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Ann Thorac Surg 1996;61:42-47
© 1996 The Society of Thoracic Surgeons
Division of Cardiac Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland
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Abstract |
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 TopFootnotes Abstract IntroductionPatients and MethodsResultsCommentAcknowledgmentsReferences |
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Methods. We performed a prospective analysis of 1,000 consecutive patients undergoing cardiac operations requiring cardiopulmonary bypass, without hypothermic circulatory arrest. Of the 1,000 patients, 71 had previously documented stroke (study group); 2 control patients with no history of stroke were selected for each of these patients (control group, n = 142). There were no significant differences between the study and control patients with respect to established risk factors for neurologic complications.
Results. Compared with controls, study patients took longer to awaken (12.6 ± 10.9 versus 3.5 ± 2.1 hours; p < 0.001) and longer to extubate (29.5 ± 29.3 versus 9.1 ± 5.2 hours; p < 0.001), and had a greater incidence of reintubation (7 of 71, 9.9% versus 2 of 142, 1.4%; p < 0.01) and postoperative confusion (26 of 71, 36.6% versus 7 of 142, 4.9%; p < 0.001). There was a higher incidence of focal neurologic deficit among study patients (31 of 71, 43.7% versus 2 of 142, 1.4%; p < 0.001). These deficits included new stroke (6 of 71, 8.5%) as well as the reappearance of previous deficits (19 of 71, 26.8%) or worsening of previous deficits (6 of 71, 8.5%), without new abnormalities on head computed tomography or magnetic resonance imaging. Study patients with neurologic deficit had longer cardiopulmonary bypass times than did study patients without deficit (146 ± 48.5 versus 110 ± 43.3 minutes; p < 0.001). The 30-day mortality rate was greater in study patients than in controls (5 of 71, 7% versus 1 of 142, 0.7%; p < 0.02), with four deaths among the 6 study patients with a new stroke (66.7%).
Conclusion. This analysis identifies a group of patients at high risk for neurologic sequelae and confirms the vulnerability of the previously injured brain to cardiopulmonary bypass, as evidenced by reappearance or exacerbation of focal deficits in such patients.
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Introduction |
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TopFootnotesAbstractIntroductionPatients and MethodsResultsCommentAcknowledgmentsReferences |
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Two percent to 6% of adult patients undergoing cardiac operations sustain neurologic injury in the perioperative period [1–4]. Although the majority of patients with focal deficits make a good functional recovery within 6 to 12 months [3, 4], 1% to 3% of patients overall suffer permanent neurologic disability [4]. In addition, in 30% to 60% of adult cardiac patients, more subtle neuropsychologic changes develop [5, 6], the long-term significance of which remains to be fully defined.
Risk factors for stroke include age, ascending aortic atherosclerosis, carotid artery disease, diabetes, hypertension, time on cardiopulmonary bypass (CPB), and perioperative hypotension [1, 2]. Previous neurologic deficit as a risk factor, however, remains controversial. Although several authors have demonstrated an increased incidence of cerebrovascular accident in cardiac patients with a history of stroke [7–9], others have found no additional risk [10]. In a retrospective study, Beall and associates [11] addressed this question specifically and found no difference in the neurologic outcome in these patients. To resolve this issue and to delineate the postoperative course and outcome of this group of patients, we prospectively analyzed patients with a history of a completed stroke who were undergoing heart operations at our institution over a 9-month period.
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Patients and Methods |
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TopFootnotesAbstractIntroductionPatients and MethodsResultsCommentAcknowledgmentsReferences |
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The 71 study and 142 control patients underwent a standard neurologic evaluation preoperatively. This examination included evaluation of cranial nerves, the central and peripheral nervous systems, and higher mental functions. Details regarding established preoperative risk factors for stroke were recorded. A standard approach to treatment of carotid artery disease was adopted for all patients. Those with asymptomatic carotid bruits and those with known disease or a history suggestive of carotid artery disease underwent Doppler echocardiography studies and oculoplethysmography, and, if indicated, carotid angiography. Patients with standard indications for surgical intervention underwent carotid endarterectomy first, if their cardiac condition permitted. Unstable patients with severe carotid disease underwent a combined endarterectomy and cardiac procedure. The latter group of patients were excluded from the study; there were 3 patients with previous stroke who were excluded on this basis.
