ 0.15; Table 3). The propensity score analysis found no difference between mild and moderate patients in the major outcomes of operative mortality, TND, DDRF, or mediastinal reexploration for bleeding. However, PND was significantly lower in the patients who received mild hypothermic circulatory arrest (Table 4).
Variables and Outcomesa
Moderate (n ⫽ 223)
HCA temperature, °C Cardiopulmonary bypass time, min Cross-clamp time, min Circulatory arrest time, min Death Neurologic dysfunction Permanent Temporary Dialysis-dependent renal failure Mediastinal reexploration Post-op mechanical ventilation, hours Length of stay Intensive care unit, days Hospital, days
24.3 ⫾ 1.3 197 ⫾ 60
28.6 ⫾ 1.2 184 ⫾ 57
⬍0.001b 0.01b
154 ⫾ 62 25.8 ⫾ 9.2
148 ⫾ 55 25.3 ⫾ 9.2
0.29 0.54
16 (7.2)
14 (5.1)
0.32
16 (7.2) 14 (6.3) 9 (4.1)
7 (2.5) 12 (4.3) 11 (4.0)
0.01b 0.33 0.97
Table 4. Propensity Regression Adjustment Adjusted Odds Ratios
16 (7.2)
20 (7.2)
0.98
Outcome
68.8 ⫾ 123
45.8 ⫾ 104.3
0.03
p Value
5.1 ⫾ 5.6
4.2 ⫾ 5.8)
0.06
10.5 ⫾ 7.0
9.5 ⫾ 8.1)
0.15
a Continuous data are presented as mean ⫾ standard deviation and b Statistically significant (p ⱕ 0.05). categoric data as number (%).
HCA ⫽ hypothermic circulatory arrest.
Death Neurologic dysfunction Permanent Temporary DDRF Bleeding a
Mild vs Moderate AOR (95% CI)
p Value
0.94 (0.43–2.05)
0.87
0.28 (0.10–0.82) 0.81 (0.34–1.92) 1.75 (0.67–4.56) 1.32 (0.64–2.74)
0.02a 0.63 0.25 0.46
Statistically significant (p ⱕ 0.05).
AOR ⫽ adjusted odds ratio; CI ⫽ confidence interval; dialysis-dependent renal failure.
DDRF ⫽
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LESHNOWER ET AL HEMIARCH RECONSTRUCTION AT 28°C
or overall hospital lengths of stay between the two groups.
HCA temperature, °C Cardiopulmonary bypass time, min Cross-clamp time, min. Circulatory arrest time, min Death Neurologic dysfunction Permanent Temporary Dialysis-dependent renal failure Mediastinal reexploration Post-op mechanical ventilation, hours Length of stay Intensive care unit, days Hospital, days
Moderate (n ⫽ 146)
Mild (n ⫽ 212)
p Value
24.2 ⫾ 1.3 202 ⫾ 60
28.6 ⫾ 1.3 183 ⫾ 56
⬍0.001b 0.01b
165 ⫾ 59 23.6 ⫾ 6.7
151 ⫾ 54 23.2 ⫾ 7.2
0.02b 0.63
7 (4.8)
9 (4.3)
0.80
7 (4.8) 8 (5.5) 1 (0.7)
4 (1.9) 8 (3.8) 5 (2.4)
0.12 0.44 0.23
10 (6.9) 57 ⫾ 115
14 (6.6) 35 ⫾ 83
0.93 0.05b
4.3 ⫾ 4.8 9.6 ⫾ 6.2
3.6 ⫾ 5.3 8.5 ⫾ 6.6
0.23 0.13
a Continuous data are presented as mean ⫾ standard deviation; categoric b Statistically significant (p ⱕ 0.05). data as number (%).
HCA ⫽ hypothermic circulatory arrest.
Analysis 2: Elective Mild vs Moderate Table 5 lists the major perioperative data and outcomes from elective hemiarch cases performed under mild or moderate hypothermic circulatory arrest with uSACP. In mild patients, circulatory arrest was initiated at significantly warmer mean core body temperatures of 28.6° ⫾ 1.3°C vs 24.2° ⫾ 1.3°C in moderate patients (p ⬍ 0.001). Cardiopulmonary bypass (183 ⫾ 56 vs 201⫾ 60 min, p ⬍ 0.01) and cross-clamp times (151 ⫾ 54 vs 165 ⫾ 59 min., p ⫽ 0.02) were significantly reduced in the mild group. Circulatory arrest times were equivalent. Operative mortality was similar in mild (4.8%) and moderate (4.2%) patients. There was no difference in PND, TND, DDRF, or the mediastinal reexploration rate between the two groups. Mild patients had significantly shorter postoperative ventilator requirements (35 ⫾ 83 hours) vs moderate patients (57 ⫾ 115 hours; p ⫽ 0.05), and a trend toward a shorter hospital length of stay.
Analysis 3: Emergency Repair in Mild vs Moderate Table 6 lists the major perioperative data and outcomes from emergency type A repairs requiring hemiarch reconstruction performed under mild or moderate hypothermic circulatory arrest with uSACP. Mild patients underwent circulatory arrest at warmer mean core body temperatures (28.4° ⫾ 1.0°C) vs moderate (24.5° ⫾ 1.3°C, p ⬍ 0.001). Cardiopulmonary bypass, cross-clamp, and circulatory arrest times were equivalent between the two groups. There was no significant difference in operative mortality between mild (7.7%) and moderate (11.7%) patients (p ⫽ 0.43). The incidence of PND, TND, and DDRF was equivalent. There was no difference in mediastinal reexploration rate, ventilator requirements, ICU,
Comment Antegrade cerebral perfusion has enabled surgeons to alter traditional cerebral protection strategies and safely perform arch reconstructions under moderate rather than deep levels of hypothermic circulatory arrest [1– 6]. Avoiding profound hypothermia in circulatory arrest cases has been associated with a reduction in cardiopulmonary bypass times, postoperative inflammation, organ dysfunction, and bleeding [3]. In 2004 the paradigm of moderate hypothermic circulatory arrest with uSACP was established at Emory as the primary cerebral protection strategy for aortic arch operations. In a previous study, we reported the safety of this technique with hemiarch and total arch replacements and demonstrated that temperature was not an independent risk factor for operative death or adverse neurologic outcomes [1]. In this study, we focused on evaluating the safety of performing hemiarch reconstruction at milder levels of hypothermia (28.6°C), by comparing outcomes with a contemporary cohort that received hemiarch replacements at moderate hypothermic circulatory arrest (24.3°C). Reports of aortic arch replacement conducted under mild hypothermia (⬍ 28°C) with ACP are beginning to surface in the literature [6 – 8]. The current study distinguishes itself from its predecessors by the inclusion of a control group that underwent hemiarch replacement with an identical surgical technique at a deeper level of hypothermia. Table 6. Emergency Operation in Mild vs Moderate Variables and Outcomesa
Moderate (n ⫽ 77)
HCA temperature, °C 24.5 ⫾ 1.3 Cardiopulmonary bypass 187 ⫾ 59 time, min Cross-clamp time, min 130 ⫾ 62 Circulatory arrest time, 30.4 ⫾ 8.9 min Death 9 (11.7) Neurologic dysfunction Permanent 9 (11.7) Temporary 6 (7.8) Dialysis-dependent renal 8 (10.4) failure Mediastinal reexploration 6 (7.8) Post-op mechanical 92 ⫾ 134 ventilation, hours Length of stay Intensive care unit, days 6.9 ⫾ 6.7 Hospital, days 12.5 ⫾ 8.2
Mild (n ⫽ 65)
p Value
28.5 ⫾ 0.9 186 ⫾ 63
⬍0.001b 0.92
136 ⫾ 58 33.1 ⫾ 11.4
0.60 0.14
5 (7.7)
0.43
3 (4.6) 4 (6.2) 6 (9.2)
0.13 0.70 0.82
6 (9.2) 81 ⫾ 151
0.76 0.63
6.0 ⫾ 7 13.0 ⫾ 11.4
0.45 0.74
a Continuous data are presented as mean ⫾ standard deviation; categoric b Statistically significant (p ⱕ 0.05). data as number (%).
