Outcome after carotid endarterectomy for asymptomatic carotid stenosis.

OBJECTIVE: To compare the long-term outcome in patients with asymptomatic carotid stenosis (ACS) among those treated with carotid endarterectomy (CE) or medical therapy. BACKGROUND: Until randomized trials are completed, treatment of ACS will depend on identification of subgroups likely to benefit from CE. METHODS: A retrospective cohort study was done on 215 patients with ACS: 107 underwent CE, and 108 were treated medically (MED). A neurologist reviewed medical records and performed a telephone interview to detect outcome (stroke and death). Mean follow-up was 3.8 years; only 4% were lost to follow-up. RESULTS: Among CE patients, there was a 4.7% risk of postoperative ipsilateral stroke within 30 days. Four of five postoperative strokes occurred among patients with prior contralateral symptoms. There was no significant difference between CE and MED in the cumulative life-table 5-year risk of ipsilateral stroke, any stroke, or survival free of any stroke. Among diabetics, however, there were no ipsilateral strokes at 5 years after CE compared to 20% in MED (p = 0.03). Excluding postoperative complications, the 5-year risk of ipsilateral stroke was reduced among CE patients who "ever smoked" (CE 1%, MED 8%, p = 0.03) and the 5-year risk of any stroke was reduced among CE patients who had no prior myocardial infarction (CE 6%, MED 16%, p = 0.02). Among those with prior contralateral carotid territory symptoms, the 5-year risk of any stroke was worse in the MED patients (CE 5% MED 32%, p = 0.004). Among CE patients, a Cox proportional hazards model determined that the independent predictors of worse long-term outcome were: a history of myocardial infarction; admission systolic blood pressure greater than 160 mm Hg; and age greater than 65. CONCLUSION: The approach to patients with ACS will await completion of large, randomized clinical trials, now in progress. Even if these studies are negative, there may remain specific subgroups of patients who show clear benefit from carotid endarterectomy.

Thiopental effect on cerebral blood flow during carotid endarterectomy.

To investigate the effect of thiopental on cerebral blood flow (CBF) during carotid endarterectomy, five patients receiving isoflurane-N2O anesthesia were studied. During the period of temporary bypass shunting, a baseline CBF was measured using i.v. Xe washout, and global CBF was calculated from the mean of 10 detectors. Thiopental was given in a dose sufficient (mean 4.5, range 2.6-5.8 mg/kg) to result in burst-suppression on the electroencephalogram (EEG) of approximately 1:1 duration and CBF was measured again. Data were compared using repeated measures analysis of variance. Thiopental significantly reduced mean (+/-SE) CBF (ml/100 g/min) from 37 +/- 6 to 18 +/- 2 (p <0.02). Corresponding PaCO2 (mm Hg) values were 42.8 +/- 1.2 and 41.2 +/- 1.6 and mean systemic blood pressure (mm Hg) was 101 +/- 3 and 100 +/- 6, respectively (NS). Mean % change in CBF was 48 +/- 5 (range 32-62%). There was no relationship between the dose administered and the change in CBF. During steady-state anesthesia, a small dose of thiopental capable of suppressing EEG resulted in a profound reduction in CBF.

A comparison of cerebral blood flow reactivity to CO2 during halothane versus isoflurane anesthesia for carotid endarterectomy.

The effects of isoflurane or halothane on cerebral blood flow (CBF) reactivity to changes in arterial carbon dioxide tension (PaCO2) during carotid endarterectomy were compared using the intravenous method of 133Xe-CBF determination. Patients, aged 65 +/- 3 yr (mean +/- SE), received O2 and N2O (1:1) and either 0.75% isoflurane (n = 7) or 0.5% halothane (n = 7). Patient demographic and clinical data were similar for both groups and followed the expected strata of patients with ischemic cerebrovascular disease. Measurements were made during the period of temporary bypass shunting. In the isoflurane group, increasing PaCO2 from 33.3 +/- 1.4 to 43.4 +/- 1.3 mm Hg resulted in a significant (P less than 0.05) increase in CBF from 21 +/- 1 to 35 +/- 4 mL.100 g-1.min-1. In the halothane group, increasing PaCO2 from 31.1 +/- 1 to 39.4 +/- 1.6 mm Hg resulted in a significant increase in CBF from 26 +/- 3 to 37 +/- 3 mL.100 g-1.min-1. Mean CBF reactivity to changes in PaCO2 (mL.100 g-1.min-1.mm Hg-1) was 1.74 +/- 0.39 for isoflurane and 1.78 +/- 0.4 for halothane (not significant), corresponding to a relative change of 4.8% +/- 0.8% and 5.2% +/- 1.3% per mm Hg, respectively. There is no significant difference between halothane and isoflurane in their effects on CO2 reactivity in the mildly hypocapnic to normocapnic range.

