Original Cardiovascular
Moderate Hypothermic Circulatory Arrest with Antegrade Cerebral Perfusion for Rapid Total Arch Replacement in Acute Type A Aortic Dissection Ligang Liu1
Xin Feng1
Yuan Wang1
1 Department of Cardiovascular Surgery, Tongji Hospital, Tongji
Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China Thorac Cardiovasc Surg
Abstract
Keywords
► acute type A aortic dissection ► cerebral protection ► frozen elephant trunk procedure ► moderate hypothermia ► total aortic arch replacement
Tiecheng Pan1
Xiang Wei1
Address for correspondence Xiang Wei, MD, PhD, Department of Cardiovascular Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095# Jiefang Avenue, Wuhan 430030, Hubei, PR China (e-mail: [email protected]).
Background The optimal hypothermic level during circulatory arrest is controversial. The aim of our study was to comprehensively assess the impact of moderate hypothermic circulatory arrest with antegrade cerebral perfusion (ACP) on total aortic arch replacement. Methods From 2010 to 2013, data were collected from 99 consecutive patients with acute type A aortic dissection. All patients underwent total arch replacement plus frozen elephant trunk procedure. There were 51 patients in the deep hypothermia circulatory arrest (DHCA) group and 47 in the moderate hypothermia circulatory arrest (MHCA) group. Either unilateral or bilateral ACP was applied for cerebral protection. Perioperative data and measured outcomes were compared. Results Overall mean circulatory arrest time was 29.9 ± 6.0 minutes. Temporary neurologic dysfunction incidence was lower in the MHCA group compared with the DHCA group (21.3 vs. 40.4%, p ¼ 0.041). The total 30-day mortality was 17.2% (14.9 vs. 19.2%, p ¼ 0.568) and permanent neurologic dysfunction morbidity was 3.0% overall. In MHCA, less blood products were used than in DHCA. Moderate hypothermia was a protective factor for the composite outcome of temporary and permanent neurologic dysfunctions (odds ratio ¼ 0.385; 95% confidence interval ¼ 0.162–0.919). Hypothermic level did not significantly affect the perioperative alanine aminotransferase and serum creatinine levels. Conclusion Within a short circulatory arrest time, MHCA combined with ACP seemed to be a safe and effective method to protect cerebral and visceral organs during total aortic arch replacement.
Introduction Surgical repair of acute type A aortic dissection (AAAD) remains a challenge for cardiac surgeons. Substantial risks of ischemic injury to the brain and visceral organs during total
received December 17, 2014 accepted after revision April 28, 2015
Min Hu1
aortic arch replacement in circulatory arrest (CA) contribute to high perioperative mortality of up to 25%.1 Maximal metabolic rate suppression efficiently minimizes oxygen consumption and helps to ensure a sufficient time period for the arch procedure.2 Therefore, deep hypothermia (DH) is
© Georg Thieme Verlag KG Stuttgart · New York
DOI http://dx.doi.org/ 10.1055/s-0035-1555752. ISSN 0171-6425.
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Mingjia Ma1
widely used for brain protection early in CA.3 However, deep hypothermic circulatory arrest (DHCA) has many drawbacks, such as extended cardiopulmonary bypass (CPB) time, coagulation system disturbances, and other complications that result from temperature-related systemic vasoconstriction.4 A growing number of hospitals have attempted to raise the hypothermic level during CA, but the most optimal temperature level for organ protection is still controversial.3 Recently at our hospital, moderate hypothermic circulatory arrest (MHCA > 20°C) with antegrade cerebral perfusion (ACP) was introduced for aortic arch surgery. We conducted this retrospective study on the modified hypothermia strategy to assess the clinical impact of MHCA on total aortic arch replacement.
Patients and Methods We continuously collected perioperative data from 155 patients with type A aortic dissection in our hospital from 2010 to 2013. A total of 104 patients underwent total arch replacement plus frozen elephant trunk procedure. The indications of this procedure were as follows: (1) primary or reentry tears located in arch or proximal descending thoracic aorta; (2) severe arch vessel lesions, including dissection, occlusion, stenosis, or aneurysm changes; (3) Marfan syndrome; and (4) descending aorta dilatation with diameter over 5 cm. When primary tear located in ascending aorta without items described above, hemi-arch or ascending aorta replacements would be used for the patients. Patients with subacute and chronic type A aortic dissection (20 cases), intramural hematomas (12 cases), and patients who underwent hemi-arch replacement (19 cases) were excluded. Finally, the data from
Ma et al. 99 patients were included in this study cohort. All the included surgeries were completed by the same professional team within the past 3 years. This study was approved by the local ethics committee. Patients were retrospectively divided into two groups: the DHCA group (52 patients, nasopharyngeal temperature 14.6– 19.0°C) and the MHCA group (47 patients, nasopharyngeal temperature 21.1–26.5°C). The discerning border of hypothermia was drawn according to a standard classification.5 Five patients with hypothermia between 20.0 and 21.0°C were excluded to avoid suspected temperature overlap. Details of the preoperative data are listed in ►Table 1.
Monitoring Intraoperatively monitored parameters included invasive blood pressure in the left radial artery and ipsilateral dorsalis pedis artery, noninvasive blood pressure, oxygen saturation by pulse oximetry, rectal and nasopharyngeal temperature, electroencephalogram, cerebral regional oxygen saturation (rsO2), and regular monitoring of arterial blood gas. Intraoperative acid-base homeostasis was managed according to the Alpha state. Alanine aminotransferase (ALT) and creatinine (Cr) were used as indicators of hepatic and renal function, respectively. The preoperative and postoperative ALT and Cr values at 6 and 24 hours in the same patient were compared. These time points were considered when the inner environment was stable and devoid of any potential confounding effects of intensive care unit (ICU) treatment.
Surgical Technique After routine anesthesia, the patient was placed in a supine position. The right axillary artery was initially isolated. In
Table 1 Preoperative demographics and clinical characteristics Variables
DHCA (n ¼ 52)
MHCA (n ¼ 47)
p-Value
Male/female
41/11
43/4
0.097
Age (y)
49.5 10.2
46.8 10.8
0.420
Marfan syndrome
3 (5.8%)
2 (4.3%)
> 0.999
Preoperative dialysis
1(1.9%)
1(2.1%)
> 0.999
Preoperative shock
0
1 (2.1%)
0.475
CAD
2 (3.8%)
2 (4.3%)
> 0.999
Hypertension
37 (71.2%)
27 (57.4%)
0.154
Diabetes mellitus
13 (24.5%)
14 (29.8%)
0.593
Emergency surgery
29 (55.8%)
11 (23.4%)
0.001
Weight (kg)
71.9 10.2
76.7 11.5
0.033
Height (m)
1.69 0.05
1.72 0.05
0.005
BMI
25.2 2.6
26.0 3.4
0.394
HBV
4 (7.7%)
9 (19.1%)
0.092
HCV
0
1 (2.1%)
0.475
LVEF (%)
56.5 10.8
53.0 9.8
0.092
Abbreviations: AD, aortic dissection type A; BMI, body mass index; CAD. coronary artery disease; DHCA, deep hypothermic circulatory arrest; HBV, hepatitis B virus; HCV, hepatitis C virus; LVEF, left ventricular ejection fraction; MHCA, moderate hypothermic circulatory arrest. Note: p-Value < 0.05 is highlighted in bold type. Thoracic and Cardiovascular Surgeon
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MHCA with ACP for Rapid Total Arch Replacement in AAAD
some emergency cases, in which unstable hemodynamics or risk of aortic aneurysm rupture was suspected, the right femoral artery and vein were chosen to initiate CPB. A median sternotomy was performed. After systemic heparinization (400 IU/kg), the right axillary artery was cannulated directly using a 24-Fr arterial cannula (Medtronic, Minneapolis, Minnesota, United States) and venous cannulation was performed using a two-stage cannula (Medtronic, Minneapolis, Minnesota, United States) in the right atrium. A drain was placed in the left ventricle via the right superior pulmonary vein. Once CPB and systemic cooling were initiated, an ice cap was placed in the patient to cool the head topically. After cardiac fibrillation, the ascending aorta was cross-clamped and myocardial protection was achieved using antegrade cold blood cardioplegia perfusion. During systemic cooling, the root procedure was completed. Nasopharyngeal temperature was used as a criterion of CA, rather than rectal temperature measured simultaneously, to prevent the body from overcooling in a short CA time. The interval between the two sides was maintained within 4°C during the cooling and warming processes. Once the nasopharyngeal temperature reached the predetermined hypothermic level, circulation was arrested. The patient was placed in the Trendelenburg position. The proximal ends of the innominate artery, left carotid artery, and left subclavian artery were clamped. Unilateral antegrade cerebral perfusion (UACP) was initiated via the right axillary artery, at a flow rate of approximately 6 2 mL/(kg min). Bilateral antegrade cerebral
Ma et al.
