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INTRODUCTION — Transient ischemic attack (TIA) is a brief episode of neurologic dysfunction resulting from focal temporary cerebral ischemia not associated with cerebral infarction. TISSUE-BASED DEFINITION As endorsed by 2009 guidelines from the American Heart Association and American Stroke Association (AHA/ASA), transient ischemic attack (TIA) is defined as a transient episode of neurologic dysfunction caused by focal brain, spinal cord, or retinal ischemia, without acute infarction [1 ]. Ischemic stroke is defined as infarction of central nervous system tissue. TIA was originally defined as a sudden onset of a focal neurologic symptom and/or sign lasting less than 24 hours, presumably brought on by a transient decrease in blood supply, which rendered the brain ischemic in the area producing the symptom. However, this classic definition of TIA was inadequate for several reasons. Most notably, there is risk of permanent tissue injury (ie, infarction) even when focal transient neurologic symptoms last less than one hour. Thus, the benign connotation of "TIA" has been replaced by an understanding that even relatively brief ischemia can cause permanent brain injury. (See 'Relationship of symptom duration and infarction' below.) An earlier proposal for a tissue-based TIA definition noted that clinical symptoms of TIA typically last less than one hour [2 ]. While this is true, the AHA/ASA did not incorporate the phrase "typically less than one hour" in the new definition of TIA because there is no time cutoff that reliably distinguishes whether a symptomatic ischemic event will result in ischemic infarction [1 ]. Another important clinical implication is that TIA, when using the new tissue-based definition, is a low-risk condition [6 ]. It is not an emergency anymore. This is in clear contrast to the conventional time-based definition, in which TIA is regarded as a sign of an imminent stroke. According to a pooled analysis of 3206 patients with TIA who were evaluated with diffusion-weighted MRI, the risk of stroke at seven days was much lower in patients with no infarction compared with those with infarction (0.4 versus 7.1 percent) [4 ]. Thus, prognostic models that incorporate information from acute diffusion-weighted MRI may improve the accuracy of stroke risk prediction after TIA. This issue is discussed separately. (See "Initial evaluation and management of transient ischemic attack and minor stroke", section on 'ABCD2 score'.) OTHER TERMINOLOGY The terms "acute neurovascular syndrome" and "transient symptoms with infarction" (or "cerebral infarction with transient signs") have been proposed to supplement TIA in the description of transient symptoms related to ischemia. Acute neurovascular syndrome With the new tissue-based definitions of stroke and TIA, there may be uncertainty regarding the diagnosis if immediate neuroimaging is not available to detect infarction when transient symptoms of brain ischemia occur [1 ]. The AHA/ASA has proposed (but not formally endorsed) consideration of a term such as "acute neurovascular syndrome" that can be used in this setting until the diagnostic evaluation is completed, or if a diagnostic evaluation is not performed. Transient symptoms with infarction The awareness that a classically defined TIA (<24 hours in duration) can be associated with irreversible ischemic brain injury led to a proposal to label these events as "transient symptoms associated with infarction" (TSI) or "cerebral infarction with transient signs" and to distinguish them from transient symptoms without infarction [7 ].
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Page 1: Tia, Carotid Disease, Cea, Cus

INTRODUCTION — Transient ischemic attack (TIA) is a brief episode of neurologic dysfunction resulting from focal temporary cerebral ischemia not associated with cerebral infarction.

TISSUE-BASED DEFINITION — As endorsed by 2009 guidelines from the American Heart Association and American Stroke Association (AHA/ASA), transient ischemic attack (TIA) is defined as a transient episode of neurologic dysfunction caused by focal brain, spinal cord, or retinal ischemia, without acute infarction [1]. Ischemic stroke is defined as infarction of central nervous system tissue.

TIA was originally defined as a sudden onset of a focal neurologic symptom and/or sign lasting less than 24 hours, presumably brought on by a transient decrease in blood supply, which rendered the brain ischemic in the area producing the symptom. However, this classic definition of TIA was inadequate for several reasons. Most notably, there is risk of permanent tissue injury (ie, infarction) even when focal transient neurologic symptoms last less than one hour. Thus, the benign connotation of "TIA" has been replaced by an understanding that even relatively brief ischemia can cause permanent brain injury. (See 'Relationship of symptom duration and infarction' below.)

An earlier proposal for a tissue-based TIA definition noted that clinical symptoms of TIA typically last less than one hour [2]. While this is true, the AHA/ASA did not incorporate the phrase "typically less than one hour" in the new definition of TIA because there is no time cutoff that reliably distinguishes whether a symptomatic ischemic event will result in ischemic infarction [1].

Another important clinical implication is that TIA, when using the new tissue-based definition, is a low-risk condition [6]. It is not an emergency anymore. This is in clear contrast to the conventional time-based definition, in which TIA is regarded as a sign of an imminent stroke. According to a pooled analysis of 3206 patients with TIA who were evaluated with diffusion-weighted MRI, the risk of stroke at seven days was much lower in patients with no infarction compared with those with infarction (0.4 versus 7.1 percent) [4]. Thus, prognostic models that incorporate information from acute diffusion-weighted MRI may improve the accuracy of stroke risk prediction after TIA. This issue is discussed separately. (See "Initial evaluation and management of transient ischemic attack and minor stroke", section on 'ABCD2 score'.)

OTHER TERMINOLOGY — The terms "acute neurovascular syndrome" and "transient symptoms with infarction" (or "cerebral infarction with transient signs") have been proposed to supplement TIA in the description of transient symptoms related to ischemia.

Acute neurovascular syndrome — With the new tissue-based definitions of stroke and TIA, there may be uncertainty regarding the diagnosis if immediate neuroimaging is not available to detect infarction when transient symptoms of brain ischemia occur [1]. The AHA/ASA has proposed (but not formally endorsed) consideration of a term such as "acute neurovascular syndrome" that can be used in this setting until the diagnostic evaluation is completed, or if a diagnostic evaluation is not performed.

Transient symptoms with infarction — The awareness that a classically defined TIA (<24 hours in duration) can be associated with irreversible ischemic brain injury led to a proposal to label these events as "transient symptoms associated with infarction" (TSI) or "cerebral infarction with transient signs" and to distinguish them from transient symptoms without infarction [7].

While TSI in general has smaller infarct volumes than classically defined ischemic stroke (where neurologic deficits persist for ≥24 hours), there is no unique size that differentiates TSI from ischemic stroke [7].

Patients with TSI have a higher short-term risk of recurrent ischemic stroke than patients who have transient symptoms without infarction. This conclusion is supported by a number of head CT and diffusion-weighted MRI studies [4,7-11].

Cerebrovascular disease is caused by one of several pathophysiologic processes involving the blood vessels of the brain:

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The process may be intrinsic to the vessel, as in atherosclerosis, lipohyalinosis, inflammation, amyloid deposition, arterial dissection, developmental malformation, aneurysmal dilation, or venous thrombosis.

The process may originate remotely, as occurs when an embolus from the heart or extracranial circulation lodges in an intracranial vessel.

The process may result from inadequate cerebral blood flow due to decreased perfusion pressure or increased blood viscosity.

The process may result from rupture of a vessel in the subarachnoid space or intracerebral tissue.