Intraoperative 133Xe cerebral blood flow measurements by intravenous versus intracarotid methods.

To document the comparability of cerebral blood flow (CBF) values determined by quantification of 133Xe washout after either intravenous or intracarotid administration, 12 patients undergoing elective carotid endarterectomy anesthetized with N2O/O2 and either isoflurane or halothane were studied. Scintillation counters were placed over the middle cerebral artery territory ipsilateral to the operated carotid artery. CBF was measured by the intravenous method during dissection of the carotid sheath and was calculated as the initial slope index from head washout curves collected for 11 min after injection of 10-20 mCi 133Xe in saline into a large vein. Immediately prior to carotid occlusion, CBF was determined by direct injection of 1 mCi 133Xe in saline into either the internal carotid artery or the common carotid artery with the external carotid artery occluded. For the intracarotid injections, the initial slope was calculated from the 1st min of washout. Data were analyzed by linear regression and analysis of variance. Values are expressed as mean +/- SD. The mean CBF for intravenous and intracarotid methods were both 29 +/- 10 ml.100 g-1.min-1. The correlation between CBF measured by intravenous and intracarotid methods was excellent and was described by the line y = x + 0.6, r = 0.92. We conclude that in the flow range studied, the intravenous technique may be applied to measure CBF in physiologically stable situations in which direct intracarotid injection is not feasible.

Three-minute blood flow index for assessment of cerebrovascular reserve.

Regional cerebral blood flow studies with xenon-133 are useful in the functional assessment of cerebrovascular diseases. Conventional models for cerebral blood flow calculation employ 11 minutes of data collection. However, in many circumstances it is not possible to maintain steady-state physiologic conditions for 11 minutes. We compared a monocompartmental model that requires only 3 minutes of data collection with the bicompartmental model that requires 11 minutes of data collection. The correlation between the absolute values for global cerebral blood flow (initial slope index, intravenous method) in 72 anesthetized patients was r = 0.88; for 54 awake patients inhaling xenon-133, the correlation was r = 0.77. Cerebral blood flow was determined with intravenous xenon-133 at baseline and during a CO2 challenge in 50 patients during cerebrovascular surgery under general anesthesia. Reactivity to a 10-mm Hg rise in PaCO2 was calculated in absolute terms and as a percentage change from baseline using both the 3-minute and the 11-minute models. The correlation of CO2 reactivity calculated with the two models was r = 0.9 for the absolute values and r = 0.8 for the relative change. Cerebral blood flow calculated with the two models correlated well in both awake and anesthetized patients. In addition, there was a good correlation between CO2 reactivity calculated with the two models. In situations in which physiologic conditions cannot be held stable for 11 minutes, the 3-minute initial slope index may be used to quantitatively assess cerebrovascular reserve with a CO2 challenge.

Perfusion insufficiency in limb-shaking transient ischemic attacks.

We describe a 63-year-old man with severe bilateral internal carotid artery disease who presented with repeated, brief attacks of left limb shaking precipitated by his standing up. Cerebral blood flow measured by xenon-133 inhalation showed reduced resting flows and a focal perfusion deficit in the right dorsofrontal and upper rolandic regions. Blood flow velocity and pulsatility index of the right middle cerebral artery measured by transcranial Doppler ultrasonography were also reduced. With hypercapnic challenge, both hemispheric tissue perfusion and blood flow velocity showed impaired reactivity. With induced hypotension, the focal perfusion deficit in the right dorsofrontal region was accentuated. Following right internal carotid endartectomy, resting cerebral blood flow and blood flow velocity improved, as did hypercapnic vasoreactivity. These reversible deficits in cerebral blood flow and vasoregulation, which were maximal in the dorsofrontal region, are consistent with low perfusion in the border zone territory or the distal fields and demonstrate that hemodynamic failure is the likely mechanism for limb-shaking transient ischemic attacks from severe carotid artery disease.

A comparison of the cerebral hemodynamic effects of sufentanil and isoflurane in humans undergoing carotid endarterectomy.

