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Ann Thorac Surg 1999;67:1900-1903
© 1999 The Society of Thoracic Surgeons

Does retrograde cerebral perfusion affect risk factors for stroke and mortality after hypothermic circulatory arrest?

^a Cardiothoracic Surgical Unit, University Hospital Birmingham, Queen Elizabeth Medical Centre, Birmingham, United Kingdom

Address reprint requests to Mr Bonser, Cardiothoracic Surgical Unit, University Hospital Birmingham, Queen Elizabeth Medical Centre, Edgbaston, Birmingham B15 2TH, UK
e-mail: r.s.bonser{at}bham.ac.uk

Presented at the Aortic Surgery Symposium VI, April 30–May 1, 1998, New York, NY.

	Abstract

Top Abstract Introduction Patients and methods Results Discussion References

 
Background. In aortic surgery requiring hypothermic circulatory arrest (HCA), retrospective studies identify age and duration of the arrest period as predictors of stroke and mortality. Retrograde cerebral perfusion (RCP) has been reported to reduce the risk of stroke when compared with historical controls. The aim of this study was to ascertain if RCP affected mortality, stroke, or the risk factors for these end points in a consecutive series of HCA patients.

Methods. We investigated the impact of RCP in 130 patients, mean age 62.7 years (range 20–84); 78 were men and 35% were emergencies. Overall mortality was 16.9% (elective 9.5%) and the incidence of stroke was 6.9%. Mean HCA time was 30.1 min (95% confidence interval [CI] 27.9–34). RCP was instituted in 96 cases for a mean of 24.4 min (95% CI 21.9–27.0).

Results. Perioperative univariate predictors of mortality were emergency status, acute rupture, long HCA and cardiopulmonary bypass duration, and postoperative complications. For stroke, age (p = 0.007), hypertension (p = 0.05), and long HCA duration (p = 0.01) were predictive. RCP did not decrease mortality (p = 0.18, OR 0.55) or incidence of stroke (p = 0.57, OR 1.26). Mortality after stroke was 44.4% (p = 0.04, OR 4.6). Multiple logistic regression showed severe aortic atherosclerosis and RCP duration (p = 0.038) as risk factors for mortality, and myocardial ischemic time (p = 0.012) and HCA duration (p = 0.05) as risk factors for stroke. HCA and RCP groups differed in HCA duration (HCA mean 25 min [10–80], RCP mean 32 min [10–69]; p < 0.019).

Conclusions. Age and HCA duration remain risk factors for stroke and mortality despite RCP. However, HCA times were longer in the RCP patients, and the patients were not randomized. The role of RCP in cerebral protection requires further prospective randomized studies.

	Introduction

Top Abstract Introduction Patients and methods Results Discussion References

 
In many institutions, profound hypothermic circulatory arrest (HCA) is now a standard technique for cerebral protection in adults undergoing operations for aortic aneurysms and dissections. However, surgery involving HCA has a higher incidence of stroke and mortality in retrospective studies than coronary artery or valve surgery [1]. After HCA, the perioperative mortality has been reported as 8%–15%, the incidence of permanent stroke as 4%–11%, and the occurrence of transient neurological deficit as 19%–25% [2–5]. Late subtle neuropsychological deficits have also been reported [6], with the risk of complications increasing with duration of HCA.

Retrograde cerebral perfusion (RCP) was first described by Mills and Ochsner [7] as a salvage technique for arterial air embolism. Nonrandomized retrospective comparisons of RCP cases with historic HCA controls have suggested that RCP is safe [8]. Improvement in outcome has also been reported with use of RCP, but these better results may be explained by a lower prevalence of risk factors including diabetes mellitus, aortic dissection, and cerebral vascular disease in more contemporary cases [9]. Thus, although a beneficial effect of RCP remains unproven, available data suggest that RCP may either improve operative results or modify the predictive significance of risk factors contributing to outcome.

