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Ann Thorac Surg 2002;74:422-425
© 2002 The Society of Thoracic Surgeons


Original article: cardiovascular

Effects of deep hypothermic circulatory arrest on outcome after resection of ascending aortic aneurysm

Franz F. Immer, MD*a, Hanna Barmettler, MDa, Pascal A. Berdat, MDa, Alexsandra S. Immer-Bansi, MDa, Lars Englberger, MDa, Eva S. Krähenbühl, MDa, Thierry P. Carrel, MDa

a Department of Cardiovascular Surgery and Institute of Anesthesiology, University Hospital, Berne, Switzerland

Accepted for publication April 16, 2002.

* Address reprint requests to Dr Immer, Department of Cardiovascular Surgery, University Hospital, 3010 Berne, Switzerland
e-mail: franzimmer{at}yahoo.de


    Abstract
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Comment
 References
 
Background. Aneurysm of the ascending aorta is a common finding especially in patients with aortic valve diseases. The aim of this study was to analyze early and midterm outcome in patients operated on for aneurysm of the ascending aorta with or without the use of deep hypothermic circulatory arrest (DHCA).

Methods. Between January 1996 and December 2000, 133 of 410 patients with thoracic aortic pathology were operated on for an aortic aneurysm limited mainly to the ascending aorta. Early and midterm outcomes were assessed and quality of life (QOL) evaluated using the Short-Form 36 Health Survey Questionnaire (SF-36).

Results. Sixty patients (group 1) were operated on with DHCA and 73 patients (group 2) without DHCA. In-hospital mortality was identical in both groups (9.6% versus 6.7%; p = not significant) whereas postoperative transient neurologic events were significantly more frequent in group 1 (6.7% versus 0%; p < 0.05). Midterm clinical outcome was not different between groups but QOL showed significant impairment in daily functional physical and emotional activity in group 1 patients compared with group 2 and an age-matched standard population.

Conclusions. The risk of transient neurologic complications is significantly increased with the use of DHCA and QOL is impaired without benefits in the long-term outcome especially among older patients.


    Introduction
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Comment
 References
 
Aneurysm of the ascending aorta is a frequent finding in patients with aortic valve disease, especially in those with bicuspid aortic valve [1]. In these patients the aortic wall is assumed to be less stable owing to an unknown tissue disease or to be exposed to a higher stress secondary to the valve pathology, which favors poststenotic dilatation of the ascending aorta [2, 3]. The indication to replace the ascending aorta depends on the size of the aorta, the structure and function of the aortic valve, the patient’s age, comorbidity, and the pathology of the aortic wall [4]. The decision whether to use deep hypothermic circulatory arrest (DHCA) depends on the distal extension of the ascending aortic aneurysm and the presumed facility to perform a safe distal anastomosis. Aortic aneurysms extending into the proximal aortic arch require DHCA if a complete resection is attempted. Nevertheless, the impact of DHCA on early and late outcome and quality of life (QOL) is not clear. In a recent article the Stanford group demonstrated no benefit of DHCA in a large collective of 307 patients undergoing surgery for acute type A aortic dissection over a time interval of 32 years [5]. As patients with acute type A dissection represent a very heterogeneous group and the surgical techniques used for this type of disease have evolved during the observation period, we assessed the potential early and midterm risks and benefits of DHCA in a group of patients with a more uniform pathology, namely an aneurysm confined to the ascending aorta and and its impact on QOL.


    Patients and methods
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Comment
 References
 
Patients
Between January 1996 and December 2000, 410 adult patients underwent surgery for thoracic aortic disease in our institution. Of these, 133 patients operated on for an aneurysm limited to the ascending aorta (AAA) were selected for this study. In order to avoid a selection bias very restrictive inclusion criterias were defined and patients with disease of the aortic arch and acute type A aortic dissection were not included in the present study. The decision whether to perform a circulatory arrest was depending on the surgeon’s preference and according to the clinical findings. Of four surgeons who performed surgery of the thoracic aorta two of them were restrictive with the use of DHCA in this particular setting whereas the other two were less so. Preoperative patient characteristics are presented in Table 1. Sixty patients (45.1%) were operated on using DHCA (group 1) and 73 (54.9%) without using DHCA (group 2).