HCA ⫽ hypothermic circulatory arrest.
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Table 5. Elective Operation in Mild vs Moderate Variables and Outcomesa
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Analysis of the entire study population demonstrated that patients undergoing hemiarch replacement at warmer temperatures (28.6°C) had significantly shorter cardiopulmonary bypass times and postoperative ventilator requirements, resulting in a trend toward shorter postoperative ICU and hospital lengths of stay. Operative mortality was reduced in the mild group patients (5.1%) compared with moderate patients (7.2%), but the difference was not statistically significant (p ⫽ 0.32). The level of hypothermia had no effect on TND, but there was a significant reduction in the incidence of PND in the mild patients (2.5%) compared with moderate patients (7.2%, p ⫽ 0.01). Isolated evaluation of the elective cases produced similar results to those found in the analysis of the entire study cohort. Low elective operative mortality rates were observed in mild (4.2%) and moderate (4.8%) patients (p ⫽ 0.81), with shorter cardiopulmonary bypass and cross-clamp times in the mild group. The reductions in postoperative ventilator requirement and hospital length of stay in the mild group were also observed in elective cases. PND was reduced in the mild group (1.9%) vs the moderate group (4.8%) but did not reach statistical significance (p ⫽ 0.12). In the emergency cases, there was no difference in cardiopulmonary bypass, cross-clamp, and circulatory arrest times in mild and moderate patients undergoing type A dissection repair. Operative mortality was lower in the mild group (7.7%) vs the moderate group (11.6%), but the difference did not reach statistical significance (p ⫽ 0.43). Again, a trend toward a reduction in PND was observed in mild patients (4.6%) vs moderate patients (1.2%, p ⫽ 0.13), but there was no difference in TND. There were also no significant differences in the postoperative ventilator requirements, ICU, or hospital lengths of stay. Since our initial report using moderate hypothermia and uSACP, we have been gradually performing arch replacements at milder levels of hypothermia, especially in cases requiring short circulatory arrest periods for hemiarch replacement [1]. Therefore, a propensity score analysis was conducted to eliminate any possibility that improved surgical technique had a significant effect on outcomes. Furthermore, because this is a nonrandomized, retrospective study, the propensity score analysis serves to eliminate any possibility that selection bias may have influenced the results. As determined by the propensity score analysis, the groups had equivalent rates of operative mortality, TND, DDRF, and mediastinal reexploration for bleeding; however, PND was significantly reduced in the mild group (adjusted odds ratio, 0.28; p ⫽ 0.02). Postoperative neurologic dysfunction after arch operations can be a devastating complication that has been shown to significantly increase length of stay and inhospital death [9]. Two distinctly different types of neurologic injury have been well described. PND is a permanent focal deficit caused by embolic phenomena from atherosclerotic plaques originating in the ascending aorta and arch. TND is a reversible, diffuse, subtle injury that is attributed to global cerebral ischemic injury secondary to inadequate cerebral protection [10]. Patients
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with TND can experience transient confusion, agitation, delirium, prolonged obtundation, or parkinsonism without localizing signs in the immediate postoperative period. The risk of PND can be influenced by the arterial cannulation site and is lowest with right axillary artery cannulation [11]. All patients in the current series were cannulated through an 8-mm Dacron (DuPont, Wilmington, DE) graft sewn to the axillary artery. Therefore, the 60% relative reduction in PND observed in elective and emergency mild patients was an unexpected finding. Two previous studies comparing outcomes of patients after arch replacement at two different levels of hypothermia did not report a protective effect of warmer temperatures on the incidence of PND: ●
●
Pacini and colleagues [12] reported equivalent PND rates in elective and emergency arch replacements at 22°C (1.7%) or 26°C (3.1%, p ⫽ 0.72) with bilateral ACP and various sites of arterial cannulation (axillary artery, ascending aorta and femoral artery). Kamiya and colleagues [3] also reported equivalent PND rates in elective and emergency arch replacements at 23°C (8.0%) or 26°C (5.1%, p ⫽ 0.27) with bilateral ACP and ascending aortic cannulation.
The mechanism by which mild hypothermia has a beneficial effect on PND in our report is unclear. Thus, we can only hypothesize that the atherosclerotic burden might have been greater in the moderate patients, and we will continue to study this trend as we move forward in our use of mild hypothermia in the future. The reduction in postoperative ventilator requirements in mild patients translated into an approximate 24-hour reduction in ICU and overall hospital lengths of stay. These results were largely due to shorter times observed in the elective patients, which were absent in the emergency type A cases. The etiology of the reduced ventilator requirement is likely multifactorial. The shorter cardiopulmonary bypass times in the elective mild group (183 ⫾ 56 minutes) compared with the moderate group (202 ⫾ 60 minutes; p ⬍ 0.001) may have translated into a reduction in postoperative pulmonary dysfunction, a well-recognized complication of cardiopulmonary bypass [13]. However, the absolute reduction was only 19 minutes, and unlikely to fully account for a 24-hour reduction in hospital length of stay (Table 5). We acknowledge the overall postoperative ventilator requirements for both groups are high and may reflect a learning curve regarding postoperative ICU care of patients undergoing aortic operations. Such a learning curve may have affected our results. When this variable was examined in the propensity score analysis, the reduction in postoperative ventilator requirement observed in mild patients did not reach statistical significance (p ⫽ 0.29). Although we moved to a more aggressive extubation protocol later in the series, early extubation remains an area for improvement. The other notable finding was that the level of hypothermia did not have an effect on postoperative coagu-
lopathy. The incidence of mediastinal reexploration for bleeding was equivalent in mild and moderate patients in both the elective and emergency settings. This differs from the work of others who have reported that deeper levels of hypothermia and prolonged cardiopulmonary bypass times were significant risk factors for increased bleeding after arch operations [3, 14]. Limitations of the current study are its retrospective nature, the lack of randomization, and the absence of long-term data regarding the neurocognitive function of these patients after circulatory arrest. The propensity score analysis was performed in an attempt to limit any influence of selection bias on our results. We acknowledge that without neurocognitive testing, the long-term effect of our cerebral protection strategy (mild or moderate hypothermia with uSACP) on cognitive function is unknown. A protocol of preoperative and postoperative neuropsychiatric assessment questionnaires for all patients undergoing arch operations has been implemented, and the results will be included in all future studies. In conclusion, data from the current report support the safe use of a cerebral protection strategy of mild hypothermic circulatory arrest and uSACP during hemiarch reconstruction in elective and emergency settings. When directly compared with patients undergoing hemiarch replacement at deeper levels of hypothermia, no difference in operative mortality or temporary neurologic dysfunction was observed. The reduction in stroke rates observed in patients undergoing hemiarch reconstruction at 28°C suggests that mild hypothermia offers adequate levels of neurologic protection compared with deeper levels of hypothermia. Future studies will investigate this hypothesis and the long-term effect of mild hypothermia on neurocognitive function. We thank Kim Baio, Deborah Canup, and Iman F. Aziz for their assistance with this manuscript.
