Carotid endarterectomy (CEA) was initially introduced in the early 1950s. An intuitively appealing procedure, the number of procedures rose steadily until 1985, when CEA was ranked the third most common operation performed in the United States. Its popularity shifted over the subsequent years as questions arose regarding its efficacy and the wide variation in reported morbidity and mortality associated with the procedure. However, several large, well-designed, randomized trials have confirmed the benefit of this procedure in selected patients and current guidelines for CEA define an important role for this operation, combined with best medical therapy, in the prevention of stroke.
CEA remains the gold standard surgical procedure for the prevention of stroke. However, over the past two decades considerable interest has accompanied the emergence of carotid angioplasty and stenting (CAS) procedures for treating extracranial, as well as intracranial, occlusive vascular disease. Based on the results of several well-designed, prospective trials, current guidelines identify CAS as an alternative to CEA in appropriately selected patients. , , , ,
Both CEA and CAS will remain important treatments for the prevention of stroke. Both these operations are directed at patients with advanced cerebrovascular disease and represent challenging procedures from the anesthesiologist’s perspective because many of the patients are elderly and have significant coexisting disease. This chapter reviews the anesthetic considerations for, and management of, patients undergoing CEA and explores the roles for CEA and CAS procedures for the prevention of stroke.
Physiologic considerations
Carotid revascularization procedures involve the manipulation of the blood supply to the brain. As a consequence, the rationale and recommendations for the management of patients undergoing these procedures are founded on an understanding of neurovascular anatomy and physiology.
The brain is highly active metabolically but is essentially devoid of oxygen and glucose reserves, making it dependent on the continuous delivery of oxygen and glucose by the cerebral circulation. Cerebral blood flow (CBF) is provided by the internal carotid arteries (approximately 80%) and the vertebral arteries (approximately 20%). These major arteries anastomose at the base of the brain to form the circle of Willis, which provides the primary collateral vascular channel between the cerebral hemispheres. However, other collateral channels between the intracranial and extracranial circulations (e.g., through the orbit) may become well developed in patients with occlusive disease of the internal carotid artery.
CBF depends on cerebral perfusion pressure (CPP) and cerebral vascular resistance (CVR) according to the following equation:
where CPP represents the difference between mean arterial blood pressure and intracranial pressure or central venous pressure, whichever is greater, and CVR is a function of blood viscosity and the diameter of the cerebral vessels. Normally CBF is autoregulated in response to cerebral metabolic requirements, a process common to many specialized vascular beds. During CEA, however, optimization of CBF is hampered by the fact that the only factors readily amenable to intraoperative manipulation are arterial blood pressure and arterial carbon dioxide tension (PaCO 2 ), which affect CPP and CVR, respectively. Confounding this situation, our current understanding of the physiology of CBF is incomplete. For example, much of our understanding of cerebral hemodynamic changes during anesthesia is based on the assessment of changes that occur in larger vessels using techniques such as computed tomography (single-photon emission computed tomography [SPECT]) or transcranial Doppler ultrasonography (TCD) studies. However, work using orthogonal polarization spectral imaging of the sublingual microcirculation suggests that the flow observed in larger vessels after the induction of anesthesia may not parallel changes in flow observed in the capillary network. These findings raise questions about our ability to predict microvascular perfusion consistently on the basis of the dynamic behavior of large vessels.
Carbon Dioxide Tension
CBF is exquisitely sensitive and directly related to PaCO 2 . CBF changes 1 to 2 mL/100 g/min for every 1-mmHg change in PaCO 2 within the range of 20–80 mmHg. The most appropriate level of PaCO 2 during CEA has not been definitively established. Hypocapnia has been advocated on the premise that vasoconstriction in areas of normal (CO 2 -responsive) brain will potentially divert blood flow toward ischemic regions, the “Robin Hood” effect. , Conversely, deliberate hypercapnia has been postulated to increase global CBF and as a consequence may improve perfusion to potentially ischemic regions. However, both concepts have been criticized on the grounds that studies of regional cerebral blood flow during carotid cross-clamping have demonstrated that the regional CBF response to changes in PaCO 2 is not entirely predictable. Cerebral autoregulation has been reported to be completely lost during carotid cross-clamping under hypercapnic conditions and partially lost during hypocapnia, illustrating the relatively greater importance of blood pressure control during CEA. Furthermore, increasing PaCO 2 causes vasodilation in normal brain and has been reported to result in a potential steal of blood flow from ischemic zones in up to 23% of patients. A similar steal phenomenon has also been reported during CEA in association with cerebral vasodilatation that accompanies the administration of volatile anesthetic drugs such as sevoflurane.
A recent review of the scant clinical literature pertaining to the influence of carbon dioxide on cerebral autoregulation concluded that hypercapnia is likely to be associated with relative cerebral hyperperfusion but that there is insufficient published evidence to delineate the underlying cerebrovascular response to this condition at the microvascular level. In contrast, hypocapnia is associated with a decrease in cerebral blood flow that is compounded by concommittant hypotension irrespective of whether it is produced by hemorrhage or anesthetic drugs. The authors caution that these conditions could be associated with ischemia and emphasize that wide inter-individual variability around the lower limit of autoregulation compromises the reliability of this parameter to consistently reflect the adequacy of cerebral perfusion in individual patients.
Further confounding decisions regarding the appropriate management of PaCO 2 during CEA is the fact that other disease processes also may alter the response to changes in arterial carbon dioxide tension. For example, patients with diabetes mellitus, a common condition among patients presenting for CEA, have been reported to display impairment of cerebrovascular responsiveness to hypercapnia during anesthesia with propofol, sevoflurane, or isoflurane. , Although the level of impairment was observed to be related to the severity of the diabetes (i.e., glycosylated hemoglobin value and extent of retinopathy), the level of impairment observed among individual patients was not consistently predictable.
In the absence of a clear clinical benefit associated with either hypercapnia or hypocapnia, or a readily available means to titrate either to a cerebrovascular effect, the most prudent approach to the ventilatory management of patients undergoing CEA is maintenance of normocapnia. This is accomplished by reference to preoperative arterial blood gas measurements or, if these are not available, by ventilating to a PaCO 2 value that produces a normal pH in a patient who does not have a coexisting metabolic acidosis. This approach attempts to achieve a balance between the optimization of CBF and the avoidance of cerebral steal.
Blood Pressure
Traditionally, many textbooks report that CBF is maintained relatively constant within the range of mean arterial blood pressure (MAP), from approximately 50 to 150 mmHg. Beyond this range the limit of vasomotor activity is exceeded and CBF becomes directly dependent on changes in CPP. In patients with preexisting chronic hypertension, both the upper and lower limits of autoregulation are shifted toward higher pressures. However, several investigators have noted that most available evidence suggests that, based on MAP, the lower limit of autoregulation in humans is substantially higher on average than 50 mmHg (at least 70 mmHg) and subject to large inter-individual variation. , As a consequence, as noted previously, caution is advised when using these traditional values to guide blood pressure management at the lower limit of autoregulation.
A deliberate increase in intraoperative blood pressure has been advocated during CEA based on the premise that autoregulation will maintain normal CBF in areas of healthy brain while flow will be increased in areas of the brain that are hypoperfused owing to vasomotor paralysis or atherosclerotic narrowing. The CBF response to changes in PaCO 2 is depressed in patients with cerebrovascular disease as well as during carotid cross-clamping (as discussed previously), suggesting that blood vessels distal to regions of atherosclerotic narrowing are operating near the limits of autoregulatory vasodilation. Under these conditions, improvement in CBF is likely to depend on increases in CPP. Higher stump pressures and reversal of ischemic changes on the electroencephalogram (EEG) have been reported in response to induced hypertension during cross-clamping. , The use of deliberate hypertension during carotid cross-clamping continues to be advocated by some investigators. Routine phenylephrine-induced systolic hypertension to 200 mmHg (and selectively up to 240 mmHg for persistent cross-clamp intolerance) during the period of cross-clamp application has been reported to reduce the need for intraoperative shunting during CEA performed under regional anesthesia in low-risk patients. While the incidence of cross-clamp intolerance was reported to be reduced, the potential for cardiac ischemic events (a risk reported to accompany the use of pharmacologically induced hypertension during these procedures) was not specifically evaluated.
