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Ann Thorac Surg 2002;74:474-480
© 2002 The Society of Thoracic Surgeons
a Bristol Heart Institute, Bristol Royal Infirmary, Bristol, United Kingdom
Accepted for publication April 25, 2002.
* Address reprint requests to Mr Angelini, Bristol Heart Institute, Bristol Royal Infirmary, Bristol BS2 8HW, United Kingdom
e-mail: gd.angelini{at}bristol.ac.uk
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Abstract |
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Methods. From April 1996 to March 2001, data from 4,077 patients undergoing CABG were prospectively entered into a database. The association of preoperative and perioperative factors with stroke was investigated by univariate analyses. Factors observed to be significantly associated with stroke in these analyses were further investigated using multiple logistic regression to estimate the strength of the associations with the occurrence of stroke, after taking account of the other factors.
Results. During the study period, 4,077 patients underwent CABG and of these 923 (22.6%) had off-pump surgery. Forty-five patients suffered a perioperative stroke (1.1%). Overall there were 46 in-hospital deaths (1.1%), of whom 6 also suffered a stroke. Brain imaging of the stroke patients showed embolic lesions in 58%, watershed in 28%, and mixed in 14%. Multivariate regression analysis identified several preoperative factors as independent predictors of stroke, ie, age, unstable angina, serum creatinine greater than 150 mcg/ml, previous cerebrovascular accident (CVA), peripheral vascular disease (PVD), and salvage operation. When operative risk factors were added to the adjusted model, off-pump surgery was associated with a substantial, but not significant, protective effect against stroke (odds ratio = 0.56, 95% confidence interval 0.20 to 1.55). Survival for stroke patients was 93% and 78% at 1 and 5 years, respectively.
Conclusions. Overall incidence of stroke is relatively low in our series. Age, unstable angina, previous CVA, PVD, serum creatinine greater than 150 mcg/ml, and salvage operation are independent predictors of stroke. These factors should be taken into account when informing each individual patient on the possible risk of stroke and in the decision-making process on the surgical strategy.
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Introduction |
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The objective of this study was to estimate the associations between patient’s preoperative characteristics, surgical factors, and postoperative management, and the occurrence of stroke in a representative population undergoing myocardial revascularization. Knowledge of important risk factors for stroke may be useful in order to optimize a patient’s preoperative physiological status, the surgical techniques used, and postoperative management.
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Material and methods |
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Cases were defined as patients who had suffered a stroke and controls were defined as all other patients in the cohort. The prevalence of preoperative characteristics, surgical factors, and aspects of postoperative management were compared between cases and controls. A detailed neurological examination was carried on the day before the surgery and patients more than 54 years old who had a cervical bruit, or who fulfilled one or more of the criteria suggested by Berens and colleagues [5] as significant predictors of carotid disease (female gender, evidence of peripheral vascular disease, smoking, and left main stem disease) were screened for underlying extracranial vascular pathology using an ATL MK 600 scanner (Advanced Techology Laboratories, Hertfordshire, UK) employing a 7 and 5 MHz mechanical sector transducer (UM9 HDI). All imaging studies (computed tomographic [CT] scan) were reported by radiologists, who were unware of the surgical technique used. Acute infarcts were classified radiographically as being embolic (large artery), watershed (border-zone), or lacunar (small vessel) in nature. Cerebral distribution was described according to vascular territory and the region of brain affected.
Assessment of long-term survival and neurological functional status for stroke patients was carried out by telephone interviews, and the Rankin Scale [6] was used to assess functional status. This method of score ranges from 0 to 6; a score of 0 indicates symptom-free status and a score of 6 indicates that the patients had died.
Operative technique and postoperative management
Anesthetic technique and heparin management were standardized and have previously been reported [7]. When on-pump surgery was carried out, cardiopulmonary bypass (CPB) was instituted using ascending aortic cannulation and two-stage venous cannulation of the right atrium. Myocardial protection was achieved with intermittent antegrade hyperkalemic warm blood cardioplegia [7]. When off-pump surgery was carried out, two methods of exposure and stabilization of the heart previously described were used [8].
Postoperative management was in accordance with unit protocol as previously reported [7].
