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Ann Thorac Surg 2007;83:2122-2129
© 2007 The Society of Thoracic Surgeons

Original Articles: Cardiovascular

Impact of Perfusion Strategy on Neurologic Recovery in Acute Type A Aortic Dissection

Andreas Zierer, MDa, Marc R. Moon, MDa,*, Spencer J. Melby, MDa, Nader Moazami, MDa, Jennifer S. Lawton, MDa, Nicholas T. Kouchoukos, MDa, Michael K. Pasque, MDb, Ralph J. Damiano, Jr, MDa

a Division of Cardiothoracic Surgery and the Center for Diseases of the Thoracic Aorta, Washington University School of Medicine, Barnes Jewish Hospital, St. Louis, Missouri
b Department of Cardiothoracic Surgery, Missouri Baptist Medical Center, St. Louis, Missouri

Accepted for publication January 9, 2007.

* Address correspondence to Dr Moon, Division of Cardiothoracic Surgery, Washington University School of Medicine, 3108 Queeny Tower, #1 Barnes-Jewish Plaza, St. Louis, MO 63110-1013 (Email: moonm{at}wustl.edu).

Presented at the Fifty-third Annual Meeting of the Southern Thoracic Surgical Association, Tucson, AZ, Nov 8–12, 2006.


   Abstract
Top
 Abstract
Introduction
 Material and Methods
 Results
 Comment
 Discussion
 References
 
Background: The optimal perfusion strategy during surgery of acute type A aortic dissection is controversial. The purpose of this study was to determine the impact of retrograde cerebral perfusion during hypothermic circulatory arrest on short-term and long-term outcome in this specific patient population.

Methods: Between 1984 and 2005, 175 consecutive patients underwent repair of an acute type A dissection. Three different surgical approaches were used: aortic cross-clamping without hypothermic circulatory arrest in 50 (29%), hypothermic circulatory arrest alone in 69 (39%), and hypothermic circulatory arrest with supplemental retrograde cerebral perfusion in 56 (32%).

Results: Operative mortality was 18% ± 3% (± 70% confidence interval), and adverse outcomes (death or cerebrovascular accident) occurred in 21% ± 3% of patients (p = 0.97 between groups). Multivariate analysis identified valve replacement (p = 0.04), preoperative flow complications (p = 0.03), and non-Marfan syndrome (p = 0.04) as predictors of operative mortality. Intraoperative dissection (p < 0.001) and history of cerebrovascular disease (p = 0.02) were predictors for permanent neurologic deficit, and retrograde cerebral perfusion was shown to have a protective effect on transient neurologic deficits (p = 0.008). Kaplan-Meier survival was 75% ± 3% at 1 year (131 patients at risk), 63% ± 4% at 5 years (87 patients at risk), and 49% ± 4% at 10 years (48 patients at risk) and was independent of surgical approach (p = 0.37). Long-term survival was diminished with increased age (p < 0.001), earlier operative year (p < 0.001), and coronary artery disease (p = 0.02).

Conclusions: The current investigation suggests improved neurologic recovery with circulatory arrest and supplemental retrograde cerebral perfusion. Operative mortality and long-term survival were comparable among groups.


   Introduction
Top
 Abstract
 Introduction
Material and Methods
 Results
 Comment
 Discussion
 References
 
Cerebral protection is a primary concern during operations on the aortic arch, particularly if an acute type A aortic dissection is present. For the management of this rare but life-threatening emergency situation, the original technique entailed aortic cross-clamping at the level of the innominate artery with simultaneous repair of the ascending aortic pathology [1–3]. An open distal anastomosis for repair of acute type A aortic dissection with hypothermic circulatory arrest (HCA) has since been advocated and gained widespread acceptance [4–6]. Retrograde cerebral perfusion (RCP) was introduced in the mid-1990s as an adjunct to HCA during aortic arch repair [7–9]. Most recently, antegrade cerebral perfusion has been used for elective aortic arch procedures [10, 11], but application of this adjunct has been limited in acute dissection owing to concerns with axillary vessel integrity and flow dynamics in the emergency setting [12].