Deliberate hypertension is not devoid of risk. Excessive increases in CPP may cause cerebral hemorrhage or edema formation in regions of the brain that have lost autoregulation ability. In addition, patients most at risk for the development of cerebral ischemia—those with inadequate collateral blood flow—have been shown to be the least responsive to induced hypertension. However, these patients are most in need of safe maneuvering, including judiciously induced hypertension that may increase flow to the ischemic region. In patients with ischemic heart disease, systemic vasoconstriction may lead to an adverse myocardial oxygen balance. The incidence of myocardial ischemia has been reported to be higher among patients who receive phenylephrine infusions or metaraminol to increase blood pressure during CEA. ,
On the basis of the available evidence, the routine intraoperative elevation of blood pressure above the patient’s normal level is not recommended. Instead, the extent and patency of the collateral circulation should be discussed prior to induction of anesthesia. In patients with patent collateral vessels, careful maintenance of blood pressure within the normal preoperative range is recommended. Spontaneous increases in systolic blood pressure of up to 20% above normal at the time of cross-clamping are acceptable. In patients with poor collaterals, blood pressure may be cautiously increased up to about 20% to 30% above baseline, with consideration of the concerns previously described. Excessive spontaneous increases may reflect cerebral ischemia, a possibility that should be considered before the increase in blood pressure is controlled pharmacologically.
Preoperative considerations
Carotid endarterectomy and carotid stenting procedures are interventions designed to reduce the risk of stroke among patients with advanced cerebrovascular disease. Most patients presenting for these procedures are elderly with a variety of comorbidities including, coronary artery disease, arterial hypertension, peripheral vascular disease, chronic obstructive pulmonary disease, diabetes mellitus, renal insufficiency, or a combination of such conditions Based on the medical characteristics of the patients included in NASCET (1991) and the GALA study (2008), published 17 years apart, the burden of these conditions remains substantial among patients presenting for CEA ( Table 16.1 ). As a consequence of these conditions, it is not surprising that CEA and CAS procedures also carry a substantial risk of death or serious morbidity. The benefit of these procedures resides in the fact that for the majority of patients with advanced disease, the risk of stroke or death without intervention is higher than the risk associated with the procedure. Hence, appropriate selection and optimization of candidates for these procedures represent important opportunities to mitigate perioperative risk.
| Proportion of Patients (%) | ||
|---|---|---|
| NASCET a | GALA b | |
| Medical Condition | (n = 2256) | (n = 3526) |
| Angina | 24 | |
| Previous myocardial infarction | 20 | |
| Coronary artery disease | 36 | |
| Hypertension | 60 | 77 |
| Peripheral vascular disease | 14 | 25 |
| Smoker (current or previous) | 77 | 80 |
| Diabetes mellitus | 19 | 25 |
Patient Selection
Overwhelming evidence supports the efficacy of CEA combined with best medical therapy for the prevention of stroke among appropriately selected patients. Three large multicenter randomized trials conducted in North America , and Europe over two decades ago validated the role of CEA in the treatment of patients with symptomatic high-grade carotid disease. Current American Heart Association (AHA) guidelines recommend CEA in symptomatic patients with carotid stenosis of 50% to 99% if the risk of perioperative stroke or death is less than 6%. , Pooled data from the major CEA trials involving symptomatic patients with stenosis greater than 50% support these recommendations and show that the number of patients needed to treat (NNT) to prevent one stroke over a 2-year period is nine for men and 36 for women. Benefit is also greater in older rather than younger patients, particularly those older than 75 years, with an NNT value of 5.
For asymptomatic patients the data are less robust. The risk of stroke is lower in asymptomatic patients than in patients with symptomatic disease and, as a consequence, the benefit of surgical intervention is realized only if the procedure can be performed with a lower 30-day risk of stroke and death. AHA guidelines , recommend CEA for asymptomatic patients with carotid stenosis of 60% to 99% if the perioperative risk of stroke or death is less than 3%.
It is noteworthy in relation to perioperative risk that many studies that support the preceeding recommendations included exclusion criteria that eliminated patients with significant comorbid conditions and many also required that participating surgeons performed a suitable volume of procedures. Consequently, current recommendations for CEA are also influenced by clinical factors that may modify the risk and the potential for benefit (stroke prevention), such as life expectancy, age, gender, the presence of coexisting medical conditions, and the outcome performance of the surgeon and surgical team who perform the procedure. It has been noted that published outcomes following CEA as well as CAS procedures, particularly the 30-day incidence of stroke, have been progressively improving over the past two decades, , an observation that has been attributed to recognition of the important impact of surgical training and case volume on outcome as well as to the evolution of medical therapy including better management of comorbid conditions such as hypertension, dyslipidemia and diabetes.
The Role for Carotid Angioplasty and Stenting
Over the past three decades there has been an exponential increase in interest in and use of endovascular approaches for the treatment of carotid artery stenosis. This increase has paralleled the growth in the use of these techniques in other vascular specialties, especially in the coronary and peripheral vascular beds. Further impetus has come from advances in catheter, balloon, stent, and endovascular emboli trapping device development and has been encouraged by recognition of the many potential advantages of endovascular approaches, particularly in high-risk patients ( Table 16.2 ). The benefits of an endovascular approach include: it is “minimally invasive”; it avoids surgical wounds and their complications; and endovascular procedures can generally be accomplished with local anesthesia and sedation.
| Previous carotid endarterectomy |
| Contralateral carotid artery occlusion |
| Previous radical neck dissection or radiation therapy to neck region |
| Target lesion above C2 (level of jaw) or low cervical carotid lesions |
| Carotid dissection |
| Tandem lesions with ≥ 70% stenosis, intracranial stenosis, or occlusion |
| Significant cardiorespiratory comorbidity |
| Requires concurrent major cardiac or aortic surgery |
| Inability to extend neck |
| Contralateral laryngeal nerve palsy |
| At risk for wound infection (e.g., immunosuppressed, tracheostomy) |
The technique employs standard endovascular approaches from a transfemoral arterial approach. Patients are routinely pre-medicated with ASA 325 mg and clopidogrel 75 mg 3–5 days prior to the procedure. A diagnostic catheter is advanced under fluoroscopic guidance and the vascular anatomy of the aorta, neck, and head are imaged. Once the vessel to be treated is fully defined, an 8.0 F guiding catheter or 6.0 F long sheath is placed from the femoral artery and proximal to the lesion in the mid-low cervical common carotid artery. After systemic heparinization is given (70–100 units/kg) and an activated clotting time (ACT) is confirmed to be increased by two times the baseline, a fine (e.g., 0.014″) steerable guide wire, in combination with a distal filter protection device, is advanced across the stenosis and deployed 2–4 cm distal to the lesion to be treated. The distal filter devices are expandable umbrella-like devices that are deployed distal to the stenosis to trap emboli that may be released during the angioplasty and stent deployment. The appropriate size (e.g., 2.5–4 mm × 20–40 mm) angioplasty balloon is then placed across the stenosis, and once positioned it is inflated to high pressure (up to 8–12 atm) for 60–120 seconds to pre-dilate the stenotic lesion. Aggressive balloon dilation may increase the risk of complications with vessel dissection and/or embolization of the plaque, and residual stenosis is mostly related to calcification, which does not resolve with repeated dilations. Thereafter a nitinol or stainless steel self-expanding stent of appropriate length (2–4 cm) and diameter (4–10 mm) is then deployed across the lesion to completely bridge and cover the plaque in both the cervical internal and/or common carotid arteries. Following stent deployment, a larger angioplasty balloon, which matches the normal luminal diameter of the cervical internal carotid and/or the common carotid arteries are then used to dilate the lesion to > 80–100% of the normal lumen, to ensure maximal restoration to normal vessel size is achieved.
Following final balloon angioplasty across the stented lesion, the distal filter protection device is then recaptured, and withdrawn. A post-stent angiogram is then performed to insure restoration of normal luminal diameter, full patency of the stent, and normal filling of the more distal intracranial blood vessels are maintained. The patient is then rechecked neurologically, and in most instances, a femoral arterial closure device is placed to ensure hemostasis. Patients are usually monitored in the neuro ICU or another high-dependency monitoring environment for 24 hours and, if stable, discharged home on ASA 325 mg indefinitely and clopidogrel 75 mg for at least 6–12 weeks post stenting.