Clinical data collection, monitoring, and definitions
Patients characteristics, intraoperative and postoperative data were entered prospectively into the PATS database. At our institution, patients with focal neurological deficits (motor weakness, dysphagia, aphasia, cognitive deficits, seizures, or coma) are evaluated by staff intensivists. The clinical diagnosis of stroke is made by the intensivist and confirmed by a neurologist on the basis of the clinical findings alone, independent of the brain imaging findings. A CT scan is routinely performed in these patients as soon as the clinical condition allows the patient to be moved.
Perioperative myocardial infarction, ST segment changes, pacing, arrhythmias, and inotropic requirement were recorded and defined as previously reported [7]. Low cardiac output was defined as requirement of either intraaortic balloon pump (IABP) or inotropic support (more than 5 µg/kg/min of dopamine) for greater than 30 minutes to maintain a systolic blood pressure greater than 90 mmHg and a cardiac index greater than 2.2 L/min/m2. Renal complication included acute renal failure (ARF) as defined by the requirement of hemodialysis. Pulmonary complication included chest infection, ventilation failure, reintubation, and tracheostomy. Postoperative blood loss was defined as total chest tube drainage. Finally, infective complication included septicemia and sternal and leg wound infection, as defined by positive culture and requiring antibiotic therapy.
Sample size
Even with over 4,000 patients (see Table 1),
the power of the analysis was limited because of the rarity of postoperative stroke (about 1%). The power of the analyses to detect clinically important associations depended on both the prevalence of the risk factor among controls and the magnitude of the risk conferred, as well as the incidence of stroke. The analyses had 80% power to detect an odds ratio of 3.0 for risk factors with a prevalence of 20% or greater at a 5% (two-tailed) significance level or an odds ratio of 2.5 for risk factors with a prevalence of 30% or greater. Risk factors with odds ratios of less than 2.5 were unlikely to be detected by the analyses.
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Data were complete for greater than 99% of cases for 29 of the 33 predictor variables (see Tables 1 and 2) considered in the analyses reported here. Exceptions were: body mass index (4,036/4,077; 99.0%), preoperative creatinine level greater than 150 µm/l (4,023/4,077; 98.7%) and preoperative arryhthmia (3,901/4,077; 95.7%). A wide range of variables was available in the PATS database than is described here. A decision about the key variables of interest to investigate was made before conducting any analyses, and all variables selected at the outset for investigation are listed in Table 1.
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Results |
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Predictors of stroke
Several preoperative factors were associated with a significant increase in the risk of stroke (odds ratios [ORs] ranging from 2.26 to 17.0; see Table 2) including: presence of unstable angina, hypertension, preoperative creatinine greater than 150 µm/l, previous cerebrovascular accident (CVA) or preoperative carotid bruit, peripheral vascular disease (PVD), preoperative use of IABP, increasing age, Canadian Cardiac Score (CCS), New York Heart Association (NYHA) classification score, Parsonnet score, decreasing preoperative ejection fraction, and salvage operation. In addition, several surgical and postoperative factors were also significantly associated with an increased risk of stroke, namely increasing number of grafts, transfusion of red blood cells, platelets, and fresh frozen plasma, de novo requirement for an IABP, and postoperative arrhythmia on the ward (ORs ranging from 2.96 to 8.54; see Table 2).
Multiple logistic regression modeling identified six preoperative factors that were independently associated with the risk of any stroke (see Table 2); age (OR = 1.06 per year, 95% confidence interval [CI] 1.02 to 1.09), preoperative unstable angina (OR = 2.69, 95% CI 1.49 to 4.86), preoperative creatinine greater than 150 µm/l (OR = 2.64, 95% CI 1.20 to 5.80), previous CVA (OR = 2.26, 95% CI 0.88 to 5.83), preexisting PVD (OR = 2.99, 95% CI 1.51 to 5.92), and salvage operation (OR = 14.6, 95% CI 1.83 to 116.7).
Operative risk factors (off-pump surgery and number of grafts) were added to the adjusted model containing preoperative predictors. Off-pump surgery was associated with a substantial, but nonsignificant, protective effect against stroke (OR = 0.56, 95% CI 0.20 to 1.55). The number of grafts carried out did not appear to be an important risk factor for stroke. The ORs for all preoperative variables were essentially unchanged.