 

The first three processes can lead to transient cerebral ischemia (transient cerebral ischemic attack or TIA) or permanent cerebral infarction (ischemic stroke), while the fourth results in either subarachnoid hemorrhage or an intracerebral hemorrhage (primary hemorrhagic stroke).

PATHOPHYSIOLOGIC MECHANISMS — A transient ischemic attack (TIA) should be considered a syndrome. These syndromes are conveniently divided into three pathophysiologic mechanisms:

 

Large artery low-flow TIA (true TIA) Embolic TIA, which may be artery-to-artery, or due to a cardioaortic or unknown source Lacunar or small penetrating vessel TIA

 

Large artery low flow TIA — Large artery low-flow TIAs are brief (usually minutes to a few hours), recurrent, and stereotyped. They are often associated with a tightly stenotic atherosclerotic lesion at the internal carotid artery origin or in the intracranial portion of the internal carotid artery (siphon) when collateral flow from the circle of Willis to the ipsilateral middle or anterior cerebral artery is impaired (figure 1 and figure 2). Other important causes include atherosclerotic stenotic lesions in the middle cerebral artery stem (figure 3) or at the junction of the vertebral and basilar artery. Any obstructive vascular process in the extracranial or intracranial arteries can cause a low-flow TIA syndrome if collateral flow to the potentially ischemic brain also is impaired.

Embolic TIA — Embolic TIAs are characterized by discrete, usually single, more prolonged (hours) episodes of focal neurologic symptoms. As an example, in one study that divided patients with TIAs into those with symptoms of short duration (less than 60 minutes) or long duration (60 minutes or greater), the latter group was more likely to have an embolic source (86 versus 46 percent) [7]. The embolus may arise from a pathologic process in an artery, usually extracranial, or from the heart (eg, atrial fibrillation or left ventricular thrombus). An ischemic stroke with infarction has occurred if symptoms or signs persist beyond 24 hours. However, as previously mentioned, symptoms that last less than 24 hours (often only as long as one hour) also may be associated with some infarction. If the primary pathologic process is thought to be embolic, a diligent search for its source is necessary before therapy to prevent future stroke can be initiated. (See "Secondary prevention for specific causes of ischemic stroke and transient ischemic attack".)

Lacunar TIA — Lacunar or penetrating or small vessel TIAs are due to transient cerebral ischemia induced by stenosis of one of the intracerebral penetrating vessels arising from the middle cerebral artery stem, the basilar or vertebral artery (figure 4), or the circle of Willis (figure 1 and figure 2). Occlusion of these small intracerebral penetrating vessels usually is due to lipohyalinosis from hypertension, but also may arise because of atheromatous disease at their origin. Occasionally, recurrent stereotyped TIAs occur; in this setting, the term lacunar or small vessel TIAs seems appropriate.

CLINICAL MANIFESTATIONS — The symptoms of a transient ischemic attack (TIA) depend upon the pathophysiologic subtype.

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Low-flow TIA — Low-flow TIAs usually are short-lived (minutes) and often recurrent. They may occur as little as several times per year but typically occur more often (once per week or up to several times per day).

Low-flow TIAs are generally stereotyped, especially when they are due to hemodynamically significant stenotic lesions at the origin of the internal carotid artery, at the siphon portion of the internal carotid artery where collateral flow to the circle of Willis is inadequate, or in the middle cerebral artery stem. Symptoms due to ischemia from these lesions often include hand, arm, leg, face, tongue, or cheek numbness or weakness together, or a combination of one or more. Recurrent aphasic syndromes appear when there is focal ischemia in the dominant hemisphere, and recurrent neglect occurs in the presence of focal or nondominant hemisphere ischemia.

In contrast, recurrent symptoms are often not stereotyped when the stenotic lesion that obstructs flow involves the vertebrobasilar junction or the basilar artery. The many closely packed neuronal structures in the brainstem preclude consistent manifestations of recurrent focal ischemia in this area.

Nevertheless, certain generalizations about recurrent low-flow TIA symptoms in the posterior circulation can be made.

 

Obstructive lesions in the distal vertebral artery or at the vertebrobasilar junction usually cause disorganized dizziness that may or may not include spinning or vertigo. The patient may complain that the room is tilting or that the floor is coming up at them, rather than spinning dizziness. Patients most often use the word dizziness to describe a myriad of symptoms, not necessarily spinning. Other symptoms may include numbness of one side of the body or face, dysarthria, or diplopia.

Ischemia in the pons from stenotic lesions in the proximal to midbasilar artery can cause bilateral leg and arm weakness or numbness and a feeling of heaviness in addition to dizziness. Patients often say it feels as though all of their energy has been drained. They may speak of a feeling of impending doom.

Ischemia in the territory of the top of the basilar artery or proximal posterior cerebral artery may present with all of the above recurrent symptoms as well as overwhelming drowsiness, vertical diplopia, eyelid drooping, and an inability to look up. Transient ischemia at the top of the basilar artery is usually due to embolism rather than low-flow TIA.

 

Embolic TIA — Embolic TIAs typically last hours rather than minutes as in low-flow TIAs. They may be infrequent since they are the result of emboli from a specific source (eg, a one, two, or three-time phenomenon). When the source of the embolus is in a proximal vessel, recurrent emboli can lodge in different branches of the parent vessel giving different symptoms.

Emboli are subject to natural thrombolysis and migration since they typically break off of fresh thrombus. They may produce transient ischemia on many occasions, but an element of silent infarction remains. Emboli may be better referred to as acceptable minor embolism (ACME), a term coined by C Miller Fisher.

Embolic TIAs are best divided into those in the anterior cerebral circulation (carotid, ACA, MCA territory) and those in the posterior cerebral circulation (vertebrobasilar, posterior cerebral artery territory). Symptoms in both circulations depend upon the size of the embolic fragment in relation to the size of the artery occluded.

Embolic TIAs in the anterior circulation may be large enough to occlude the middle cerebral artery stem, producing a contralateral hemiplegia secondary to ischemia in the deep white matter and basal ganglion/internal capsule lenticulostriate territory (figure 5). In addition, they may produce cortical surface symptoms when pial collateral flow is inadequate. These include aphasic syndromes in the dominant hemisphere and anosognosia or neglect in the nondominant hemisphere.

Smaller emboli that occlude branches of the middle cerebral artery stem result in more focal symptoms, including hand alone or arm and hand numbness, weakness, and/or heaviness induced by

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ischemia to the frontal area of the contralateral frontal lobe motor system (figure 3). The symptoms also may be as specific as thumb or hand numbness or a swollen feeling, suggesting focal ischemia in the hand area of the sensory strip or parietal association cortex. Transient unilateral visual obstruction often signifies atherothrombotic disease in the internal carotid artery proximal to the ophthalmic artery takeoff. Atherothrombotic disease is most often responsible for these syndromes, although carotid dissection and embolism from the aorta, heart, or an unknown source also should be considered.

Posterior circulation territory embolic TIAs are generally produced by emboli arising from atherothrombotic disease at the origin or distal segment of one of the vertebral arteries or of the proximal basilar artery. Emboli arising from the aortic arch, the heart, an unknown source, or from a dissecting lesion in the vertebral artery should also be considered.