perfusion (BACP) was randomly performed on 12 patients, using a 16-Fr urethral catheter (B.Braun, Bayan Lepas, Penang, Malaysia) placed in the left carotid artery. Total arch replacement was performed using a four-branched graft (Maquet, Rastatt, Baden-Württemberg, Germany) plus an intraoperative stent graft (MicroPort, Shanghai, China) (►Fig. 1). The arch was resected transversely to the orifice of the left subclavian artery, and branch vessel root was ligated. The 10-cm long modified stent graft (prepared in a bound, compressed state and attached to a shaft) was inserted into the true lumen of the descending thoracic aorta in an antegrade manner under direct vision. When the stent was located properly, the self-expanding stent was released by drawing out the pull ring beside the shaft. The auxiliary devices (shaft, pull ring, and wire) were removed. The diameter of the stent graft was determined by the preoperative computed tomography (CT) measure and intraoperative judgment. The proximal end of the stent graft and the aortic wall were anastomosed to the tube graft end with 3–0 prolene (Ethicon, Cincinnati, Ohio, United States) using running sutures. After this procedure, the proximal end of the graft was clamped again. Lower body blood perfusion was resumed via one branch. The left carotid artery was initially anastomosed to the vascular graft and the rewarming procedure was initiated. Subsequently, the proximal tube graft anastomosis was completed. After carefully removing all the air, standard CPB was resumed. The heart was resuscitated automatically or using defibrillation. Anastomosis of the left subclavian artery and
Fig. 1 Key steps of frozen elephant trunk procedure and postoperative computed tomography angiography. (A) The aortic arch was transected under circulatory arrest, orifice of the true lumen of the descending thoracic aorta is indicated by arrow. (B) The bound and compressed stent graft was inserted into the true lumen of the descending thoracic aorta in antegrade manner under direct vision. (C) The stent graft was released by drawing out the pull ring. (D) The proximal end of the stent graft with the aortic wall was anastomosed to the tube graft end using running sutures. (E) Postoperative computed tomography angiography of Bentall procedure with reconstructed aortic arch and stent graft. Thoracic and Cardiovascular Surgeon
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MHCA with ACP for Rapid Total Arch Replacement in AAAD
MHCA with ACP for Rapid Total Arch Replacement in AAAD innominate artery to the branches of the vascular graft was performed sequentially. CPB was gradually reduced until the patient was hemodynamically stable and the temperature returned to normal.
Concomitant Aortic Root Procedures Valve-sparing aortic root repair was used in the absence of structural valve defects and annular ectasia. The Bentall procedure was used to treat either the original dilated aortic root with defective valves or which was involved by aortic dissection (►Fig. 1). Patients with aortic valve defects without sinus involvement were treated using the Wheat procedure. Coronary artery bypass grafting (CABG) was performed depending on the preoperative diagnosis and intraoperative inspection.
Ma et al.
Results Patient Characteristics Preoperative characteristics of the patients are shown in ►Table 1. Of the 99 patients in this study, 15 were female (15.2%). The mean age of the patients was 48.2 10.5 years (range, 21–70 years). There were 19 patients (19.2%) who were over 60 years. There were 64 (64.6%) patients with hypertension, 5 of whom were regularly monitored and controlled for blood pressure. Emergency surgeries were performed in 40 patients. Overall, the mean wait time for surgery was 2.0 1.6 days, and 73.7% of the patients underwent surgery within the first 72 hours after admission. No additional operation was performed before aortic arch replacement.
DHCA was defined as initiation of CA coinciding with nasopharyngeal temperature of 14.1 to 20°C. Moderate hypothermia (MH) was defined as the temperature of 20.1 to 28°C. Temporary neurological dysfunction (TND) was defined as unconsciousness, delirium, confusion, and mania during the immediate period after surgery, but the symptoms disappeared before discharge, and no imaging change was found using a head CT. Permanent neurological dysfunction (PND) was defined as a stroke or persistent focal neurologic dysfunction, often accompanied by changes in brain imaging. Emergency surgeries were operations performed within 24 hours after admission in patients with hemodynamic instability, tamponade, or malperfusion syndrome. The criteria for renal injury after cardiac operation were defined as elevation of serum creatinine (Cr) level greater than 221 μmol/L (2.5 mg/dL) or the requirement of transient renal replacement therapy.
Statistical Analysis Continuous variables were presented as the mean standard deviation or the median and interquartile ranges (IQR). Unpaired t-test, chi-square test or Fisher exact test, or the Mann–Whitney U-test was used for univariate variable analysis. ALT and Cr values were compared between the two groups using analysis of variance (ANOVA) for repeated measurements, followed by a post hoc least significant difference (LSD). Statistical significance was defined as a two-sided p-value < 0.05. Stepwise multivariable logistic regression was used to assess the potential risk factors of 30-day mortality and neurological adverse events (TND and PND). Adjusted parameters and binary dependent variables (age, gender, hypertension, diabetes, emergency surgery, body mass index, duration of operation, preoperative LVEF%, hepatitis B virus, duration of CPB, CA, coronary artery disease, preoperative shock, preoperative dialysis, CA over 40 minutes, consumption of red blood cells [RBC] and fresh-frozen plasma [FFP], and hypothermia groups) were included in the multivariate logistic regression models. Results of the regression models were presented as the odds ratio (OR) and 95% confidence interval (CI). SPSS Statistics 19.0 (IBM, Somers, New York, United States) was used for statistical analysis. Thoracic and Cardiovascular Surgeon
Overall, the mean surgical duration was 508.8 80.0 minutes. Mean CA time was 29.9 6.0 minutes. The CA was longer than 40 minutes for 10 patients. Bilateral cerebral perfusion was used randomly for 12 patients. Bentall procedure was used as the most common concomitant procedure in aortic root (33 patients). CABG was performed in nine patients, of whom four were preoperatively diagnosed with three-vessel or left main coronary artery disease, three patients had a tear in their right coronary artery that was involved in aortic dissection, and two patients had significantly calcified pathological changes in their anterior descending branch that was observed during the intraoperative inspection. The proportion of patients with concomitant procedures was not significantly different between the groups (►Table 2). The transfusions of both FFP and RBC were less in the MHCA group than in the DHCA group.
Postoperative Outcomes Re-exploration for bleeding did not occur in either group. Most postoperative properties were comparable between the two groups, as shown in ►Table 3. The mean duration in the ICU was significantly longer in the DHCA group than in the MHCA group (p ¼ 0.047). There were more patients whose ICU stay exceeded 7 days in DHCA group compared with the MHCA group (p ¼ 0.006). The incidence of composite neurological adverse events was 34.3%, and there were 31 patients (31.3%) with TND and 3 patients (3.0%) with PND. All three patients with PND underwent emergency surgeries. One of them in the DHCA group had preoperative lacunar infarction, while new lesion was detected postoperatively (Appendix Fig. 1). There was a significant difference in the TND incidence between the two groups (p ¼ 0.041). One-third of the patients with TND underwent brain CT scan following recommendations of the neurologist. Mean duration of main manifestations (unconsciousness, delirium, and/or mania) was 7.1 4.3 days, ranged from 1 to 22 days. Detailed data of TND were summarized in ►Table 4. No postoperative paraplegia occurred. After excluding the cases of death and voluntary discharge during therapy, the mean duration of hospitalization was 29.2 9.5 days. The overall mortality within 30 days was 17.2% (17 patients) compared with a rate of 17.5% (7 deaths in
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Cardiopulmonary Bypass and Surgical Details Relevant Concept Definitions
MHCA with ACP for Rapid Total Arch Replacement in AAAD
Ma et al.