Major Randomized Trials Comparing Carotid Artery Stenting versus Carotid Endarterectomy
The SAPPHIRE (Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy) trial was a non-inferiority randomized controlled clinical trial in which 334 patients, judged to be at high risk for CEA, and who were either symptomatic (transient ischemic attack (TIA) or stroke) with a > 50% stenosis or asymptomatic with a > 80% stenosis were randomized to CEA (n = 167) or CAS (n = 167). The primary endpoint was a composite of death, stroke, or myocardial infarction (MI) within 30 days or ipsilateral stroke and/or death from 31 days to 1 year. There was no statistical difference between CAS versus CEA at 30 days (cumulative incidence 20.1%; absolute difference, − 7.9%; p = 0.004 for non-inferiority). At 1 year, carotid restenosis requiring treatment was less for CAS than CEA (cumulative incidence, 0.6% vs. 4.3%; p = 0.04). In symptomatic patients at 1 year, the primary endpoint for CAS was 16.8% vs. CEA was 16.5% (p = 0.95). For asymptomatic patients at 1 year, the primary endpoint for CAS was 9.9% vs. CEA was 21.5% (p = 0.02).
The Stent-Supported Percutaneous Angioplasty of the Carotid Artery vs. Endarterectomy (SPACE) trial was a non-inferiority study comparing CAS vs. CEA in symptomatic patients. A total of 1200 patients, were randomly assigned to CAS (n = 605) versus CEA (n = 595) within 180 days of a TIA or stroke. The primary endpoint was ipsilateral ischemic stroke or death at 30 days post procedure. For CAS, the endpoint was 6.84% vs. CEA of 6.34% (absolute difference, 0.51%; 95% confidence interval; p = 0.09 for non-inferiority). Embolic protection devices were only used in a small percent of cases. At 30 days and 2 years, the outcomes between the two groups were comparable.
The Endarterectomy versus Angioplasty in Patients with Symptomatic Severe Carotid Stenosis (EVA-3S) trial was a multicenter non-inferiority randomized controlled trial comparing CAS vs. CEA in asymptomatic patients with a stenosis > 60%. The primary endpoint was the incidence of any stroke or death within 30 days. At 6-month follow-up, the incidence of any stroke or death for CAS was 11.7% vs. CEA 6.1% (p = 0.02). The trial was stopped prematurely after 527 of the 872 intended patients were enrolled, for safety and futility. Major criticisms of this study were that embolic protection devices were not required in the CAS arm, and that many of the CAS operators lacked adequate training. At the 4-year follow-up, the death or stroke rate still favored CEA, driven by the 30-day event rate. However, beyond 30 days, no difference in adverse outcomes between CAS and CEA was observed.
The largest randomized controlled trial to date was the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST). A total of 2502 patients, both symptomatic and asymptomatic, with a > 70% stenosis by ultrasound were randomized at 108 centers. Training standards, experience, and competency levels were established prior to enrollment, and an embolic protection system was required in CAS cases. The primary endpoint was a composite of stroke, MI, or death of any cause up to 30 days post procedure, or any ipsilateral stroke during the 4-year follow-up. The primary composite endpoint over a median follow-up period of 2.5 years for CAS was 7.2% vs. CEA 6.8% (Hazard Ratio (HR) = 1.11; 95% CI 0.81–1.51; p = 0.51) and demonstrated no difference. There was no significant difference in the frequency of the primary endpoint between symptomatic and asymptomatic patients. The periprocedure mortality rates were similar, but there were significantly different rates of stroke between CAS of 4.1% vs. CEA 2.3% (p = 0.01) and MI (CAS 1.1% vs. CEA 2.3% [p = 0.03]). The 4-year rate of any ipsilateral stroke for CAS was 2.0% vs. CEA of 2.4% (p = 0.85). The 4-year rate of death alone was similar for CAS of 11.3% vs. CEA of 12.6% (p = 0.45). In terms of quality of life, major and minor strokes had a greater negative impact on quality of life scores (–15.8 points) than did MI (–4.5 points). There was no difference in the primary endpoint rate between men and women with either treatment. Long-term (10-year) results for CREST have been published recently and reported no significant difference in risk between patients who underwent stenting versus endarterectomy in relation to the composite outcomes of peri-procedural stroke, myocardial infarction, or death and for subsequent ipsilateral stroke. Individually, consistent with the 4-year follow-up results, the rate of peri-procedural stroke remained higher among patients who underwent stenting and the rate of peri-procedural myocardial infarction was higher in patients who underwent CEA. The rate of postprocedural ipsilateral stroke did not differ between groups.
The International Carotid Stenting Study (ICSS) was a multicenter randomized controlled trial which enrolled 1713 symptomatic patients with carotid stenosis. The primary endpoint was the long-term rate of any fatal or disabling stroke. An interim safety analysis showed the 120 day rate of stroke, death, or procedure MI for CAS was 8.5% versus CEA of 5.2% (HR: 1.69; 95% confidence intervals (CI) 1.16–2.45; p = 0.006). The incidence of disabling stroke or death at 120 days did not differ between CAS of 4.0% and CEA of 3.2%, but there was an excess of overall strokes in the CAS group (HR: 1.92, 95% CI 1.27–2.89; p = 0.002). The use of an embolic protection device was not mandated. The final results demonstrated that the 5-year risk incidence of a fatal or disabling stroke did not differ between CAS of 6.4% and CEA of 6.5%. Beyond 30 days following carotid artery treatment, there was no difference in the rates of ipsilateral stroke for CAS, which was 4.7% vs. CEA of 3.4% (HR: 1.29, 95% CI 0.74–2.24). There was an excess number of strokes in the CAS patients that persisted, with a 5-year cumulative risk of 15.2% vs. CEA of 9.4% (HR: 1.71, 95% CI 1.28–2.30; p < 0.001), although this did not translate into differences in functional disability and quality of life, as assessed by the modified Rankin scale and EQ-5D questionnaire. In this trial, various stents and protection devices were used for CAS patients at the discretion of the interventionist with only 72% of patients receiving distal protection during the index stent procedure. The study concluded that long-term functional outcome and the risk of fatal or disabling stroke are similar for CAS and CEA for symptomatic carotid stenosis.
A meta-analysis of randomized controlled trials which included 3754 patients treated with CAS vs. 3723 patients undergoing CEA showed that at 30 days, CAS was associated with a significant elevated risk of stroke (Odds Ratio (OR): 1.53, 95% CI 1.23–1.91; p < 0.001), death or stroke (OR: 1.54, 95% CI 1.25–1.89; p < 0.001), while MI (OR: 0.48, 95% CI 0.29–0.78; p = 0.003) and cranial nerve injuries (OR: 0.09, 95% CI 0.05, 0.16; p < 0.001) were significantly reduced compared to CEA. Beyond 30 days, the efficacy of the CAS group vs. CEA for ipsilateral stroke prevention, restenosis rates and the need for repeat revascularization was comparable in all trials.
A retrospective study analyzed data on 22,516 Medicare patients with a mean age of 76.3 years from the Centers for Medicare & Medicaid Services (CMS) database who underwent CAS with embolic protection between 2005 and 2009. Approximately half of the patients were symptomatic, 91.2% were at high surgical risk, and 97.4% had carotid stenosis > 70%. Overall, patients had high medical comorbidities which included ischemic heart disease, heart failure, diabetes, and peripheral arterial disease. Approximately 25% had undergone coronary artery bypass graft (CABG) during the prior year, and 27.8% were admitted nonelectively for CAS. At 30 days the mortality was 1.7% with stroke or TIA in 3.3%. From 30 days to 4 years of follow-up, the mortality rate was 32.0% and the stroke or TIA rate was 9.1%. Periprocedure mortality and stroke/TIA risks were highest for patients who were symptomatic, > 80 years of age, treated nonelectively with CAS, and at high surgical risk with a symptomatic stenosis > 50%. The mortality risk exceeded one-third for patients who were > 80 years old, symptomatic, at high surgical risk with symptomatic carotid stenosis > 50% and admitted nonelectively. This paper suggested that the benefits of treatment seen in randomized controlled trials may not apply to the wider population, especially for patients who are older, > 80 years of age, and with a high burden of comorbidities.