Symptoms vary according to the vertebral or basilar artery branch in which the emboli lodges (figure 6). Emboli can produce transient ataxia, dizziness, diplopia, dysarthria, quadrantanopsia, hemianopsia, numbness, crossed face and body numbness, and focal hearing loss. When the top of the basilar artery is embolized, sudden, overwhelming stupor or coma may ensue due to bilateral medial thalamic, subthalamus, and medial rostral midbrain reticular activating system ischemia. Emboli in the more distal branches of the posterior cerebral artery may result in a homonymous field defect or in memory loss (inferior medial temporal lobe ischemia).

Lacunar or small vessel TIA — Lacunar or small vessel TIAs are thought to be caused by atherothrombotic obstructive lesions at the origin of the penetrating vessel or lipohyalinosis distally. Embolism is rarely proposed as the mechanism. These small vessel TIAs cause symptoms that are similar to the lacunar strokes that are likely to follow. Thus, face, arm, and leg weakness or numbness due to ischemia in the internal capsule, pons, or thalamus may occur, similar to the symptoms due to ischemia from embolism or large vessel atherothrombotic disease or dissection. As a result, serious disease in the parent vessel must be excluded before the diagnosis of lacunar or small vessel TIA can be established with confidence.

Lacunar infarcts may be preceded by lacunar TIAs consisting of brief repetitive stereotyped clinical symptoms and signs, and lacunar stroke onset may be stepwise and progressive rather than abrupt [8-10]. Such a pattern of TIAs, or nonsudden onset in association with a lacunar syndrome, is highly suggestive of small vessel lipohyalinotic etiology [11].

IMPORTANT PATHOLOGIC PROCESSES — There are four pathologic processes that give rise to low-flow "true" TIAs or embolic TIAs and that can produce sudden devastating stroke if not recognized and treated.

 

Atherothrombotic stenotic lesions at the origin of the internal carotid artery that are narrowed more than 70 percent

Intracranial atherothrombotic disease that produces low-flow or embolic TIA due to lesions at the distal vertebral artery/vertebrobasilar junction/proximal basilar artery

Emboli to the top of the basilar artery or the middle cerebral artery stem that come from a source below, either arterial, aortic, or cardiac

Dissection lesions at the origin of the petrous portion of the internal carotid artery or at the C1-2 level of the vertebral artery as it enters the foramen transversarium

 

Internal carotid artery TIA — An atherothrombotic stenotic lesion at the origin of the internal carotid artery that is narrowed to more than 70 percent of its normal lumen diameter poses a threat of embolic or low-flow TIA or stroke [12-15]. Even a 50 percent stenosis may be important when considering carotid endarterectomy for prevention of a secondary stroke or of a primary stroke when a TIA has occurred. (See "Management of symptomatic carotid atherosclerotic disease".)

Prospective natural history studies of asymptomatic atherothrombotic disease at the origin of the internal carotid artery (mostly asymptomatic carotid artery bruits) suggest that the rate of ipsilateral stroke increases dramatically when the residual lumen diameter narrows to greater than 70 percent

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stenosis (figure 7 and figure 8) [16-18]. In one series of 500 patients, for example, the incidence of stroke was 1.7 percent per year overall but 5.5 percent per year in those with more than a 75 percent carotid artery stenosis [17].

This degree of stenosis corresponds to a residual lumen diameter of 1.5 mm, the precise point at which pressure drops across the stenotic lesion [19,20]. When the pressure drops, flow to the ipsilateral middle cerebral artery stem is in part supplied by collateral circulation from the circle of Willis and from the external carotid to ophthalmic to distal internal carotid artery system (figure 1 and figure 2). Less flow is provided by the internal carotid artery as the lesion further narrows. We believe that this provides a milieu for thrombus formation at the site of the stenosis and subsequent embolism. When the circle of Willis is compromised, low-flow "true" TIA ensues.

Intracranial atherothrombotic disease — Intracranial atherothrombotic disease that produces low-flow or embolic TIA most commonly occurs at the distal vertebral artery/vertebrobasilar junction/proximal basilar artery site. The potential of this lesion to precipitate a disastrous stroke by thrombosis, thrombus propagation, and embolism is extremely important. The other two most important, but less common, sites include the siphon portion of the internal carotid artery and the middle cerebral artery stem. The common carotid origin and the vertebral artery origin are much less problematic since they only rarely give rise to artery-to-artery emboli.

The ability to noninvasively diagnose and follow these intracranial arterial lesions with precision through MRI angiography, duplex Doppler, and transcranial Doppler flow assessment allows for important preventive therapeutic considerations. (See "Secondary prevention for specific causes of ischemic stroke and transient ischemic attack".)

Arterial, aortic, or cardiac sources of emboli — Emboli at the top of the basilar artery or in the middle cerebral artery stem that come from a source below — arterial, aortic, or cardiac — are extremely important to recognize since they may produce fluctuating symptoms or TIAs prior to a devastating stroke. Transient focal symptoms due to an embolus at these sites occur because blood flow reestablishes itself around the embolus.

The symptoms may return in abundance and produce a stroke when the embolus itself causes a thrombus that further occludes the artery. This can occur hours or even days after the embolus has lodged at the site because it did not migrate or lyse. Acute antithrombotic therapy with heparin may be highly effective in preventing this thrombus propagation and provide the time for spontaneous thrombolysis, although this has not been proven definitively.

Dissection lesions — Dissection lesions at the origin of the petrous portion of the internal carotid artery or at the C1-2 level of the vertebral artery as it enters the foramen transversarium cause symptoms of cerebral ischemia due to low flow or embolism, which occur within minutes, hours, or even days prior to a devastating stroke. Modern Doppler and neurologic imaging technology can establish the diagnosis noninvasively with the necessary precision to permit potentially stroke-saving therapeutic strategies (eg, intravenous heparin).

PROGNOSIS — Patients with transient ischemic attack (TIA) or minor stroke are at increased risk of recurrent stroke. Clinical TIAs associated with neuroimaging evidence of infarction (ie, transient symptoms with infarction or TSI) may be at particularly high risk of ischemic stroke. Therefore, TIA is a neurologic emergency.

SUMMARY AND RECOMMENDATIONS

 

The initial evaluation of suspected TIA and minor (ie, nondisabling) ischemic stroke includes brain imaging, neurovascular imaging, and a cardiac evaluation. Laboratory testing is helpful in ruling out metabolic and hematologic causes of neurologic symptoms. (See 'Initial evaluation' above.)

TIA and minor ischemic stroke are associated with a high early risk of recurrent stroke. The stroke risk in the first two days after TIA is approximately 4 to 10 percent. The ABCD2 score (table 1) may identify patients at high risk of ischemic stroke in this time period, but its predictive performance is not optimal. Risk models that combine information from brain

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imaging, neurovascular imaging, and presumed TIA etiology in addition to the clinical ABCD2score may improve the accuracy of stroke risk prediction after TIA. (See 'Prognosis' above.)

Accumulating evidence suggests that immediate evaluation and intervention after a TIA or minor ischemic stroke reduces the risk of recurrent stroke. For patients who present with TIA or minor ischemic stroke, we recommend implementation of appropriate diagnostic evaluation and stroke prevention treatment without delay, preferably within one day of the ischemic event (Grade 1B). (See 'Urgent treatment' above.)

Risk factor management is appropriate for all patients with ischemic stroke or TIA, and most patients should be treated with all available risk reduction strategies. Currently viable strategies include blood pressure reduction, statins, antiplatelet therapy, and lifestyle modification, including smoking cessation. These interventions are discussed in greater detail separately. (See "Secondary prevention of stroke: Risk factor reduction".)