Table 2 Cardiopulmonary bypass data and surgical procedures DHCA (n ¼ 52)
MHCA (n ¼ 47)
p-Value
RAA
49 (94.2)
46 (97.9)
0.683
RAA þ femoral artery
3 (5.8)
1 (2.1)
33 (63.5)
25 (53.2)
0.300
RR
9 (17.3)
5 (10.6)
0.342
Bentall
14 (26.9)
19 (40.4)
0.155
Wheat
5 (9.6)
2 (4.3)
0.518
CABG
4 (7.7)
5 (10.6)
0.874
Variables Cannulation site (%)
AAR with AV preservation (%) Combined procedure (%)
UACP
44 (84.6)
43 (91.5)
0.295
BACP
8 (15.4)
4 (8.5)
0.295
Operation time (min)
511.7 82.4
505.6 78.1
0.392
Duration of CPB (min)
236.3 35.7
218.6 37.1
0.018
Cross clamp time (min)
128.6 22.7
126.5 24.8
0.653
CA (min)
31.5 5.7
28.0 6.0
0.007
CA > 40 min (%)
7 (13.5)
3 (6.4)
0.405
Nasopharyngeal temp. (°C)
17.9 1.2
23.6 1.4
< 0.001
Rectal temp. (°C)
20.0 2.2
25.9 1.6
< 0.001
Transfusion RBC (IU)
6.3 3.0
5.0 2.8
0.044
FFP (mL) SD
930.8 377.1
737.5 389.3
0.002
975 (800–1,000)
650 (400–950)
Median (IQR) Platelet (IU) SD Median (IQR)
1.70 0.6
1.6 0.8
2 (1–2)
2 (1–2)
0.706
Abbreviations: AAR, ascending aorta replacement; AV, aortic valve; BACP, bilateral antegrade cerebral perfusion; CA, circulatory arrest; CABG, coronary artery bypass graft; CPB, cardiopulmonary bypass; DHCA, deep hypothermic circulatory arrest; FFP, fresh-frozen plasma; IQR, interquartile range; MHCA, moderate hypothermic circulatory arrest; RAA, right axillary artery; RBC, red blood cell; RR, root repair; SD, standard deviation; temp., temperature; UACP, unilateral antegrade cerebral perfusion. Note: p-Value < 0.05 is highlighted in bold type.
40 patients) in patients who underwent emergency surgery. The most common reasons for deaths were septic shock with multiple organ dysfunction syndrome (eight patients, 47.1%) and cardiogenic shock (five patients, 29.5%). Death resulted from cardiac arrest in other four patients (23.5%). Postoperative renal injury occurred in seven patients: four (7.7%) in the DHCA group and three (6.4%) in the MHCA group. New renal failure occurred in one patient (1.92%) in the DHCA group and two patients (4.25%) in the MHCA group. Perioperative biomarker values are summarized in Appendix Table 1. Hypothermic level had no significant interaction with perioperative Cr and ALT variance (p ¼ 0.982 and 0.364, respectively). Pairwise comparisons revealed no significant differences in either Cr or ALT values, across three time points. Multivariate logistic regression analysis revealed that diabetes (p ¼ 0.033; OR ¼ 3.56; CI ¼ 1.11–11.42), coronary artery disease (p ¼ 0.02; OR ¼ 13.89; CI ¼ 1.52–126.68), and
RBC transfusion (p ¼ 0.009; OR ¼ 1.28; CI ¼ 1.06–1.54) were independent predictors of 30-day mortality. Multivariate analysis identified the hypothermic level as an independent predictor of composite neurologic dysfunction (p ¼ 0.031; OR ¼ 0.385; CI ¼ 0.162–0.919).
Discussion Since Griepp introduced the concept of DHCA into cerebral and visceral organ protection for aortic arch surgery,6 this challenging surgery has become safer and effective. In the past, DH in CA either combined with cerebral perfusion or alone was used as the dominant pattern for organ protection during aortic arch replacement.7 DH suppressed cerebral metabolism to the level of electrocerebral inactivity, and insured adequate time for the surgical procedure during CA.8 However, prolonged CPB time, vasospasm, acidosis, and inflammation activity are considered drawbacks for improving surgical outcomes.9 Thoracic and Cardiovascular Surgeon
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Perfusion data
MHCA with ACP for Rapid Total Arch Replacement in AAAD
Ma et al.
Table 3 Postoperative morbidity and mortality DHCA (n ¼ 52)
MHCA (n ¼ 47)
p-Value
30-day mortality (%)
10 (19.2)
7 (14.9)
0.568
LCOS (%)
7 (13.5)
6 (12.8)
0.918
Sudden cardiac arrest (%)
5 (9.6)
1 (2.1)
0.255
Pulmonary infection (%)
18 (34.6)
10 (21.3)
0.141
MODS (%)
6 (11.5)
2 (4.3)
0.338
Mediastinal infection (%)
3 (5.8)
0
0.278
Tracheotomy
9 (17.3)
4 (8.5)
0.196
Postoperative dialysis (%)
2 (3.8)
3 (6.4)
0.908
TND (%)
21 (40.4)
10 (21.3)
0.041
PND (%)
2 (3.8)
1 (2.1)
> 0.999
M vent. (h) SD
111.1 119.0
92.9 91.7
0.331
77.8 (25.4–129)
48 (20–142)
9.4 7.3
6.2 4.4
Median (IQR) ICU stay time (d) SD Median (IQR)
7 (4–10)
5 (3–8)
ICU stay > 7 d (%)
31 (59.6)
15 (31.9)
0.047 0.006
Abbreviations: DHCA, deep hypothermic circulatory arrest; ICU, intensive care unit; IQR, interquartile range; LCOS, low cardiac output syndrome; M vent., mechanical ventilation; MHCA, moderate hypothermic circulatory arrest; MODS, multiple organ dysfunction syndrome; PND, permanent neurological dysfunction; SD, standard deviation; TND, temporary neurological dysfunction. Note: p-Value < 0.05 is highlighted in bold type.
