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Original Articles: Adult Cardiac

What Is the Best Strategy for Brain Protection in Patients Undergoing Aortic Arch Surgery? A Single Center Experience of 636 Patients

Department of Cardiac Surgery, Heart Center, University of Leipzig, Leipzig, Germany

Accepted for publication January 31, 2012.

^_* Address correspondence to Dr Leontyev, Universität Leipzig, Herzzentrum, Klinik für Herzchirurgie, Strümpellstr 39, Leipzig 04289, Germany (Email: sergey.leontyev{at}med.uni-leipzig.de).

	Abstract

Top Abstract Introduction Patients and Methods Results Comment Footnotes References

 
Background: Cerebral protection during aortic arch surgery can be performed using various surgical strategies. We retrospectively analyzed our results of different brain protection modalities during aortic arch surgery.

Methods: Between January 2003 and November 2009, 636 consecutive patients underwent aortic arch replacement surgery using unilateral antegrade cerebral perfusion (UACP [n = 123]), bilateral antegrade cerebral perfusion (BACP [n = 242]), retrograde cerebral perfusion (RCP [n = 51]), or deep hypothermia and circulatory arrest (DHCA [n = 220]). Mean age of patients was 62 ± 14 years, 64% were male, 15% were reoperations, and 37% were performed for acute type A dissections. Mean follow-up was 4.9 ± 0.1 years and was 97% complete.

Results: Circulatory arrest time was 22 ± 17 minutes UACP, 23 ± 21 minutes BACP, 18 ± 12 minutes RCP, and 15 ± 13 minutes DHCA; p < 0.001). Early mortality was 11% (n = 72) and was not different between the surgical groups. Stroke rate was 9% for ACP patients (n = 33) versus 15% (n = 39) for patients who did not receive ACP (p = 0.035). Independent predictors of stroke were type A aortic dissection (odds ratio [OR], 1.9; 95% confidence interval [CI], 1.3 to 3.2; p < 0.001), age (OR, 1.04; 95% CI, 1.01 to 1.06; p = 0.001), duration of circulatory arrest (OR, 1.01, 95% CI, 1.002 to 1.03; p = 0.02), and total aortic arch replacement (OR, 2.7; 95% CI, 1.3 to 5.7; p = 0.005). Five year survival was 68% ± 4% and was not significantly different between groups.

Conclusions: Antegrade cerebral perfusion is associated with significantly less neurologic complications than RCP and DHCA, despite longer circulatory arrest times. Medium-term survival is worse for patients with postoperative permanent neurologic deficit and preoperative type A aortic dissection.

	Introduction

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Aortic arch surgery with deep hypothermic circulatory arrest (DHCA) is still a surgical challenge associated with increased mortality and a significant risk of permanent neurologic injury [1–3]. Different cerebral protection strategies have been used during operative treatment of various pathologies of the aortic arch, such as atherosclerotic aneurysms or type A aortic dissection. We herein present the results of different cerebral protection options that have been employed at our institution during aortic arch surgery over a 7-year period. Our cerebral protection strategy has evolved from the use of DHCA alone, to DHCA with a short duration of retrograde cerebral perfusion (RCP), to moderate hypothermia with unilateral antegrade cerebral perfusion (UACP) or bilateral antegrade cerebral perfusion (BACP), over the study period. This evolvement in our strategy allows us to retrospectively review and assess the outcomes associated with each cerebral protection technique.

The objectives of this study were, therefore, (1) to describe the clinical characteristics of patients undergoing aortic arch surgery; (2) to compare the clinical outcome of patients with different strategies of cerebral protection; and (3) to determine predictors of mortality, neurologic complications, and midterm survival for such patients and, therefore, to determine the safest method for aortic arch surgery with regard to neurologic protection.

	Patients and Methods

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Between January 2003 and November 2009, 636 consecutive patients underwent partial or total aortic arch surgery at the Leipzig Heart Center. All patients were included in our analysis. Data were prospectively collected in a database for later analysis. Retrospective data analysis of our database was approved by the local Ethics Committee. An individual consent for the study was waived.

Choice of cerebral protection strategy was left to the discretion of the surgeon. As stated above, however, our preferred cerebral protection strategy slowly evolved from DHCA alone, to DHCA with a brief duration of RCP, to moderate hypothermia with either UACP or BACP over time. Patients were followed up annually by mailed questionnaire or, when needed, by contacting the referring cardiologist or family physician. Follow-up was complete for 97% of patients.