An overview of the treatment for specific causes of TIA and ischemic stroke is provided separately. (See "Secondary prevention for specific causes of ischemic stroke and transient ischemic attack".)

Some important recommendations apply to select patients with TIA:

 

 

For patients with TIA or ischemic stroke of atherothrombotic, lacunar (small vessel occlusive), or cryptogenic type, we recommend treatment with an antiplatelet agent (Grade 1A). This issue and the choice among specific antiplatelet agents (ie, aspirin, aspirin plus extended-release dipyridamole, or clopidogrel) are discussed separately. (See "Antiplatelet therapy for secondary prevention of stroke".)

For patients with atrial fibrillation and a recent ischemic stroke or TIA, we recommend oral anticoagulation (Grade 1A). We recommend aspirin for patients with atrial fibrillation and cardioembolic stroke who have contraindications to anticoagulant therapy (Grade 1B). Prevention of recurrent stroke in patients with atrial fibrillation reviewed in detail elsewhere. (See "Antithrombotic therapy to prevent embolization in atrial fibrillation".)

Selected patients with recently symptomatic carotid stenosis of 50 to 99 percent who have a life expectancy of at least five years are generally treated with carotid endarterectomy. This issue is discussed in detail separately. (See "Management of symptomatic carotid atherosclerotic disease".)

For patients with TIA or ischemic stroke having carotid endarterectomy, we recommend aspirin at a dose of 81 to 325 mg/day started before surgery (Grade 1A). (See "Carotid endarterectomy", section on 'Aspirin'.)

MECHANISM OF SYMPTOMS — Carotid atherosclerosis is usually most severe within 2 cm of the bifurcation of the common carotid artery, and predominantly involves the posterior wall of the vessel. The plaque encroaches on the lumen of the internal carotid artery and often extends caudally into the common carotid artery. An hourglass configuration to the stenosis typically develops with time.

Regardless of their location, carotid plaques were associated with an increased risk of stroke in an observational study of elderly men and women [2] and an increased risk of mortality in an observational study of elderly men [3]. In addition to a reduction in vessel diameter induced by the enlarging plaque, thrombus can become superimposed on the atheroma which will further increase the degree of stenosis. Thus, the mechanism of stroke may be embolism of the thrombotic material or low flow due to the stenosis with inadequate collateral compensation [1,4-8].

The most compelling argument for emboli as the cause of transient ischemic attack (TIA) and stroke has been the angiographic evidence of a stem or branch occlusion above a carotid stenosis. In

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addition, several investigators have observed material passing through small retinal arteries during an attack of monocular ischemia, and transcranial Doppler ultrasound has verified the passage of formed element emboli into the intracranial cerebral circulation downstream from severe internal carotid artery stenosis [9].

Transient ischemic attacks — Transient ischemic attacks may be due to either low flow or embolization. When TIAs are due to low flow with inadequate collateral blood supply, they are brief, repetitive, stereotyped spells [8,10]. They often herald strokes occurring in the territory of the internal carotid artery.

In comparison, embolic TIAs are usually single and more prolonged, and the symptoms are related to the vascular territories involved. Most often, an embolic ischemic event related to carotid artery stenosis will produce symptoms referable to the middle cerebral artery territory, although the anterior cerebral artery can also be involved. Amaurosis fugax refers to transient monocular blindness caused by a small embolus to the ophthalmic artery.

Total carotid artery occlusion — When the internal carotid artery occludes completely, it can also cause low flow or embolic ischemic events depending upon the adequacy of collateral flow through the orbit and across the circle of Willis. The greatest risk of low flow TIA or stroke is at the time of occlusion; the risk diminishes after the first year [11-13]. There is, however, a phenomenon of delayed stroke, occurring many months after carotid occlusion, presumably due to propagation of thrombus or embolism from the distal portion of the clot [12].

Impaired vasoreactivity — An alteration in cerebral hemodynamic function may be an important factor in the occurrence of symptoms and stroke in patients with carotid stenosis. The prognosis of patients with a stroke due to carotid occlusion may be related to collateral flow [14]. Moreover, symptomatic patients have more impaired cerebrovascular reserve compared to those who are asymptomatic [15].

PLAQUE MORPHOLOGY AND PATHOLOGY — Various features of plaque morphology can be used to identify symptomatic risk. These include:

 

Plaque ulceration Plaque structure and composition Plaque volume

 

Plaque ulceration and rupture — Accumulating evidence supports the notion that carotid plaque ulceration is associated with carotid origin stroke. (See 'Clinicopathologic correlates' below.)

In addition, the presence of ulceration has been linked to transcranial Doppler detection of downstream emboli. However, some earlier studies suggested that ulceration may not increase the risk of carotid symptoms [24]. Furthermore, ulceration is significantly more prevalent in plaques producing severe stenosis. Because symptomatic risk is related to the degree of stenosis, a relationship between ulceration and stroke risk may be explained on this basis alone [22].

Plaque rupture is often the precipitating event in acute coronary syndromes and a similar process may occur with carotid plaques [25-27]. In one report of endarterectomy specimens from 19 symptomatic and 25 asymptomatic patients, plaque rupture was significantly more common in patients with symptoms (74 versus 32 percent) [25].

The pathogenesis of carotid plaques is not as well understood as that of coronary artery plaques, but similar processes are thought to be involved, and a number of factors appear to increase plaque vulnerability to rupture. These include morphologic features (eg, plaque geometry, fibrous cap thickness or thinning, neovascularization, smooth muscle cell proliferation, intraplaque hemorrhage, and endothelial erosion), biochemical mechanisms (eg, inflammation and oxidative stress), and local hemodynamic forces operating along the plaque (eg, wall sheer stress and local pressure) [28-33]. Carotid plaque ulceration and rupture most often involves the upstream (proximal) shoulder of the plaque, where sheer stress is maximal [28,32].

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Oxidative stress, particularly peroxidation of low density lipoproteins that contain arachidonic and linoleic acid, plays a role in the development of atherosclerosis and may promote plaque instability [34]. Inflammation is probably another important contributor to plaque rupture. Studies in coronary artery plaques have shown that the immediate site of plaque rupture or erosion is marked by an active inflammatory process consisting of activated monocytes and macrophages and, to a lesser degree, T cells. With the use of FDG-PET scanning, inflammation can be visualized noninvasively in carotid plaques; the degree of inflammation is significantly greater in symptomatic plaques [35]. The possible clinical use of FDG-PET to target surgery to high risk plaques remains to be determined.

Intraplaque hemorrhage — Several studies suggest that intraplaque hemorrhage is an important marker of symptomatic risk [36-38]. As an example, a systematic review and meta-analysis found that the presence of intraplaque hemorrhage on MRI in 335 patients with symptomatic carotid disease was associated with a marked increase in the risk for recurrent ipsilateral cerebral ischemic events (odds ratio 12.2, 95% CI 5.5-27.1) [38]. Furthermore, the prevalence of intraplaque hemorrhage is increased in patients with carotid stenosis when patients are studied in close proximity to the onset of symptoms [39]. The diminishing prevalence of this finding with increasing time from symptoms is believed to represent indirect evidence that intraplaque hemorrhage is related to symptom production.