In an animal experiment, Cavus et al demonstrated that in the presence of ACP, there was a higher consumption of energy stores in the cerebral cells during CA and rewarming in DH than in MH.10 Therefore, when CA was performed within a short duration, more composite benefits might be obtained from MH than DH. MH using an adjunctive perfusion technique has been attempted by many institutions in aortic arch surgery as a promising approach for advanced organ protection.11–13 In our institution, MH with nasopharyngeal temperature over 20°C was initially performed successfully on only a few patients in 2010. As the CA time for aortic arch replacement was controllable, we tended to implement MH more often during the past 3 years (►Fig. 2). Currently, MHCA is utilized for a majority of aortic arch operations. DH was retained for
complex arch procedure or hemi-arch replacement requiring total CA. In this study, the surgical 30-day mortality of AAAD was comparable to similar published series, ranging from 8.1 to 27.8%.12,14 The 30-day mortality tended to be lower in the MHCA group than in the DHCA group, but was not statistically significant. The MH did not increase the risk of mortality. In contrast, a lower mortality was observed with MH in other studies.13,15 Therefore, a study conducted in larger populations may present a different result. In addition, it was usually believed that emergency surgery led to bad outcomes.16 Multivariate analysis revealed that emergent state negatively influenced the 30-day mortality in our study. TND morbidity decreased with the use of MHCA. Multivariable analysis showed that MH was an independent
Table 4 Detailed data of temporary neurological dysfunction Variables
DHCA (n ¼ 21)
MHCA (n ¼ 10)
p-Value
Duration of TND (d)
7.7 5.0
5.8 1.8
0.268
13 (61.9)
5 (50)
0.701
Main manifestations Unconsciousness (%) Delirium (%)
7 (33.3)
0
0.012
Mania (%)
11 (52.4)
5 (50)
>0.999
Brain CT scan (%)
6 (28.6)
4 (40)
0.685
Neurologist consultation (%)
9 (42.9)
4 (40)
>0.999
Abbreviations: CT, computed tomography; DHCA, deep hypothermic circulatory arrest; MHCA, moderate hypothermic circulatory arrest; TND, temporary neurological dysfunction. Note: p-Value < 0.05 is highlighted in bold type. Thoracic and Cardiovascular Surgeon
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Variables
MHCA with ACP for Rapid Total Arch Replacement in AAAD
protective factor against composite neurologic adverse events. These findings were in line with the consequence of a previous study and can be explained with the experimental consequence conducted by Cavus et al.10,17 No significant difference in neurological morbidity (either TND or PND) was observed between BACP and UACP (25 vs. 35.6%; p ¼ 0.687). There is a lack of evidence demonstrating BACP’s superiority18 and the technique might be considered an alternative to UACP in cases of hypoperfusion. Compared with the DHCA group, less blood products were consumed and shorter ICU stays were observed in the MHCA group. The differences in outcome were also described in the study conducted by Zierer et al,15 which largely favored MH. In addition to mortality and morbidity of neurologic dysfunction, safety of visceral organs during CA is also a concern.12,19 We found that there was no significant pathologic elevation in the Cr value after operation in either the DHCA or the MHCA groups, and morbidities between the groups were comparable. More patients infected with hepatitis B virus (HBV) and hepatitis C virus (HCV) in the MHCA group might contribute to the preoperative difference in ALT levels. Hemi-arch replacement was considered to be a relatively safe procedure, but there were also fears of a dissected distal aorta degeneration, which required secondary extensive interventions.20 The frozen elephant trunk procedure we applied was feasible and safe in appropriate patients, which helped to reduce the re-intervention rate.14 We also minimized the distal anastomosis using running sutures, which reduced the CA time resulting in acceptable outcome. In addition, no paraplegia or mesenteric ischemia occurred. Despite the extended CA time period, MH with UACP was adequate for distal organ protection. The retrospective nature and the relatively small sample size are the main limitations of this study. Use of MHCA with UACP in our hospital has gradually become the preferred method for total arch replacement over time. Thus, no DHCA control group can be included concurrently with the MHCA group, and the patient characteristics cannot be matched
exactly in pairs. Our institution is a tertiary referral hospital, with over 90% of the patients transferred from peripheral or remote hospitals. Improvements in early diagnosis and treatment before admission affect the short-term outcome of surgery over time. Meanwhile changes in perioperative therapy policy and surgical team cooperation were unavoidable. The impact of MH upon the patients’ long-term outcome is also unknown. Further follow-up of the patients in the study and a larger study are required. In conclusion, this study is consistent with other studies indicating that MH with UACP is feasible and safe for cerebral and distal organ protection during CA, which is required for total aortic arch replacement and frozen elephant trunk procedure. MH helped to decrease TND morbidity after surgery. In short periods of CA, MH did not increase 30-day mortality and distal organ morbidity. MH might also help to reduce the blood product consumption and ICU stays.
Conflict of Interest None declared.
Acknowledgment We would like to thank the associate operative surgeons for their surgical expertise and editorial assistance. We must thank Dr. Hui Gao (School of Public Health, Tongji Medical College, Huazhong University of Science and Technology) for statistical consulting. We also thank Dr. Sishu Yuan (Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology) for radiological consulting.
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Fig. 2 Temporal distribution of hypothermia strategies. DHCA, deep hypothermic circulatory arrest; MHCA, moderate hypothermic circulatory arrest.
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19
20
operative mortality? J Thorac Cardiovasc Surg 2014;148(3): 963–970, discussion 970–972 Zierer A, Aybek T, Risteski P, Dogan S, Wimmer-Greinecker G, Moritz A. Moderate hypothermia (30 degrees C) for surgery of acute type A aortic dissection. Thorac Cardiovasc Surg 2005;53(2):74–79 Kunihara T, Grün T, Aicher D, et al. Hypothermic circulatory arrest is not a risk factor for neurologic morbidity in aortic surgery: a propensity score analysis. J Thorac Cardiovasc Surg 2005;130(3): 712–718 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(2):501–509 Numata S, Thomson DS, Seah P, Singh T. Simplified cerebral protection using unilateral antegrade cerebral perfusion and moderate hypothermic circulatory arrest. Heart Lung Circ 2009; 18(5):334–336 Pacini D, Pantaleo A, Di Marco L, et al. Visceral organ protection in aortic arch surgery: safety of moderate hypothermia. Eur J Cardiothorac Surg 2014;46(3):438–443 Vallabhajosyula P, Szeto WY, Pulsipher A, et al. Antegrade thoracic stent grafting during repair of acute Debakey type I dissection promotes distal aortic remodeling and reduces late open distal reoperation rate. J Thorac Cardiovasc Surg 2014;147(3):942–948
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MHCA with ACP for Rapid Total Arch Replacement in AAAD
MHCA with ACP for Rapid Total Arch Replacement in AAAD
Ma et al.
Appendix Fig. 1 Postoperative brain noncontrast computed tomography axial scans. (A): The postoperative imaging showed no change in patient with temporary neurological dysfunction. (B): Left frontal encephalomalacia (indicated by arrow) was detected 10 days after the operation for another patient.
Variables
DHCA (n ¼ 52)
MHCA (n ¼ 47)
p-Value
115.5 232.6
88.3 87.0
0.107
79.5 (67.0–90.8)
74.0 (54.0–89.0)
120.3 119.5
93.5 54.1
86.5 (67.3–116.0)
89 (56–118)
119.1 182.8
90.7 74.4
70.5 (58.3–96.9)
65.0 (45–90)
24.6 26.9
50.9 129.8
16.5 (12–26)
32 (14–42)
41.2 42.2
79.8 269.1
35 (24–64)
31 (17–64)
Serum creatinine (μmg/L) T1 mean SD Median (IQR) T2 mean SD Median (IQR) T3 mean SD Median (IQR)
0.490 0.268
Alanine aminotransferase (U/L) T1 mean SD Median (IQR) T2 mean SD Median (IQR) T3 mean SD Median (IQR)
106.8 473.6
71 143.6
36 (20–54)
35 (24–64)
0.006 0.228 0.718
Abbreviations: DHCA, deep hypothermic circulatory arrest; IQR, interquartile range; MHCA, moderate hypothermic circulatory arrest; SD, standard deviation; T1, before operation; T2, 6 hours after operation; T3, 24 hours after operation.
Thoracic and Cardiovascular Surgeon
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Appendix Table 1 Biochemical measurement
Moderate Hypothermic Circulatory Arrest with Antegrade Cerebral Perfusion for Rapid Total Arch Replacement in Acute Type A Aortic Dissection Ligang Liu1
Xin Feng1
Yuan Wang1
1 Department of Cardiovascular Surgery, Tongji Hospital, Tongji
Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China Thorac Cardiovasc Surg
Abstract
Keywords
► acute type A aortic dissection ► cerebral protection ► frozen elephant trunk procedure ► moderate hypothermia ► total aortic arch replacement
Tiecheng Pan1
Xiang Wei1
Address for correspondence Xiang Wei, MD, PhD, Department of Cardiovascular Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095# Jiefang Avenue, Wuhan 430030, Hubei, PR China (e-mail: [email protected]).