Operative Technique
All patients were operated on through a midline sternotomy. Arterial cannulation was performed through the axillary artery (arterial cannula, 6.5 mm; Sorin Group, Milan, Italy; or Fem-Flex, 18F; Edwards Lifesciences, Irvine, CA) in 53% of patients, 67% of whom presented with an acute type A aortic dissection. The ascending aorta was directly cannulated (Fem-Flex, 18F to 22F) in 33% of patients, and the femoral artery (Fem-Flex–II, 16F to 18F) was used in 14% of patients. The right atrium was cannulated with a double-stage cannula (Thin-Flex dual-stage venous drainage cannula, 29F/37F; Edwards Lifesciences), and the left ventricle was vented through the right upper pulmonary vein. Patients were cooled, and systemic circulatory arrest was established at the temperature chosen by the operating surgeon.

At the predetermined target temperature, patients were placed in the Trendelenburg position, and the head was cooled topically. In cases of right axillary cannulation, antegrade cerebral perfusion (ACP) was initiated before circulatory arrest and opening of the aorta by clamping the brachiocephalic trunk and unilateral perfusion through the right carotid artery with a flow rate of 10 mL · kg^–1 · min^–1 with oxygenated cold blood at a temperature of 24°C. After partial or total arch resection, the left carotid artery was checked for sufficient back flow and, if present, clamped to prevent steal phenomenon. In complex cases, additional ACP was administered through the left carotid artery (True Flow RDB cannula, 14F to 17F; Conecto Medical, Bologna, Italy) initiated with an additional flow rate of 5 mL · kg^–1 · min^–1. In cases where cannulation of the ascending aorta was performed, BACP was initiated through direct cannulation of the brachiocephalic trunk and the left common carotid artery (with True Flow RDB cannulas) after Trendelenburg positioning and circulatory arrest. The left subclavian artery was occluded with an 8/14F Fogarty occlusion catheter (Edwards Lifesciences) or with a tourniquet to prevent steal phenomenon.

The RCP was initiated through the superior vena cava before circulatory arrest was initiated with flow rate of 100 to 300 mL/min using a 24F venous cannula (Terumo, Ann Arbor, MI) and clamping of the superior vena cava above the right atrium. In the majority of such cases, however, RCP was used mainly as a method of cerebral deairing after circulatory arrest. Aortic arch surgery in patients without any form of cerebral perfusion was performed under DHCA (22°C ± 2°C). For the last 5 years, this technique has been completely replaced by UACP or BACP with moderate hypothermia.

Surgical procedures performed consisted of partial arch replacement with replacement of the ascending aorta with or without aortic root surgery (Bentall operation, valve-sparing procedure, or isolated aortic valve reconstruction or replacement). Total aortic arch replacement was reserved for patients who had extensive aneurysmal involvement of the arch or proximal descending aorta, as well as in type A aortic dissection patients with an entry site or reentry tear in the aortic arch. Such operations were performed with or without an elephant trunk procedure. The brachiocephalic vessels were reimplanted either as a complete island or separately through side arms of a multibranched graft, developed by Spielvogel and associates [4].

Definitions
In accordance with The Society of Thoracic Surgeons guidelines, early mortality was defined as all-cause mortality at 30 days [5]. Operations were considered emergent if performed within 24 hours of hospital admission for cardiovascular instability, and as urgent if performed during the same hospital admission.

All patients with suspected neurologic complications on physical examination underwent computed tomography or magnetic resonance imaging. Neurologic complications were defined as permanent neurologic deficit (PND) for patients with stroke, and temporary neurologic deficit for patients with reversible deficits. Stroke was defined as a new postoperative focal neurologic deficit that persisted more than 72 hours, or a new focal lesion of the brain detected by computer tomographic scanning. Temporary neurologic deficit was defined as a focal neurologic deficit lasting less than 72 hours, or postoperative delirium, agitation, confusion, or decreased level of consciousness without any new structural abnormality observed on imaging [6, 7].

Statistical Analysis
Continuous variables are expressed as mean ± SD and categorical data as proportions. Categorical variables were compared using the ² test or Fisher's exact test. Independent continuous variables were compared by unpaired Student's t test for comparison of normally distributed data between two groups or Kruskal-Wallis for the comparison of more than two groups, as appropriate.

We examined 34 potential preoperative risk factors for early and late mortality by univariate and multivariate testing (Table 1). Dichotomous adverse perioperative or postoperative outcome events were analyzed using a univariate and multivariate logistic regression model with backward stepwise elimination, and were expressed as odds ratios (OR) with 95% confidence intervals (CI). Event-free survival was calculated by Kaplan-Meier methods with 95% CI. Independent predictors of medium-term survival were determined with Cox proportional hazards analysis. All p values less than 0.05 were considered statistically significant. All statistical analyses were performed using SPSS version 17.0 software (SPSS, Chicago, IL).