References 1. Leshnower BG, Myung RJ, Kilgo PD, et al. Moderate hypothermia and unilateral selective antegrade cerebral perfu-
LESHNOWER ET AL HEMIARCH RECONSTRUCTION AT 28°C
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
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sion: a contemporary cerebral protection strategy for aortic arch surgery. Ann Thorac Surg 2010;90:547–54. Minatoya K, Ogino H, Matsuda H, et al. Evolving selective cerebral perfusion for aortic arch replacement: high flow rate with moderate hypothermic circulatory arrest. Ann Thorac Surg 2008;86:1827–31. Kamiya H, Hagl C, Kropivnitskaya I, et al. The safety of moderate hypothermic lower body circulatory arrest with selective cerebral perfusion: a propensity score analysis. J Thorac Cardiovasc Surg 2007;133:501–9. DiEusanio M, Tan ME, Schepens MA, et al. Surgery for acute type A using antegrade selective cerebral perfusion: experience with 122 patients. Ann Thorac Surg 2003;75:514 –9. Khaladj N, Shrestha M, Meck S, et al. Hypothermic circulatory arrest with selective antegrade cerebral perfusion in ascending aortic and aortic arch surgery: a risk factor analysis for adverse outcome in 501 patients. J Thorac Cardiovasc Surg 2008;135:908 –14. Zierer A, Detho F, Dzemali O, et al. Antegrade cerebral perfusion with mild hypothermia for aortic arch replacement: single-center experience in 245 consecutive patients. Ann Thorac Surg 2011;91:1868 –74. Khaladj N, Shrestha M, Peterss S, et al. Ascending aortic cannulation in acute aortic dissection type A: the Hannover experience. Eur J Cardiothorac Surg 2008;34:792– 6. Bakhtiary F, Dogan S, Zierer A, et al. Antegrade cerebral perfusion for acute type A aortic dissection in 120 consecutive patients. Ann Thorac Surg 2008;85:465–9. Hagl C, Ergin MA, Galla JD, et al. Neurologic outcome after ascending aorta-aortic arch operations: effect of brain protection technique in high-risk patients. J Thorac Cardiovasc Surg 2001;121:1107–21. Ergin MA, Griepp EB, Lansman SL, Galla JD, Levy M, Griepp RB. Hypothermic circulatory arrest and other methods of cerebral protection during operations on the thoracic aorta. J Card Surg 1994;9:525–37. Svensson LG, Blackstone EH, Rajeswaran J, et al. Does the arterial cannulation site for circulatory arrest influence stroke risk? Ann Thorac Surg 2004;78:1274 – 84. Pacini D, Leone A, DiMarco L, et al. Antegrade selective cerebral perfusion in thoracic aorta surgery: safety of moderate hypothermia. Eur J Cardiothorac Surg 2007;31:618 –22. Hammon JW Jr, Edmunds LH Jr. Extracoporeal circulation: organ damage. In: Cohn LH, Edmunds LH Jr, editors. Cardiac surgery in the adult. New York: McGraw-Hill; 2003:361– 88. Harrington DK, Lilley JP, Rooney SJ, Bonser RS. Nonneurologic morbidity and profound hypothermia in aortic surgery. Ann Thorac Surg 2004;78:596 – 601.
DISCUSSION DR VINAY BADHWAR (Pittsburgh, PA): You mentioned at the end that you used propensity matching for your conclusion, so basically it’s a stroke benefit. DR LESHNOWER: There is a stroke benefit, yes. DR BADHWAR: In your experience as it has evolved, what about the use of adjunctive neurologic monitoring such as electroencephalogram (EEG) or cerebral oximetry? Have you added that to your regimen and do you think that may have a role in your perfusion management? DR LESHNOWER: For all these cases, I did not mention this previously, we used continuous EEG monitoring, and we used
the cerebral oximetry for both groups throughout the entire experience. DR MUHAMMAD MUMTAZ (Norfolk, VA): I am a congenital surgeon, and most of my practice is in children and not in adults. I just want to share a couple of things with you. Perfusion through one of the cranial arteries, instead of the normal 4 that God has given us, assumes that the circle of Willis is complete. What measures did you take to make sure that this was the case? Even in newborns, I have anecdotally found completely isolated 2 halves of the circle of Willis on the magnetic resonance angiography (MRA). In addition, there is a case report in the Annals from last year reporting cerebral ischemia in one side of the brain of a baby after a Norwood procedure due to steal
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phenomenon from the Blalock-Taussig shunt and an incomplete circle of Willis. So I would strongly propose obtaining a preoperative MRA and magnetic resonance imaging of the brain. That is my first question. ADULT CARDIAC
DR LESHNOWER: That is a question that we get a lot, actually, with this technique. We do not do any pre-op imaging to look at the circle of Willis. With our cerebral oximetry what we do do is when we go on circulatory arrest and clamp the innominate, if we see a significant drop in the left-sided cerebral oximetry monitoring, we will clamp the left common carotid. This eliminates any steal and also pressurizes the system, and opens any right to left extracranial collateral flow. We have not had a problem with it. And there is also a recent report in the European Journal of Cardiothoracic Surgery where they looked at cannulating either the right or left common carotid and doing the same technique unilateral selective antegrade cerebral perfusion, and they saw no difference, and they didn’t do any preoperative imaging either. DR MUMTAZ: However, you do note that you have a 5% incidence of stroke. This is quite significant. If you want to take the field one step forward with the goal of going from 5% to 0%, I would strongly propose getting a preoperative MRA. Some of these strokes may be related to that. And that brings me to the second point. You are relying on EEG, which becomes unreliable below the temperature of 30°C and with the deep anesthetics. I am curious to know what you think about this. Similarly, at low temperature the near-infrared spectroscopy (NIRS) may be unreliable too. I have seen the NIRS, for example, in circulatory arrest cases for 15 minutes, it may be normal, possibly because there is little or no brain oxygen consumption. A number of authors and other surgeons in the congenital field have noted that at below the temperature of 28°, the NIRS may take a longer time to demonstrate ischemia. What happens to EEG? How reliable is that?
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ses or anything like that that there might be an optimal hypothermic temperature at which to perform this? That would be the first question. And the second question, different topic. Did you do any MRI or neurocognitive studies? Because I think we all appreciate that gross neurologic outcomes are probably not as sensitive a way to analyze neurologic outcomes after such a big operation. DR LESHNOWER: Two good questions that we also asked ourselves. We did do the analysis asking the question of whether there is an optimal temperature at which patients essentially do better, and it fell out in our 500 patients at 28°. I didn’t present that data. We acknowledge the a limitation that we have in our aortic program is the lack of follow-up with the Mini-Mental Status Examination or some sort of neurocognitive examination pre-op and post-op, which we plan to implement in the future. But, no, we don’t have that currently. DR WILLIAM T. BRINKMAN (Plano, TX): Brad, a great talk, and this is something I am very interested in. My concern when you are circ arresting at moderate hypothermia or mild hypothermia is the spinal cord, the kidneys, those sorts of things. That is why I feel safer; if I get caught with a difficult arch tear or something, I feel safer. What are your thoughts on that? DR LESHNOWER: That is a good question. We saw no incidence of paraplegia, and we have not, for any of our cases done with this technique. We have started to measure liver function tests (LFTs), especially in our prolonged periods of circ arrest, not in this population but in total arches, and so far we have not seen any significant signs of liver ischemia or inflammation, that kind of thing.