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Table 1. Characteristics of Patients Operated on With DHCA and Without DHCA

 
Methods
All preoperative, intraoperative, and postoperative data were assessed. We referred to the American College of Cardiologists/American Heart Association guidelines for reporting postoperative neurologic events in the present study to allow comparison with other study groups. Only type 1 postoperative neurologic events associated with major focal neurologic deficits, stupor, and coma were reported in the present study. In all patients with type 1 postoperative neurologic events computed tomography (CT) scan of the brain was performed. Neurologic deficits that returned to normal within 72 hours postoperatively were qualified as transient in comparison with persistent neurologic events. Follow-up focused on freedom from reoperation and QOL was assessed with the Short-Form 36 Health Survey Questionnaire (SF-36) [68]. The SF-36 consists of 36 short questions mirroring health and QOL in eight different aspects: bodily pain (2 items); mental health (5); vitality (4); social functioning (2); general health (5); physical functioning (10); and role functioning, both emotional (3) and physical (4). Role functioning reflects the impact of emotional and physical disability on work and regular activity (the person’s normal everyday role). Raw points were transformed, generating a score for each dimension ranging from 0 to 100, with 100 reflecting best functioning. Swedish normal population (n = 8,930) scores were used as a standard population for comparison (range 85 to 115).

Clinical follow-up was complete in all patients whereas QOL could be assessed in only 89 of the 118 survivors (75.4%). As the SF-36 is not validated in French and Italian, 15 patients (12.7%) were excluded. Two additional patients (1.7%) were not able to answer, 1 because of psychiatric disease and 1 because of a persistent perioperative neurologic deficit. Twelve patients (10.2%) were contacted by phone but refused to answer the questionnaire.

Surgical procedures
Twenty-nine patients (48.3%) from group 1 and 35 patients (47.9%) from group 2 received a composite graft (button technique). In 8 patients (27.6%) of the 29 from group 1 and in 9 patients (25.7%) of the 35 from group 2 the intervention was combined with additional coronary artery bypass grafting (CABG). In 31 patients (51.7%) from group 1 and in 38 patients (52.1%) from group 2 supracoronary replacement of the ascending aorta was performed. Mean operation time was 231 ± 68 minutes. in group 1 and 206 ± 57 minutes. in group 2 (p < 0.05). Mean duration of DHCA was 15.7 ± 8.1 minutes in patients from group 1 with a core temperature of less than or equal to 20°C. Pentothal was administered in all group 1 patients 2 to 3 minutes before initiation of DHCA. Cerebral perfusion during DHCA was only applied in patients with an expected circulatory arrest of more than 20 minutes and was used in 8 patients (13.3%) in an antegrade (7 patients) or retrograde fashion (1 patient).

Statistical analysis
Data are presented as mean values ± their first standard deviation. The Mann-Whitney U test and {chi}2 test were used for comparison between groups of continuous and nominal variables, respectively. A p value of less than 0.05 was considered significant. The SF-36 questionnaire was analyzed in accordance to the SF-36 manual, replacing missing values using the described algorithm [6]. Scores were adjusted for sex and age in order to be comparable with the normal population. Data were analyzed using the StatView 4.1 statistical package (Abacus Concepts, Berkley, CA).


    Results
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Comment
 References
 
Early outcome
Patients of group 1 were significantly older (60.8 ± 13.5 versus 57.4 ± 14.1; p < 0.05), had a higher percentage of reoperation (30.0% versus 16.4%; p < 0.05), and had a larger diameter of the ascending aorta (6.4 ± 1.5 cm versus 5.6 ± 0.9 cm; p < 0.05) compared with group 2 (Table 1). Postoperative persistent neurologic events (type 1) were similar in both groups (5.0% versus 2.7%; p = not significant) whereas transient neurologic events were significantly more frequent in group 1 (6.7% versus 0%; p < 0.05; Table 1).