All operations were performed at moderate hypothermia (26° to 30°C) with hypothermic crystalloid or blood cardioplegia. During CPB, mean systemic blood pressures were maintained between 50 and 70 mm Hg, and flows on CPB were maintained at 40 to 60 mL•kg-1• min-1. A standardized anesthetic protocol was employed using high-dose narcotics (fentanyl 50 to 80 µg/kg at induction), benzodiazepines (valium 20 to 30 mg/kg at induction), and muscle relaxants (pancuronium 0.1 mg/kg). Ascending aortic atherosclerotic disease was assessed by palpation in the operating room. The condition of the aorta was described as either normal; moderately diseased, if the sites of aortic cannulation, cross-clamp, and proximal anastomoses were altered from standard locations in the presence of palpable plaque; or severely diseased, when palpable plaque was extensive and the proximal anastomoses were performed with the cross-clamp on.
We recorded the time to awaken, time to extubate, incidence of depressed level of consciousness, aspiration and reintubation, perioperative hypotension, arrhythmia, and length of stay in the intensive care unit (ICU). Time to awaken was defined as the number of hours from arrival in the ICU to the point at which the patient opened his or her eyes and obeyed commands. Extubation criteria included a state of alertness, a demonstrable cough and gag reflex, satisfactory arterial blood gas and minute ventilation on minimal ventilatory support, a negative inspiratory force of -20 cm H2O, and a spontaneous vital volume of greater than 10 mL/kg. Level of consciousness was described as depressed when a patient was noted to have a reduced response to auditory and tactile stimuli. Aspiration was diagnosed when a patient developed respiratory distress or failure in association with endotracheal or nasotracheal suctioning of inhaled stomach contents, with supportive radiologic evidence. Reintubation was done for patients in whom severe hypoxemia or hypercapnea developed because of aspiration or respiratory muscle failure. Perioperative hypotension was defined as a sustained mean blood pressure of less than 40 mm Hg. Intraaortic balloon pumps were placed in patients who failed to wean from CPB because of left ventricular dysfunction or in those who demonstrated low output syndrome postoperatively. Patients were transferred from the ICU after they were extubated and were breathing comfortably, were hemodynamically stable without inotropic agents, and demonstrated satisfactory diuresis.
Postoperatively, all patients were assessed daily for evidence of confusion or focal neurologic deficit. Confusion was defined as disturbed orientation to person, time, or place for more than 24 hours that was not attributable to sedatives or other drugs. The daily examination was performed by a senior cardiac surgical resident. Any patient showing evidence of neurologic deficit was seen by a neurologist and underwent detailed evaluation, including CT or MRI examination, or both. Old CT and MRI films and reports were used for comparison when available; patients were then judged to have a new stroke or reappearance or worsening of a previous neurologic deficit. The postoperative course and rehabilitation of all patients were documented.
Values are expressed as mean ± standard deviation. Data between groups were compared using 
2 analysis or Student's t test of significance where appropriate. For data that were not normally distributed, the nonparametric Mann-Whitney rank sum test was used. A p value less than 0.05 was considered significant.
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Results |
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TopFootnotesAbstractIntroductionPatients and MethodsResultsCommentAcknowledgmentsReferences |
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). The proportions of coronary artery bypass grafting, valve operations, combined procedures, and reoperations were similar. Both groups received similar quantities of fentanyl (5305 ± 850 µg/patient in the study group versus 4908 ± 692 µg/patient in the control group; p = not significant) and diazepam (20 ± 8 versus 22 ± 12 g/patient, p = not significant). The frequencies of established risk factors for neurologic injury were similar in both groups (Table 2). The incidences of hypertension and diabetes mellitus did not differ significantly. In the entire patient population, the incidence of carotid artery disease was 23%. Asymptomatic noncritical carotid artery disease (internal carotid artery stenosis of 70% or less by preoperative Doppler echocardiographic studies) occurred with similar frequency in each group. The proportions of patients who had symptomatic disease or asymptomatic critical disease (bilateral internal carotid artery disease of 70% or greater) and who had undergone carotid endarterectomy preoperatively were similar in each group (8 of 71, 11.3% in the study group versus 13 of 142, 9.2% in the control group; p = not significant). The incidences of moderate and severe ascending aortic atherosclerotic disease did not differ significantly between the groups. Overall, 29.6% of study patients and 27.5% of controls had moderate aortic disease, requiring alteration of cannulation, cross-clamp, or proximal vein graft anastomotic sites; a similar fraction of study and control patients had severe disease, requiring alteration of the above sites and performance of the proximal anastomoses with the cross-clamp on (see Table 2). Durations of CPB were similar, as were the incidence of perioperative hypotension, the requirement for perioperative intraaortic balloon counterpulsation, and the incidence of postoperative atrial arrhythmia. No patient in either group had mural thrombus based on echocardiographic results.