DR LESHNOWER: It still remains flat at that temperature.
DR CULLEN MORRIS (Athens, GA): Brad and Ed, a great paper. I guess all these patients had aprotinin. What are you all using now for your circ arrest cases in terms of tranexamic acid and all that, number one? And number two, I know I have gone from using the tape like Ed showed me to use to using a clamp on the innominate. What are you all doing with that?
DR JOHN V. CONTE (Baltimore, MD): If I understand your study right, you went and just found the median, and that happened to be at 27° and that is how you did your analysis. Have you identified with receiver operator characteristic analy-
DR LESHNOWER: We are using the clamp, Cullen, instead of the umbilical tape and Rummel now. And the patients get tranexamic acid but no aprotinin. I think maybe early in the experience they were still using that, but not now.
Bradley G. Leshnower, MD, Richard J. Myung, MD, Vinod H. Thourani, MD, Michael E. Halkos, MD, Patrick D. Kilgo, MS, John D. Puskas, MD, and Edward P. Chen, MD Clinical Research Unit, Division of Cardiothoracic Surgery, Joseph B. Whitehead Department of Surgery, and the Rollins School of Public Health, Emory University School of Medicine, Atlanta, Georgia
Background. During the past decade, use has increased of moderate hypothermic circulatory arrest with antegrade cerebral perfusion for cerebral protection during aortic arch operations. This study examined the use of mild hypothermia in conjunction with unilateral selective antegrade cerebral perfusion (uSACP) for hemiarch replacement for proximal aortic arch reconstruction. Methods. A retrospective review of the Emory Aortic Database identified 708 patients who underwent aortic arch replacement between 2004 and 2011. Of these, 500 underwent hemiarch replacement at temperatures of 22°C or higher with uSACP. Outcomes were analyzed and compared between 277 patients undergoing hemiarch at a temperature of 28.6°C (mild) and 233 undergoing hemiarch at a temperature of 24.3°C (moderate). Propensity scores were generated and analyzed between the groups to adjust for confounding factors such as selection bias.
Results. Operative mortality was equivalent between mild and moderate groups in elective (4.2% vs 4.8%, p ⴝ 0.80) and emergency (7.7% vs 11.7%, p ⴝ 0.43) settings. No differences occurred in the incidence of temporary neurologic dysfunction, dialysis-dependent renal failure, or mediastinal reexploration for bleeding between mild and moderate patients. The incidence of permanent neurologic deficit was significantly reduced in mild (2.5%) vs moderate patients (7.2%, p ⴝ 0.01), which was confirmed by the propensity score analysis (adjusted odds ratio, 0.28; p ⴝ 0.02). Conclusions. Hemiarch replacement can be safely performed at 28°C with uSACP in emergency and elective settings. Mild hypothermia with uSACP offers adequate levels of neurologic protection compared with deeper levels of hypothermia. (Ann Thorac Surg 2012;93:1910 – 6) © 2012 by The Society of Thoracic Surgeons
D
In a previous report, we described our initial experience of performing hemiarch and total arch reconstructions with a cerebral protection strategy of moderate hypothermic circulatory arrest (ⱖ22°C) using adjunctive unilateral selective antegrade cerebral perfusion (uSACP) through right axillary artery inflow [1]. Since that time, our technique has continued to evolve by performing aortic arch procedures at milder degrees of hypothermia, especially in the case of hemiarch reconstruction that requires brief periods of lower body circulatory arrest. This study examined the safety of performing elective and emergency hemiarch reconstructions under mild hypothermic circulatory arrest with uSACP.
uring the past decade, antegrade cerebral perfusion (ACP) with hypothermic circulatory arrest has become a preferred cerebral protection strategy for aortic arch operations in many high-volume aortic centers [1– 6]. ACP provides uninterrupted physiologic perfusion to the brain during reconstruction of the arch and has changed the paradigm from total body hypothermic circulatory arrest to isolated lower body circulatory arrest. The application of continuous, antegrade cold cerebral perfusion has led to a departure from the traditional use of deep hypothermia (18° to 22°C) for lower body protection during circulatory arrest. Many groups have moved to a strategy of moderate hypothermia with ACP for aortic arch reconstruction. The impetus for this change is to minimize the adverse effects of profound hypothermia, which include prolonged durations of cardiopulmonary bypass, leading to an increased systemic inflammatory response and subsequent increased risk of bleeding and organ dysfunction [3].
Accepted for publication Feb 23, 2012. Presented at the Fifty-eighth Annual Meeting of the Southern Thoracic Surgical Association, San Antonio, TX, Nov 9 –12, 2011. Address correspondence to Dr Chen, Division of Cardiothoracic Surgery, The Emory Clinic, 1365 Clifton Rd, Ste A2236, Atlanta, GA 30322; e-mail: [email protected].
© 2012 by The Society of Thoracic Surgeons Published by Elsevier Inc
Patients and Methods A retrospective review of the Emory Aortic Surgery Database identified 708 patients who underwent aortic arch operations at the 3 primary hospitals within the Emory Healthcare system between January 2004 and October 2011. Inclusion criteria were all patients undergoing hemiarch reconstruction with right axillary artery cannulation, moderate hypothermic circulatory arrest (ⱖ 22°C), and uSACP. Exclusion criteria were femoral or ascending aortic cannulation, deep hypothermic circula0003-4975/$36.00 doi:10.1016/j.athoracsur.2012.02.069
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Operative Technique Technical details of our operative technique have been published [1]. We used a Foley catheter with a temperature probe to measure core body temperature. Transcutaneous cerebral oximetry (INVOS 3100-SD, Troy, Mich) and continuous electroencephalogram monitoring were routinely performed. Intraoperative transesophageal echocardiography was used in all patients. The goal core body temperature was determined by each surgeon and depended on several factors, including age, preoperative renal function, aortic pathology, and the complexity of the planned hemiarch reconstruction. Upon reaching the goal core body temperature, the innominate artery was occluded proximally. Cerebral perfusion was initiated at 16°C at a rate of 10 mL/kg/min and adjusted to maintain cerebral perfusion pressures of 60 to 70 mm Hg. If cerebral oximetry saturations dropped below 10% below baseline values after lower body circulatory arrest was initiated, the left common carotid artery was isolated and occluded. Upon completion of the circulatory arrest period, vigorous maneuvers were performed to remove air before reinstitution of full flow cardiopulmonary bypass and rewarming was initiated. Proximal aortic procedures and any coronary or valve interventions were typically performed during the rewarming period.