Background The optimal hypothermic level during circulatory arrest is controversial. The aim of our study was to comprehensively assess the impact of moderate hypothermic circulatory arrest with antegrade cerebral perfusion (ACP) on total aortic arch replacement. Methods From 2010 to 2013, data were collected from 99 consecutive patients with acute type A aortic dissection. All patients underwent total arch replacement plus frozen elephant trunk procedure. There were 51 patients in the deep hypothermia circulatory arrest (DHCA) group and 47 in the moderate hypothermia circulatory arrest (MHCA) group. Either unilateral or bilateral ACP was applied for cerebral protection. Perioperative data and measured outcomes were compared. Results Overall mean circulatory arrest time was 29.9 ± 6.0 minutes. Temporary neurologic dysfunction incidence was lower in the MHCA group compared with the DHCA group (21.3 vs. 40.4%, p ¼ 0.041). The total 30-day mortality was 17.2% (14.9 vs. 19.2%, p ¼ 0.568) and permanent neurologic dysfunction morbidity was 3.0% overall. In MHCA, less blood products were used than in DHCA. Moderate hypothermia was a protective factor for the composite outcome of temporary and permanent neurologic dysfunctions (odds ratio ¼ 0.385; 95% confidence interval ¼ 0.162–0.919). Hypothermic level did not significantly affect the perioperative alanine aminotransferase and serum creatinine levels. Conclusion Within a short circulatory arrest time, MHCA combined with ACP seemed to be a safe and effective method to protect cerebral and visceral organs during total aortic arch replacement.
Introduction Surgical repair of acute type A aortic dissection (AAAD) remains a challenge for cardiac surgeons. Substantial risks of ischemic injury to the brain and visceral organs during total
received December 17, 2014 accepted after revision April 28, 2015
Min Hu1
aortic arch replacement in circulatory arrest (CA) contribute to high perioperative mortality of up to 25%.1 Maximal metabolic rate suppression efficiently minimizes oxygen consumption and helps to ensure a sufficient time period for the arch procedure.2 Therefore, deep hypothermia (DH) is
© Georg Thieme Verlag KG Stuttgart · New York
DOI http://dx.doi.org/ 10.1055/s-0035-1555752. ISSN 0171-6425.
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Mingjia Ma1
widely used for brain protection early in CA.3 However, deep hypothermic circulatory arrest (DHCA) has many drawbacks, such as extended cardiopulmonary bypass (CPB) time, coagulation system disturbances, and other complications that result from temperature-related systemic vasoconstriction.4 A growing number of hospitals have attempted to raise the hypothermic level during CA, but the most optimal temperature level for organ protection is still controversial.3 Recently at our hospital, moderate hypothermic circulatory arrest (MHCA > 20°C) with antegrade cerebral perfusion (ACP) was introduced for aortic arch surgery. We conducted this retrospective study on the modified hypothermia strategy to assess the clinical impact of MHCA on total aortic arch replacement.
Patients and Methods We continuously collected perioperative data from 155 patients with type A aortic dissection in our hospital from 2010 to 2013. A total of 104 patients underwent total arch replacement plus frozen elephant trunk procedure. The indications of this procedure were as follows: (1) primary or reentry tears located in arch or proximal descending thoracic aorta; (2) severe arch vessel lesions, including dissection, occlusion, stenosis, or aneurysm changes; (3) Marfan syndrome; and (4) descending aorta dilatation with diameter over 5 cm. When primary tear located in ascending aorta without items described above, hemi-arch or ascending aorta replacements would be used for the patients. Patients with subacute and chronic type A aortic dissection (20 cases), intramural hematomas (12 cases), and patients who underwent hemi-arch replacement (19 cases) were excluded. Finally, the data from
Ma et al. 99 patients were included in this study cohort. All the included surgeries were completed by the same professional team within the past 3 years. This study was approved by the local ethics committee. Patients were retrospectively divided into two groups: the DHCA group (52 patients, nasopharyngeal temperature 14.6– 19.0°C) and the MHCA group (47 patients, nasopharyngeal temperature 21.1–26.5°C). The discerning border of hypothermia was drawn according to a standard classification.5 Five patients with hypothermia between 20.0 and 21.0°C were excluded to avoid suspected temperature overlap. Details of the preoperative data are listed in ►Table 1.
Monitoring Intraoperatively monitored parameters included invasive blood pressure in the left radial artery and ipsilateral dorsalis pedis artery, noninvasive blood pressure, oxygen saturation by pulse oximetry, rectal and nasopharyngeal temperature, electroencephalogram, cerebral regional oxygen saturation (rsO2), and regular monitoring of arterial blood gas. Intraoperative acid-base homeostasis was managed according to the Alpha state. Alanine aminotransferase (ALT) and creatinine (Cr) were used as indicators of hepatic and renal function, respectively. The preoperative and postoperative ALT and Cr values at 6 and 24 hours in the same patient were compared. These time points were considered when the inner environment was stable and devoid of any potential confounding effects of intensive care unit (ICU) treatment.
Surgical Technique After routine anesthesia, the patient was placed in a supine position. The right axillary artery was initially isolated. In
Table 1 Preoperative demographics and clinical characteristics Variables
DHCA (n ¼ 52)
MHCA (n ¼ 47)
p-Value
Male/female
41/11
43/4
0.097
Age (y)
49.5 10.2
46.8 10.8
0.420
Marfan syndrome
3 (5.8%)
2 (4.3%)
> 0.999
Preoperative dialysis
1(1.9%)
1(2.1%)
> 0.999
Preoperative shock
0
1 (2.1%)
0.475
CAD
2 (3.8%)
2 (4.3%)
> 0.999
Hypertension
37 (71.2%)
27 (57.4%)
0.154
Diabetes mellitus
13 (24.5%)
14 (29.8%)
0.593
Emergency surgery
29 (55.8%)
11 (23.4%)
0.001
Weight (kg)
71.9 10.2
76.7 11.5
0.033
Height (m)
1.69 0.05
1.72 0.05
0.005
BMI
25.2 2.6
26.0 3.4
0.394
HBV
4 (7.7%)
9 (19.1%)
0.092
HCV
0
1 (2.1%)
0.475
LVEF (%)
56.5 10.8
53.0 9.8
0.092
Abbreviations: AD, aortic dissection type A; BMI, body mass index; CAD. coronary artery disease; DHCA, deep hypothermic circulatory arrest; HBV, hepatitis B virus; HCV, hepatitis C virus; LVEF, left ventricular ejection fraction; MHCA, moderate hypothermic circulatory arrest. Note: p-Value < 0.05 is highlighted in bold type. Thoracic and Cardiovascular Surgeon
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MHCA with ACP for Rapid Total Arch Replacement in AAAD
some emergency cases, in which unstable hemodynamics or risk of aortic aneurysm rupture was suspected, the right femoral artery and vein were chosen to initiate CPB. A median sternotomy was performed. After systemic heparinization (400 IU/kg), the right axillary artery was cannulated directly using a 24-Fr arterial cannula (Medtronic, Minneapolis, Minnesota, United States) and venous cannulation was performed using a two-stage cannula (Medtronic, Minneapolis, Minnesota, United States) in the right atrium. A drain was placed in the left ventricle via the right superior pulmonary vein. Once CPB and systemic cooling were initiated, an ice cap was placed in the patient to cool the head topically. After cardiac fibrillation, the ascending aorta was cross-clamped and myocardial protection was achieved using antegrade cold blood cardioplegia perfusion. During systemic cooling, the root procedure was completed. Nasopharyngeal temperature was used as a criterion of CA, rather than rectal temperature measured simultaneously, to prevent the body from overcooling in a short CA time. The interval between the two sides was maintained within 4°C during the cooling and warming processes. Once the nasopharyngeal temperature reached the predetermined hypothermic level, circulation was arrested. The patient was placed in the Trendelenburg position. The proximal ends of the innominate artery, left carotid artery, and left subclavian artery were clamped. Unilateral antegrade cerebral perfusion (UACP) was initiated via the right axillary artery, at a flow rate of approximately 6 2 mL/(kg min). Bilateral antegrade cerebral
Ma et al.
