CHAPTER 350 Carotid Endarterectomy
Treatment of carotid occlusive disease, in particular by carotid endarterectomy (CEA), is unique among neurosurgical procedures in that there is extensive evidence from large, well-conducted, multi-institutional, randomized controlled trials to guide physicians in their decision making. Specifically, the North American Symptomatic Carotid Endarterectomy Trial (NASCET)1 and the European Carotid Surgery Trial (ECST)2 for symptomatic carotid occlusive disease and the Asymptomatic Carotid Atherosclerosis Study (ACAS)3 and the Asymptomatic Carotid Surgery Trial (ACST)4 for asymptomatic disease provide very explicit guidelines for the advisability of CEA by taking into account a number of patient factors. Nonetheless, there can still be a fair amount of controversy and at times uncertainty when treating patients with cervical internal carotid artery (ICA) narrowing. This chapter reviews the indications, technical aspects of the procedure, postoperative care and potential complications, and follow-up for CEA.
History
C. Miller Fisher, a neurologist at Harvard, was the first to accurately report the clinical syndrome associated with cervical ICA occlusion in 1951.5 He reported the autopsy findings in 4 patients and suggested that the cause of occlusion appeared to be primary atherosclerosis. Previously, a variety of causes had been suggested for ICA thrombosis, including syphilis, hypertension, history of head injury (remote or recent), retrograde thrombosis from a cerebral aneurysm, and retrograde thrombosis from intracerebral arteries.6 That same year, Johnson and Walker from Johns Hopkins reported the angiographic findings from 6 of their patients who suffered cervical ICA thrombosis and reviewed the cases of an additional 101 patients in the world literature in whom thrombosis was diagnosed by angiography.6 They emphasized the value of angiography in establishing the diagnosis and agreed with Moniz and colleagues that spontaneous ICA thrombosis is probably much more common than originally thought inasmuch as many of these patients had been clinically suspected of having a brain tumor, aneurysm, or “some vague cerebrovascular accident” before angiography revealed the occluded ICA.6,7 During that decade, Millikan, Siekert, and Whisnant at the Mayo Clinic further defined the syndrome of transient ischemic attack (TIA) as a harbinger of carotid artery stenosis.8
Who actually performed the first CEA is hotly debated. Several surgeons pioneered work in this area shortly after Miller’s publications in the early 1950s. Ed Laws reported that a neurosurgeon, William Spence, performed the first successful CEA in 1951 but that his report was rejected for publication in the Journal of Neurosurgery.9 Numerous prominent surgeons did report successful surgical treatment of carotid occlusive disease with a variety of techniques around that time, including carotid-carotid anastomosis,10 primary resection of the diseased segment and reanastomosis,11 arterial grafting,12 interposition vein grafting,13 and endarterectomy.14–17 The concept of surgical revascularization of the cervical segment of the ICA for atherosclerotic narrowing or occlusion firmly took hold in the second half of the 20th century.
According to data from the National Hospital Discharge Survey, the number of CEAs performed in the United States dramatically increased from 15,000 in 1971 to 107,000 in 1985.18 Based on regression estimates, it was predicted that 127,000 CEAs would be performed in the United States in 1986. However, several important publications in the mid-1980s raised concern about higher than previously reported rates of morbidity and mortality and questioned the indications for CEA, particularly in asymptomatic patients, which probably quelled the otherwise almost exponential rise in the number of procedures performed.19–25 In fact, only 83,000 CEAs were performed in 1986.18
Interestingly, prerelease of the results from NASCET and ACAS in 1991 and 1994, respectively, again resulted in a surge in the number of CEAs performed in the United States.26 Data from acute care hospitals in seven states were reviewed between 1989 and 1996. For 2 years before 1991 the rate of CEA per 100,000 persons did not change. However, the CEA rate increased 3.4% each month for the 6 months after release of the NASCET clinical alert in February 1991. Even more notable, after publication of the ACAS clinical alert in 1994, the CEA rate increased approximately 7% each month for 7 months with a total increase of 42% per 100,000 persons.26 Other studies have also shown increased rates of CEA since release of the randomized controlled trials.27,28 By 1995, about 132,000 CEAs were performed in the United States. With the introduction of carotid artery angioplasty and stenting, the number of CEAs is probably decreasing. According to data from the most recently available Hospital Discharge Survey on the number of CEA procedures performed on patients aged 75 to 84 years (the age group with the highest rate), the rate of CEA in 1990 was 19.8 per 10,000 population, peaked at 32.8 per 10,000 in the year 2000, and was 29.5 per 10,000 in 1996.29