Statistical Analysis Univariate (unadjusted) associations between preoperative and intraoperative variables and clinical outcomes were determined using t tests and 2 tests. To adjust for potential selection bias, propensity scores (PS) were generated for each patient that represented the probability of being assigned to mild hypothermia. The PS was estimated from 19 preoperative variables (variables from Table 1 and also year of operation). The PS was relatively balanced between the mild and moderate groups, indicating that the covariate patterns of the two groups were similar. Once the PSs were generated, analyses were performed in quintile strata of PSs (which represent homog-
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Table 1. Preoperative Demographics in Mild or Moderate Hypothermia Patients Risk Factora Age, years BMI, kg/m2 Male sex History of CVA NYHA class III/IV Diabetes mellitus Hypertension Renal failure Myocardial infarction COPD None Mild Moderate Severe Ejection fraction Aneurysm size, cm
Moderate (n ⫽ 223)
Mild (n ⫽ 277)
57.9 ⫾ 14.1 28.6 ⫾ 6.9 160 (73.4) 11 (2.3) 52 (32.5) 25 (11.5) 47 (21.6) 30 (13.8) 23 (10.6)
57.7 ⫾ 14.1 28.8 ⫾ 6.0 181 (70.4) 19 (7.4) 74 (42.1) 28 (10.9) 49 (19.1) 21 (8.2) 27 (10.5)
176 (81.9) 30 (14.0) 3 (1.4) 6 (2.8) 0.545 ⫾ 0.118 5.6 ⫾ 1.1
210 (82.0) 31 (12.1) 9 (3.5) 6 (2.3) 0.547 ⫾ 0.113 5.5 ⫾ 1.1
p Value 0.88 0.69 0.47 0.29 0.07 0.84 0.50 0.05b 0.99 0.48
0.88 0.11
a Continuous data are presented as mean ⫾ standard deviation and b categoric data are number (%). Statistically significant (p ⱕ 0.05). BMI ⫽ body mass index; COPD ⫽ chronic obstructive pulmonary disease; CVA ⫽ cerebrovascular accident; NYHA ⫽ New York Heart Association.
enous groups of patients) and outcomes analyzed by mild vs moderate hypothermia. In addition, to take advantage of the strength of the full sample, a logistic regression model was constructed that modeled each outcome as a function of temperature (mild vs moderate), adjusted for the PS. Adjusted odds ratios and 95% confidence intervals (CI) were computed. The data were analyzed with SAS 9.2 software (SAS Institute, Cary, NC). All data are presented as means ⫾ standard deviation. Statistical tests were evaluated at the ␣ ⫽ 0.05 level. All comparisons and model terms were preplanned.
Results Entire Series A total of 500 patients underwent hemiarch replacement under mild or moderate hypothermic circulatory arrest with uSACP. Of these, 142 patients (28%) received emergency hemiarch replacement for acute type A aortic dissection, and the remaining 358 (72%) underwent elective ascending aortic and hemiarch replacement for aneurysmal disease (91%), chronic type A dissection (6%), or other etiologies. Concomitant procedures in 380 patients (80%) included root replacement, aortic valve replacement, mitral valve replacement, and coronary artery bypass grafting. A total of 240 (48%) patients required concomitant aortic root replacement, including 80 patients (16%) who received a David V valve-sparing procedure. The series included 78 patients (15.6%) who required redo sternotomy for their aortic operation. The mean core body temperature at the initiation of circulatory arrest for the entire series was 26.7° ⫾ 2.5°C. Permanent neurologic dysfunction (PND) occurred in
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tory arrest (⬍22°C), retrograde cerebral perfusion, and total arch replacement. The analysis is based on data from 500 patients who met these strict criteria. The median core body temperature at the initiation of circulatory arrest for these 500 patients was 27°C. Patients were divided into two groups according to this median temperature, and a comparative analysis was performed: 223 received hemiarch replacement using moderate hypothermic circulatory arrest with core temperatures of 22° to 26°C (moderate group), and 277 received hemiarch replacement using mild hypothermic circulatory arrest with core temperatures of 27° to 34°C (mild group). Medical records were reviewed for preoperative, intraoperative, and postoperative variables. This study was approved by the Institutional Review Board at Emory University in compliance with Health Insurance Portability and Accountability Act regulations and the Declaration of Helsinki. The Institutional Review Board waived the need for individual patient consent.
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Table 2. Procedures in Mild or Moderate Hypothermia Patients
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Proceduresa
Moderate (n ⫽ 223)
Mild (n ⫽ 277)
p Value
Elective Emergency type A Reoperative Aortic root replacement David V Artic valve replacement CABG
156 (65.5) 77 (34.5) 39 (17) 109 (49) 35 (16) 36 (16) 41 (18)
212 (76.5) 65 (23.5) 39 (14) 131 (47) 45 (16) 51 (18) 36 (13)
0.45 ⬍0.01b 0.34 0.65 0.75 0.72 0.24
a All data are presented as number (%). 0.05).
b
Statistically significant (p ⱕ
CABG ⫽ coronary artery bypass grafting.
4.6% and temporary neurologic dysfunction (TND) in 5.2%. The incidence of dialysis-dependent renal failure (DDRF) was 4.0%. Thirty-six patients (7.2%) required mediastinal re-exploration for bleeding. No paraplegia occurred in the series. Operative mortality for the entire series was 6% (30 of 500). Mortality was 4.5% for elective procedures and 9.9% for emergency type A dissection repairs.
Preoperative Demographics Table 1 lists the preoperative demographics for mild and moderate group patients. Both groups were a mean age of 58 ⫾ 14 years and were similar with respect to body mass Table 3. Overall Outcomes in Mild or Moderate Hypothermia Patients Mild (n ⫽ 277)
index, sex, and the preoperative risk factors of prior cerebrovascular accident, diabetes mellitus, hypertension, chronic obstructive pulmonary disease, and myocardial infarction. Moderate group patients had a higher incidence of preoperative renal failure (13.8%) than the mild group (8.2%, p ⫽ 0.05). Both cohorts had normal preoperative left ventricular function and similar aneurysm sizes.
Analysis 1: Overall Mild vs Moderate Group Table 2 lists the operative procedures performed in each group. The moderate cohort contained a significantly higher percentage of patients who received emergency operations for acute type A dissection (35%) vs the mild group (24%; p ⬍ 0.01). The incidence of redo sternotomy, aortic root replacement, aortic valve replacement, and coronary artery bypass grafting were similar between the two groups. Circulatory arrest was initiated at a significantly warmer core body temperature in the mild group (28.6° ⫾ 1.2°C) vs the moderate group (24.3° ⫾ 1.3°C, p ⬍ 0.001) Cardiopulmonary bypass times (minutes) were reduced in the mild patients (184 ⫾ 57) vs the moderate group (197 ⫾ 60; p ⫽ 0.01), but cross-clamp and circulatory arrest times were equivalent. Operative mortality did not differ significantly between mild (5.1%) and moderate (7.2%) patients. The incidence of PND was significantly less in the mild group (2.5%) vs the moderate group (7.2%, p ⫽ 0.01); however, there was no difference in TND, DDRF, or mediastinal reexploration for bleeding between the two groups. Mild patients required significantly less postoperative ventilator support (46 ⫾ 104 hours) compared with moderate patients (69 ⫾ 123 hours; p ⫽ 0.03) and had shorter intensive care unit (ICU) stays. This translated into a trend toward a shorter hospital length of stay of 9.5 ⫾ 8.1 days for mild patients vs 10.5 ⫾ 7.0 days for moderate patients (p ⫽ 0.15; Table 3). The propensity score analysis found no difference between mild and moderate patients in the major outcomes of operative mortality, TND, DDRF, or mediastinal reexploration for bleeding. However, PND was significantly lower in the patients who received mild hypothermic circulatory arrest (Table 4).