perfusion (BACP) was randomly performed on 12 patients, using a 16-Fr urethral catheter (B.Braun, Bayan Lepas, Penang, Malaysia) placed in the left carotid artery. Total arch replacement was performed using a four-branched graft (Maquet, Rastatt, Baden-Württemberg, Germany) plus an intraoperative stent graft (MicroPort, Shanghai, China) (►Fig. 1). The arch was resected transversely to the orifice of the left subclavian artery, and branch vessel root was ligated. The 10-cm long modified stent graft (prepared in a bound, compressed state and attached to a shaft) was inserted into the true lumen of the descending thoracic aorta in an antegrade manner under direct vision. When the stent was located properly, the self-expanding stent was released by drawing out the pull ring beside the shaft. The auxiliary devices (shaft, pull ring, and wire) were removed. The diameter of the stent graft was determined by the preoperative computed tomography (CT) measure and intraoperative judgment. The proximal end of the stent graft and the aortic wall were anastomosed to the tube graft end with 3–0 prolene (Ethicon, Cincinnati, Ohio, United States) using running sutures. After this procedure, the proximal end of the graft was clamped again. Lower body blood perfusion was resumed via one branch. The left carotid artery was initially anastomosed to the vascular graft and the rewarming procedure was initiated. Subsequently, the proximal tube graft anastomosis was completed. After carefully removing all the air, standard CPB was resumed. The heart was resuscitated automatically or using defibrillation. Anastomosis of the left subclavian artery and
Fig. 1 Key steps of frozen elephant trunk procedure and postoperative computed tomography angiography. (A) The aortic arch was transected under circulatory arrest, orifice of the true lumen of the descending thoracic aorta is indicated by arrow. (B) The bound and compressed stent graft was inserted into the true lumen of the descending thoracic aorta in antegrade manner under direct vision. (C) The stent graft was released by drawing out the pull ring. (D) The proximal end of the stent graft with the aortic wall was anastomosed to the tube graft end using running sutures. (E) Postoperative computed tomography angiography of Bentall procedure with reconstructed aortic arch and stent graft. Thoracic and Cardiovascular Surgeon
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MHCA with ACP for Rapid Total Arch Replacement in AAAD
MHCA with ACP for Rapid Total Arch Replacement in AAAD innominate artery to the branches of the vascular graft was performed sequentially. CPB was gradually reduced until the patient was hemodynamically stable and the temperature returned to normal.
Concomitant Aortic Root Procedures Valve-sparing aortic root repair was used in the absence of structural valve defects and annular ectasia. The Bentall procedure was used to treat either the original dilated aortic root with defective valves or which was involved by aortic dissection (►Fig. 1). Patients with aortic valve defects without sinus involvement were treated using the Wheat procedure. Coronary artery bypass grafting (CABG) was performed depending on the preoperative diagnosis and intraoperative inspection.
Ma et al.
Results Patient Characteristics Preoperative characteristics of the patients are shown in ►Table 1. Of the 99 patients in this study, 15 were female (15.2%). The mean age of the patients was 48.2 10.5 years (range, 21–70 years). There were 19 patients (19.2%) who were over 60 years. There were 64 (64.6%) patients with hypertension, 5 of whom were regularly monitored and controlled for blood pressure. Emergency surgeries were performed in 40 patients. Overall, the mean wait time for surgery was 2.0 1.6 days, and 73.7% of the patients underwent surgery within the first 72 hours after admission. No additional operation was performed before aortic arch replacement.
DHCA was defined as initiation of CA coinciding with nasopharyngeal temperature of 14.1 to 20°C. Moderate hypothermia (MH) was defined as the temperature of 20.1 to 28°C. Temporary neurological dysfunction (TND) was defined as unconsciousness, delirium, confusion, and mania during the immediate period after surgery, but the symptoms disappeared before discharge, and no imaging change was found using a head CT. Permanent neurological dysfunction (PND) was defined as a stroke or persistent focal neurologic dysfunction, often accompanied by changes in brain imaging. Emergency surgeries were operations performed within 24 hours after admission in patients with hemodynamic instability, tamponade, or malperfusion syndrome. The criteria for renal injury after cardiac operation were defined as elevation of serum creatinine (Cr) level greater than 221 μmol/L (2.5 mg/dL) or the requirement of transient renal replacement therapy.
Statistical Analysis Continuous variables were presented as the mean standard deviation or the median and interquartile ranges (IQR). Unpaired t-test, chi-square test or Fisher exact test, or the Mann–Whitney U-test was used for univariate variable analysis. ALT and Cr values were compared between the two groups using analysis of variance (ANOVA) for repeated measurements, followed by a post hoc least significant difference (LSD). Statistical significance was defined as a two-sided p-value < 0.05. Stepwise multivariable logistic regression was used to assess the potential risk factors of 30-day mortality and neurological adverse events (TND and PND). Adjusted parameters and binary dependent variables (age, gender, hypertension, diabetes, emergency surgery, body mass index, duration of operation, preoperative LVEF%, hepatitis B virus, duration of CPB, CA, coronary artery disease, preoperative shock, preoperative dialysis, CA over 40 minutes, consumption of red blood cells [RBC] and fresh-frozen plasma [FFP], and hypothermia groups) were included in the multivariate logistic regression models. Results of the regression models were presented as the odds ratio (OR) and 95% confidence interval (CI). SPSS Statistics 19.0 (IBM, Somers, New York, United States) was used for statistical analysis. Thoracic and Cardiovascular Surgeon
Overall, the mean surgical duration was 508.8 80.0 minutes. Mean CA time was 29.9 6.0 minutes. The CA was longer than 40 minutes for 10 patients. Bilateral cerebral perfusion was used randomly for 12 patients. Bentall procedure was used as the most common concomitant procedure in aortic root (33 patients). CABG was performed in nine patients, of whom four were preoperatively diagnosed with three-vessel or left main coronary artery disease, three patients had a tear in their right coronary artery that was involved in aortic dissection, and two patients had significantly calcified pathological changes in their anterior descending branch that was observed during the intraoperative inspection. The proportion of patients with concomitant procedures was not significantly different between the groups (►Table 2). The transfusions of both FFP and RBC were less in the MHCA group than in the DHCA group.
Postoperative Outcomes Re-exploration for bleeding did not occur in either group. Most postoperative properties were comparable between the two groups, as shown in ►Table 3. The mean duration in the ICU was significantly longer in the DHCA group than in the MHCA group (p ¼ 0.047). There were more patients whose ICU stay exceeded 7 days in DHCA group compared with the MHCA group (p ¼ 0.006). The incidence of composite neurological adverse events was 34.3%, and there were 31 patients (31.3%) with TND and 3 patients (3.0%) with PND. All three patients with PND underwent emergency surgeries. One of them in the DHCA group had preoperative lacunar infarction, while new lesion was detected postoperatively (Appendix Fig. 1). There was a significant difference in the TND incidence between the two groups (p ¼ 0.041). One-third of the patients with TND underwent brain CT scan following recommendations of the neurologist. Mean duration of main manifestations (unconsciousness, delirium, and/or mania) was 7.1 4.3 days, ranged from 1 to 22 days. Detailed data of TND were summarized in ►Table 4. No postoperative paraplegia occurred. After excluding the cases of death and voluntary discharge during therapy, the mean duration of hospitalization was 29.2 9.5 days. The overall mortality within 30 days was 17.2% (17 patients) compared with a rate of 17.5% (7 deaths in
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Cardiopulmonary Bypass and Surgical Details Relevant Concept Definitions
MHCA with ACP for Rapid Total Arch Replacement in AAAD
Ma et al.