Prompted by reports of potentially deleterious cerebral vasodilation by the synthetic opioid sufentanil, the authors compared the effects of either isoflurane/N2O and sufentanil/N2O on cerebral blood flow (CBF), arteriovenous difference in oxygen content (AVDO2), and CBF reactivity to changes in PaCO2 during carotid endarterectomy. Cerebral blood flow was measured using the iv method of 133-Xe CBF determination and AVDO2 was measured using systemic arterial-jugular venous oxygen content differences. Patients, age 68 +/- 1 yr (mean +/- SE), received either isoflurane (n = 10), 0.75% in O2 and N2O, 1:1; or sufentanil (n = 10), 1.5-2 micrograms/kg bolus and then 0.2-0.3 micrograms.kg-1.h-1 infusion in addition to O2 and N2O, 2:3. Measurements were made immediately before carotid occlusion, and then at two levels of PaCO2 (approximately 32 and 42 mmHg) after insertion of a temporary in-dwelling bypass shunt. Prior to carotid occlusion, there was no significant difference in CBF (ml.100 g-1.min-1) between patients receiving isoflurane (22 +/- 3) or sufentanil (20 +/- 2). Similarly, there was no difference in AVDO2 (vol-%) between isoflurane (4.5 +/- 0.7) and sufentanil (5.4 +/- 0.8) groups. Using a two-way ANOVA design with anesthetic as the between-group factor and elevation of PaCO2 as the within-group repeated measure, there was a significant effect of hypercarbia to increase CBF (P less than 0.0001) and decrease AVDO2 (P less than 0.001). The product of AVDO2 and CBF, which reflects cerebral metabolic oxygen consumption, remained constant (P = 0.364).(ABSTRACT TRUNCATED AT 250 WORDS)

Cerebral blood flow and metabolism in patients undergoing anesthesia for carotid endarterectomy. A comparison of isoflurane, halothane, and fentanyl.

The effects of isoflurane, halothane, and fentanyl on cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRO2) during anesthesia prior to carotid endarterectomy were compared using the intravenous method of 133-Xenon CBF determination. Patients, mean (+/- SE) age 68 +/- 2, received either isoflurane (N = 16), 0.75% in O2 and N2O, 50:50; halothane (N = 11), 0.5% in O2 and N2O, 50:50; or fentanyl (N = 10), 5-6 micrograms/kg bolus and then 1-2 micrograms.kg-1.h-1 infusion in addition to O2 and N2O, 40:60. Measurements were made immediately before carotid occlusion. Mean (+/- SE) CBF (ml.100 g-1.min-1) was 23.9 +/- 2.1 for isoflurane, 33.8 +/- 4.8 for halothane, and 19.3 +/- 2.4 for fentanyl. CMRO2 (ml.100 g-1.min-1) was available from 22 patients and was 1.51 +/- 0.28 for isoflurane (N = 7), 1.45 +/- 0.24 for halothane (N = 6), and 1.49 +/- 0.21 for fentanyl (N = 9). Although CBF was greater during halothane than during isoflurane or fentanyl anesthesia (p less than 0.05), there were no demonstrable differences in CMRO2 among the 3 agents. We conclude that choice of anesthetic agent for cerebrovascular surgery with comparable anesthetic regimens should not be made on the basis of "metabolic suppression." During relatively light levels of anesthesia, vasoactive properties of anesthetics are more important than cerebral metabolic depression with respect to effects on the cerebral circulation.

Carotid endarterectomy: what is its current status?

The plethora of recent articles regarding carotid endarterectomy has tended to confuse rather than clarify its indications, efficacy, and acceptability. The National Institutes of Health has recently funded two large multicenter controlled clinical trials, one including asymptomatic persons with carotid stenoses, and the other, patients having transient ischemic episodes or minor strokes. Eight academic professors of neurology (four), neurosurgery (two), and vascular surgery (two) with a long and abiding interest in cerebrovascular disease prepared a statement delineating acceptable levels of mortality and morbidity from this procedure. These might serve as guidelines until the large trials have been completed.

Rapid monitoring of intraoperative cerebral blood flow using 133Xe.