However, intraplaque hemorrhage is common in asymptomatic severe plaques and may be unrelated to the production of symptoms. In a series of 43 patients who underwent carotid endarterectomy, for example, examination of the removed plaques revealed no differences with respect to intraplaque hemorrhage or other parameters, between symptomatic and asymptomatic patients [23]. Plaque volume may represent a more accurate marker of plaque evolution and symptomatic risk.

Plaque emboli — Emboli in the carotid and intracranial circulations can be detected by ultrasound. Because of increased impedance, emboli produced an audible chirp and a visual signal on the velocity spectrum. Formed element emboli have been found in patients with cardiac disease and carotid stenosis and in those undergoing invasive vascular procedures, such as coronary artery bypass grafting, endarterectomy, and angioplasty. There is some evidence that an increased number of emboli in patients with asymptomatic carotid stenosis places these patients at higher risk of future symptoms [40].

Together, the results of these studies suggest that plaque ulceration, thrombosis, and inflammation are important in the pathogenesis of carotid origin stroke. Plaque thrombosis may remain active and provide a continual source of embolic material for many months after symptom onset.

CLINICAL MANIFESTATIONS — The clinical manifestations of carotid artery stenosis are a carotid bruit and symptoms of ischemia. Carotid stenosis may also exist in the absence of any clinical signs or symptoms. Classification of the symptomatic status of the artery is important to the neurologist in making diagnostic and treatment decisions. A history of more than one discrete episode occurring in the same carotid territory, especially the combination of ipsilateral ophthalmic and hemispheric events (see 'Ischemic symptoms' below), is very suggestive of underlying carotid disease.

Carotid bruit — An important sign of carotid stenosis is a carotid bruit heard over the site of the stenosis [46]. However, a carotid bruit in asymptomatic patients is a poor predictor for the presence of an underlying carotid stenosis and for the subsequent development of stroke. Similarly, ocular bruits and abnormalities or asymmetries of facial pulses are not reliable predictors of carotid stenosis. These relationships can be illustrated by the following observations:

Some experienced clinicians believe that there are several characteristics of a carotid bruit, if they can be heard, that give an indication of the location and severity of the stenosis [54]:

 

A focal bruit suggests an internal carotid artery stenosis, as opposed to a transmitted cardiac or aortic murmur

A high-pitched bruit suggests increased blood flow velocity in the region of arterial stenosis A long duration bruit in systole suggests a tighter stenosis

 

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These bruit characteristics are most often heard at the origin of the internal carotid artery when the stenosis is ≥70 percent of the lumen diameter and/or the residual lumen diameter is ≤1.5 mm. With that degree of stenosis, the blood pressure drops across the stenotic lesion and cerebral autoregulation begins to compensate for the diminished pressure distal to the lesion [55,56].

Ischemic symptoms — Other symptoms and signs of internal carotid artery stenosis and occlusion reflect ipsilateral ocular and cerebral hemisphere ischemia. These may be transient, representing TIAs, or permanent, resulting in cerebral infarction.

 

Features of ocular ischemia or infarction include partial or complete blindness in one eye and an absent pupillary light response. Funduscopic examination may demonstrate arterial occlusion or ischemic damage to the retina. (See "Etiology and clinical manifestations of transient ischemic attack".)

Hemispheric signs of cerebral infarction from carotid disease include contralateral homonymous hemianopsia, hemiparesis, and hemisensory loss. Specific signs of left hemisphere ischemia include aphasia, while right hemisphere ischemia may be manifest by left visuospatial neglect, constructional apraxia (ie, inability to perform purposeful movements) and dysprosody [10]. (See "Clinical diagnosis of stroke subtypes".)

Atypical symptoms of internal carotid artery stenosis include unilateral limb shaking and transient loss of monocular vision upon exposure to bright light [10,57]. These generally occur as ischemic symptoms downstream from severe internal carotid artery disease. Syncope may be a rare consequence of bilateral carotid occlusive disease.

 None of the above symptoms and signs is specific to carotid stenosis.

Various features of plaque morphology can be used to identify symptomatic risk. These include plaque ulceration, plaque structure and composition, and plaque volume.

Four diagnostic modalities are used to directly image the internal carotid artery:

 

Cerebral angiography Carotid duplex ultrasound Magnetic resonance angiography Computed tomographic angiography

CONVENTIONAL CEREBRAL ANGIOGRAPHY — Cerebral angiography is the gold standard for imaging the carotid arteries. The development of intraarterial digital subtraction angiography (DSA) reduces the dose of contrast, uses smaller catheters, and shortens the length of the procedure. Although there is lower spatial resolution, DSA has largely replaced conventional angiography [7].

Advantages — Cerebral angiography permits an evaluation of the entire carotid artery system, providing information about tandem atherosclerotic disease, plaque morphology, and collateral circulation which may affect management [8]. In addition, the results from one study suggested that the presence of associated intracranial atherosclerotic disease identifies a group that is particularly likely to benefit from carotid endarterectomy [9]. However, pathologic evaluation of the plaque

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specimen provides the most useful data on plaque composition, which may have a bearing on prognosis [10,11].

Disadvantages — The disadvantages of angiography include its invasive nature, high cost, and risk of morbidity and mortality. In a review of prospective studies using cerebral angiography, the risk of all neurologic complications was approximately 4 percent and the risk of serious neurologic complications or death was approximately 1 percent (range 0 to 6 percent) [7]. The risk of morbidity is increased with cerebrovascular symptoms, advanced age, diabetes, hypertension, elevated serum creatinine, and peripheral vascular disease. The size of the catheter, amount of contrast, and procedure duration also affect the likelihood of complications [10]. One study found that embolic events following angiography occur more frequently than the apparent neurologic complication rate [12]; the clinical significance of this finding is unclear.

Although often considered the "gold standard" of carotid neurovascular imaging methods, conventional DSA has the disadvantage of a limited number of projections, typically two or three, depicting the carotid artery and bifurcation. This limitation could lead to an underestimation of the degree of carotid stenosis in arteries that have asymmetrical rather than concentric stenotic lumens [13,14]. Rotational angiography provides 16 to 32 projections and is far less subject to this problem, but it is seldom used in practice.

CAROTID DUPLEX ULTRASOUND — Carotid duplex ultrasound (CDUS) uses B-mode ultrasound imaging and Doppler ultrasound to detect focal increases in blood flow velocity indicative of high grade carotid stenosis [15-17]. The peak systolic velocity is the most frequently used measurement to gauge the severity of the stenosis (image 1), but the end-diastolic velocity, spectral configuration, and the carotid index (or peak internal carotid artery velocity to common carotid artery velocity ratio) provide additional information [18,19].

Color Doppler flow imaging may improve the efficiency of the test, but it has not been shown to improve accuracy [15,17,20,21].

Advantages — Carotid duplex ultrasound (CDUS) is a noninvasive, safe, and relatively inexpensive technique for evaluation of the carotid arteries. It is 81 to 98 percent sensitive and 82 to 89 percent specific in detecting a significant stenosis of the internal carotid artery [15-17,32]. Data based upon the NASCET method of calculating angiographic stenosis showed that a carotid index (peak internal carotid artery velocity ÷ common carotid artery velocity) >4 provided the highest accuracy (sensitivity 91 percent, specificity 87 percent, overall accuracy 88 percent) for predicting a high grade stenosis (70 to 99 percent) [33].