The ACT 1 clinical trial published in 2016, compared carotid artery stenting with embolic protection and carotid endarterectomy in patients < 79 years of age who had severe carotid stenosis and were asymptomatic without a prior stroke, TIA, or amaurosis fugax in the 180 days before enrollment, and who were not considered to be at high risk for surgical complications. The trial was designed to enroll 1658 patients but was halted early, after only 1453 patients underwent randomization, because of slow enrollment. Patients were followed up to 5 years. The primary composite end point of death, stroke, or myocardial infarction within 30 days after the procedure or ipsilateral stroke within 1 year was tested at a non-inferiority margin of 3%. Stenting was non-inferior to endarterectomy with regard to the primary composite end point (event rate, 3.8% and 3.4% respectively; P = 0.01 for non-inferiority). The rate of stroke or death within 30 days was 2.9% in the stent group vs. 1.7% in the CEA group (P = 0.33). From 30 days to 5 years after the procedure, the rate of freedom from ipsilateral stroke was 97.8% in the stent group vs. 97.3% in the CEA group. In conclusion, for asymptomatic patients with severe carotid stenosis who were not at high risk for surgical complications, stenting was non-inferior to CEA with regard to the rate of the primary composite end point at 1 year. At 5 years of follow up, there were no significant differences between the study groups in the rates of non-procedure-related stroke, all stroke, and survival.
In summary, although carotid angioplasty and stenting has become integrated into many clinical practices, additional ongoing clinical trials will further define the most suitable patients, the long-term patency, and the benefits of embolic protection devices and other endovascular techniques such as flow reversal, proximal and distal balloon protection, proximal cerebral protection, and direct puncture of the common carotid artery combined with carotid artery stenting. Current clinical trials , indicate that carotid stenting for both symptomatic patients and for patients with asymptomatic severe carotid stenosis who were not at high risk for surgical complications is non-inferior to CEA both in the peri-procedure period and at long term follow up. Additional clinical trials are still on-going regarding randomizing asymptomatic patients with severe carotid stenosis to best medical treatment vs. stenting vs. CEA.
Preanesthesia Assessment
The aims of preoperative assessment of CEA include: (1) risk stratification, (2) evaluation of the benefits and risks of revascularization to guide the decision to either proceed to CEA or alternative therapy such as carotid stenting, (3) optimization of preexisting medical conditions, (4) identification of occult cardiac conditions or risk factors that warrant immediate and/or long-term management, and (5) formulation of an anesthetic plan, particularly in relation to the choice of anesthetic techniques and intraoperative neurological monitoring. However, achieving all these aims is challenging because current evidence suggests that outcomes are improved by timely access to surgery. On the basis of a combined 5-year analysis of symptomatic patients in the North American Symptomatic Carotid Endarterectomy Trial (NASCET) and European Carotid Surgery Trial (ECST), the benefit of CEA is highest (greatest risk reduction for perioperative stroke or death) when the procedure is performed within 2 weeks of the ischemic event. These investigators report that the NNT is 5 if patients were randomly assigned to therapy within 2 weeks of the index event and 125 if they were randomly assigned more than 12 weeks after the index event. Furthermore, the benefit from surgery declines more rapidly in women than in men.
Despite the clear benefit of timely surgery, many centers are challenged to perform surgeries within 2 weeks of the onset of symptoms. , Current AHA guidelines for symptomatic patients suggest it is reasonable to proceed to revascularization (CEA or CAS) within 2 weeks of the index event when there are no contraindications to early intervention. Preoperative assessment, investigation and optimization should be conducted in an efficient and timely manner with special consideration of the rapid decline of treatment benefits in symptomatic CEA patients.
The preoperative visit should include an assessment of the patient’s state of health based on history, pertinent physical examination, and chart review. The head and neck should be examined to identify potential airway problems or evidence of positional ischemia. Catheter angiography or magnetic resonance angiography should also be reviewed to identify patients at higher risk due to high-grade contralateral carotid disease or poor collateral circulation. Special attention should be directed toward the assessment of coexisting disease.
A variety of indices have been proposed over the years to identify patients at risk of perioperative stroke or death. The risk stratification scheme for patients undergoing CEA that was proposed and validated by Sundt and colleagues , combines medical, neurologic, and radiologic risk factors to determine the risks of postoperative morbidity (neurologic and cardiac) and mortality ( Tables 16.3 and 16.4 ). This scheme has been in widespread use in the neurosurgical field since the mid-1970s and continues to provide a helpful overview of some factors that contribute to perioperative complications.
| Risk Group | Characteristics | Total Morbidity and Mortality (%) |
|---|---|---|
| 1 | Neurologically stable, no major medical or angiographic risk | 1 |
| 2 | Neurologically stable, significant angiographic risk, no major medical risk | 2 |
| 3 | Neurologically stable, major medical risk, major angiographic risk | 7 |
| 4 | Neurologically unstable, major medical or angiographic risk | 10 |
| Type of Risk | Risk Factors |
|---|---|
| Medical risk | Angina |
| Myocardial infarction (< 6 months) | |
| Congestive heart failure | |
| Severe hypertension (> 180/110 mmHg) | |
| Chronic obstructive lung disease | |
| Age > 70 years | |
| Severe obesity | |
| Neurologic risk | Progressing deficit |
| New deficit (< 24 hours) | |
| Frequent daily transient ischemic attacks | |
| Multiple cerebral infarcts | |
| Angiographic risk | Contralateral carotid artery occlusion |
| Internal carotid artery siphon stenosis | |
| Proximal or distal plaque extension | |
| High carotid bifurcation | |
| Presence of soft thrombus |
Two relatively newer indices were developed from large population-based cohorts addressing the perioperative risks of stroke and death associated with CEA—the Halm index was proposed in 2005 and revisited in 2009 and the Tu index proposed in 2003 ( Table 16.5 ). As expected, the performance of two these indices is heavily affected by the characteristics of the study population from which the cohorts were derived. The Tu index was derived from a study of Canadian patients with a substantially higher burden of symptomatic carotid disease (69% of study population) and lower incidence of coronary artery disease (CAD), whereas, the Halm index was derived from an American population that included more asymptomatic CEA patients (71% of study population) with a much higher incidence of underlying CAD. It is unclear whether the Tu index represents a more reliable predictor in circumstances in which the majority of patients presenting for CEA have symptomatic disease and the Halm index represents a better model for asymptomatic patients. Despite the fact that these two large cohorts were derived from two substantially different populations, they share many common factors. The presence of significant heart disease (especially a history of coronary artery disease, congestive heart failure and atrial fibrillation), the presence of significant contralateral carotid occlusion, and a history of recent TIA or stroke as the indication of surgery are associated with higher risks of perioperative stroke or death. Similarly, consistent with the risk factors identified by Sundt and colleagues, , Halm and coworkers found the patients presenting with acute stroke or unstable ischemic neurologic symptoms (e.g., crescendo TIAs and stroke-in-evolution), face a particularly ominous prognosis in relation to CEA, with combined rates of death and stroke of 28.6% and 57.1%, respectively, on the basis of this study experience.
| Odds Ratio for Death and Stroke (95% CI) * | Odds Ratio for Fatal and Nonfatal Stroke (95% CI) | |
|---|---|---|
| Halm Index (n = 9308) | ||
| Stroke as indication for sugery | 2.4 (1.74–3.31 | 2.54 (1.79–3.59) |
| Active coronary artery disease | 1.51 (1.2–1.91) | 1.38 (1.08–1.75) |
| Contralateral stenosis (> 50%) | 1.44 (1.15–1.79) | 1.42 (1.11–1.80) |
| Tu Index (n = 6038) | ||
| History of stroke and transient ischemic attack(s) (< 6 months) | 1.75 (1.39–2.20) | 1.84 (1.42–2.39) |
| Contralateral carotic occlusion | 1.72 (1.25–2.38) | Not applicable |
| History of atrial fibrillation | 1.89 (1.29–2.76) | 1.83 (1.18–2.83) |
| History of congestive heart failure | 1.80 (1.15–2.81) | 1.86 (1.12–3.08) |
| History of diabetes | 1.28 (1.01–1.63) | Not applicable |
* “Death and stroke” indicates the rate of death and nonfatal stroke combined within 30 days.