This study examined the feasibility of rapid rCBF monitoring using 133Xe as a tracer during operative procedures. We compared the initial slope index derived from two bicompartmental and one monocompartmental physiological models. The single-compartment model requires only 3 min of monitoring, whereas the bicompartmental models, thought to be more reliable, require 11 min of clearance. Data were collected from 26 patients undergoing carotid endarterectomy. Approximately 20 mCi of 133Xe in saline was injected i.v. for up to five measurements per patient, for a total of 117 measurements. The robustness of the regression for the three parameters (r = 0.781-0.99, p less than 0.0001) suggests that the three parameters are closely related. This is supported by similarity of the slopes of the regression lines (between 0.944 and 1.25) and the mean +/- SD of the three rCBF models (24.9-27.5 +/- 12.0-14.3 ml 100 g-1 min-1). Similar results were obtained for individual detectors, despite the expected higher variability. For intraoperative use in surgical procedures in which physiological conditions may change rapidly and i.v. injections of tracer must be used, a rCBF index that quickly and accurately reflects flow conditions is useful. Our data suggest that the single-compartmental Wyper index may be used to provide information about cerebral perfusion that is as accurate and robust as bicompartmental models, but requires only one-quarter of the data collection time.

Reduced hypercapnic vasoreactivity in moyamoya disease.

We measured cerebral perfusion at rest and in response to CO2 in eight patients with moyamoya disease (MMD), using the 133xenon inhalation method to determine the effect of large-vessel occlusive disease on vasoreactivity. We studied three other groups for comparison, including four with bilateral internal carotid artery occlusions (BICAO), 11 with unilateral carotid occlusion (UICAO), and six with unilateral middle cerebral artery stem occlusion (UMCAO). Resting flows appeared to correlate with the severity of occlusive disease overall. Normocapnic perfusion was lowest in the group with BICAO and decreased in proportion to the degree of contralateral stenosis in the group with UICAO. Hypercapnic perfusion correlated with the apparent adequacy of angiographic collaterals. Reactivity was lowest in the MMD group (0.79%/mm Hg) whose collateral supply was limited to leptomeningeal anastomosis from the posterior cerebral artery, but highest in the patients with BICAO (2.72%/mm Hg), each of whom showed excellent posterior communicating artery flow. The clinical course of the MMD group was compatible with the syndrome of perfusion insufficiency with repeated ischemic attacks or a saltatory progression of an ischemic deficit; CT showed infarction in the borderzone territory. These results suggest that a severely reduced hypercapnic response may help to identify patients with ischemic syndromes due to perfusion failure in the borderzones, as in MMD.

Rupture of a previously documented asymptomatic aneurysm enhances the argument for prophylactic surgical intervention.

A case is presented of an incidentally discovered 6-mm aneurysm that was left untreated and subsequently produced a subarachnoid hemorrhage. The patient had no previous history of intracranial hemorrhage from any other source. A case of this type has not been previously documented in the literature. This experience points out the potential for catastrophe in small unruptured aneurysms found in patients without previous subarachnoid hemorrhage. The extremely low operative morbidity for repair of these types of lesions in otherwise healthy individuals would argue strongly for prophylactic surgery in properly selected patients.

Electroencephalographic monitoring for ischemia during carotid endarterectomy: visual versus computer analysis.

In a retrospective study, we compared the use of computer-generated spectral electroencephalographic descriptors with a neurologist's interpretation of raw EEG data. Data were collected from patients undergoing carotid endarterectomy and anesthetized with isoflurane in nitrous oxide and oxygen. The EEG was recorded on magnetic tape during the period immediately before and after occlusion. These tapes were then analyzed off-line using a computer to generate averaged changes in 18 spectral descriptors. A strip-chart of raw EEG before and after the carotid occlusion was interpreted by a neurologist, who assigned changes in the EEG following occlusion to one of four visual inspection groups, depending on the severity of change. A descriptive examination of the distribution of changes in spectral descriptors revealed that no single descriptor adequately reflected the neurologist's interpretation of the raw EEG. Using data from 20 patients, the percent change from preocclusion to postocclusion values for total power, spectral edge frequency, spectral variance, and log spectral variance was examined. Only for the visual inspection group judged by the electroencephalographer to have the most severe ischemic change was there a significant difference in total power and log spectral variance. Although computer-processed EEG devices are of value as trending devices for detecting visual patterns associated with inadequate cerebral perfusion, single descriptors in this study did not consistently reflect a neurologist's diagnosis of ischemia. Single descriptors of spectral EEG analysis may not be sufficient to use as alarm variables in the recognition of cerebral ischemia.

Lack of association between carotid plaque hematoma and ischemic cerebral symptoms.