Disadvantages — The absence of flow in the internal carotid artery may be due to occlusion, but hairline residual lumens can be missed on carotid duplex ultrasound (CDUS) [36]. In addition, several studies have found that CDUS tends to overestimate the degree of stenosis [32,37].

CDUS imaging may be limited by features such as calcific carotid lesions, tortuous or kinked carotid arteries, and patient body habitus. Furthermore, CDUS must be interpreted carefully in patients with contralateral carotid occlusion to avoid overestimation of an ipsilateral carotid stenosis, since the peak systolic velocity is often increased in the presence of a contralateral internal carotid occlusion [38]. Another limitation of CDUS is that only the cervical portion of the internal carotid artery can be evaluated, although transcranial Doppler may provide some information about intracranial vessels. (See 'Transcranial Doppler' below.)

TRANSCRANIAL DOPPLER — As an adjunct to carotid Doppler ultrasound (CDUS), transcranial Doppler (TCD) examines the major intracerebral arteries through the orbit and at the base of the brain. TCD is often used in conjunction with CDUS to evaluate the hemodynamic significance of internal carotid artery (ICA) stenosis, and it can be used to improve the accuracy of CDUS in identifying surgical carotid disease [41].

TCD can evaluate the intracranial hemodynamic consequences of high grade carotid lesions, such as the development of collateral flow patterns in the circle of Willis, reversal of flow in the ophthalmic and anterior cerebral arteries, absence of ophthalmic or carotid siphon flow, and reduced MCA flow velocity and pulsatility [42,43].

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An assessment of TCD by the American Academy of Neurology (AAN) concluded that TCD is possibly useful for the evaluation of severe extracranial ICA stenosis or occlusion, but in general CDUS and MRA are the tests of choice [44]. The AAN report noted that the clinical utility of TCD to detect impaired cerebral hemodynamics distal to high grade extracranial ICA stenosis or occlusion and assist with stroke risk assessment requires evaluation and confirmation in randomized clinical trials.

TCD can also be used for detection of middle cerebral artery microemboli that arise from the heart or carotid artery [46]. These are visualized as high intensity signal transients (HITS) within the Doppler spectrum. Mounting evidence from observational studies suggests that asymptomatic cerebral embolism detected by TCD is associated with an increased risk of ischemic stroke in patients with asymptomatic carotid atherosclerotic occlusive disease. This issue is discussed elsewhere. (See "Management of asymptomatic carotid atherosclerotic disease", section on 'Asymptomatic embolism'.)

MR ANGIOGRAPHY — The magnetic resonance angiography (MRA) techniques most often employed for evaluating the extracranial carotid arteries utilize either two or three dimensional time-of-flight (TOF) MRA or gadolinium-enhanced MRA (also known as contrast enhanced MRA or CEMRA). (See "Principles of magnetic resonance imaging".)

MRA produces a reproducible three dimensional image of the carotid bifurcation with good sensitivity for detecting high grade carotid stenosis (image 2). In earlier studies, MRA was found to generally overestimate the degree and length of stenosis [16,55]. However, a later study of three dimensional TOF MRA found that it did not overestimate the degree of stenosis when corresponding MRA and digital subtraction angiography (DSA) projections were compared [56].

Contrast enhanced magnetic resonance angiography (CEMRA) offers several advantages over traditional TOF techniques. The use of a paramagnetic agent acting as a vascular contrast allows for higher quality images that are less prone to artifacts.

Both TOF MRA and CEMRA are accurate for the identification of high-grade carotid artery stenosis and occlusion, but appear to be less accurate for detecting moderate stenosis [57]. The sensitivities of either MRA technique for the identification of carotid artery occlusion or severe stenosis were similar and ranged from 91 to 99 percent, while specificities ranged from 88 to 99 percent.

Compared with carotid duplex ultrasound, MRA is less operator-dependent and does produce an image of the artery. However, MRA is more expensive and time-consuming than carotid duplex ultrasound and is less readily available. Furthermore, MRA may not be performed if the patient is critically ill, unable to lie supine, or has claustrophobia, a pacemaker or ferromagnetic implants [16]. In different series, up to 17 percent of MRA studies are incomplete because the patient could not tolerate the study or could not lie still enough to produce an image of adequate quality for interpretation [58]. Renal insufficiency is a relative contraindication to the use of gadolinium.

Advanced magnetic resonance imaging techniques are being studied to assess whether changes in carotid plaque characteristics – such as rupture of fibrous cap and intraplaque hemorrhage – are reliably associated with an increased risk of subsequent stroke in patients with asymptomatic carotid atherosclerosis [59-61]. (See "Pathophysiology of symptoms from carotid atherosclerosis", section on 'Plaque morphology and pathology'.)

CT ANGIOGRAPHY — Computed tomography angiography (CTA) provides an anatomic depiction of the carotid artery lumen and allows imaging of adjacent soft tissue and bony structures. Three dimensional reconstruction allows relatively accurate measurements of residual lumen diameter. CTA may be particularly useful when carotid duplex ultrasound is not reliable (eg, in cases with severe kinking, severe calcification, short neck, or high bifurcation) or when an overall view of the vascular field is required [62].

An earlier systematic review and meta-analysis that compared CTA with arteriography or digital subtraction angiography concluded that CTA is an accurate method for detection of severe carotid artery disease, particularly for detection of carotid occlusion, where CTA had a sensitivity and specificity of 97 and 99 percent, respectively [63].

CT angiography requires a contrast bolus comparable to that administered during a conventional angiogram. As a result, impaired renal function is a relative contraindication for its use, particularly in

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patients with diabetes or congestive heart failure. (See "Pathogenesis, clinical features, and diagnosis of contrast-induced nephropathy".)

DIAGNOSIS OF COMPLETE OCCLUSION — No surgical treatment has been proven to be of benefit for preventing a subsequent stroke in patients with complete carotid artery occlusion. Thus, it is important to adequately distinguish between completely occluded vessels and those with some remaining flow since the latter group may benefit from carotid revascularization.

Nevertheless, in current practice the combination of MRA and CDUS is probably sufficient for identifying patients with carotid artery occlusion. This was illustrated in a study of 274 patients in whom angiography identified 37 total and 21 near occlusions [70]. Ultrasound adequately identified all angiographically determined total occlusions, but 3 of 21 near occlusions (14 percent) were reported as totally occluded on ultrasound, and one of the three patients was a candidate for carotid endarterectomy. MRA correctly identified 34 of 37 near total occlusions (92 percent) and all total occlusions. The authors concluded that no further imaging is necessary when complete occlusion is suspected on the basis of an initial CDUS study and confirmed on MRA.

CHOICE OF IMAGING TEST — Conventional cerebral angiography has been considered the gold standard for the evaluation of internal carotid artery stenosis [71]. However, angiography is associated with a small but real risk of stroke, which makes it ill suited for use as a screening test. In addition, most patients with ischemic symptoms referable to the carotid vascular territory do not have severe carotid stenosis [72,73]. In one series of 261 patients with carotid territory ischemic strokes and 813 patients with carotid territory TIA, carotid disease was absent in 55 and 64 percent, respectively (and in 69 and 77 percent of those without a carotid bruit) [73].