Cardiac complications have been reported to be a primary source of mortality associated with CEA and CAS. , , , There are several widely used risk stratification schemes that have been developed over the past few decades to predict the perioperative risk of major cardiac events in patients undergoing noncardiac surgery (not specific to CEA), these include the American Society of Anesthesiologists Physical Status Classification system (ASA Classification), the index proposed by Goldman and colleagues, the index proposed by Detsky and associates, and the Revised Cardiac Risk Index (RCRI) ( Table 16.6 ). In addition, the American College of Surgeons (ACS) has recently developed two new risk assessment tools that are based on prospective data derived from more than 1 million operations (not including CEA) across more than 525 hospitals in the United States.
| Revised Cardiac Risk Index (n = 2893) | OR for Major Cardiac Complications (95% CI)* |
|---|---|
| 1. High-risk type of surgery | 2.8 (1.6–4.9) |
| 2. Ischemic heart disease | 2.4 (1.3–4.2) |
| 3. History of congestive heart failure | 1.9 (1.1–3.5) |
| 4. History of cerebrovascular disease | 3.2 (1.8–6.0) |
| 5. Insulin therapy for diabetes mellitus | 3.0 (1.3–7.1) |
| 6. Preoperative serum creatinine level (> 2.0 mg/dL) | 3.0 (1.4–6.8) |
The ACS National Surgical Quality Improvement Program (NSQIP) Myocardial Infarction and Cardiac Arrest (MICA) tool provides an estimate of the risk of perioperative myocardial infarction or cardiac arrest based on an assessment of functional status, creatinine level, ASA Classification, age and surgical site. The authors report that the MICA tool has higher discriminative power for predicting major cardiac events than RCRI in non-cardiac vascular surgery ( http://www.surgicalriskcalculator.com/miorcardiacarrest ).
The ACS NSQIP Surgical Risk Calculator uses 21 patient characteristics and comorbid disease factors to estimate procedure specific risk for 11 different perioperative outcomes including pneumonia, cardiac complications, surgical site infection, venous thromboembolism, renal failure, reoperation, discharge to a high dependency facility and death. The risk stratification indices in current common clinical use (i.e., the ASA Physical Status Classification and the Goldman, Detsky and RCR indices) appear to perform similarly as predictors of postoperative cardiac complications in patients presenting for CEA with one comparative study, using patient data collected originally to derive the Halm index, reporting areas under the ROC curve ranging from 0.58 to 0.66. Each of the four indices also performed similarly as predictors of noncardiac medical complications. Multivariate odds ratios for predicting postoperative cardiac complications following CEA using the RCRI are presented in Table 16.6 . The role of the ACS NSQIP MICA tool or Surgical Risk Calculator for risk stratification for patients presenting for CEA is yet to be evaluated.
The presence of extracranial cerebrovacular disease has been reported to be a strong predictor for CAD. , As a consequence, it is not surprising that patients undergoing CEA are known to have a high incidence of CAD. According to data from Halm’s study, 61% of patients were known to have CAD, 9.4% of patients had a history of congestive heart failure and 4% of patients had active coronary diseases. The incidence of coronary artery disease or previous MI among patients enrolled in the NASCET or the GALA trial was lower but still substantial at 44% and 36%, respectively (see Table 16.1 ). Some investigators have advocated routine coronary angiography prior to CEA to screen for occult CAD; however, little evidence supports the premise that routine preoperative coronary angiography, and consequent prophylactic coronary revascularization, improves cardiac outcome in patients with stable CAD. , It seems more reasonable to assume that all patients presenting for CEA have atherosclerotic heart disease and to evaluate perioperative risk in relation to each patient’s functional status. Current AHA guidelines support the consideration of additional noninvasive testing, such as exercise stress testing, dobutamine stress echocardiography, and dipyridamole myocardial perfusion imaging, in patients scheduled for CEA (elevated risk surgery) with poor or unknown functional capacity. , Testing should be directed toward patients for whom the results are likely to influence perioperative management in light of the time-sensitive nature of CEA in symptomatic patients. Patients with other coexisting cardiac conditions, such as congestive heart failure, arrhythmias and conduction disorders, valvular heart disease or adult congenital heart disease, have significantly higher risks of perioperative cardiac complications and require specific preoperative evaluation and treatment.
Patients with concomitant carotid stenosis and severe CAD may be considered for staged or combined carotid revascularization and CABG procedures. Since the patients with either symptomatic or asymptomatic carotid stenosis undergoing CABG have a significantly higher risk of perioperative stroke, the 2011 AHA guidelines on the management of patients with extracranial carotid and vertebral artery disease recommends that preoperative carotid duplex ultrasound screening is reasonable if any of the following are present: carotid bruit, age > 65 years, peripheral arterial disease, history of TIA or stroke, cigarette smoking, or left main coronary artery disease. Patients with severe carotid stenosis (greater than 80%) who have been symptomatic within the preceding 6 months could be considered for either a staged carotid revascularization procedure (CEA or CAS) prior to CABG or concomitant myocardial and carotid revascularization. However, the benefit of carotid revascularization combined with myocardial revascularization, whether staged or concurrent, for patients with asymptomatic carotid stenosis, including stenotic lesions classified as severe, is not convincing. CABG alone is reasonable for patients with severe asymptomatic carotid stenosis.
Available evidence remains inadequate, due to insufficient prospective data, to allow definitive conclusions to be drawn regarding the staging of CEA with CABG surgery. Some studies have found staged operations are associated with lower risk of perioperative stroke, but with higher risk of myocardial ischemia. In contrast, some case series have reported combined operations are associated with lower risks of MI, stroke, and death than staged operations in patients with symptomatic carotid stenosis. If the procedures are to be staged, complication rates are lower when carotid revascularization precedes CABG. Reviews of the national experiences with CABG alone and combined CEA and CABG operations from the United States and Canada found combined operations have a higher procedural risk of stroke (9.5% and 13%, respectively) compared to CABG surgery alone; however, the overall mortality rates of combined operations in both studies were similar to the rates for CABG alone. Reflecting the state of the literature, a Cochrane systematic review focused on outcome following prophylactic CEA combined with best medical care (versus best medical care alone) in patients undergoing CABG failed to identify any suitably constructed prospective, randomized trials for inclusion and as a consequence was unable to draw any meaningful conclusion.
Carotid angioplasty and stenting is an intuitively less invasive, but unproven option for treating patients requiring carotid revascularization prior to coronary revascularization. In one nonrandomized cohort study, carotid stenting prior to CABG was found to be associated with a lower incidence of stroke (2.4% vs. 3.9%), but similar in-hospital mortality, compared to CEA prior to CABG. More patients with acute coronary syndrome, renal failure, chronic lung disease and hypertension were selected to undergo CAS prior CABG in this cohort, which reflects a clinical preference to use CAS over CEA in patients with multiple comorbidities and the selection bias of this study. In contrast, two systematic reviews reported 30-day outcomes for composite stroke or death following staged CAS and CABG procedures of 9.1% and 12.3% in study populations that were predominantly asymptomatic. , As a consequence, similar to CEA, there is little rigorous published evidence supporting the use of CAS for revascularization prior to, or concomitant with, CABG particularly in neurologically asymptomatic patients.
In addition to the preceding considerations, CAS patients are treated with the platelet-inhibitor clopidogrel for at least 1 month following the procedure to prevent stent thrombosis and stroke but, if continued preoperatively, this treatment would significantly increase the bleeding risk during a subsequent CABG procedure. For patients who can defer CABG for 4–5 weeks, awaiting the completion of antiplatelet therapy is a reasonable option. Alternatively, intravenous heparin therapy may be used to bridge the period between the CAS procedure and proceeding to coronary revascularization.
Over the past decade, considerable interest has also focused on pharmacologic interventions that may reduce the risk of perioperative cardiac events in high-risk patient groups. The aim of therapy is to mitigate perioperative conditions that lead to myocardial supply–demand imbalances or to promote stabilization of the coronary plaque and thereby reduce the incidence of ischemic events. β-Blockers, statins, and aspirin are the most prominent drugs used in this manner.