Preoperative Evaluation
Symptomatic Patients
The differential diagnosis and detailed work-up of every patient with possible symptoms of cerebral ischemia are beyond the scope of this chapter. Flemming and colleagues provided a detailed review of the evaluation and management of TIA and minor cerebral infarction.30 A patient with a history and findings on physical examination consistent with TIA or minor stroke of the anterior circulation should undergo routine laboratory evaluation (complete blood count, prothrombin time, activated partial thromboplastin time, electrolytes, fasting glucose, creatinine, erythrocyte sedimentation rate), electrocardiography, chest radiography, and computed tomography (CT) of the head without contrast enhancement. If carotid artery disease is still in the differential diagnosis, screening ultrasonography of the carotid arteries should be undertaken. If ultrasound demonstrates high-grade stenosis, a confirmatory examination is performed, typically gadolinium-enhanced magnetic resonance angiography (MRA).31 If there appears to be a discrepancy between the ultrasound and MRA findings, formal cerebral angiography may be performed.32 There continues to be much controversy regarding what imaging is necessary to establish the diagnosis of carotid stenosis. Ultrasound, MRA, and CT angiography have all been extensively compared with conventional digital subtraction angiography. All modalities have high specificity and sensitivity for detecting carotid stenosis, and MRA in particular may have some added value in detecting other characteristics of atherosclerotic plaque, such as lipid content and intraplaque hemorrhage, among other findings.33–40
Asymptomatic Patients
Although stroke is the leading cause of death and hospitalization in nearly all European countries and consistently the third major cause of death in the United States, widespread mass screening for carotid occlusive disease is not recommended.41,42 Whitty and associates argued that screening strategies for asymptomatic carotid stenosis are unlikely to be effective and might even be harmful in populations in which the prevalence is between 1% and 25%.43 The prevalence of moderate asymptomatic carotid stenosis (>50%) in a recent meta-regression analysis published in 2009 was 4.2%, and the prevalence of severe stenosis (>70%) was 1.7%.44 Age older than 70 years and male sex increased the chance of finding significant stenosis.44 The best screening strategy would involve evaluating patients at high risk for carotid stenosis (based on age, male sex, hypertension, tobacco abuse, peripheral vascular disease) who are surgical candidates and who would undergo surgery if recommended. Identifying this population and the true benefit to them and society as a whole remains highly controversial.45–51
Indications Based on Randomized Controlled Trials
Symptomatic Patients
As noted earlier, two major trials, NASCET and ECST, have clearly demonstrated the efficacy of CEA in selected patients with amaurosis fugax, hemispheric TIA, or nondisabling stroke within the previous 4 to 6 months.1,2 Several caveats of the trials are worth noting to guide patient selection.
North American Symptomatic Carotid Endarterectomy Trial
Between January 1988 and February 1991, NASCET enrolled 659 patients at 50 clinical centers in the United States and Canada with symptomatic carotid stenosis in whom symptoms occurred within 120 days before entry into the trial. To qualify as a trial center, each institution had to have performed at least 50 CEA procedures in the previous 2 years with a 30-day stroke and mortality rate of less than 6%. All patients included in the study had to be younger than 80 years and have ipsilateral ICA stenosis of 30% to 99% as assessed by angiography. Exclusion criteria are listed in Table 350-1. Patients were randomized to aspirin, 1300 mg/day, and other stroke reduction therapy as needed (e.g., antihypertensives, lipid-lowering therapy), and those assigned to surgery also underwent CEA. Three hundred thirty-one patients were randomized to medical therapy and 328 to surgery. There were no significant dissimilarities between the groups on careful analysis. The rate of occurrence of any perioperative stroke and death for the surgical group was 5.8%; for major stroke and death it was 2.1%.1
TABLE 350-1 Exclusion Criteria from the North American Symptomatic Carotid Endarterectomy Trial
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Had a stroke on either hemisphere that would probably deprive the patient of useful function in the affected territory