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). They took longer to wean from mechanical ventilation and to extubate. Depressed level of consciousness occurred more frequently among the study patients (19 of 71, 26.8% versus 10 of 142, 7%; p < 0.01) than in controls, and there was a higher incidence of aspiration (4 of 71, 7.0% versus 1 of 142, 0.7%; p < 0.01) and reintubation among the study patients. Study patients stayed in the ICU significantly longer than controls (see Table 3).
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). This persisted for a mean of 2.5 ± 1.9 days and had resolved in 25 of 26 patients (96.2%) before discharge.
Focal neurologic deficit was found in 31 of the 71 study patients (43.7%) and included reappearance of old stroke in 19 (26.8%), worsening of old stroke in 6 (8.5%), and new stroke in 6 (8.5%). This rate was significantly higher than that in controls (see Table 3). The deficits were noted soon after extubation in 22 of the 31 patients (70.9%). In the remaining 9 patients (29.1%), the deficit became clinically apparent between 24 and 48 hours after surgery.
In 19 patients who had completely recovered from their original stroke, the postoperative deficit closely resembled their previous stroke. The clinical distribution was similar in all these patients, and the severity and degree of disability were reported to be the same (10 of 19, 52.6%) or less (9 of 19, 47.4%) by patients and their families. Computed tomography scanning in these patients demonstrated no new lesion; the previous stroke was identified in 16 of 19 patients (84.2%). No abnormality, new or old, was found in the remaining 3 patients, even using MRI. Old CT and MRI films or reports were available for comparison in 15 of these patients (78.9%).
In 6 patients, 3 of whom had residual deficit preoperatively, a postoperative deficit developed that was clinically worse than the previous stroke; the distribution was similar, but the deficit was more severe. Neither CT scan nor MRI demonstrated new lesions; 1 patient showed no radiologic change in the old lesion, whereas the remainder demonstrated an increase in size. Previous films or reports were available in all 6 patients.
Six patients had clinical and radiologic evidence of a new stroke postoperatively. In 2 patients, the new deficit was ipsilateral to the old stroke in the site of the anterior circulation and was of the large-vessel type. Three patients had deficits contralateral to the previous stroke: Two were in the site of the anterior circulation, one lacunar and one large-vessel type; the other was a large-vessel infarct involving the posterior circulation. The remaining patient had profound deficits postoperatively, with multiple bihemispheric infarcts. This was the only study patient with severe ascending aortic atherosclerosis who had a focal deficit postoperatively. Previous films or reports were available in all 6 patients. The incidence of new stroke was significantly greater in the study group than in control patients (6 of 71, 8.5% versus 2 of 142, 1.4%; p < 0.05).
The mortality rate in the study group was 7% (5 of 71), which was significantly higher than that for the control group (Tables 3 and 4). Four of the patients in the study group who died had new postoperative infarcts. The patient with multiple bilateral new strokes died of multiple-system organ failure. In the 3 other patients with new strokes and 1 patient with worsening of a previous infarct who died, the postoperative neurologic deficit contributed substantially to the patients' deaths.
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). Three of the patients with worsening of the previous deficit had recovered by the time of discharge, and 4 of the 6 patients (66.7%) were at preoperative baseline by 6 months. Both of the surviving patients with new strokes had made a partial recovery at the time of discharge to a rehabilitation facility. The hospital stay of the study patients overall was significantly longer than that of controls (see Table 3). Two patients in the control group (1.4%) had neurologic deficits postoperatively. One patient had multiple bihemispheric infarcts; this patient died of multiple-system organ failure. This was the only control patient with severe aortic atherosclerosis who had a stroke postoperatively. In the other patient, a visual field defect developed without a clearly defined lesion on CT scan, the cause of which was likely posterior cortical ischemia or a retinal infarct.
Study patients with and without postoperative neurologic deficit were compared (Table 5). Those with deficit were significantly older and had longer CPB times. Reasons for the longer CPB times were that a larger number of patients required valve and coronary procedures, and the mean number of bypass grafts was greater by 1.5. All other perioperative risk factors for stroke were similar. The time that elapsed between the original stroke and the operation was calculated for each patient; an interval of less than 1 year was considered recent, greater than 1 year and less than 5 years was considered intermediate, and greater than 5 years was designated remote. The interval was not related to the occurrence of postoperative focal deficit (see Table 5). However, study patients without deficit were significantly younger at the time of their original stroke. In fact, 5 study patients with a mean age of 47.6 years (range, 28 to 55 years) who underwent a surgical procedure within 2 months of their stroke had no postoperative neurologic sequelae.