β-Blockers have attracted widespread interest, with numerous small studies reporting a reduction in the risk of perioperative myocardial infarction with their use. However, many were also heavily criticized for methodologic inadequacies including inadequate power and selection bias. The Perioperative Ischemic Evaluation (POISE) , study was a large-scale multicenter trial designed to address these concerns and reported that the perioperative administration of extended-release metoprolol (100 mg administered orally commencing 2–4 hours preoperatively) to high-risk patients undergoing noncardiac surgery (including major vascular procedures but excluding CEA) reduced the incidence of perioperative myocardial infarction, but was associated with a higher incidence of death, nonfatal stroke, and clinically significant hypotension and bradycardia compared to patients receiving placebo therapy. The 2014 AHA guidelines for the perioperative cardiovascular evaluation and management of patients undergoing noncardiac surgery recommends the perioperative continuation of β-blockers for patients taking long-term β-blocker therapy for established indications, such as the treatment of myocardial infarction, because preoperative discontinuation of established β-blocker treatment has been shown to be associated with increased risk. , , These guidelines also suggest that it may be appropriate to initiate β-blocker therapy for patients undergoing surgery with elevated cardiac risk due to documented cardiac ischemia by preoperative testing and for those with three of more RCRI risk factors prior to surgery. When β-blocker therapy is initiated preoperatively, it is preferable to commence treatment at least 2 to 7 days prior to surgery. β-Blocker treatment should not be initiated on the day of surgery. Notably, although patients undergoing CEA were not included in many previous studies, including the POISE study, the foregoing recommendations regarding the initiation of β-blocker therapy would seem particularly prudent for patients scheduled for CEA, given the nature of the procedure and the attendant risk of stroke. Until further evidence is available to clarify the issue in this group of patients, β-blocker therapy should be only used very cautiously.
The use of statins in the perioperative period has garnered considerable interest over the past decade. While abundant evidence links statin use to primary and secondary prevention of cardiovascular events and stroke in high-risk populations, evidence demonstrating similar benefits in the perioperative setting, particularly among patients undergoing CEA, has been less robust. A recent Cochrane meta-analysis of perioperative statin use for CABG surgery reported a reduction in perioperative atrial fibrillation and length of ICU and total hospital stay as well as a trend toward a lower incidence of myocardial infarction, but no differences in the incidence of death or stroke in this population. However, a similar meta-analysis involving studies that included patients undergoing vascular surgery, including CEA, was unable to draw conclusions due to inadequate evidence. This study reported trends favoring statin use for all-cause mortality and perioperative nonfatal MI (within 30 days), but the trends did not achieve statistical significance. A very recent systematic review of statin use in patients undergoing vascular surgery or endovascular procedures (including CEA and CAS procedures) evaluated data from four randomized controlled trials (RCTs) and 20 observational cohort or case-control studies. The randomized studies contributed 675 patients, and the observational studies contributed 22,861 patients to the analysis. Statin therapy was associated with a lower risk of all-cause mortality, myocardial infarction, stroke, and the composite outcomes of myocardial infarction, stroke, and death. However, these benefits were not reflected in analyses that included only data from the RCTs.
The current AHA guideline for the perioperative cardiovascular evaluation and management of patients undergoing noncardiac surgery support the continuation of statin therapy in patients who are taking these medications prior to surgery. The guidelines also recommend that preoperative initiation of statin therapy would be reasonable for patients undergoing vascular surgery or for patients with indications that support the use of statins who are undergoing an elevated-risk procedure. Perioperative cardiac benefits are believed to relate to plaque-stabilizing properties as well as antioxidant and anti-inflammatory effects. Similar effects have been reported in relation to carotid plaque.
Most patients who present for CEA are currently taking low-dose ASA as medical therapy for the prevention of stroke. Although data from observational studies suggest that preoperative ASA withdrawal increases the risk of adverse cardiac events and thrombotic complications, the POISE-2 trial, which did not include CEA patients, failed to demonstrate any benefit from 200 mg of ASA compared to placebo for major cardiac events or death. In view of its well-established beneficial effects in relation to stroke prevention, most surgeons performing CEA prefer that patients continue low-dose ASA throughout the perioperative period.
Several studies have reported that uncontrolled or inadequately controlled preoperative arterial hypertension (systolic blood pressure > 150–170 mmHg) increases the risk of postoperative hypertension and adverse neurologic outcome after CEA. , Aggressive perioperative control of blood pressure in patients undergoing CEA, including adequate preoperative treatment of hypertension, has been associated with improved outcome. A review of the patient’s blood pressure record to establish a baseline blood pressure range often provides a useful aid to intraoperative hemodynamic management.
For patients with diabetes mellitus, blood glucose levels should be carefully managed throughout the perioperative period to avoid both hypo- and hyperglycemia. Following acute stroke, current clinical and experimental evidence suggests that hyperglycemia lowers the neuronal ischemic threshold, may increase ischemic volume, and is associated with higher morbidity and mortality. , , Similar findings have also been reported specifically in association with CEA; higher risks for stroke, myocardial infarction, and death have been associated with the presence of hyperglycemia—defined as a blood glucose level greater than 200 mg/dL (11.1 mmol/L)—at the time of surgery.
Hypoglycemia also represents a deleterious condition for the brain. It has also been noted that the development of hypoglycemia is a significant risk when aggressive glycemic control is adopted. , In view of these concerns, perioperative management of blood glucose levels in diabetic patients presenting for CEA should probably be more conservative, in keeping with the recommendations of the AHA guidelines for the management of acute stroke, with blood glucose levels maintained in the range of 140 to 185 mg/dL (7.8–10.3 mmol/L).
Preoperative considerations
Carotid endarterectomy and carotid stenting procedures are interventions designed to reduce the risk of stroke among patients with advanced cerebrovascular disease. Most patients presenting for these procedures are elderly with a variety of comorbidities including, coronary artery disease, arterial hypertension, peripheral vascular disease, chronic obstructive pulmonary disease, diabetes mellitus, renal insufficiency, or a combination of such conditions Based on the medical characteristics of the patients included in NASCET (1991) and the GALA study (2008), published 17 years apart, the burden of these conditions remains substantial among patients presenting for CEA ( Table 16.1 ). As a consequence of these conditions, it is not surprising that CEA and CAS procedures also carry a substantial risk of death or serious morbidity. The benefit of these procedures resides in the fact that for the majority of patients with advanced disease, the risk of stroke or death without intervention is higher than the risk associated with the procedure. Hence, appropriate selection and optimization of candidates for these procedures represent important opportunities to mitigate perioperative risk.
| Proportion of Patients (%) | ||
|---|---|---|
| NASCET a | GALA b | |
| Medical Condition | (n = 2256) | (n = 3526) |
| Angina | 24 | |
| Previous myocardial infarction | 20 | |
| Coronary artery disease | 36 | |
| Hypertension | 60 | 77 |
| Peripheral vascular disease | 14 | 25 |
| Smoker (current or previous) | 77 | 80 |
| Diabetes mellitus | 19 | 25 |
Patient Selection
Overwhelming evidence supports the efficacy of CEA combined with best medical therapy for the prevention of stroke among appropriately selected patients. Three large multicenter randomized trials conducted in North America , and Europe over two decades ago validated the role of CEA in the treatment of patients with symptomatic high-grade carotid disease. Current American Heart Association (AHA) guidelines recommend CEA in symptomatic patients with carotid stenosis of 50% to 99% if the risk of perioperative stroke or death is less than 6%. , Pooled data from the major CEA trials involving symptomatic patients with stenosis greater than 50% support these recommendations and show that the number of patients needed to treat (NNT) to prevent one stroke over a 2-year period is nine for men and 36 for women. Benefit is also greater in older rather than younger patients, particularly those older than 75 years, with an NNT value of 5.
For asymptomatic patients the data are less robust. The risk of stroke is lower in asymptomatic patients than in patients with symptomatic disease and, as a consequence, the benefit of surgical intervention is realized only if the procedure can be performed with a lower 30-day risk of stroke and death. AHA guidelines , recommend CEA for asymptomatic patients with carotid stenosis of 60% to 99% if the perioperative risk of stroke or death is less than 3%.
It is noteworthy in relation to perioperative risk that many studies that support the preceeding recommendations included exclusion criteria that eliminated patients with significant comorbid conditions and many also required that participating surgeons performed a suitable volume of procedures. Consequently, current recommendations for CEA are also influenced by clinical factors that may modify the risk and the potential for benefit (stroke prevention), such as life expectancy, age, gender, the presence of coexisting medical conditions, and the outcome performance of the surgeon and surgical team who perform the procedure. It has been noted that published outcomes following CEA as well as CAS procedures, particularly the 30-day incidence of stroke, have been progressively improving over the past two decades, , an observation that has been attributed to recognition of the important impact of surgical training and case volume on outcome as well as to the evolution of medical therapy including better management of comorbid conditions such as hypertension, dyslipidemia and diabetes.