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The study was stopped early because of a clear and highly significant benefit in patients with high-grade (70% to 99%) stenosis. By 2 years after randomization, the risk for any ipsilateral stroke was 26% in the medical group and 9% in the surgical group (P < .001), a relative reduction in risk of 65%. The risk for ipsilateral major or fatal stroke was reduced from 13.1% in the medical group to 2.5% in the surgical group, and even the risk for any major stroke or death was reduced from 18.1% in the medical group to 8% in the surgical group. The treatment groups did not differ significantly in total mortality. The early disadvantage in the surgical group of the risk associated with the operation was negated by the 3-month follow-up, at which time the benefit of reduction in stroke and death overcame any perioperative risk.1
Additional analysis of the moderate stenosis group also revealed a statistical benefit in study patients who had 50% to 69% stenosis and underwent CEA in comparison to the medical group.52 The 5-year risk for any ipsilateral stroke was reduced from 22.2% in the medical cohort to 15.7% in the surgical group (P = .045).52
Further information acquired from analysis of the study revealed that patients 75 years and older benefited more from CEA than did younger patients.53 Baseline variables predictive of increased surgical risk for all patients undergoing CEA for symptomatic disease included hemispheric versus retinal TIA on initial evaluation, left-sided procedure, contralateral carotid occlusion, ipsilateral ischemic lesion on CT, and an irregular or ulcerated plaque.54
European Carotid Surgery Trial
A very similar trial to NASCET was undertaken at 97 centers in 12 European countries and the results reported in 1998.2 There were 1807 patients in the surgery arm and 1211 patients in the best medical management arm for analysis. To be eligible, patients had to have had symptoms within the previous 6 months of randomization. In this trial the overall perioperative (within 30 days of surgery) risk for nonfatal major stroke or death was 7.0%. The most striking finding in this trial was that for the combined outcome of surgical events, ipsilateral major ischemic strokes, and other major strokes, no overall effect was seen below about 70% to 80% stenosis.2
It is worth noting that one of the few controversial issues regarding these studies relates to how ICA stenosis was calculated. For NASCET, percent stenosis was determined by using the diameter at the point of the greatest narrowing as the numerator and the diameter of the artery beyond the bulb where the walls of the artery again become parallel as the denominator.1 ECST also used the lumen diameter at the most stenotic point as the numerator, but the estimated probable original diameter at the site of maximal stenosis was used as the denominator.2 This probably resulted in more observer variation in estimating the degree of stenosis, but it is generally thought that 80% stenosis in ECST would correlate to 70% stenosis in NASCET.2
Pooled analysis of the data from NASCET and ECST, as well as from the Veterans Affairs Trial 309,55 which was stopped early after the NASCET results became available, allows some additional conclusions.56 The degree of stenosis is very important in predicting the benefit from CEA. No benefit was seen with less than 50% stenosis of the luminal diameter. Benefit was noted in patients with 50% to 69% stenosis, but the number needed to treat to prevent one stroke over a 5-year period was 22. CEA was highly beneficial for symptomatic patients with stenosis greater than 70%, and the number needed to treat to prevent one stroke over a 5-year period was just 6.3. No benefit was observed when there was “near occlusion” of the symptomatic artery.56 Surgery within 2 weeks of the last symptom improved outcomes relative to later surgery (especially in women), and there was no increased operative risk when operating within 2 weeks of a nondisabling hemispheric stroke.57
Contralateral carotid stenosis in the face of an ipsilateral symptomatic high-grade stenosis deserves special mention. This subgroup of patients was analyzed in NASCET and the results may seem somewhat contradictory.58 Medically treated patients with an occluded contralateral ICA were twice as likely to have an ipsilateral stroke as patients who still had flow through the contralateral artery. However, the perioperative risk was higher in this subgroup, especially if the contralateral artery was occluded. Despite this risk, the overall evidence supports performing CEA on a recently symptomatic ICA with greater than 70% stenosis even if the contralateral artery is severely narrowed or occluded.58
Asymptomatic Patients
The indications for CEA in asymptomatic patients are much more controversial than those for symptomatic patients despite two very thorough randomized controlled trials.3,4 ACAS and ACST evaluated the efficacy of CEA in asymptomatic patients, and the results were published in 1995 and 2004, respectively.