To investigate the association between carotid plaque hematoma and symptoms of cerebral ischemia a retrospective review of 200 consecutive carotid endarterectomies at the Neurological Institute of New York was carried out. Data analyzed included cerebral ischemic symptoms, angiographic findings, preoperative use of antithrombotic agents, and microscopic pathology of endarterectomy specimens. No association was found between ischemic symptoms ipsilateral to the endarterectomy and presence, size, or age of plaque hematomas. Plaque hematomas were less common among patients who took antithrombotic agents preoperatively than among those who did not. The presence of plaque hematoma was associated with angiographic carotid cross-sectional area stenosis of greater than 75%. Patients with stenosis of less than 75% were more likely than those with stenosis of greater than 75% to have ischemic symptoms ipsilateral to the endarterectomy, suggesting that criteria for surgical treatment of carotid atherosclerosis differ for those who are symptomatic vs. those who are asymptomatic. These results demonstrate the limitation of using a surgical series to extend causal inferences about the relation between plaque hematoma and cerebral ischemic symptoms to the general population of people with carotid atherosclerosis.

Incidence and etiology of intracerebral hemorrhage following carotid endarterectomy.

In a consecutive series of 1930 carotid endarterectomies there were eight cases of postoperative intracerebral hemorrhage. One of these patients was operated on 2 weeks following cerebral infarction and had severe uncontrollable hypertension after surgery. A second patient had an intraoperative embolus and bled while fully heparinized on the 3rd postoperative day. Only one patient in the series bled into an area of documented cerebral infarction. The remainder of the cases represented hemorrhage into essentially normal brain. Seven of the eight patients with intracerebral hemorrhage had high-grade internal carotid artery stenosis preoperatively. Although several factors have contributed to the brain hemorrhages in this series of patients, postoperative cerebral hyperperfusion which often follows endarterectomy may have played an important role. Defective cerebrovascular autoregulation in chronically ischemic brain regions may predispose patients to intracerebral hemorrhage after removal of a high-grade stenosis of the internal carotid artery.

Basal arterial occlusive disease.

Seventeen patients with basal occlusive disease have been seen over the past 4 years. Nine of these had a classical moyamoya appearance on angiography. Of these nine, seven were adults and two were children. Eight had ischemic episodes, and one had a hemorrhage. One had neurofibromatosis with a chiasmal glioma and had received radiotherapy. Eight patients underwent superficial temporal-middle cerebral artery (STA-MCA) bypass, and one refused operation. Six patients improved, one had a stroke on the opposite side, and one died. Eight patients had unilateral basal arterial occlusive disease. Of these, three had ischemic episodes, four had hemorrhages, and one had only headaches. Four were adults, and four were children. Five underwent STA-MCA bypass with improvement, one with headaches had an aneurysm treated, and two were not operated upon. Considerations regarding the cause, therapeutic options, and disease course in these patients are discussed.

Computerized electroencephalogram monitoring and carotid artery shunting.

During carotid artery surgery, ischemic electroencephalogram (EEG) changes were detected by computerized analysis in 27 of 225 carotid clamping intervals. All but 7 of these changes resolved spontaneously before the restoration of blood flow. Restored flow was associated, after variable delay, with an improved EEG pattern in 6 of 7 cases. Of 27 EEG episodes, there were 5 cases in which the EEG event persisted for 10 minutes or longer. All 5 patients developed new neurological deficits; none of the other patients did. It is suggested that all patients undergoing carotid artery surgery be monitored with EEG and that a shunt be placed if a persistent EEG change is noted.

Prognostic value of computerized EEG analysis during carotid endarterectomy.

A single-channel EEG, analyzed in real time to produce a density spectral array (DSA) display was recorded during 111 carotid endarterectomies. A simple protocol that emphasized loss of high frequency activity was used to identify serious ischemic EEG events. In 70 patients (78 operations) with no preoperative neurologic deficits, new postoperative neurologic deficits appeared only in the seven patients who had ischemic EEG events that lasted 10 min or longer. The EEG was not predictive in the 31 patients (33 operations) who had preoperative neurologic deficits: one patient with no intraoperative change in EEG developed a new postoperative deficit, and one patient with EEG changes lasting 13 min had no demonstrable new deficit postoperatively. This EEG monitoring technique was simple and convenient to use, and appears to be predictive of gross neurologic outcome following carotid endarterectomy in patients without preoperative neurologic deficits.