Table 2 Cardiopulmonary bypass data and surgical procedures DHCA (n ¼ 52)
MHCA (n ¼ 47)
p-Value
RAA
49 (94.2)
46 (97.9)
0.683
RAA þ femoral artery
3 (5.8)
1 (2.1)
33 (63.5)
25 (53.2)
0.300
RR
9 (17.3)
5 (10.6)
0.342
Bentall
14 (26.9)
19 (40.4)
0.155
Wheat
5 (9.6)
2 (4.3)
0.518
CABG
4 (7.7)
5 (10.6)
0.874
Variables Cannulation site (%)
AAR with AV preservation (%) Combined procedure (%)
UACP
44 (84.6)
43 (91.5)
0.295
BACP
8 (15.4)
4 (8.5)
0.295
Operation time (min)
511.7 82.4
505.6 78.1
0.392
Duration of CPB (min)
236.3 35.7
218.6 37.1
0.018
Cross clamp time (min)
128.6 22.7
126.5 24.8
0.653
CA (min)
31.5 5.7
28.0 6.0
0.007
CA > 40 min (%)
7 (13.5)
3 (6.4)
0.405
Nasopharyngeal temp. (°C)
17.9 1.2
23.6 1.4
< 0.001
Rectal temp. (°C)
20.0 2.2
25.9 1.6
< 0.001
Transfusion RBC (IU)
6.3 3.0
5.0 2.8
0.044
FFP (mL) SD
930.8 377.1
737.5 389.3
0.002
975 (800–1,000)
650 (400–950)
Median (IQR) Platelet (IU) SD Median (IQR)
1.70 0.6
1.6 0.8
2 (1–2)
2 (1–2)
0.706
Abbreviations: AAR, ascending aorta replacement; AV, aortic valve; BACP, bilateral antegrade cerebral perfusion; CA, circulatory arrest; CABG, coronary artery bypass graft; CPB, cardiopulmonary bypass; DHCA, deep hypothermic circulatory arrest; FFP, fresh-frozen plasma; IQR, interquartile range; MHCA, moderate hypothermic circulatory arrest; RAA, right axillary artery; RBC, red blood cell; RR, root repair; SD, standard deviation; temp., temperature; UACP, unilateral antegrade cerebral perfusion. Note: p-Value < 0.05 is highlighted in bold type.
40 patients) in patients who underwent emergency surgery. The most common reasons for deaths were septic shock with multiple organ dysfunction syndrome (eight patients, 47.1%) and cardiogenic shock (five patients, 29.5%). Death resulted from cardiac arrest in other four patients (23.5%). Postoperative renal injury occurred in seven patients: four (7.7%) in the DHCA group and three (6.4%) in the MHCA group. New renal failure occurred in one patient (1.92%) in the DHCA group and two patients (4.25%) in the MHCA group. Perioperative biomarker values are summarized in Appendix Table 1. Hypothermic level had no significant interaction with perioperative Cr and ALT variance (p ¼ 0.982 and 0.364, respectively). Pairwise comparisons revealed no significant differences in either Cr or ALT values, across three time points. Multivariate logistic regression analysis revealed that diabetes (p ¼ 0.033; OR ¼ 3.56; CI ¼ 1.11–11.42), coronary artery disease (p ¼ 0.02; OR ¼ 13.89; CI ¼ 1.52–126.68), and
RBC transfusion (p ¼ 0.009; OR ¼ 1.28; CI ¼ 1.06–1.54) were independent predictors of 30-day mortality. Multivariate analysis identified the hypothermic level as an independent predictor of composite neurologic dysfunction (p ¼ 0.031; OR ¼ 0.385; CI ¼ 0.162–0.919).
Discussion Since Griepp introduced the concept of DHCA into cerebral and visceral organ protection for aortic arch surgery,6 this challenging surgery has become safer and effective. In the past, DH in CA either combined with cerebral perfusion or alone was used as the dominant pattern for organ protection during aortic arch replacement.7 DH suppressed cerebral metabolism to the level of electrocerebral inactivity, and insured adequate time for the surgical procedure during CA.8 However, prolonged CPB time, vasospasm, acidosis, and inflammation activity are considered drawbacks for improving surgical outcomes.9 Thoracic and Cardiovascular Surgeon
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Perfusion data
MHCA with ACP for Rapid Total Arch Replacement in AAAD
Ma et al.
Table 3 Postoperative morbidity and mortality DHCA (n ¼ 52)
MHCA (n ¼ 47)
p-Value
30-day mortality (%)
10 (19.2)
7 (14.9)
0.568
LCOS (%)
7 (13.5)
6 (12.8)
0.918
Sudden cardiac arrest (%)
5 (9.6)
1 (2.1)
0.255
Pulmonary infection (%)
18 (34.6)
10 (21.3)
0.141
MODS (%)
6 (11.5)
2 (4.3)
0.338
Mediastinal infection (%)
3 (5.8)
0
0.278
Tracheotomy
9 (17.3)
4 (8.5)
0.196
Postoperative dialysis (%)
2 (3.8)
3 (6.4)
0.908
TND (%)
21 (40.4)
10 (21.3)
0.041
PND (%)
2 (3.8)
1 (2.1)
> 0.999
M vent. (h) SD
111.1 119.0
92.9 91.7
0.331
77.8 (25.4–129)
48 (20–142)
9.4 7.3
6.2 4.4
Median (IQR) ICU stay time (d) SD Median (IQR)
7 (4–10)
5 (3–8)
ICU stay > 7 d (%)
31 (59.6)
15 (31.9)
0.047 0.006
Abbreviations: DHCA, deep hypothermic circulatory arrest; ICU, intensive care unit; IQR, interquartile range; LCOS, low cardiac output syndrome; M vent., mechanical ventilation; MHCA, moderate hypothermic circulatory arrest; MODS, multiple organ dysfunction syndrome; PND, permanent neurological dysfunction; SD, standard deviation; TND, temporary neurological dysfunction. Note: p-Value < 0.05 is highlighted in bold type.
In an animal experiment, Cavus et al demonstrated that in the presence of ACP, there was a higher consumption of energy stores in the cerebral cells during CA and rewarming in DH than in MH.10 Therefore, when CA was performed within a short duration, more composite benefits might be obtained from MH than DH. MH using an adjunctive perfusion technique has been attempted by many institutions in aortic arch surgery as a promising approach for advanced organ protection.11–13 In our institution, MH with nasopharyngeal temperature over 20°C was initially performed successfully on only a few patients in 2010. As the CA time for aortic arch replacement was controllable, we tended to implement MH more often during the past 3 years (►Fig. 2). Currently, MHCA is utilized for a majority of aortic arch operations. DH was retained for
complex arch procedure or hemi-arch replacement requiring total CA. In this study, the surgical 30-day mortality of AAAD was comparable to similar published series, ranging from 8.1 to 27.8%.12,14 The 30-day mortality tended to be lower in the MHCA group than in the DHCA group, but was not statistically significant. The MH did not increase the risk of mortality. In contrast, a lower mortality was observed with MH in other studies.13,15 Therefore, a study conducted in larger populations may present a different result. In addition, it was usually believed that emergency surgery led to bad outcomes.16 Multivariate analysis revealed that emergent state negatively influenced the 30-day mortality in our study. TND morbidity decreased with the use of MHCA. Multivariable analysis showed that MH was an independent
Table 4 Detailed data of temporary neurological dysfunction Variables
DHCA (n ¼ 21)
MHCA (n ¼ 10)
p-Value
Duration of TND (d)
7.7 5.0
5.8 1.8
0.268
13 (61.9)
5 (50)
0.701
Main manifestations Unconsciousness (%) Delirium (%)
7 (33.3)
0
0.012
Mania (%)
11 (52.4)
5 (50)
>0.999
Brain CT scan (%)
6 (28.6)
4 (40)
0.685
Neurologist consultation (%)
9 (42.9)
4 (40)
>0.999
Abbreviations: CT, computed tomography; DHCA, deep hypothermic circulatory arrest; MHCA, moderate hypothermic circulatory arrest; TND, temporary neurological dysfunction. Note: p-Value < 0.05 is highlighted in bold type. Thoracic and Cardiovascular Surgeon
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Variables
MHCA with ACP for Rapid Total Arch Replacement in AAAD
protective factor against composite neurologic adverse events. These findings were in line with the consequence of a previous study and can be explained with the experimental consequence conducted by Cavus et al.10,17 No significant difference in neurological morbidity (either TND or PND) was observed between BACP and UACP (25 vs. 35.6%; p ¼ 0.687). There is a lack of evidence demonstrating BACP’s superiority18 and the technique might be considered an alternative to UACP in cases of hypoperfusion. Compared with the DHCA group, less blood products were consumed and shorter ICU stays were observed in the MHCA group. The differences in outcome were also described in the study conducted by Zierer et al,15 which largely favored MH. In addition to mortality and morbidity of neurologic dysfunction, safety of visceral organs during CA is also a concern.12,19 We found that there was no significant pathologic elevation in the Cr value after operation in either the DHCA or the MHCA groups, and morbidities between the groups were comparable. More patients infected with hepatitis B virus (HBV) and hepatitis C virus (HCV) in the MHCA group might contribute to the preoperative difference in ALT levels. Hemi-arch replacement was considered to be a relatively safe procedure, but there were also fears of a dissected distal aorta degeneration, which required secondary extensive interventions.20 The frozen elephant trunk procedure we applied was feasible and safe in appropriate patients, which helped to reduce the re-intervention rate.14 We also minimized the distal anastomosis using running sutures, which reduced the CA time resulting in acceptable outcome. In addition, no paraplegia or mesenteric ischemia occurred. Despite the extended CA time period, MH with UACP was adequate for distal organ protection. The retrospective nature and the relatively small sample size are the main limitations of this study. Use of MHCA with UACP in our hospital has gradually become the preferred method for total arch replacement over time. Thus, no DHCA control group can be included concurrently with the MHCA group, and the patient characteristics cannot be matched
exactly in pairs. Our institution is a tertiary referral hospital, with over 90% of the patients transferred from peripheral or remote hospitals. Improvements in early diagnosis and treatment before admission affect the short-term outcome of surgery over time. Meanwhile changes in perioperative therapy policy and surgical team cooperation were unavoidable. The impact of MH upon the patients’ long-term outcome is also unknown. Further follow-up of the patients in the study and a larger study are required. In conclusion, this study is consistent with other studies indicating that MH with UACP is feasible and safe for cerebral and distal organ protection during CA, which is required for total aortic arch replacement and frozen elephant trunk procedure. MH helped to decrease TND morbidity after surgery. In short periods of CA, MH did not increase 30-day mortality and distal organ morbidity. MH might also help to reduce the blood product consumption and ICU stays.