The aim of this study was to examine a consecutive series of patients undergoing thoracic aortic surgery using HCA with and without RCP, and to determine factors predictive of mortality and stroke. Further, we sought to assess any beneficial effect of RCP on outcome or on risk factors that predispose to stroke and mortality.

	Patients and methods

Top Abstract Introduction Patients and methods Results Discussion References

 
From July 1991 to April 1998, 130 consecutive patients underwent thoracic aortic surgery using profound hypothermic circulatory arrest. The mean age was 62.7 years (range 20–84); there were 52 women and 78 men. Emergent procedures constituted 46/130 operations (35.4%).

Cardiopulmonary bypass and hypothermic circulatory arrest
Patients were heparinized, cannulated, and cooled on CPB to 15°C using a nonpulsatile roller pump at a flow of 2.4 L/min/m². Activated clotting time was maintained above 700 s. Thermal gradients were maintained at less than 10°C. Alpha-stat pH management was used in all cases. A mean arterial blood pressure of 50–55 mm Hg was maintained, and hyperglycemia (> 15 mmol/L) was treated with a sliding-scale infusion of insulin. Aprotinin was infused either throughout the operation or postarrest in 119 of 130 cases. Nasopharyngeal temperature was monitored for institution of HCA. Approximately 20 min before circulatory arrest, dexamethasone (100 mg) and mannitol (1 g/kg) were administered. In 89 of 130 cases, low dose thiopentone (5 mg/kg) was given. During circulatory arrest, the head was cooled topically, and the patient placed in a Trendelenburg position. Myocardial ischemia lasted for a mean of 95 min (range 26–189), and mean circulatory arrest duration was 30.1 min (range 2–80).

Retrograde cerebral perfusion
RCP was used in 96 of 130 (73.8%) HCA cases for a mean duration of 24.4 min (range 8–53). The brain was perfused via the SVC cannula as previously described [10]. Flows were adjusted to achieve a maximum jugular bulb pressure of 20–25 mm Hg. In 70 of 96 RCP cases, the IVC cannula was left open to the pump reservoir to allow drainage during retrograde perfusion, and blood entering the operative field from the head vessels was returned to the reservoir using roller pump suction [11]. In 26 of 96 cases, the IVC cannula was clamped during the interval of RCP.

Operative technique
Operative techniques were as previously described [12]. The myocardium was protected using intermittent crystalloid cardioplegia and topical cooling. Homograft aortic root replacement supplemented by prosthetic aortic grafting was undertaken in 6 cases, and 13 patients underwent elephant trunk procedures. Eight cases involved reoperations, and 23 patients (17.7%) had concomitant myocardial revascularization procedures.

Data and statistical analysis
Patient records were retrospectively reviewed. Thirty risk factors thought to influence outcome were analyzed, and divided into premorbid, operative, technical, and postoperative factors. Preoperative factors such as age over 70 years, sex, emergent status, Marfan’s syndrome, COPD, diabetes mellitus, treated hypertension, stroke or myocardial infarction, presence of peripheral vascular disease, aortic dissection, and contained rupture were analyzed (Table 1). Technical factors included use of aprotinin, low-dose thiopentone, bypass duration over 3 h, myocardial ischemic time > 2 hours, and HCA duration exceeding 60 min. Use of RCP was analyzed as a risk factor in predicting outcome. Operative factors included use of a homograft root, previous thoracic procedures, elephant trunk, arch atherosclerosis, concomitant coronary artery surgery, and extent of aortic replacement, arbitrarily subdivided into proximal, arch, and more distal procedures. Perioperative mortality was defined as death within 30 days of operation. Patients who died intraoperatively, unable to be weaned from CPB, were classified as having succumbed to myocardial failure. Postoperative stroke was defined as the clinical finding of a new permanent neurological deficit and/or lesion on CT scans. Respiratory failure was defined as a ventilation requirement exceeding 3 days, development of adult respiratory distress syndrome, or need for tracheotomy. Renal failure was defined as a need for dialysis. Low cardiac output syndrome represented inability to wean from CPB, or need for an intra-aortic balloon pump or prolonged inotropic support (> 24 hours).