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Comment |
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TopFootnotesAbstractIntroductionPatients and MethodsResultsCommentAcknowledgmentsReferences |
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These findings suggest that the previously injured brain is more susceptible to the adverse effects of CPB. Certainly, brain tissue surrounding an infarct in the so-called ischemic penumbra may be more vulnerable to ischemia and hypoxia [14], which could explain at least in part the reappearance or worsening of prior deficits noted in this study after cardiac procedures. Furthermore, recent evidence suggests that the recovery process after focal injury in the brain may involve reorganization of the cortical somatosensory map by the unmasking of latent intracortical connections [13, 14]. Such compensatory neuronal circuitry may be inherently more vulnerable to injury during conditions of metabolic stress.
Recovery from brain injury involves a variety of neuronal rearrangements, including regeneration, pruning, and sprouting [15]. This, in addition to the finding that advanced age is associated with a reduction in gray matter blood flow [16], may explain why younger patients recover better from cerebral injury than do older patients. Thus, it is not surprising that patient age at the time of the original neurologic deficit, rather than the interval between stroke and surgery, is associated with the occurrence of postoperative focal deficit. The interval between stroke and surgery, however, appears to be related to the type of postoperative neurologic deficit: A recent stroke is associated with reappearance or worsening of a previous deficit, whereas a remote stroke is associated with a new postoperative focal deficit.
The finding that patients with previous stroke are at increased risk of a new postoperative focal deficit is at variance with the analysis of Beall and associates [11]. They found that a new postoperative focal deficit developed in only 1 of 43 patients with a stroke history (2.3%); the stroke rate for 1,120 patients without a previous stroke was 1.5%. However, in a retrospective chart review, Rorick and Furlan [7] demonstrated a new stroke rate of 13.4% among 127 patients with a stroke history undergoing cardiac operations at the Cleveland Clinic; their predicted stroke rate was 5.2%. Tuman and associates [3] and Gardner and colleagues [1] also demonstrated an increased risk of postoperative stroke in patients with previous neurologic abnormality. The higher rate of postoperative focal deficit for patients with prior stroke in this analysis (43.7%) may reflect the prospective nature of the study.
There were no significant differences in the preoperative risk factors for stroke between patients in the study and the control groups. In particular, the extent of carotid artery and ascending aortic disease was similar. Thus, it is not clear from this analysis why the study patients had had previous strokes and the control group had not. It is possible that had all patients in the study undergone extensive preoperative evaluation, including Holter monitoring, carotid angiography, and, in particular, intraoperative epiaortic ultrasonic examination of the ascending aorta, differences between groups may have emerged to explain the presence or absence of a previous stroke. Furthermore, the difference in the incidence of severe ascending aortic atherosclerosis (5.6% in study patients versus 2.1% in controls) may have achieved statistical significance had the patient population in the study been larger.
Recently, neuropsychologic testing has demonstrated that more than 50% of patients undergoing cardiac surgical procedures are affected by subtle brain injury [5, 6]. This may result in impairment of concentration, memory, and other higher mental functions. A battery of such tests is currently under evaluation at our institution and was not specifically performed on patients in this study.
Although this analysis relied extensively on head CT scan and MRI findings, preoperative and postoperative brain imaging was not performed on all study and control patients. Other reports in which patients have undergone CT scanning before and after operations have demonstrated an appreciable incidence of new postoperative CT or MRI lesions, but no corresponding clinical neurologic deficits [17]. Therefore, brain imaging was performed in this study only when clinically indicated.
The findings in this study have several implications for the clinical setting. They permit more accurate prediction of postoperative recovery for this group of patients and may contribute substantially to the determination of operability, particularly in elderly patients who sustained their stroke at an older age and may require prolonged CPB. This study confirms the safety of operating on younger patients who have had recent strokes and suggests that a fresh infarct need not be a contraindication to operation in the younger patient. In contrast, a stroke, no matter how remote, is not inconsequential if it occurred at an older age. The increased morbidity with its attendant prolonged ICU and hospital stays in this group of patients may have considerable financial consequences. Finally, as new pharmacologic and other neuroprotective strategies are introduced into clinical practice, it would seem appropriate to direct these toward this group of high-risk patients.
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Acknowledgments |
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TopFootnotesAbstractIntroductionPatients and MethodsResultsCommentAcknowledgmentsReferences |
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Footnotes |
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TopFootnotesAbstractIntroductionPatients and MethodsResultsCommentAcknowledgmentsReferences |
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Address reprint requests to Dr Baumgartner, Division of Cardiac Surgery, Johns Hopkins Hospital, Blalock 618, 600 N Wolfe St, Baltimore, MD 21287.
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TopFootnotesAbstractIntroductionPatients and MethodsResultsCommentAcknowledgmentsReferences |
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