Conflict of Interest None declared.
Acknowledgment We would like to thank the associate operative surgeons for their surgical expertise and editorial assistance. We must thank Dr. Hui Gao (School of Public Health, Tongji Medical College, Huazhong University of Science and Technology) for statistical consulting. We also thank Dr. Sishu Yuan (Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology) for radiological consulting.
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compared with moderate hypothermia in repair of acute type A aortic dissection. J Thorac Cardiovasc Surg 2014;148(6): 2888–2894 McCullough JN, Zhang N, Reich DL, et al. Cerebral metabolic suppression during hypothermic circulatory arrest in humans. Ann Thorac Surg 1999;67(6):1895–1899, discussion 1919–1921 Englum BR, Andersen ND, Husain AM, Mathew JP, Hughes GC. Degree of hypothermia in aortic arch surgery - optimal temperature for cerebral and spinal protection: deep hypothermia remains the gold standard in the absence of randomized data. Ann Cardiothorac Surg 2013;2(2):184–193 Harrington DK, Lilley JP, Rooney SJ, Bonser RS. Nonneurologic morbidity and profound hypothermia in aortic surgery. Ann Thorac Surg 2004;78(2):596–601 Yan TD, Bannon PG, Bavaria J, et al. Consensus on hypothermia in aortic arch surgery. Ann Cardiothorac Surg 2013;2(2):163–168 Griepp RB, Stinson EB, Hollingsworth JF, Buehler D. Prosthetic replacement of the aortic arch. J Thorac Cardiovasc Surg 1975; 70(6):1051–1063 Ziganshin BA, Rajbanshi BG, Tranquilli M, Fang H, Rizzo JA, Elefteriades JA. Straight deep hypothermic circulatory arrest for cerebral protection during aortic arch surgery: safe and effective. J Thorac Cardiovasc Surg 2014;148(3):888–898, discussion 898–900 Thoracic and Cardiovascular Surgeon
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Fig. 2 Temporal distribution of hypothermia strategies. DHCA, deep hypothermic circulatory arrest; MHCA, moderate hypothermic circulatory arrest.
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circulatory arrest: I. Effects of cooling on electroencephalogram and evoked potentials. Ann Thorac Surg 2001;71(1):14–21 Cooper WA, Duarte IG, Thourani VH, et al. Hypothermic circulatory arrest causes multisystem vascular endothelial dysfunction and apoptosis. Ann Thorac Surg 2000;69(3):696–702, discussion 703 Cavus E, Hoffmann G, Bein B, et al. Cerebral metabolism during deep hypothermic circulatory arrest vs moderate hypothermic selective cerebral perfusion in a piglet model: a microdialysis study. Paediatr Anaesth 2009;19(8):770–778 Numata S, Tsutsumi Y, Monta O, et al. Aortic arch repair with antegrade selective cerebral perfusion using mild to moderate hypothermia of more than 28°C. Ann Thorac Surg 2012;94(1): 90–95, discussion 95–96 Qian H, Hu J, Du L, Xue Y, Meng W, Zhang EY. Modified hypothermic circulatory arrest for emergent repair of acute aortic dissection type a: a single-center experience. J Cardiothorac Surg 2013; 8:125 Tsai JY, Pan W, Lemaire SA, et al. Moderate hypothermia during aortic arch surgery is associated with reduced risk of early mortality. J Thorac Cardiovasc Surg 2013;146(3):662–667 Ma WG, Zheng J, Zhang W, et al. Frozen elephant trunk with total arch replacement for type A aortic dissections: does acuity affect
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operative mortality? J Thorac Cardiovasc Surg 2014;148(3): 963–970, discussion 970–972 Zierer A, Aybek T, Risteski P, Dogan S, Wimmer-Greinecker G, Moritz A. Moderate hypothermia (30 degrees C) for surgery of acute type A aortic dissection. Thorac Cardiovasc Surg 2005;53(2):74–79 Kunihara T, Grün T, Aicher D, et al. Hypothermic circulatory arrest is not a risk factor for neurologic morbidity in aortic surgery: a propensity score analysis. J Thorac Cardiovasc Surg 2005;130(3): 712–718 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(2):501–509 Numata S, Thomson DS, Seah P, Singh T. Simplified cerebral protection using unilateral antegrade cerebral perfusion and moderate hypothermic circulatory arrest. Heart Lung Circ 2009; 18(5):334–336 Pacini D, Pantaleo A, Di Marco L, et al. Visceral organ protection in aortic arch surgery: safety of moderate hypothermia. Eur J Cardiothorac Surg 2014;46(3):438–443 Vallabhajosyula P, Szeto WY, Pulsipher A, et al. Antegrade thoracic stent grafting during repair of acute Debakey type I dissection promotes distal aortic remodeling and reduces late open distal reoperation rate. J Thorac Cardiovasc Surg 2014;147(3):942–948
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MHCA with ACP for Rapid Total Arch Replacement in AAAD
MHCA with ACP for Rapid Total Arch Replacement in AAAD
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Appendix Fig. 1 Postoperative brain noncontrast computed tomography axial scans. (A): The postoperative imaging showed no change in patient with temporary neurological dysfunction. (B): Left frontal encephalomalacia (indicated by arrow) was detected 10 days after the operation for another patient.
Variables
DHCA (n ¼ 52)
MHCA (n ¼ 47)
p-Value
115.5 232.6
88.3 87.0
0.107
79.5 (67.0–90.8)
74.0 (54.0–89.0)
120.3 119.5
93.5 54.1
86.5 (67.3–116.0)
89 (56–118)
119.1 182.8
90.7 74.4
70.5 (58.3–96.9)
65.0 (45–90)
24.6 26.9
50.9 129.8
16.5 (12–26)
32 (14–42)
41.2 42.2
79.8 269.1
35 (24–64)
31 (17–64)
Serum creatinine (μmg/L) T1 mean SD Median (IQR) T2 mean SD Median (IQR) T3 mean SD Median (IQR)
0.490 0.268
Alanine aminotransferase (U/L) T1 mean SD Median (IQR) T2 mean SD Median (IQR) T3 mean SD Median (IQR)
106.8 473.6
71 143.6
36 (20–54)
35 (24–64)
0.006 0.228 0.718
Abbreviations: DHCA, deep hypothermic circulatory arrest; IQR, interquartile range; MHCA, moderate hypothermic circulatory arrest; SD, standard deviation; T1, before operation; T2, 6 hours after operation; T3, 24 hours after operation.
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Appendix Table 1 Biochemical measurement