As a result, patients are generally selected for angiography using one of the noninvasive tests:

 

Carotid duplex ultrasonography (CDUS) Time of flight magnetic resonance angiography (TOF MRA) Contrast enhanced magnetic resonance angiography (CEMRA) Computed tomography angiography (CTA)

 

These noninvasive tests have essentially replaced conventional cerebral angiography in the presurgical evaluation of carotid stenosis. The choice among the noninvasive carotid artery imaging methods depends mainly upon the clinical indications for imaging and the availability and expertise at individual centers [74].

Our general approach to patients with suspected carotid stenosis is to first perform CDUS. Those with stenosis <50 percent are followed with serial examinations, usually on an annual basis, to determine if there is progression. Those with stenosis ≥50 percent are evaluated with transcranial Doppler examination and MRA. CTA is performed in lieu of MRA if there is a contraindication to magnetic resonance imaging and in cases where the CDUS and MRA do not agree. We believe this approach provides optimal care and likely avoids unnecessary carotid revascularization procedures with endarterectomy and stenting [39,40]. However, there is no consensus regarding the optimal imaging evaluations for patients with asymptomatic carotid stenosis detected by ultrasound. Some experts are not persuaded by the limited data suggesting improved outcomes for patients who undergo additional imaging modalities, and question whether additional imaging in asymptomatic patients might actually increase the risk of unneeded interventions in addition to increasing the cost. As noted earlier, many centers rely on a single noninvasive imaging test (most often CDUS) for preprocedural carotid artery evaluation and for serial evaluation of patients with asymptomatic high-grade carotid stenosis.

Conventional angiography is rarely performed; indications include patients who cannot tolerate an MRA and in whom the risk of dye is sufficient to warrant bypassing CTA in favor of the gold standard examination. Angiography is also done if nonatherosclerotic disease is suspected (eg, dissection, vasculitis). Other potential reasons for conventional catheter cerebral angiography include the following [74]:

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Suspected disease affecting the proximal common carotid artery or the origins of the great vessels from the aortic arch

Severe multi-vessel disease, such as combined carotid and vertebral artery disease, for which assessment of blood flow direction and collateral patterns may be informative; however, this information can usually be established using noninvasive methods, and is of questionable value for patients who are asymptomatic

Poor quality of noninvasive imaging Discordant results of noninvasive imaging

ANATOMY AND PHYSIOLOGY — The left common carotid artery (CCA) originates from the aortic arch, whereas the right CCA originates from the innominate artery (figure 1). The CCA divides into the internal carotid artery (ICA) and external carotid artery (ECA) at the level of the superior border of the thyroid cartilage corresponding to the C3/C4 disc space.

External carotid artery — The ECA has multiple branches that supply the face and scalp and provide collateral circulation to the brain. These branches include (caudal to cranial) the superior thyroid, lingual, facial, ascending pharyngeal, occipital, posterior auricular, maxillary, and superficial temporal arteries.

Internal carotid artery — The ICA has no branches in the neck. The cervical segment of the internal carotid extends from the carotid bifurcation until it enters the carotid canal anterior to the jugular foramen. Detailed surgical anatomy of the internal carotid artery is described elsewhere. (See "Carotid endarterectomy", section on 'Internal carotid artery'.)

Carotid baroreceptors — Baroreceptors are stretch-sensitive mechanoreceptors that respond to alterations in blood pressure. The carotid sinus baroreceptors are located within the adventitia of the origin of the internal carotid artery and are innervated by the sinus nerve of Hering, which is a branch of glossopharyngeal nerve. In response to low blood pressure, the nerve fibers decrease their firing rates stimulating the sympathetic nervous system and inhibiting the parasympathetic nervous system via a centrally-acting mechanism.

Carotid sinus reactivity may be impaired in patients with carotid atherosclerosis. (See "Pathophysiology of symptoms from carotid atherosclerosis", section on 'Impaired vasoreactivity'.)

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During carotid stenting, balloon inflation to expand the carotid stent may lead to excessive stimulation of the carotid baroreceptor resulting in hypotension. (See 'Stent placement and dilation' below.)

INDICATIONS — Carotid artery stenting (CAS) is most commonly performed for symptomatic or asymptomatic high-grade (>60 or 70 percent) internal carotid artery stenosis. The indications for CAS are discussed in detail elsewhere. (See "Management of symptomatic carotid atherosclerotic disease", section on 'Carotid endarterectomy' and "Management of asymptomatic carotid atherosclerotic disease", section on 'Carotid endarterectomy'.)

Other considerations

Bilateral carotid stenosis — For patients with severe bilateral carotid stenosis, we suggest a staged approach rather than simultaneous carotid artery stenting [1-3]. A staged approach limits the length of the procedure and intravenous contrast load, whereas simultaneous CAS theoretically increases the risk for cerebral hyperperfusion syndrome, and the risk of severe bradycardia or hypotension related to bilateral baroreceptor irritation [4]. (See 'Carotid baroreceptors' above.)

Prophylactic carotid stenting — Given that prophylactic carotid endarterectomy (CEA) is generally not supported, it may be unreasonable to offer CAS. A decision to proceed should be individualized based upon the risk of perioperative stroke weighed against the risk of bleeding associated with ongoing antiplatelet therapy (eg, clopidogrel, aspirin), which is recommended following CAS. (See 'Perioperative antiplatelet therapy' below and "Coronary artery bypass grafting in patients with cerebrovascular disease", section on 'Carotid artery stenting' and "Carotid endarterectomy", section on 'Prophylactic carotid endarterectomy'.)

Contraindications — Contraindications to carotid stenting include [5] (see 'Risk assessment' below):

 

Absolute:

 

 

Visible thrombus within the lesion Inability to gain vascular access Active infection

 

 

Relative:

 

 

Severe plaque calcification, circumferential carotid plaque Heavily calcified aortic arch Severe carotid tortuosity Near occlusion of the carotid artery (ie, string sign) Inability to deploy a cerebral protection device Age >80

 

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RISK ASSESSMENT — In general, older patients and those with complex calcified aortic arches, or calcified carotid index lesions are considered to have an increased risk of thromboembolic complications and poor outcomes following CAS. With the exception of age, data regarding CAS complication rates in various subgroups are largely drawn from registries and case series. Further evidence from large controlled trials is needed before reaching firm conclusions about the safety and effectiveness of CAS in these various subgroups.

Many of the risk factors identified for carotid stenting (symptomatic carotid disease, increasing degrees of carotid stenosis, and hemispheric TIA) parallel those identified in major trials of carotid endarterectomy, although prospective studies are needed to confirm these findings. (See "Carotid endarterectomy", section on 'Perioperative risk assessment'.)

 

Age – Data from the SPACE trial [6], CREST [7,8], prospective series [9-11], and retrospective reports [2] suggest that patients ≥80 years old have a significantly higher risk of stroke and death at 30 days than younger patients who have CAS. In addition, a retrospective study suggests that patients older than 80 have a higher incidence of unfavorable arterial factors that increase the technical difficulty of CAS, such as aortic arch elongation, arch calcification, common carotid and innominate artery origin stenosis, common and internal carotid artery tortuosity, and a higher risk of residual stenosis post-stenting due to underlying vessel calcification [12].