	Results

Top Abstract Introduction Patients and methods Results Discussion References

 
Hospital survival was 83.1%: 22 patients died in hospital for an overall mortality of 16.9%. The mortality for elective surgery was 9.5% (8/84). There was a high proportion of emergent cases, with a relative higher mortality of 30.4% (14/46, p = < 0.001, odds ratio [OR] = 4.2). Surgery for acute dissection carried a mortality of 16.7%; surgery for acute rupture of a degenerative aneurysm or dissection had a mortality of 37.5%.

The causes of death are detailed in Table 2. Five patients died intraoperatively when it was not possible to wean them from CPB. Stroke, renal, and respiratory failure were prominent causes of death, with a stroke-related mortality of 44.4%. There were no deaths due to excessive bleeding or gastrointestinal complications.

Multivariate analysis by forward step-wise logistic regression showed severe aortic atherosclerosis and RCP time (p = 0.038) as significant risks for mortality. Myocardial ischemic time (p = 0.012) and HCA duration were the only significant multivariate predictors for stroke (p = 0.05).

	Discussion

Top Abstract Introduction Patients and methods Results Discussion References

 
Although HCA periods < 40 minutes are regarded as clinically safe, a significant fraction of patients may still develop transient and permanent neurological deficits [4]. RCP can theoretically reduce ischemic and embolic injury by providing nutritive flow and by flushing gaseous and particulate emboli from the extracranial arterial tree. Although the use of RCP has been accepted as safe, it has not unequivocally been shown to improve outcome [11]. In this study, we were unable to demonstrate improved outcome associated with RCP, but it should be noted that patients with RCP had longer HCA times than those with HCA alone.

The high overall mortality rate in this series reflects the large proportion of emergency procedures: the elective mortality rate and overall incidence of stroke are comparable with other published series. In agreement with previous published series, we found that advanced age and emergency status predicts adverse outcome, and that perioperative stroke has a major impact on mortality. These findings are important since it is possible that emergency status could theoretically be modified by early referral of aortic aneurysms to specialized centers for appropriate follow-up and elective intervention when the risk of rupture exceeds operative risk.

Severe aortic atherosclerosis was a multivariate risk factor for mortality. While this may reflect a summation of comorbidities such as advanced age, coronary, and cerebrovascular disease, it may also indicate a specific increasing hazard related to aortic atherosclerosis. Embolization from aortic atheroma has been correlated with stroke in CABG [13], and stroke is a major predictor of mortality in HCA surgery.

Improving outcome in patients requiring aortic surgery utilizing HCA is largely dependent on reducing the risk of neurological deficit. Important factors that cannot be controlled, such as advanced age and emergency status, nevertheless are important in relation to preoperative counseling of patients and their relatives. Adjuncts to improve cerebral protection are urgently required, together with methods of real-time monitoring of their efficacy. At present, exact expeditious surgery to minimize the arrest period and meticulous attention to factors that may reduce atheroembolism remain the key determinants of a favorable outcome. Since these factors can be modified by surgical experience and technique, they support the argument for centralization of aortic surgical services.

This study has several limitations. We were not able reliably to report the incidence of transient neurological deficit, including delayed recovery of consciousness, and therefore have not presented any data regarding this aspect of neurological recovery. Furthermore, since this study was not randomized, the significant correlation of RCP duration with mortality may be explained—and a possible beneficial effect of RCP may have been obscured—by clinical decisions to utilize RCP in more complex cases with anticipated longer arrest periods. A prospective controlled study is needed. Incorporation of actual measures of cerebral perfusion and embolic load during RCP may increase the power of a future analysis to determine the role of RCP as factor predictive of outcome. In this study, RCP did not improve outcome.

	References

Top Abstract Introduction Patients and methods Results Discussion 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): Carl H. Wong Robert S. Bonser Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wong, C. H. Articles by Bonser, R. S. Search for Related Content PubMed PubMed Citation Articles by Wong, C. H. Articles by Bonser, R. S.