Despite all of the surgical advances, acute type A aortic dissections still remain a major challenge, with operative mortality rates of 15% to 28% and stroke rates of 2% to 15% [1, 2, 13–18]. Transient neurologic dysfunction (TND), defined as prolonged postoperative confusion, agitation, or transient delirium with resolution of symptoms before discharge, is also common and occurs in 12% to 37% of patients [14–16].

A previous report from our unit failed to show an impact of RCP on neurologic recovery in 72 patients undergoing aortic arch procedures with HCA (36 with RCP, 36 without RCP) [19]. This study was quite heterogeneous, however, because two thirds of the patients had chronic pathology, and all patients who underwent cross-clamping without HCA were excluded. The purpose of the current investigation was therefore to determine how the three different approaches used at our institution during last two decades (cross-clamping without HCA versus HCA alone versus HCA with supplemental RCP) influenced operative mortality, neurologic outcome, and long-term survival in acute type A dissection.


   Material and Methods
Top
 Abstract
 Introduction
 Material and Methods
Results
 Comment
 Discussion
 References
 
This retrospective review includes 175 consecutive patients that underwent surgery for acute type A aortic dissection between June 1984 and November 2005 at Washington University School of Medicine (Barnes-Jewish Hospital, St. Louis, MO) by 22 different surgeons. The study was approved by the Washington University Institutional Review Board, and informed consent and permission for the release of information were obtained from each patient. There were 108 (62%) men and 67 (38%) women with a mean age of 62 ± 15 years (range, 21 to 88 years). Three different perfusion strategies included aortic cross-clamping without HCA in 50 (29%), HCA alone in 69 (39%), and HCA with supplemental RCP in 56 (32%). The specific techniques used were similar to those previously described [15, 19]. Figure 1 demonstrates the distribution of perfusion technique by surgical era. Selected preoperative patient characteristics are summarized in Table 1. Preoperative comorbidities were equally distributed among the three groups, except that hypertension was least common in the cross-clamping group. Marfan syndrome was diagnosed in 9 patients (5%). Late follow-up for survival for the entire series was 100%.


Figure 1
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  		Fig 1. Distribution of perfusion technique by surgical era: Cross-clamping without hypothermic circulatory arrest (HCA) (black), HCA alone (white), HCA with retrograde cerebral perfusion (RCP) (gray).

 

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  		Table 1 Patient Demographics for Patients Undergoing Surgery for Acute Type A Aortic Dissection a
 
Retrograde Cerebral Perfusion
There was variability in the specific operative techniques used among the 22 surgeons during this 21-year period; however, the following reflected the general operative approach if supplemental RCP was used. After bicaval cannulation, RCP was done through an arteriovenous shunt to a superior vena cava cannula (28F to 32F). RCP was initiated at 100 mL/min and increased to 300 to 500 mL/min to keep the innominate vein pressure (central venous pressure) below 20 to 25 mm Hg. The patient was placed in the Trendelenburg position during RCP, and dark blood was verified emanating from the brachiocephalic orifices in all patients. The temperature of inflow blood during RCP was 10°C.

Data Analysis
Study end points were neurologic morbidity, operative mortality, and long-term survival. Adverse outcome was defined as operative death or permanent neurologic deficit at the time of discharge from the hospital, whether focal (embolic stroke) or global (diffuse coma). Transient neurologic dysfunction was defined as the occurrence of prolonged postoperative confusion, agitation, transient delirium, or ischemic deficits, with resolution of symptoms before discharge. Perioperative mortality included any death that occurred during the initial hospitalization or within 30 days of operation for discharged patients.

Cumulative survival rates were calculated using Kaplan-Meier analysis, and survival curves were compared using the log-rank test. Continuous data are reported as mean ± one standard deviation and compared using analysis of variance. Clinically important ratios are reported with 70% confidence limits. Categoric variables were analyzed using the {chi}2 test or Fisher exact tests, as appropriate. Odds ratios (OR) are reported with 70% confidence intervals (CI). Multivariate analysis (stepwise backward regression) was used to determine preoperative and intraoperative risk factors that were significant independent predictors of adverse neurologic outcome, increased operative mortality, and impaired long-term survival (SigmaStat 2.03, SPSS Inc, Chicago, IL).