The Role for Carotid Angioplasty and Stenting
Over the past three decades there has been an exponential increase in interest in and use of endovascular approaches for the treatment of carotid artery stenosis. This increase has paralleled the growth in the use of these techniques in other vascular specialties, especially in the coronary and peripheral vascular beds. Further impetus has come from advances in catheter, balloon, stent, and endovascular emboli trapping device development and has been encouraged by recognition of the many potential advantages of endovascular approaches, particularly in high-risk patients ( Table 16.2 ). The benefits of an endovascular approach include: it is “minimally invasive”; it avoids surgical wounds and their complications; and endovascular procedures can generally be accomplished with local anesthesia and sedation.
| Previous carotid endarterectomy |
| Contralateral carotid artery occlusion |
| Previous radical neck dissection or radiation therapy to neck region |
| Target lesion above C2 (level of jaw) or low cervical carotid lesions |
| Carotid dissection |
| Tandem lesions with ≥ 70% stenosis, intracranial stenosis, or occlusion |
| Significant cardiorespiratory comorbidity |
| Requires concurrent major cardiac or aortic surgery |
| Inability to extend neck |
| Contralateral laryngeal nerve palsy |
| At risk for wound infection (e.g., immunosuppressed, tracheostomy) |
The technique employs standard endovascular approaches from a transfemoral arterial approach. Patients are routinely pre-medicated with ASA 325 mg and clopidogrel 75 mg 3–5 days prior to the procedure. A diagnostic catheter is advanced under fluoroscopic guidance and the vascular anatomy of the aorta, neck, and head are imaged. Once the vessel to be treated is fully defined, an 8.0 F guiding catheter or 6.0 F long sheath is placed from the femoral artery and proximal to the lesion in the mid-low cervical common carotid artery. After systemic heparinization is given (70–100 units/kg) and an activated clotting time (ACT) is confirmed to be increased by two times the baseline, a fine (e.g., 0.014″) steerable guide wire, in combination with a distal filter protection device, is advanced across the stenosis and deployed 2–4 cm distal to the lesion to be treated. The distal filter devices are expandable umbrella-like devices that are deployed distal to the stenosis to trap emboli that may be released during the angioplasty and stent deployment. The appropriate size (e.g., 2.5–4 mm × 20–40 mm) angioplasty balloon is then placed across the stenosis, and once positioned it is inflated to high pressure (up to 8–12 atm) for 60–120 seconds to pre-dilate the stenotic lesion. Aggressive balloon dilation may increase the risk of complications with vessel dissection and/or embolization of the plaque, and residual stenosis is mostly related to calcification, which does not resolve with repeated dilations. Thereafter a nitinol or stainless steel self-expanding stent of appropriate length (2–4 cm) and diameter (4–10 mm) is then deployed across the lesion to completely bridge and cover the plaque in both the cervical internal and/or common carotid arteries. Following stent deployment, a larger angioplasty balloon, which matches the normal luminal diameter of the cervical internal carotid and/or the common carotid arteries are then used to dilate the lesion to > 80–100% of the normal lumen, to ensure maximal restoration to normal vessel size is achieved.
Following final balloon angioplasty across the stented lesion, the distal filter protection device is then recaptured, and withdrawn. A post-stent angiogram is then performed to insure restoration of normal luminal diameter, full patency of the stent, and normal filling of the more distal intracranial blood vessels are maintained. The patient is then rechecked neurologically, and in most instances, a femoral arterial closure device is placed to ensure hemostasis. Patients are usually monitored in the neuro ICU or another high-dependency monitoring environment for 24 hours and, if stable, discharged home on ASA 325 mg indefinitely and clopidogrel 75 mg for at least 6–12 weeks post stenting.
Major Randomized Trials Comparing Carotid Artery Stenting versus Carotid Endarterectomy
The SAPPHIRE (Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy) trial was a non-inferiority randomized controlled clinical trial in which 334 patients, judged to be at high risk for CEA, and who were either symptomatic (transient ischemic attack (TIA) or stroke) with a > 50% stenosis or asymptomatic with a > 80% stenosis were randomized to CEA (n = 167) or CAS (n = 167). The primary endpoint was a composite of death, stroke, or myocardial infarction (MI) within 30 days or ipsilateral stroke and/or death from 31 days to 1 year. There was no statistical difference between CAS versus CEA at 30 days (cumulative incidence 20.1%; absolute difference, − 7.9%; p = 0.004 for non-inferiority). At 1 year, carotid restenosis requiring treatment was less for CAS than CEA (cumulative incidence, 0.6% vs. 4.3%; p = 0.04). In symptomatic patients at 1 year, the primary endpoint for CAS was 16.8% vs. CEA was 16.5% (p = 0.95). For asymptomatic patients at 1 year, the primary endpoint for CAS was 9.9% vs. CEA was 21.5% (p = 0.02).
The Stent-Supported Percutaneous Angioplasty of the Carotid Artery vs. Endarterectomy (SPACE) trial was a non-inferiority study comparing CAS vs. CEA in symptomatic patients. A total of 1200 patients, were randomly assigned to CAS (n = 605) versus CEA (n = 595) within 180 days of a TIA or stroke. The primary endpoint was ipsilateral ischemic stroke or death at 30 days post procedure. For CAS, the endpoint was 6.84% vs. CEA of 6.34% (absolute difference, 0.51%; 95% confidence interval; p = 0.09 for non-inferiority). Embolic protection devices were only used in a small percent of cases. At 30 days and 2 years, the outcomes between the two groups were comparable.
The Endarterectomy versus Angioplasty in Patients with Symptomatic Severe Carotid Stenosis (EVA-3S) trial was a multicenter non-inferiority randomized controlled trial comparing CAS vs. CEA in asymptomatic patients with a stenosis > 60%. The primary endpoint was the incidence of any stroke or death within 30 days. At 6-month follow-up, the incidence of any stroke or death for CAS was 11.7% vs. CEA 6.1% (p = 0.02). The trial was stopped prematurely after 527 of the 872 intended patients were enrolled, for safety and futility. Major criticisms of this study were that embolic protection devices were not required in the CAS arm, and that many of the CAS operators lacked adequate training. At the 4-year follow-up, the death or stroke rate still favored CEA, driven by the 30-day event rate. However, beyond 30 days, no difference in adverse outcomes between CAS and CEA was observed.
The largest randomized controlled trial to date was the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST). A total of 2502 patients, both symptomatic and asymptomatic, with a > 70% stenosis by ultrasound were randomized at 108 centers. Training standards, experience, and competency levels were established prior to enrollment, and an embolic protection system was required in CAS cases. The primary endpoint was a composite of stroke, MI, or death of any cause up to 30 days post procedure, or any ipsilateral stroke during the 4-year follow-up. The primary composite endpoint over a median follow-up period of 2.5 years for CAS was 7.2% vs. CEA 6.8% (Hazard Ratio (HR) = 1.11; 95% CI 0.81–1.51; p = 0.51) and demonstrated no difference. There was no significant difference in the frequency of the primary endpoint between symptomatic and asymptomatic patients. The periprocedure mortality rates were similar, but there were significantly different rates of stroke between CAS of 4.1% vs. CEA 2.3% (p = 0.01) and MI (CAS 1.1% vs. CEA 2.3% [p = 0.03]). The 4-year rate of any ipsilateral stroke for CAS was 2.0% vs. CEA of 2.4% (p = 0.85). The 4-year rate of death alone was similar for CAS of 11.3% vs. CEA of 12.6% (p = 0.45). In terms of quality of life, major and minor strokes had a greater negative impact on quality of life scores (–15.8 points) than did MI (–4.5 points). There was no difference in the primary endpoint rate between men and women with either treatment. Long-term (10-year) results for CREST have been published recently and reported no significant difference in risk between patients who underwent stenting versus endarterectomy in relation to the composite outcomes of peri-procedural stroke, myocardial infarction, or death and for subsequent ipsilateral stroke. Individually, consistent with the 4-year follow-up results, the rate of peri-procedural stroke remained higher among patients who underwent stenting and the rate of peri-procedural myocardial infarction was higher in patients who underwent CEA. The rate of postprocedural ipsilateral stroke did not differ between groups.