Variables and Outcomesa
Moderate (n ⫽ 223)
HCA temperature, °C Cardiopulmonary bypass time, min Cross-clamp time, min Circulatory arrest time, min Death Neurologic dysfunction Permanent Temporary Dialysis-dependent renal failure Mediastinal reexploration Post-op mechanical ventilation, hours Length of stay Intensive care unit, days Hospital, days
24.3 ⫾ 1.3 197 ⫾ 60
28.6 ⫾ 1.2 184 ⫾ 57
⬍0.001b 0.01b
154 ⫾ 62 25.8 ⫾ 9.2
148 ⫾ 55 25.3 ⫾ 9.2
0.29 0.54
16 (7.2)
14 (5.1)
0.32
16 (7.2) 14 (6.3) 9 (4.1)
7 (2.5) 12 (4.3) 11 (4.0)
0.01b 0.33 0.97
Table 4. Propensity Regression Adjustment Adjusted Odds Ratios
16 (7.2)
20 (7.2)
0.98
Outcome
68.8 ⫾ 123
45.8 ⫾ 104.3
0.03
p Value
5.1 ⫾ 5.6
4.2 ⫾ 5.8)
0.06
10.5 ⫾ 7.0
9.5 ⫾ 8.1)
0.15
a Continuous data are presented as mean ⫾ standard deviation and b Statistically significant (p ⱕ 0.05). categoric data as number (%).
HCA ⫽ hypothermic circulatory arrest.
Death Neurologic dysfunction Permanent Temporary DDRF Bleeding a
Mild vs Moderate AOR (95% CI)
p Value
0.94 (0.43–2.05)
0.87
0.28 (0.10–0.82) 0.81 (0.34–1.92) 1.75 (0.67–4.56) 1.32 (0.64–2.74)
0.02a 0.63 0.25 0.46
Statistically significant (p ⱕ 0.05).
AOR ⫽ adjusted odds ratio; CI ⫽ confidence interval; dialysis-dependent renal failure.
DDRF ⫽
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or overall hospital lengths of stay between the two groups.
HCA temperature, °C Cardiopulmonary bypass time, min Cross-clamp time, min. Circulatory arrest time, min Death Neurologic dysfunction Permanent Temporary Dialysis-dependent renal failure Mediastinal reexploration Post-op mechanical ventilation, hours Length of stay Intensive care unit, days Hospital, days
Moderate (n ⫽ 146)
Mild (n ⫽ 212)
p Value
24.2 ⫾ 1.3 202 ⫾ 60
28.6 ⫾ 1.3 183 ⫾ 56
⬍0.001b 0.01b
165 ⫾ 59 23.6 ⫾ 6.7
151 ⫾ 54 23.2 ⫾ 7.2
0.02b 0.63
7 (4.8)
9 (4.3)
0.80
7 (4.8) 8 (5.5) 1 (0.7)
4 (1.9) 8 (3.8) 5 (2.4)
0.12 0.44 0.23
10 (6.9) 57 ⫾ 115
14 (6.6) 35 ⫾ 83
0.93 0.05b
4.3 ⫾ 4.8 9.6 ⫾ 6.2
3.6 ⫾ 5.3 8.5 ⫾ 6.6
0.23 0.13
a Continuous data are presented as mean ⫾ standard deviation; categoric b Statistically significant (p ⱕ 0.05). data as number (%).
HCA ⫽ hypothermic circulatory arrest.
Analysis 2: Elective Mild vs Moderate Table 5 lists the major perioperative data and outcomes from elective hemiarch cases performed under mild or moderate hypothermic circulatory arrest with uSACP. In mild patients, circulatory arrest was initiated at significantly warmer mean core body temperatures of 28.6° ⫾ 1.3°C vs 24.2° ⫾ 1.3°C in moderate patients (p ⬍ 0.001). Cardiopulmonary bypass (183 ⫾ 56 vs 201⫾ 60 min, p ⬍ 0.01) and cross-clamp times (151 ⫾ 54 vs 165 ⫾ 59 min., p ⫽ 0.02) were significantly reduced in the mild group. Circulatory arrest times were equivalent. Operative mortality was similar in mild (4.8%) and moderate (4.2%) patients. There was no difference in PND, TND, DDRF, or the mediastinal reexploration rate between the two groups. Mild patients had significantly shorter postoperative ventilator requirements (35 ⫾ 83 hours) vs moderate patients (57 ⫾ 115 hours; p ⫽ 0.05), and a trend toward a shorter hospital length of stay.
Analysis 3: Emergency Repair in Mild vs Moderate Table 6 lists the major perioperative data and outcomes from emergency type A repairs requiring hemiarch reconstruction performed under mild or moderate hypothermic circulatory arrest with uSACP. Mild patients underwent circulatory arrest at warmer mean core body temperatures (28.4° ⫾ 1.0°C) vs moderate (24.5° ⫾ 1.3°C, p ⬍ 0.001). Cardiopulmonary bypass, cross-clamp, and circulatory arrest times were equivalent between the two groups. There was no significant difference in operative mortality between mild (7.7%) and moderate (11.7%) patients (p ⫽ 0.43). The incidence of PND, TND, and DDRF was equivalent. There was no difference in mediastinal reexploration rate, ventilator requirements, ICU,
Comment Antegrade cerebral perfusion has enabled surgeons to alter traditional cerebral protection strategies and safely perform arch reconstructions under moderate rather than deep levels of hypothermic circulatory arrest [1– 6]. Avoiding profound hypothermia in circulatory arrest cases has been associated with a reduction in cardiopulmonary bypass times, postoperative inflammation, organ dysfunction, and bleeding [3]. In 2004 the paradigm of moderate hypothermic circulatory arrest with uSACP was established at Emory as the primary cerebral protection strategy for aortic arch operations. In a previous study, we reported the safety of this technique with hemiarch and total arch replacements and demonstrated that temperature was not an independent risk factor for operative death or adverse neurologic outcomes [1]. In this study, we focused on evaluating the safety of performing hemiarch reconstruction at milder levels of hypothermia (28.6°C), by comparing outcomes with a contemporary cohort that received hemiarch replacements at moderate hypothermic circulatory arrest (24.3°C). Reports of aortic arch replacement conducted under mild hypothermia (⬍ 28°C) with ACP are beginning to surface in the literature [6 – 8]. The current study distinguishes itself from its predecessors by the inclusion of a control group that underwent hemiarch replacement with an identical surgical technique at a deeper level of hypothermia. Table 6. Emergency Operation in Mild vs Moderate Variables and Outcomesa
Moderate (n ⫽ 77)
HCA temperature, °C 24.5 ⫾ 1.3 Cardiopulmonary bypass 187 ⫾ 59 time, min Cross-clamp time, min 130 ⫾ 62 Circulatory arrest time, 30.4 ⫾ 8.9 min Death 9 (11.7) Neurologic dysfunction Permanent 9 (11.7) Temporary 6 (7.8) Dialysis-dependent renal 8 (10.4) failure Mediastinal reexploration 6 (7.8) Post-op mechanical 92 ⫾ 134 ventilation, hours Length of stay Intensive care unit, days 6.9 ⫾ 6.7 Hospital, days 12.5 ⫾ 8.2
Mild (n ⫽ 65)
p Value
28.5 ⫾ 0.9 186 ⫾ 63
⬍0.001b 0.92
136 ⫾ 58 33.1 ⫾ 11.4
0.60 0.14
5 (7.7)
0.43
3 (4.6) 4 (6.2) 6 (9.2)
0.13 0.70 0.82
6 (9.2) 81 ⫾ 151
0.76 0.63
6.0 ⫾ 7 13.0 ⫾ 11.4
0.45 0.74
a Continuous data are presented as mean ⫾ standard deviation; categoric b Statistically significant (p ⱕ 0.05). data as number (%).
HCA ⫽ hypothermic circulatory arrest.