Twenty-eight variables were analyzed: age, year of operation, gender, hypertension, diabetes mellitus, coronary artery disease, pulmonary disease, cerebrovascular disease, peripheral vascular disease, chronic renal insufficiency, smoking history, Marfan syndrome, previous cardiac operation, cardiogenic shock, aortic insufficiency, preoperative flow complications, tamponade/rupture, DeBakey classification, intraoperative dissection, HCA, RCP utilization, initial perfusion antegrade/retrograde, rewarming antegrade/retrograde, primary tear location, primary tear resected, aortic valve preservation versus replacement, ascending only versus hemiarch replacement, and concomitant coronary artery bypass grafting (CABG). Statistical differences were considered significant at a value of p < 0.05.


   Results
Top
 Abstract
 Introduction
 Material and Methods
 Results
Comment
 Discussion
 References
 
Preoperative malperfusion was present in 50 patients (29%), including coronary in 6, peripheral in 23 (leg 15, arm 8), renal in 5, bowels in 2, spine in 6, and cerebral in 8. However, no difference was found among the three surgical groups in the incidence of preoperative malperfusion (p = 0.30) and presence of aortic insufficiency (p = 0.41). Cardiogenic shock and rupture/tamponade were most common in the HCA with RCP group and least common in the HCA alone group (Table 2). An intraoperative dissection occurred in 16 patients (9%) while they were undergoing CABG (n = 12) or a valve procedure (aortic, n =2; mitral, n = 2), most often in the HCA alone and cross-clamping groups (p = 0.003).


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  		Table 2 Dissection Characteristics and Preoperative Complications for Patients Undergoing Surgery for Acute Type A Aortic Dissection a
 
Core (bladder) temperature was lowest in the HCA alone and HCA with RCP groups (p = 0.001), myocardial ischemic time was lowest in the cross-clamping group (p = 0.007), but cardiopulmonary bypass times were similar (p = 0.31; Table 3). Concomitant CABG was least common in the HCA with RCP group (p = 0.02), and aortic valve replacement tended to be most common in the cross-clamping group (p = 0.07).


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  		Table 3 Important Intraoperative Clinical Characteristics for Patients Undergoing Surgery for Acute Type A Aortic Dissection a
 
Figure 2 illustrates the distribution of aortic valve replacement by surgical era. Hemiarch replacement versus replacement of only the ascending aorta was obviously least common in the cross-clamping group (p < 0.001). The prevalence of hemiarch versus ascending aortic replacement over time is depicted in Figure 3. Although the tear tended to be located in the arch or descending aorta most commonly in the HCA alone group (p = 0.08), the incidence of the tear being resected was consistent in all groups (p = 0.94).


Figure 2
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  		Fig 2. Distribution of aortic valve replacement (AVR) (black, bottom) versus no AVR (gray, top) by surgical era. Although AVR was common early in the series, the aortic valve was preserved in 95% of patients since 2001.

 

Figure 3
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  		Fig 3. Distribution of hemiarch (black, bottom) versus ascending (gray, top) replacement by surgical era. Most recently, ascending aortic replacement was performed in most patients.

 
Initial antegrade perfusion, commonly through direct arch cannulation, was performed in 27 patients and was generally limited to patients with a DeBakey class II dissection. In 148 patients with initial retrograde (femoral) perfusion, rewarming was continued retrograde in 77 (52%) after completion of the distal anastomosis, and in 71 (48%), the cannula was repositioned to accommodate rewarming antegrade through the new graft. Rewarming was performed antegrade most commonly in the HCA with RCP group (p = 0.001). Figure 4 demonstrates the distribution of antegrade versus retrograde rewarming by surgical era.


Figure 4
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  		Fig 4. Distribution of retrograde (black, bottom) versus antegrade (gray, top) rewarming by surgical era. Since the early 1990s, the use of rewarming antegrade after completion of the distal aortic repair steadily increased.

 
Operative Mortality and Adverse Outcome
Table 4 summarizes surgical outcomes after repair of acute type A aortic dissection. Operative mortality for the entire series was 18% ± 3% (31 of 175 patients), 14% ± 5% for the aortic cross-clamping group, 19% ± 5% for HCA alone, and 20% ± 6% for HCA with RCP (p = 0.71). Multivariate regression analysis identified three factors to be independent predictors of operative mortality: (1) concomitant aortic valve replacement (p = 0.04; OR, 1.9; 75% CI, 1.5 to 2.4), (2) preoperative malperfusion (p = 0.02, OR, 2.5; 75% CI, 1.8 to 3.5), and (3) absence of Marfan syndrome (p = 0.04).