Asymptomatic Carotid Atherosclerosis Study
ACAS was a very well-designed comparison of aspirin (325 mg/day) and stroke risk factor reduction strategies versus aspirin, CEA, and stroke risk factor reduction strategies in asymptomatic patients aged 40 to 79 years who had 60% to 99% luminal diameter stenosis of the cervical ICA as defined by angiography.3 Thirty-nine centers in the United States and Canada randomized patients between 1987 and 1993. Follow-up data were available for 1659 patients after more than 42,000 had been screened during the 6 years of the study. Exclusion criteria are detailed in Table 350-2 and were primarily designed to avoid enrolling patients who had an underlying condition that might complicate surgery or produce disability or death within 5 years of enrollment. After a mean follow-up of 2.7 years with 4657 patient-years of observation, the 5-year risk for ipsilateral stroke and any perioperative stroke or death was reduced from 11.0% in the medical group to 5.1% in the surgical patients (P = .004). This correlates to 19 CEAs necessary to prevent 1 stroke over a period of 5 years. The perioperative complication rate was very low at 2.3%, and the perioperative death rate was 0.1%.3
TABLE 350-2 Exclusion Criteria for the Asymptomatic Carotid Atherosclerosis Study
There are several additional caveats regarding the results of ACAS worth noting such that many neurologists caution against widespread application of the results to all patients with asymptomatic high-grade carotid stenosis.45,59 If the outcome was restricted to just disabling stroke or any stroke or death, the benefit of surgery was no longer statistically significant. It is worth emphasizing the very low morbidity in this study and in all the other randomized trials as well. If CEA is not performed by a skilled, experienced surgeon, even a small increase in the morbidity or mortality rate in comparison to the study results will negate the benefit of surgery. Interestingly, there are numerous natural history studies that document an increased risk for ipsilateral stroke as the degree of ICA stenosis increases.60–68 In fact, as noted earlier, this was confirmed in NASCET and ECST as well, but not seen in ACAS.1,2 Surprisingly, the benefit from surgery was higher in the 60% to 69% stenosis group than in the 80% to 89% group in ACAS.3 The reason for this is not entirely clear. Finally, although not designed to detect a difference between the sexes, a subgroup analysis showed no benefit for women and a higher perioperative complication rate than in men (3.6% versus 1.7%).3
Asymptomatic Carotid Surgery Trial
ACST was the largest study to evaluate the efficacy of CEA for asymptomatic carotid stenosis.4 Between 1993 and 2003, 3120 patients were randomized to CEA within 1 month to 1 year or to continued observation. Again, 60% or greater narrowing of the ipsilateral ICA was used as criteria for entry into the study, but for this study, the degree of stenosis was based on ultrasound evaluation rather than formal angiography. Mean follow-up for all patients was 3.4 years. The medical regimen was left to the discretion of the treating physicians, and approximately 4% of the observation group eventually crossed over to undergo CEA. Once again, the operative 30-day morbidity and mortality rate was very low (3.1%). The overall results were very similar to those of ACAS. The 5-year risk for any stroke was 6.4% in the surgery cohort and 11.8% in the observation group (P < .001). CEA was also beneficial in comparison to medical therapy for fatal or disabling stroke (P = .004) and fatal stroke alone (P = .006). The benefit was seen in both men and women in this study, thus suggesting that some of the additional morbidity in women seen in ACAS may have been due to increased morbidity from angiography rather than CEA itself. There was no benefit for patients 75 years or older. As in ACAS, the degree of stenosis was not significant in establishing benefit.4
Several other randomized trials for symptomatic55 and asymptomatic69–72 carotid stenosis were attempted both before and during the aforementioned four trials but were either stopped or found to be inconclusive for a variety of reasons, and because of space issues they are not discussed in this chapter.
In summary then, we recommend CEA for the following patients:
Of course, there are numerous additional patient factors that may influence a decision regarding CEA versus medical therapy for carotid artery disease. A multidisciplinary consensus statement from the American Heart Association was released in 1995 and again in 1998 in an attempt to provide guidelines for CEA.73,74 Patients in these publications were stratified according to symptomatology, degree of ICA stenosis, and perceived surgical risk, and this can serve as a starting reference when attempting to decide on surgery in difficult cases.73,74 Complicating this even further (and beyond the scope of this chapter) is the role of carotid angioplasty and stenting (CAS) and how the numerous trials already completed and currently under way to evaluate the safety and efficacy of CAS and to compare CAS and CEA might affect these recommendations in the future.75–79
Technique
The technique described in the following sections was developed primarily by Thor Sundt, Jr., M.D., and has changed very little over the past 30 years.80 The department of Neurologic Surgery at the Mayo Clinic has performed more than 3000 CEAs and has successfully trained generations of residents in this technique.
Positioning and Exposure
Patients undergo CEA under general anesthesia at our institution. Typically, this is done with a combination of an intravenous muscle relaxant and opioids and inhaled nitrous oxide and isoflurane. All patients are monitored with 16-channel EEG, and the inhaled anesthetic is titrated (usually slightly less than 1 minimum alveolar concentration) so that it does not interfere with the recorded EEG. Patients are positioned supine with their arms tucked at their sides and the head turned to the opposite side and resting on a soft headrest. For obese patients or large barrel-chested men, a rolled blanket placed under the shoulders can assist in the exposure. Some neck extension is very helpful, but in elderly patients, caution must be exercised to avoid overextension in those with possible underlying cervical spondylosis. A curvilinear incision is made parallel to and just posterior to the anterior border of the sternocleidomastoid (SCM) muscle. We have found that placing the incision directly on the anterior border results in a more conspicuous scar, particularly in thin patients. The incision begins about 1 cm below the tip of the mastoid, curves 1 cm below the angle of the mandible, and ends 1 cm above the sternoclavicular joint. A scalpel is used to incise the skin and platysma to expose the cervical fascia (Fig. 350-1