	Results

Top Abstract Introduction Patients and Methods Results Comment Footnotes References

Operative Details and Postoperative Complications
Mean circulatory arrest time was significantly longer for patients undergoing UACP and BACP than for patients undergoing RCP and DHCA (p < 0.001; Table 3). Early postoperative outcomes were similar between groups with the exception of respiratory insufficiency, which occurred more frequently in RCP patients, and gastrointestinal complications, which occurred more frequently in UACP and RCP patients (Table 3).

Multivariate analysis identified acute type A aortic dissection (OR, 2.4; 95% CI, 1.4 to 4.2; p = 0.001), history of preoperative myocardial infarction (OR, 2.4; 95% CI, 1.07 to 5.4; p = 0.03), total aortic arch replacement with elephant trunk (OR, 1.9; 95% CI, 1.07 to 3.5; p = 0.03), and duration of CPB (OR, 1.011 per minute of CPB; 95% CI, 1.007 to 1.01; p < 0.01) as independent predictors of early mortality.

Permanent Neurologic Deficit
The overall PND rate was 11%. Unadjusted differences between the four groups were not statistically significant. Comparison of patients who underwent any form of ACP (UACP and BACP) with patients who did not receive ACP (RCP and DHCA), however, showed a significantly lower incidence of PND among ACP patients (9% versus 15%, p = 0.035). The PND rate was 11% for UACP patients versus 8% for BACP patients (p = 0.4). The PND rate was significantly lower for patients without acute type A aortic dissection, compared with patients having type A dissection (9% versus 16%, p = 0.006).

The overall incidence of temporary neurologic deficit was 15%, and was not different between cerebral protection strategy groups (p = 0.5; Table 3).

Multivariate analysis identified acute type A aortic dissection (OR, 1.9; 95% CI, 1.3 to 3.2; p < 0.001), age (OR, 1.04; 95% CI, 1.01 to 1.06; p = 0.001), duration of circulatory arrest (OR, 1.01; 95% CI, 1.002 to 1.03; p = 0.02), and total aortic arch replacement (OR, 2.7; 95% CI, 1.3 to 5.7; p = 0.005) as independent predictors of PND. The use of any form of ACP was identified as protective against the development of PND by multivariate analysis (OR, 0.4; 95% CI, 0.2 to 0.7; p = 0.005).

Predictors of Medium-Term Survival
Follow-up was complete in 97% of patients. The estimate mean survival time was 4.9 ± 0.1 years (range, 0 to 6.5; Fig 1) and a total of 1,251.3 patient years. Midterm survival was not influenced by the type of cerebral protection (log rank, p = 0.9).

View larger version (17K): [in this window] [in a new window]   Fig 1. Kaplan-Meier survival curve for patients with aortic arch surgery.

View larger version (25K): [in this window] [in a new window]   Fig 2. Kaplan-Meier survival curve for patients with and without permanent neurologic deficit (PND).

View larger version (25K): [in this window] [in a new window]   Fig 3. Kaplan-Meier survival curve for patients with (type A) and without (non-type A) acute aortic dissection.

During follow-up, 13 patients underwent redo surgery: 7 for repair of a thoracoabdominal aortic aneurysm, 2 for aortic arch aneurysm repair, 2 for endocarditis, and 2 for dissection of the aortic arch. Actuarial 5-year freedom from reoperation was 94% ± 0.1%.

	Comment

Top Abstract Introduction Patients and Methods Results Comment Footnotes References

 
The current study examines a single-center experience of cerebral protection strategies in patients undergoing aortic arch surgery. Over time, different cerebral protection strategies had been applied. Our current strategy consists of moderate hypothermia combined with antegrade unilateral or bilateral cerebral perfusion.

The reported overall mortality in patients undergoing aortic arch surgery varies between 0% and 12.8% [1, 8–13], with a significant amount of this variation due to patient selection. The early mortality observed in our study was 11%, comparable to published data from other similar case series [1, 2, 8]. Early postoperative outcome was likely influenced significantly by preoperative patient status. Our series included acute type A aortic dissection in 35% of patients, and total aortic arch replacement with the elephant trunk technique in 30%. Both type A dissection and elephant trunk arch replacement were identified as independent predictors for early mortality in our series, similar to data published by Eusanio and colleagues [14].