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  		Table 4 Surgical Outcomes for Patients Undergoing Surgery for Acute Type A Aortic Dissection a c
 
Overall, adverse outcomes were equally distributed among the three surgical groups (p = 0.97) and occurred in 37 (21% ± 3%) of 175 patients, including 6 with permanent neurologic deficit who were alive at the time of hospital discharge. Multivariate regression analysis identified two factors to be independent predictors of permanent neurological deficit: (1) intraoperative aortic dissection (p < 0.001; OR, 5.0; 75% CI, 2.7 to 9.2), and (2) history of cerebrovascular disease (p = 0.02, OR, 4.0; 75% CI, 2.4 to 6.7).

Transient Neurologic Dysfunction
The incidence of TND was 20% ± 3% overall but was lowest in the HCA with RCP group (p = 0.03; Fig 5). A multivariate subanalysis was performed for the 125 patients who underwent surgery with HCA (both, with and without RCP) to identify independent predictors of permanent neurologic deficit and TND. Significant factors in this context were supplemental RCP (p = 0.008, OR, 0.3; 75% CI, 0.1 to 0.5), which was identified to be protective, and intraoperative dissection (p = 0.01; OR, 5.5; 75% CI, 2.9 to 10.5). When only those patients undergoing HCA were analyzed, supplemental RCP was again identified as being protective for permanent neurologic deficit (p = 0.008; OR, 0.2; 75% CI, 0.1 to 0.7). Another finding affecting all patients with HCA was a trend towards a lower incidence of TND of 14% (11 of 80) with rewarming antegrade versus 30% with rewarming retrograde (13 of 43; p = 0.06).


Figure 5
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  		Fig 5. Incidence of transient neurologic deficit by perfusion technique. The three different perfusion strategies included aortic cross-clamping without hypothermic circulatory arrest (cross-clamp), hypothermic circulatory arrest alone (HCA alone), and hypothermic circulatory arrest with supplemental retrograde cerebral perfusion (HCA & RCP).

 
Long-Term Survival
At late follow-up, 87 patients (50%) were alive an average of 106 ± 66 months postoperatively. Kaplan-Meier survival was 75% ± 3% at 1 year (131 patients at risk), 63% ± 4% at 5 years (87 patients at risk), and 49% ± 4% at 10 years (48 patients at risk) and was independent of surgical approach (p = 0.37; Fig 6). Multivariate analysis identified three factors that were independent predictors of late death: (1) increased age (p < 0.001), (2) earlier operative year (p < 0.001), and (3) coronary artery disease (p = 0.02; OR, 3.4; 75% CI, 2.2 to 5.5).


Figure 6
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  		Fig 6. Long-term Kaplan-Meier survival for patients undergoing surgery for acute type A aortic dissection using aortic cross-clamping without the need for hypothermic circulatory arrest: cross-clamping (dashed line), hypothermic circulatory arrest alone: HCA alone (solid line), or hypothermic circulatory arrest with supplemental retrograde cerebral perfusion: HCA &RCP (dotted line).

 

   Comment
Top
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
Discussion
 References
 
The main principle of HCA is to cool the brain to minimize metabolic activity and oxygen consumption [4, 20]; however, this technique gives the surgeon only a limited time to complete the aortic repair [21]. A core temperature of 18°C should theoretically allow for 45 to 60 minutes of safe HCA, but HCA times beyond this limit have been associated with increased incidence of adverse neurologic outcome [17, 22]. In an attempt to prolong the safe limits of HCA, RCP through the superior vena cava has been advocated as an adjunct to HCA [23]. In general, however, owing to the heterogeneity of the aortic disease in previous studies (acute versus chronic, aneurysm versus dissection, arch versus ascending aorta), the true impact of various perfusion strategies on cerebral protection and operative mortality has been difficult to elucidate [18, 19, 24, 25]. In an attempt to address these issues, the current report focused exclusively on patients with acute type A aortic dissections and used multivariate analysis to help control for confounding preoperative and perioperative factors.