Late clinical outcome in stroke patients
Assessment of long-term outcome was achieved for all 39 stroke patients who survived to discharge from hospital. The mean duration of follow-up was 45 (standard deviation 19) months. There were eight late deaths within this group. Cause of late deaths included two further stroke, five cardiac-related, and one cancer. Overall survival was 93% and 78% at 1 and 5 years, respectively (see Fig 1).
Late neurological functional status as assessed by Rankin score was 2.1 ± 0.4 indicating an overall status of slight disability but independent. Overall late CCS was 0.5 ± 0.9, whereas NYHA class was 1.3 ± 1.0.
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Comment |
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TopAbstractIntroductionMaterial and methodsResultsCommentReferences |
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The primary objective of the present study was to identify independent predictors of perioperative stroke in a cohort of consecutive patients undergoing CABG using modern techniques. Despite the large size of the cohort, the study could only identify factors that conferred a substantial increase in risk because of the rarity of stroke. Other factors that were not found to be significantly associated with stroke from a statistical perspective may nevertheless confer a clinically important increase in risk, eg, congestive cardiac failure, previous myocardial infarction (MI), or diabetes. These potential predictors of stroke need to be investigated further in larger cohorts.
In accordance with other reports, age was identified as an independent predictor of stroke [16–17]. The increasing risk with older age has been related to the higher prevalence of diseased aorta which may lead to perioperative atheroembolism from aortic arch plaque [4]. Indeed, the identification of an atherosclerotic ascending aorta has been reported as the single, most significant marker for an adverse cerebral outcome after CABG [4], reflecting the role of aortic atheroembolism as the main cause of ischemic stroke [18].
Previous CVA or presence of carotid bruit was another independent predictor of stroke. Carotid disease has been associated with major neurological events following CABG [4]. Strokes caused by carotid disease are particularly devastating, since they often occur on the 2nd to 9th postoperative day in the midst of an apparently smooth recovery [19]. The prevalence of significant carotid disease in the current cardiac surgical population reflects the diffuse nature of the atherosclerotic process: 17% to 22% of patients have greater than or equal to 50% carotid stenosis, and 6% to 12% have 
80% carotid stenosis [4]. This highlights the importance of preoperative assessment of patients with previous history of CVA or carotid bruit. Patients turning out to have significant carotid disease might undergo preliminary elective carotid artery stenting which has been demonstrated to be safe with a very high procedural success rate [12].
Other independent predictors of stroke included unstable angina and salvage operation. It has been shown that the patient with a recent, anterior MI and residual wall-motion abnormality is at increased risk for development of a left ventricular (LV) mural thrombus and for embolization. Keren and associates [20] identified LV thrombus in 38 of 124 anterior-infarct patients (31%) and in none of 74 patients with inferior infarcts. Early thrombolytic therapy was not uniformly protective against LV thrombus, and 30% occurred after discharge. Such patients are at risk for perioperative mechanical dislodgement and systemic embolization of the LV clot.
Univariate analysis also identified association between postoperative arrhythmias and stroke. Chronic atrial fibrillation is, indeed, a hazard for thromboembolic perioperative stroke. New-onset postoperative atrial fibrillation occurs in 30% of patients undergoing CABG, with the peak incidence on the 2nd to 3rd postoperative day [21,22]. It is associated with a two-fold to threefold increase in postoperative risk for stroke [4]. A number of studies indicate that elevated serum creatinine may be an independent predictor of all-cause of cardiovascular disease mortality [22–23]. In the present study, preoperative serum creatinine greater than 150 mmol/l was independently associated with the occurrence of any stroke.
One of the findings of our study was the protective effect against stroke achieved performing surgery on the beating heart and without CPB. This is in accordance with a recent report from Cleveland and colleagues [24] who, in a review of the STS National Adult Cardiac Surgery Database including 118,140 patients (11,717 [9.9%] off-pump coronary artery bypass procedures) demonstrated a significant reduction of neurological events when surgery was performed off-pump rather than with CPB and cardioplegic arrest.
It is important to emphasize that the associations observed between predictor variables and stroke are not necessarily causal, and that significant predictors may simply be acting as proxy markers for other factors that were not documented in the database.
In conclusion, this study shows relatively low incidence of perioperative stroke. It also highlights that in the modern era of coronary surgery there are several factors that might have an independent role in determining stroke. These factors should be taken into consideration when informing each patient on the possible risk of stroke, and in the decision-making process on the surgical strategy and postoperative management.
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