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Table 5. Elective Operation in Mild vs Moderate Variables and Outcomesa
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Analysis of the entire study population demonstrated that patients undergoing hemiarch replacement at warmer temperatures (28.6°C) had significantly shorter cardiopulmonary bypass times and postoperative ventilator requirements, resulting in a trend toward shorter postoperative ICU and hospital lengths of stay. Operative mortality was reduced in the mild group patients (5.1%) compared with moderate patients (7.2%), but the difference was not statistically significant (p ⫽ 0.32). The level of hypothermia had no effect on TND, but there was a significant reduction in the incidence of PND in the mild patients (2.5%) compared with moderate patients (7.2%, p ⫽ 0.01). Isolated evaluation of the elective cases produced similar results to those found in the analysis of the entire study cohort. Low elective operative mortality rates were observed in mild (4.2%) and moderate (4.8%) patients (p ⫽ 0.81), with shorter cardiopulmonary bypass and cross-clamp times in the mild group. The reductions in postoperative ventilator requirement and hospital length of stay in the mild group were also observed in elective cases. PND was reduced in the mild group (1.9%) vs the moderate group (4.8%) but did not reach statistical significance (p ⫽ 0.12). In the emergency cases, there was no difference in cardiopulmonary bypass, cross-clamp, and circulatory arrest times in mild and moderate patients undergoing type A dissection repair. Operative mortality was lower in the mild group (7.7%) vs the moderate group (11.6%), but the difference did not reach statistical significance (p ⫽ 0.43). Again, a trend toward a reduction in PND was observed in mild patients (4.6%) vs moderate patients (1.2%, p ⫽ 0.13), but there was no difference in TND. There were also no significant differences in the postoperative ventilator requirements, ICU, or hospital lengths of stay. Since our initial report using moderate hypothermia and uSACP, we have been gradually performing arch replacements at milder levels of hypothermia, especially in cases requiring short circulatory arrest periods for hemiarch replacement [1]. Therefore, a propensity score analysis was conducted to eliminate any possibility that improved surgical technique had a significant effect on outcomes. Furthermore, because this is a nonrandomized, retrospective study, the propensity score analysis serves to eliminate any possibility that selection bias may have influenced the results. As determined by the propensity score analysis, the groups had equivalent rates of operative mortality, TND, DDRF, and mediastinal reexploration for bleeding; however, PND was significantly reduced in the mild group (adjusted odds ratio, 0.28; p ⫽ 0.02). Postoperative neurologic dysfunction after arch operations can be a devastating complication that has been shown to significantly increase length of stay and inhospital death [9]. Two distinctly different types of neurologic injury have been well described. PND is a permanent focal deficit caused by embolic phenomena from atherosclerotic plaques originating in the ascending aorta and arch. TND is a reversible, diffuse, subtle injury that is attributed to global cerebral ischemic injury secondary to inadequate cerebral protection [10]. Patients
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with TND can experience transient confusion, agitation, delirium, prolonged obtundation, or parkinsonism without localizing signs in the immediate postoperative period. The risk of PND can be influenced by the arterial cannulation site and is lowest with right axillary artery cannulation [11]. All patients in the current series were cannulated through an 8-mm Dacron (DuPont, Wilmington, DE) graft sewn to the axillary artery. Therefore, the 60% relative reduction in PND observed in elective and emergency mild patients was an unexpected finding. Two previous studies comparing outcomes of patients after arch replacement at two different levels of hypothermia did not report a protective effect of warmer temperatures on the incidence of PND: ●
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Pacini and colleagues [12] reported equivalent PND rates in elective and emergency arch replacements at 22°C (1.7%) or 26°C (3.1%, p ⫽ 0.72) with bilateral ACP and various sites of arterial cannulation (axillary artery, ascending aorta and femoral artery). Kamiya and colleagues [3] also reported equivalent PND rates in elective and emergency arch replacements at 23°C (8.0%) or 26°C (5.1%, p ⫽ 0.27) with bilateral ACP and ascending aortic cannulation.
The mechanism by which mild hypothermia has a beneficial effect on PND in our report is unclear. Thus, we can only hypothesize that the atherosclerotic burden might have been greater in the moderate patients, and we will continue to study this trend as we move forward in our use of mild hypothermia in the future. The reduction in postoperative ventilator requirements in mild patients translated into an approximate 24-hour reduction in ICU and overall hospital lengths of stay. These results were largely due to shorter times observed in the elective patients, which were absent in the emergency type A cases. The etiology of the reduced ventilator requirement is likely multifactorial. The shorter cardiopulmonary bypass times in the elective mild group (183 ⫾ 56 minutes) compared with the moderate group (202 ⫾ 60 minutes; p ⬍ 0.001) may have translated into a reduction in postoperative pulmonary dysfunction, a well-recognized complication of cardiopulmonary bypass [13]. However, the absolute reduction was only 19 minutes, and unlikely to fully account for a 24-hour reduction in hospital length of stay (Table 5). We acknowledge the overall postoperative ventilator requirements for both groups are high and may reflect a learning curve regarding postoperative ICU care of patients undergoing aortic operations. Such a learning curve may have affected our results. When this variable was examined in the propensity score analysis, the reduction in postoperative ventilator requirement observed in mild patients did not reach statistical significance (p ⫽ 0.29). Although we moved to a more aggressive extubation protocol later in the series, early extubation remains an area for improvement. The other notable finding was that the level of hypothermia did not have an effect on postoperative coagu-
lopathy. The incidence of mediastinal reexploration for bleeding was equivalent in mild and moderate patients in both the elective and emergency settings. This differs from the work of others who have reported that deeper levels of hypothermia and prolonged cardiopulmonary bypass times were significant risk factors for increased bleeding after arch operations [3, 14]. Limitations of the current study are its retrospective nature, the lack of randomization, and the absence of long-term data regarding the neurocognitive function of these patients after circulatory arrest. The propensity score analysis was performed in an attempt to limit any influence of selection bias on our results. We acknowledge that without neurocognitive testing, the long-term effect of our cerebral protection strategy (mild or moderate hypothermia with uSACP) on cognitive function is unknown. A protocol of preoperative and postoperative neuropsychiatric assessment questionnaires for all patients undergoing arch operations has been implemented, and the results will be included in all future studies. In conclusion, data from the current report support the safe use of a cerebral protection strategy of mild hypothermic circulatory arrest and uSACP during hemiarch reconstruction in elective and emergency settings. When directly compared with patients undergoing hemiarch replacement at deeper levels of hypothermia, no difference in operative mortality or temporary neurologic dysfunction was observed. The reduction in stroke rates observed in patients undergoing hemiarch reconstruction at 28°C suggests that mild hypothermia offers adequate levels of neurologic protection compared with deeper levels of hypothermia. Future studies will investigate this hypothesis and the long-term effect of mild hypothermia on neurocognitive function. We thank Kim Baio, Deborah Canup, and Iman F. Aziz for their assistance with this manuscript.