Van Arsdell and colleagues [26] noted in an autopsy series of acute type A aortic dissection that unoperated on patients often had only one entry and reentry tear compared with patients operated on with aortic cross-clamping, who generally had multiple tears. The authors speculated that mechanical trauma applied to the aortic wall during cross-clamping was responsible for this finding. Concern exists that such a mechanical trauma may increase the risk of focal cerebral injuries owing to the dispersion of intraaortic atheromatous debris or from regional malperfusion, possibly created during aortic clamping. Although an increased trend was observed towards an increased stroke rate with cross-clamping (8% with cross-clamping, 6% with HCA alone, 2% with HCA and RCP), the current series did not demonstrate a significant difference (p = 0.33). Intraoperative aortic dissection and history of cerebrovascular disease were identified as independent predictors of permanent neurologic deficit among the entire group, whereas in the circulatory arrest patients, RCP was found to be protective (OR, 0.3; 75% CI, 0.1 to 0.5).

In the Mount Sinai experience, increased age, coronary artery disease, hemodynamic instability, acute operation, and HCA duration were found to be independent predictors of TND [24]. The current report also closely examined factors associated with TND because this assessment seems to accurately reflect the quality of cerebral protection and therefore may help in determining the best possible perfusion strategy. In addition, Ergin and colleagues [27] found that the occurrence of this syndrome is a clinical marker of long-term subtle cognitive deficit.

Among circulatory arrest patients in the current report, the incidence of TND was significantly lower when RCP was used as an adjunct to HCA (p = 0.03), supporting its favorable impact on intraoperative cerebral protection and postoperative functional recovery. Of interest is that a previous investigation from our center failed to show a positive impact of supplemental RCP during HCA on neurologic outcome after aortic arch procedures [19]. That report, however, which included acute and chronic aneurysms and dissections, noted that HCA times in patients with RCP were longer, possibly consistent with a potential selection bias towards using this adjunct in more complicated cases. In contrast, the current data suggest that in the specific subgroup of high-risk patients undergoing emergency repair of an acute type A aortic dissection, supplemental RCP may provide additional cerebral protection to HCA alone. Similarly, among those who underwent repair with HCA (either with or without RCP) there was a trend towards diminished TND with rewarming antegrade versus rewarming retrograde.

Potential Limitations
The current report is subject to all the limitations of a retrospective, nonrandomized study, including a potential selection bias for which patients were operated on using adjunctive RCP. Cardiogenic shock and tamponade/rupture were more common in this group compared with HCA alone, however, suggesting a higher risk profile in these patients. The current results may thus underestimate the impact of supplemental RCP for repair of acute type A aortic dissections. Additional potential benefits, for example, regarding the incidence of permanent neurologic deficit for the entire series may have been masked by clinical decisions to use RCP in the highest-risk patients.

We acknowledge that other strategies, specifically antegrade cerebral perfusion (ACP), are not routinely used in our center for acute dissections, although we do routinely use antegrade cerebral perfusion for aneurysms and chronic dissections. It is important to note, however, that satisfactory results have been reported with this technique [28].

In summary, the three perfusion strategies used during repair of acute type A aortic dissection were associated with comparable operative and long-term survival. Furthermore, no significant difference was found in the incidence of adverse operative outcome. All three approaches thus remain viable surgical techniques in this patient population. RCP as an adjunct to HCA was, however, associated with the lowest incidence of TND and was identified as being protective for the occurrence of both permanent and transient neurologic deficits compared to HCA alone.

Surgery for acute type A aortic dissection remains a formidable technical challenge that demands precise reconstruction of markedly diseased and friable tissues. The current report suggests that RCP combined with HCA and antegrade rewarming may provide the best cerebral protection and allow additional time to perform a meticulous repair for dissections that are not isolated to the ascending aorta and require extensive resection.


   Discussion
Top
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
 Discussion
References
 
DR THORALF SUNDT (Rochester, MN): I appreciate the opportunity to discuss this paper and review the manuscript. I will say that I was relieved to discover that my departure from St. Louis was not found as an independent predictor of positive outcome. I was concerned about that. I have looked at the Mayo database, and there is not a converse relationship there.