Follow-up
Mean follow-up was 3.4 ± 1.2 years in both groups. Two patients died in each group during follow-up, both deaths not being related to surgery. Midterm survival was similar for both groups. Actuarial freedom from reoperation was 100% during follow-up, without any reoperation in either group.

Group 1 patients showed significant impairment of emotional role function (84.0 ± 47.5 versus 101.3 ± 25.8; p < 0.05) and physical role function (83.1 ± 57.9 versus 113.2 ± 26.4; p < 0.05) in an age- and sex-matched comparison with group 2 and with a standard population. Overall group 2 results were excellent, being even superior to the standard population concerning pain and general health (Fig 1). Group 1 patients between 56 and 65 years and older than 75 years, however, showed significant impairment in emotional role functioning and worsening of physical role functioning with increasing age (Figs 2 and 3).



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Fig 1. Age-matched comparison of the aspects assessed with the SF-36 for group 1 and group 2 patients. Normal value for an age- and sex-matched standard population is 100 (range 85 to 115). (BP = bodily pain; GH = general health; MH = mental health; PF = physical functioning; RE = emotional role functioning; RP= physical role functioning; SF = social functioning; VT = vitality.)

 


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Fig 2. Comparison of the aspect of emotional role function between group 1 and group 2 in relation to age (<56 years, 56 to 65 years, 66 to 75 years, and >75 years).

 


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Fig 3. Comparison of the aspect of physical role function between group 1 and group 2 in relation to age (<56 years, 56 to 65 years, 66 to 75 years, and >75 years).

 

    Comment
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Comment
 References
 
Replacement of aneurysms of the ascending aorta with the use of DHCA is thought to be a safe procedure [4, 9]. In comparison with patients suffering from acute type A aortic dissection the distal anastomosis is technically less demanding, as is reflected in a shorter duration of DHCA time [10]. DHCA improves visualization and allows a distal anastomosis using an open technique with more radical exclusion of the aneurysm in the most cranial part of the aorta. Furthermore, avoiding aortic clamping may prevent traumatic clamp lesions of the aorta and uncontrolled release of embolic particles.

Despite older age and higher percentage of reoperation in group 1 patients, both well-known risk factors for early mortality [4, 11], mortality was not significantly different between both groups. However transient neurologic deficits were significantly more frequent in group 1, reflecting the older age of this group, a more extensive form of cardiovascular disease, or technical reasons related to DHCA such as cerebral microemboli or nonuniform cerebral cooling. As epiaortic scanning was not performed routinely at our institution during this time, we were not able to analyze the calcification of the ascending aorta, which may be an important risk factor for transient neurologic deficits.

Follow-up data revealed no difference between the two groups. Mortality was similar in both groups and the actuarial freedom from reoperation was 100% in both groups. The limited follow-up period may be one reason for the low incidence of reoperations in these two groups. Nevertheless, Lai and colleagues [5] reported similar survival rates and 100% freedom from distal aortic reoperation in a follow-up period of 5 years in patients operated on for acute aortic dissection type A with DHCA compared with those without DHCA.

Looking at QOL we found a significant impairment in the aspects of physical and especially emotional role function in group 1 patients. Patients operated on with DHCA complained more frequently of being tired and having problems understanding and managing complex situations on their own. Harrington and colleagues [12] reported a high incidence of neuropsychometric deficits in patients operated on for aortic arch surgery with DHCA. Especially short-term memory and language processing had significantly deteriorated at 6 weeks, which is consistent with our findings in a longer follow-up period. An explanation of our results may be that cooling of the brain was inhomogenous and did not lead to sufficient protection or—perhaps more important—that DHCA with a core temperature of 20°C alone is most probably not sufficient to protect the brain without the use of cold antegrade cerbral perfusion. Apoptotic cell death in the hippocampus and chromatin condensation, which have been reported in pigs after DHCA in recent published studies, may also influence cerebral recovery after DHCA [13, 14]. The authors reported a positive effect of cyclosporine A on cerebral recovery in this animal model—it remains unclear if this effect is due to an inhibition of neuronal apoptosis or to an inhibition of release of cytokines or both, which thereby reduces postischemic cerebral edema [14].