Other studies have identified numerous other predictors of early mortality after aortic arch surgery such as emergency timing [8, 14], age [2], preoperative hemodynamic instability [1], history of central neurologic event [14], previous coronary artery bypass graft surgery [8], duration of CPB [1, 2, 8, 15], chronic renal failure [15], reoperation [2], and femoral cannulation [2].

It is generally accepted that neurologic complications are one of the most devastating complications in cardiac surgery. It is well known that PND is associated with longer ventilation times and prolonged intensive care unit and hospital lengths of stay [16]. The incidence of PND in patients undergoing aortic surgery is reported to be 5% [17], but is approximately twice that high in patients undergoing aortic arch surgery [1, 2, 8, 9, 11, 14, 18, 19]. Our data support these findings and also reveal the devastating effect of perioperative PND on midterm survival, with a 5-year survival rate of only 45%.

Previous investigators have identified predictors of stroke during arch surgery as urgent status [2, 6, 14, 16], acute type A aortic dissection [19], age [6], history of central neurologic event [6, 19], renal insufficiency [2], operation time [2], increasing hypothermic circulatory arrest time [2], and total cerebral protection time [6]. We observed PND in 11.3% of our patients with age, duration of circulatory arrest time, and extent of aortic arch repair being identified as independent predictors thereof. The PND rate was nearly twofold higher among patients presenting with acute type A aortic dissection.

Optimal cerebral protection strategy to prevent brain injury during complex aortic arch surgery is an area of active interest. It has been shown that DHCA without any cerebral perfusion is associated with a significant higher mortality [8] and permanent neurologic dysfunction [1] than ACP. We found that ACP (UACP or BACP) was protective against permanent neurologic injury when compared with non-ACP strategies (RCP and DHCA). However, early mortality and medium-term survival was not affected by the type of cerebral protection used. The lack of effect on mortality may be due to the higher risk profile of ACP patients, since ACP was mainly used in patients who were more symptomatic and in patients with acute type A dissection or an indication for emergency surgery.

There is an ongoing discussion regarding the necessity of BACP versus UACP during aortic arch surgery. Malvindi and coworkers [20] showed comparable results between these two strategies, with the exception that BACP allowed for longer circulatory arrest times [20]. Urbanski and colleagues [9] compared right and left UACP and showed excellent clinical outcome, with a stroke rate of 1% in all patients. Clinical and neurologic outcomes among our patients were comparable for patients undergoing BACP or UACP. We might conclude, therefore, that UACP is adequate, particularly if circulatory arrest time is limited.

The choice of the optimal arterial cannulation site is also a subject of debate. Femoral cannulation has been identified as an independent predictor for in-hospital mortality [2] and worse neurologic outcome [21], probably because of the risk of retrograde cerebral embolization. Immer and coworkers [11] showed a significantly better neurologic outcome for patients undergoing cerebral perfusion through the right axillary artery compared with selective antegrade perfusion. This access has been routinely used at our institution for aortic arch surgery over the last few years, and over a longer time period for patients presenting with acute type A aortic dissection. We did not find any effect of arterial cannulation site on neurologic or other perioperative outcomes in the current study.

Study Limitations
Several limitations of our study have to be outlined. First, it is a retrospective and nonrandomized study, but we believe that this is a reasonable approach to assess predictors of outcome in one of the largest published series of surgically treated patients with aortic arch surgery. Second, the patient cohort is somewhat inhomogenous; however, it reflects our change in cerebral protection strategies for patients undergoing aortic arch surgery over time.

In conclusion, surgical treatment of patients with aortic arch pathology continues to be a surgical challenge. Patients who presented with type A aortic dissection and patients who had postoperative stroke had significantly worse midterm survival. Antegrade cerebral perfusion with moderate hypothermia reduced permanent neurologic complications, despite longer circulatory arrest times, when compared with RCP and DHCA. Therefore, at our institution, ACP has become the standard technique for cerebral protection in patients undergoing aortic arch surgery.

	Footnotes

Top Abstract Introduction Patients and Methods Results Comment Footnotes References

 
^_* Drs Martin Misfeld and Sergey Leontyev contributed equally.

	References

Top Abstract Introduction Patients and Methods Results Comment Footnotes References

 

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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Martin Misfeld Sergey Leontyev Michael A. Borger Sven Lehmann Jean-Francois Legare Friedrich W. Mohr Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Misfeld, M. Articles by Mohr, F. W. Search for Related Content PubMed PubMed Citation Articles by Misfeld, M. Articles by Mohr, F. W. Related Collections Great vessels Related Article