The obvious question here is why are the findings in this study different from those presented at the Southern just a few years ago? Your group previously reported that retrograde cerebral perfusion is not protective in the setting of aneurysms in general. What mechanisms can you come up with to explain this difference? I would expect retrograde cerebral perfusion to be particularly useful in the setting of atherosclerotic disease where the retrograde perfusion might wash debris out of the cerebral arteries. Most people with dissection don’t have a lot of atherosclerotic debris. So if I were to predict ahead of time which group would or would not show a benefit, I would have thought the degenerative aneurysms would show a benefit with RCP and not dissection. So the first question is, do you have a mechanistic explanation for why RCP is good in the setting of dissection?

The second question relates to transient neurologic dysfunction and how you made that assessment looking retrospectively at the data. That can be a difficult diagnosis to make retrospectively by reading the hospital records. Were those data concerning the presence of transient neurologic dysfunction collected prospectively? Your conclusions really depend heavily on that for statistical significance.

And the third question is, I couldn’t help but notice that your group seems to be shifting more towards the use of cross clamp and away from the use of hypothermic circulatory arrest for an open distal anastomosis. I am not saying that this is wrong, but it is certainly at variance with what most people are thinking about the subject.

I appreciate the opportunity to review the manuscript ahead of time and enjoyed your presentation. Thanks.

DR ZIERER: Thank you very much, Dr Sundt. Regarding the first question, how we explain the difference that we have now found improved neurological outcome with retrograde cerebral perfusion, it is important to mention that, as you know best, in your series you included both chronic and acute aortic pathology with two thirds of patients either having an aneurysm or a chronic dissection. In contrast, the current series exclusively focused on patients suffering from acute type A aortic dissection. We believe that this difference in patient selection may explain the distinct findings.

Regarding the mechanism by which retrograde cerebral perfusion may improve neurological outcome, it has been shown in animal models that retrograde cerebral perfusion is not sufficiently able to provide the metabolic demands of cerebral tissue. However, there are two possible mechanisms by which retrograde cerebral perfusion may help to improve cerebral protection: one of which, as you mentioned, is the avoidance of embolism, and the second one is that it may help to achieve and maintain cerebral cooling. Since we also showed that retrograde cerebral perfusion was used more frequently in high risk patients with tamponade, rupture and cardiogenic shock, we think that, especially in these patients, improved cerebral cooling may help to allow for additional time savings during aortic repair.

According to the STS database, transient neurologic deficit was defined as the occurrence of prolonged agitation or confusion or ischemic deficit with resolution of symptoms before discharge and was prospectively collected in the database.

Finally, the reason why we moved again towards a higher incidence of cross-clamping, this decision was based on two reports, one from the Stanford group published by Lai and associates in 2002 in Circulation and another one from a French group published by Kirsch and colleagues in JTCVS in 2002. Both studies did not show a difference in outcome with cross-clamping versus open distal repair during deep hypothermic circulatory arrest. It also seems important to mention that in the current series, cross-clamping was employed either very early or in most recent years. We have the feeling that patients in recent years did well with cross-clamping, also in terms of neurologic recovery; however, further investigation will be necessary to prove if this observation is true.

DR CLINTON E. BAISDEN (San Antonio, TX): I want to congratulate you on a really interesting retrospective study that has a lot of data, and I was interested in seeing that the survival was no different in the three different methods over a very long period of time. I would be very interested in knowing what the quality of life was of the patients long term, if there were any differences in the number of patients that were able to function independently, if there was any incidence in those that had to have nursing home support, any of those that were able to return to their previous forms of employment, any early incidence of organic brain syndrome or senile differences or anything? The survival looks great, but I wonder if there are any subtle differences that show up as time goes by in the quality of life that the patient has.

DR ZIERER: Thank you very much, that is an excellent question. Unfortunately, at this time, we do not have data on quality of life for this subgroup with acute type A aortic dissection. We did present a study on quality of life following elective repair of thoracic aortic aneurysms at the STS 2006. This paper has been published in August in The Annals of Thoracic Surgery. Interestingly, return to normal activity levels was independent of age and operative techniques. In contrast to elective repair of asymptomatic aneurysms, postoperative quality of life may be less interesting in the life-threatening emergent situation of an acute type A dissection. But still, that may be an interesting idea for a future study.


   References
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 Abstract
 Introduction
 Material and Methods
 Results
 Comment
 Discussion
 References
 

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