We conclude that the use of DHCA in the replacement of the ascending aorta increases the risk of transient neurologic deterioration, impairs postoperative QOL, and has no long-term benefit for older patients. The use of DHCA should therefore be restricted to patients with ascending aortic aneurysms clearly extending into the aortic arch. In younger patients with aneurysms extending into the proximal arch, however, maximal resection using DHCA may reduce the need for later reoperations. Hypothermia of 20°C alone may not provide safe brain protection and additional protective strategies should be used.


    References
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Comment
 References
 

  1. Keane M.G., Wiegers S.E., Plappert T., Pochettino A., Bavaria J.E., Sutton M.G. Bicuspid aortic valves are associated with aortic dilatation out of proportion to coexistent valvular lesions. Circulation 2000;102(Suppl 3):35-39.[Abstract/Free Full Text]
  2. Sundt T.M., Mora B.N., Moon M.R., Bailey M.S., Pasque M.K., Gay W.A. Options for repair of a bicuspid aortic valve and ascending aortic aneurysm. Ann Thorac Surg 2000;69:1333-1337.[Abstract/Free Full Text]
  3. von Kodolitsch Y., Simic O., Schwartz A., et al. Predictors of proximal aortic dissection at the time of aortic valve replacement. Circulation 1999;100(Suppl 2):287-294.[Abstract/Free Full Text]
  4. Ergin M.A., Spielvogel D., Apaydin A., et al. Surgical treatment of the dilated ascending aorta: when and how?. Ann Thorac Surg 1999;67:1834-1839.[Abstract/Free Full Text]
  5. Lai D.T., Robbins R.C., Mitchell R.S., et al. Does hypothermic circulatory arrest (PHCA) improve survival in patients with acute type A dissection?. Circulation 2001;104(Suppl 2):524.
  6. Ware J.E., Snow K.K., Kosinski M., Gandek B. SF-36 health survey manual and interpretation guide. Boston: New England Medical Center, The Health Institute, 1993.
  7. Sullivan M., Karlsson J., Ware J.E. SF-36 health questionnaire. Swedish manual and interpretation guide. Gothenburg Sweden: Gothenburg University, 1994.
  8. Olson C., Thelin S. Quality of life in survivors of thoracic aortic surgery. Ann Thorac Surg 1999;67:1262-1267.[Abstract/Free Full Text]
  9. Ehrlich M.P., Ergin M.A., McCullough J.N., et al. Predictors of adverse outcome and transient neurological dysfunction after ascending aorta/hemiarch replacement. Ann Thorac Surg 2000;69:1755-1763.[Abstract/Free Full Text]
  10. Ehrlich M.P., Ergin M.A., McCullough J.N., et al. Results of immediate surgical treatment of all acute type A dissections. Circulation 2000;102(Suppl 3):248-252.
  11. Nashef S.A., Roques F., Michel P., Gauducheau E., Lemeshow S., Salamon R. European system for cardiac operative risk evaluation (EuroSCORE). Eur J Cardiothorac Surg 1999;16:9-13.[Abstract/Free Full Text]
  12. Harrington D., Wong C., Bonser M., Heafield T., Riddoch J., Bonser R. Neuropsychometric outcome following aortic arch surgery: a prospective randomised trial of retrograde cerebral perfusion. Circulation 2001;104(Suppl 2):524.
  13. Tatton N.A., Hagl C., Nandor S., Insolia S., Spielvogel D., Griepp R.B. Apoptotic cell death in the hippocampus due to prolonged circulatory arrest: comparison of cyclosporine A and cycloheximide on neuron survival. Eur J Cardiothorac Surg 2001;19:746-755.[Abstract/Free Full Text]
  14. Hagl C., Tatton N.A., Weisz D.J., et al. Cyclosporine A as a potential neuroprotective agent: a study of prolonged hypothermic circulatory arrest in a chronic porcine model. Eur J Cardiothorac Surg 2001;19:756-764.[Abstract/Free Full Text]



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