References 1. Leshnower BG, Myung RJ, Kilgo PD, et al. Moderate hypothermia and unilateral selective antegrade cerebral perfu-
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2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
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sion: a contemporary cerebral protection strategy for aortic arch surgery. Ann Thorac Surg 2010;90:547–54. Minatoya K, Ogino H, Matsuda H, et al. Evolving selective cerebral perfusion for aortic arch replacement: high flow rate with moderate hypothermic circulatory arrest. Ann Thorac Surg 2008;86:1827–31. Kamiya H, Hagl C, Kropivnitskaya I, et al. The safety of moderate hypothermic lower body circulatory arrest with selective cerebral perfusion: a propensity score analysis. J Thorac Cardiovasc Surg 2007;133:501–9. DiEusanio M, Tan ME, Schepens MA, et al. Surgery for acute type A using antegrade selective cerebral perfusion: experience with 122 patients. Ann Thorac Surg 2003;75:514 –9. Khaladj N, Shrestha M, Meck S, et al. Hypothermic circulatory arrest with selective antegrade cerebral perfusion in ascending aortic and aortic arch surgery: a risk factor analysis for adverse outcome in 501 patients. J Thorac Cardiovasc Surg 2008;135:908 –14. Zierer A, Detho F, Dzemali O, et al. Antegrade cerebral perfusion with mild hypothermia for aortic arch replacement: single-center experience in 245 consecutive patients. Ann Thorac Surg 2011;91:1868 –74. Khaladj N, Shrestha M, Peterss S, et al. Ascending aortic cannulation in acute aortic dissection type A: the Hannover experience. Eur J Cardiothorac Surg 2008;34:792– 6. Bakhtiary F, Dogan S, Zierer A, et al. Antegrade cerebral perfusion for acute type A aortic dissection in 120 consecutive patients. Ann Thorac Surg 2008;85:465–9. Hagl C, Ergin MA, Galla JD, et al. Neurologic outcome after ascending aorta-aortic arch operations: effect of brain protection technique in high-risk patients. J Thorac Cardiovasc Surg 2001;121:1107–21. Ergin MA, Griepp EB, Lansman SL, Galla JD, Levy M, Griepp RB. Hypothermic circulatory arrest and other methods of cerebral protection during operations on the thoracic aorta. J Card Surg 1994;9:525–37. Svensson LG, Blackstone EH, Rajeswaran J, et al. Does the arterial cannulation site for circulatory arrest influence stroke risk? Ann Thorac Surg 2004;78:1274 – 84. Pacini D, Leone A, DiMarco L, et al. Antegrade selective cerebral perfusion in thoracic aorta surgery: safety of moderate hypothermia. Eur J Cardiothorac Surg 2007;31:618 –22. Hammon JW Jr, Edmunds LH Jr. Extracoporeal circulation: organ damage. In: Cohn LH, Edmunds LH Jr, editors. Cardiac surgery in the adult. New York: McGraw-Hill; 2003:361– 88. Harrington DK, Lilley JP, Rooney SJ, Bonser RS. Nonneurologic morbidity and profound hypothermia in aortic surgery. Ann Thorac Surg 2004;78:596 – 601.
DISCUSSION DR VINAY BADHWAR (Pittsburgh, PA): You mentioned at the end that you used propensity matching for your conclusion, so basically it’s a stroke benefit. DR LESHNOWER: There is a stroke benefit, yes. DR BADHWAR: In your experience as it has evolved, what about the use of adjunctive neurologic monitoring such as electroencephalogram (EEG) or cerebral oximetry? Have you added that to your regimen and do you think that may have a role in your perfusion management? DR LESHNOWER: For all these cases, I did not mention this previously, we used continuous EEG monitoring, and we used
the cerebral oximetry for both groups throughout the entire experience. DR MUHAMMAD MUMTAZ (Norfolk, VA): I am a congenital surgeon, and most of my practice is in children and not in adults. I just want to share a couple of things with you. Perfusion through one of the cranial arteries, instead of the normal 4 that God has given us, assumes that the circle of Willis is complete. What measures did you take to make sure that this was the case? Even in newborns, I have anecdotally found completely isolated 2 halves of the circle of Willis on the magnetic resonance angiography (MRA). In addition, there is a case report in the Annals from last year reporting cerebral ischemia in one side of the brain of a baby after a Norwood procedure due to steal
ADULT CARDIAC
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phenomenon from the Blalock-Taussig shunt and an incomplete circle of Willis. So I would strongly propose obtaining a preoperative MRA and magnetic resonance imaging of the brain. That is my first question. ADULT CARDIAC
DR LESHNOWER: That is a question that we get a lot, actually, with this technique. We do not do any pre-op imaging to look at the circle of Willis. With our cerebral oximetry what we do do is when we go on circulatory arrest and clamp the innominate, if we see a significant drop in the left-sided cerebral oximetry monitoring, we will clamp the left common carotid. This eliminates any steal and also pressurizes the system, and opens any right to left extracranial collateral flow. We have not had a problem with it. And there is also a recent report in the European Journal of Cardiothoracic Surgery where they looked at cannulating either the right or left common carotid and doing the same technique unilateral selective antegrade cerebral perfusion, and they saw no difference, and they didn’t do any preoperative imaging either. DR MUMTAZ: However, you do note that you have a 5% incidence of stroke. This is quite significant. If you want to take the field one step forward with the goal of going from 5% to 0%, I would strongly propose getting a preoperative MRA. Some of these strokes may be related to that. And that brings me to the second point. You are relying on EEG, which becomes unreliable below the temperature of 30°C and with the deep anesthetics. I am curious to know what you think about this. Similarly, at low temperature the near-infrared spectroscopy (NIRS) may be unreliable too. I have seen the NIRS, for example, in circulatory arrest cases for 15 minutes, it may be normal, possibly because there is little or no brain oxygen consumption. A number of authors and other surgeons in the congenital field have noted that at below the temperature of 28°, the NIRS may take a longer time to demonstrate ischemia. What happens to EEG? How reliable is that?
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ses or anything like that that there might be an optimal hypothermic temperature at which to perform this? That would be the first question. And the second question, different topic. Did you do any MRI or neurocognitive studies? Because I think we all appreciate that gross neurologic outcomes are probably not as sensitive a way to analyze neurologic outcomes after such a big operation. DR LESHNOWER: Two good questions that we also asked ourselves. We did do the analysis asking the question of whether there is an optimal temperature at which patients essentially do better, and it fell out in our 500 patients at 28°. I didn’t present that data. We acknowledge the a limitation that we have in our aortic program is the lack of follow-up with the Mini-Mental Status Examination or some sort of neurocognitive examination pre-op and post-op, which we plan to implement in the future. But, no, we don’t have that currently. DR WILLIAM T. BRINKMAN (Plano, TX): Brad, a great talk, and this is something I am very interested in. My concern when you are circ arresting at moderate hypothermia or mild hypothermia is the spinal cord, the kidneys, those sorts of things. That is why I feel safer; if I get caught with a difficult arch tear or something, I feel safer. What are your thoughts on that? DR LESHNOWER: That is a good question. We saw no incidence of paraplegia, and we have not, for any of our cases done with this technique. We have started to measure liver function tests (LFTs), especially in our prolonged periods of circ arrest, not in this population but in total arches, and so far we have not seen any significant signs of liver ischemia or inflammation, that kind of thing.
DR LESHNOWER: It still remains flat at that temperature.
DR CULLEN MORRIS (Athens, GA): Brad and Ed, a great paper. I guess all these patients had aprotinin. What are you all using now for your circ arrest cases in terms of tranexamic acid and all that, number one? And number two, I know I have gone from using the tape like Ed showed me to use to using a clamp on the innominate. What are you all doing with that?
DR JOHN V. CONTE (Baltimore, MD): If I understand your study right, you went and just found the median, and that happened to be at 27° and that is how you did your analysis. Have you identified with receiver operator characteristic analy-
DR LESHNOWER: We are using the clamp, Cullen, instead of the umbilical tape and Rummel now. And the patients get tranexamic acid but no aprotinin. I think maybe early in the experience they were still using that, but not now.