The International Carotid Stenting Study (ICSS) was a multicenter randomized controlled trial which enrolled 1713 symptomatic patients with carotid stenosis. The primary endpoint was the long-term rate of any fatal or disabling stroke. An interim safety analysis showed the 120 day rate of stroke, death, or procedure MI for CAS was 8.5% versus CEA of 5.2% (HR: 1.69; 95% confidence intervals (CI) 1.16–2.45; p = 0.006). The incidence of disabling stroke or death at 120 days did not differ between CAS of 4.0% and CEA of 3.2%, but there was an excess of overall strokes in the CAS group (HR: 1.92, 95% CI 1.27–2.89; p = 0.002). The use of an embolic protection device was not mandated. The final results demonstrated that the 5-year risk incidence of a fatal or disabling stroke did not differ between CAS of 6.4% and CEA of 6.5%. Beyond 30 days following carotid artery treatment, there was no difference in the rates of ipsilateral stroke for CAS, which was 4.7% vs. CEA of 3.4% (HR: 1.29, 95% CI 0.74–2.24). There was an excess number of strokes in the CAS patients that persisted, with a 5-year cumulative risk of 15.2% vs. CEA of 9.4% (HR: 1.71, 95% CI 1.28–2.30; p < 0.001), although this did not translate into differences in functional disability and quality of life, as assessed by the modified Rankin scale and EQ-5D questionnaire. In this trial, various stents and protection devices were used for CAS patients at the discretion of the interventionist with only 72% of patients receiving distal protection during the index stent procedure. The study concluded that long-term functional outcome and the risk of fatal or disabling stroke are similar for CAS and CEA for symptomatic carotid stenosis.
A meta-analysis of randomized controlled trials which included 3754 patients treated with CAS vs. 3723 patients undergoing CEA showed that at 30 days, CAS was associated with a significant elevated risk of stroke (Odds Ratio (OR): 1.53, 95% CI 1.23–1.91; p < 0.001), death or stroke (OR: 1.54, 95% CI 1.25–1.89; p < 0.001), while MI (OR: 0.48, 95% CI 0.29–0.78; p = 0.003) and cranial nerve injuries (OR: 0.09, 95% CI 0.05, 0.16; p < 0.001) were significantly reduced compared to CEA. Beyond 30 days, the efficacy of the CAS group vs. CEA for ipsilateral stroke prevention, restenosis rates and the need for repeat revascularization was comparable in all trials.
A retrospective study analyzed data on 22,516 Medicare patients with a mean age of 76.3 years from the Centers for Medicare & Medicaid Services (CMS) database who underwent CAS with embolic protection between 2005 and 2009. Approximately half of the patients were symptomatic, 91.2% were at high surgical risk, and 97.4% had carotid stenosis > 70%. Overall, patients had high medical comorbidities which included ischemic heart disease, heart failure, diabetes, and peripheral arterial disease. Approximately 25% had undergone coronary artery bypass graft (CABG) during the prior year, and 27.8% were admitted nonelectively for CAS. At 30 days the mortality was 1.7% with stroke or TIA in 3.3%. From 30 days to 4 years of follow-up, the mortality rate was 32.0% and the stroke or TIA rate was 9.1%. Periprocedure mortality and stroke/TIA risks were highest for patients who were symptomatic, > 80 years of age, treated nonelectively with CAS, and at high surgical risk with a symptomatic stenosis > 50%. The mortality risk exceeded one-third for patients who were > 80 years old, symptomatic, at high surgical risk with symptomatic carotid stenosis > 50% and admitted nonelectively. This paper suggested that the benefits of treatment seen in randomized controlled trials may not apply to the wider population, especially for patients who are older, > 80 years of age, and with a high burden of comorbidities.
The ACT 1 clinical trial published in 2016, compared carotid artery stenting with embolic protection and carotid endarterectomy in patients < 79 years of age who had severe carotid stenosis and were asymptomatic without a prior stroke, TIA, or amaurosis fugax in the 180 days before enrollment, and who were not considered to be at high risk for surgical complications. The trial was designed to enroll 1658 patients but was halted early, after only 1453 patients underwent randomization, because of slow enrollment. Patients were followed up to 5 years. The primary composite end point of death, stroke, or myocardial infarction within 30 days after the procedure or ipsilateral stroke within 1 year was tested at a non-inferiority margin of 3%. Stenting was non-inferior to endarterectomy with regard to the primary composite end point (event rate, 3.8% and 3.4% respectively; P = 0.01 for non-inferiority). The rate of stroke or death within 30 days was 2.9% in the stent group vs. 1.7% in the CEA group (P = 0.33). From 30 days to 5 years after the procedure, the rate of freedom from ipsilateral stroke was 97.8% in the stent group vs. 97.3% in the CEA group. In conclusion, for asymptomatic patients with severe carotid stenosis who were not at high risk for surgical complications, stenting was non-inferior to CEA with regard to the rate of the primary composite end point at 1 year. At 5 years of follow up, there were no significant differences between the study groups in the rates of non-procedure-related stroke, all stroke, and survival.
In summary, although carotid angioplasty and stenting has become integrated into many clinical practices, additional ongoing clinical trials will further define the most suitable patients, the long-term patency, and the benefits of embolic protection devices and other endovascular techniques such as flow reversal, proximal and distal balloon protection, proximal cerebral protection, and direct puncture of the common carotid artery combined with carotid artery stenting. Current clinical trials , indicate that carotid stenting for both symptomatic patients and for patients with asymptomatic severe carotid stenosis who were not at high risk for surgical complications is non-inferior to CEA both in the peri-procedure period and at long term follow up. Additional clinical trials are still on-going regarding randomizing asymptomatic patients with severe carotid stenosis to best medical treatment vs. stenting vs. CEA.
Preanesthesia Assessment
The aims of preoperative assessment of CEA include: (1) risk stratification, (2) evaluation of the benefits and risks of revascularization to guide the decision to either proceed to CEA or alternative therapy such as carotid stenting, (3) optimization of preexisting medical conditions, (4) identification of occult cardiac conditions or risk factors that warrant immediate and/or long-term management, and (5) formulation of an anesthetic plan, particularly in relation to the choice of anesthetic techniques and intraoperative neurological monitoring. However, achieving all these aims is challenging because current evidence suggests that outcomes are improved by timely access to surgery. On the basis of a combined 5-year analysis of symptomatic patients in the North American Symptomatic Carotid Endarterectomy Trial (NASCET) and European Carotid Surgery Trial (ECST), the benefit of CEA is highest (greatest risk reduction for perioperative stroke or death) when the procedure is performed within 2 weeks of the ischemic event. These investigators report that the NNT is 5 if patients were randomly assigned to therapy within 2 weeks of the index event and 125 if they were randomly assigned more than 12 weeks after the index event. Furthermore, the benefit from surgery declines more rapidly in women than in men.
Despite the clear benefit of timely surgery, many centers are challenged to perform surgeries within 2 weeks of the onset of symptoms. , Current AHA guidelines for symptomatic patients suggest it is reasonable to proceed to revascularization (CEA or CAS) within 2 weeks of the index event when there are no contraindications to early intervention. Preoperative assessment, investigation and optimization should be conducted in an efficient and timely manner with special consideration of the rapid decline of treatment benefits in symptomatic CEA patients.
The preoperative visit should include an assessment of the patient’s state of health based on history, pertinent physical examination, and chart review. The head and neck should be examined to identify potential airway problems or evidence of positional ischemia. Catheter angiography or magnetic resonance angiography should also be reviewed to identify patients at higher risk due to high-grade contralateral carotid disease or poor collateral circulation. Special attention should be directed toward the assessment of coexisting disease.
A variety of indices have been proposed over the years to identify patients at risk of perioperative stroke or death. The risk stratification scheme for patients undergoing CEA that was proposed and validated by Sundt and colleagues , combines medical, neurologic, and radiologic risk factors to determine the risks of postoperative morbidity (neurologic and cardiac) and mortality ( Tables 16.3 and 16.4 ). This scheme has been in widespread use in the neurosurgical field since the mid-1970s and continues to provide a helpful overview of some factors that contribute to perioperative complications.
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