Carotid plaque morphology – Ulcerated carotid plaque [10], increasing degree of carotid stenosis, and longer carotid lesions are aspects of carotid disease associated with an increased risk for stroke. In one retrospective study, patients with <70, 70 to 89, and ≥90 percent carotid stenosis had stroke rates of 3.5, 5.1, and 14.9 percent, respectively, [2]. Retrospective studies also suggest that long carotid lesions (>10 mm) [2,13], or carotid segments with more than one lesion separated by normal vessel wall are associated with a higher stroke risk [2].

Prior neck irradiation – Patients with prior neck irradiation tolerate CAS with relative safety [9,14-16]. However, in most [17-19], but not all studies [20], the rate of late carotid restenosis and occlusion following CAS was higher in patients who had radiation-induced occlusive disease compared with those who had atherosclerotic carotid disease [18]. Carotid restenosis and occlusion in these reports was largely asymptomatic. (See 'Carotid thrombosis and restenosis' below.)

Contralateral disease – Prospective data suggest that the presence of contralateral carotid stenosis ≥50 percent is associated with a higher risk for stroke after CAS [10]. However, in one study of 26 patients with contralateral occlusion, there was a 96 percent procedural success, and only one patient had a minor stroke, unrelated to stent implantation [21]. There were no neurologic events after a mean follow-up of 16 months.

 These other risk factors include [10,13,22-25]:

 

Presence of aortic stenosis Diabetes mellitus with inadequate glycemic control (hemoglobin A1C >7 percent) Symptomatic compared with asymptomatic ipsilateral carotid stenosis Hemispheric TIA or minor stroke compared with retinal transient ischemic attack (TIA) or no

symptoms Chronic renal insufficiency Emergency admission

 PERIOPERATIVE ANTIPLATELET THERAPY — For carotid artery stenting (CAS), many centers employ a dual antiplatelet regimen similar to that used for percutaneous coronary intervention; however, there is limited evidence regarding the effectiveness of dual antiplatelet therapy and the optimal dosing and duration with CAS is unknown. In the absence of any other robust data, we suggest starting dual antiplatelet therapy, as per the CREST protocol, as outlined below. In addition, we suggest continuing dual antiplatelet therapy with aspirin and clopidogrel for six weeks (rather than four weeks) following the CAS procedure. Aspirin should be continued indefinitely. Radiated patients are at high risk for recurrent carotid stenosis following CAS, as high as 30 percent in some series. For this reason, we

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prefer long-term dual antiplatelet therapy with clopidogrel and aspirin following CAS for patients with a history of neck irradiation, provided the risk of bleeding remains low, although there are no studies available that have specifically evaluated such a protocol in this subset of patients.

CAROTID ARTERY STENTING — Carotid artery stenting can be performed in an angiography suite or appropriately equipped operating room.

Procedure

Percutaneous access — Percutaneous access is typically obtained via the right (or left) common femoral artery. Prior to the procedure, the patient should receive antiplatelet therapy. (See 'Perioperative antiplatelet therapy' above.)

Anticoagulation — Before manipulation of the guidewires and catheters within the carotid artery, the patient should be anticoagulated with heparin to maintain the activated whole blood clotting time (ACT) at 250 to 300 seconds. Bivalirudin can be used as an alternative to heparin. (See "Therapeutic use of heparin and low molecular weight heparin" and "Anticoagulation with direct thrombin inhibitors and factor Xa inhibitors".)

COMPLICATIONS — The most serious acute complication associated with CAS is stroke. Periprocedural stroke may develop from several mechanisms, alone or in combination, including the following:

Thromboembolism Hypoperfusion due to bradycardia and/or baroreceptor stimulation Cerebral hyperperfusion Intracerebral hemorrhage

 

The main strategies used to reduce the risk of thromboembolic complications during and following CAS are appropriate patient selection, perioperative treatment with aspirin and clopidogrel (dual antiplatelet therapy), and optimal intraoperative anticoagulation. (See 'Perioperative antiplatelet therapy' above.)

Some degree of periprocedural bradycardia or hypotension occurs in up to 68 percent of patients [49-52]. Bradycardia is due to carotid baroreceptor stimulation during inflation of the post-stent angioplasty balloon. The reaction is usually self-limited, though the patient may require treatment with atropine if the bradycardia is persistent.

Other complications include myocardial infarction, renal failure, access-related problems, restenosis of the target lesion, and carotid stent fracture.

Hyperperfusion syndrome — The cerebral hyperperfusion syndrome is an uncommon sequela of carotid stenting, and its occurrence after carotid stenting follows a similar path to that of carotid endarterectomy [53]. The syndrome is often heralded by headache ipsilateral to the revascularized internal carotid artery. Focal motor seizures and intracerebral hemorrhage may follow. As with carotid endarterectomy, hypertension is a frequent predecessor of the syndrome, underscoring the importance of adequate control of perioperative blood pressure.

Myocardial infarction — In major randomized trials, the periprocedural incidence of myocardial infarction with CAS has ranged from 1 to 4 percent [8,55]. Risk factors for cardiac complications in noncardiac surgery and management of perioperative MI are discussed in detail elsewhere. (See "Estimation of cardiac risk prior to noncardiac surgery" and "Perioperative myocardial infarction after noncardiac surgery".)

Renal dysfunction — Renal dysfunction following CAS can be related to contrast-induced nephropathy, renal atheroemboli, or renal hypoperfusion due to hemodynamic instability. The risk of contrast nephropathy following CAS is greatest in patients with moderate to severe renal insufficiency and diabetes. (See "Pathogenesis, clinical features, and diagnosis of contrast-induced nephropathy" and "Prevention of contrast-induced nephropathy".)

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Instrumentation of the aorta can lead to atheroembolic events, which in turn can result in renal dysfunction. (See "Clinical presentation, evaluation, and treatment of renal atheroemboli" and "Embolism from atherosclerotic plaque: Atheroembolism (cholesterol crystal embolism)".)

Access-related complications — Access-related issues are the most common complications following CAS and include hematoma, bleeding, pseudoaneurysm formation, and atheroembolization to the lower extremities.

Bleeding/Hematoma/Pseudoaneurysm — Following percutaneous access procedures, inadequate closure of the femoral artery puncture site may lead to bleeding, hematoma, or the formation of a pseudoaneurysm.

The risk factors for pseudoaneurysm development include inadequate post-procedure compression of the puncture site, postprocedural anticoagulation, antiplatelet therapy during the intervention, age >65 years, obesity, hypertension, peripheral artery disease, and hemodialysis. The diagnosis and treatment of access site pseudoaneurysm is discussed elsewhere. (See "Complications of diagnostic cardiac catheterization", section on 'Pseudoaneurysm'.)

The narrow profile of most carotid stenting devices requires a smaller sheath size compared with some vascular interventions (eg, iliac artery stenting) and as such, the incidence of pseudoaneurysm might be expected to be lower. However, the concomitant administration of antiplatelet therapy and anticoagulation contributes to pseudoaneurysm formation. The incidence of femoral pseudoaneurysm is about 3 percent [23,56].

Peripheral embolization — During any aortic catheterization procedure, atheromatous debris can become dislodged from the aortic wall. Clinical symptoms and signs are dependent upon the size of the debris and are discussed in detail elsewhere. (See "Embolism from atherosclerotic plaque: Atheroembolism (cholesterol crystal embolism)" and "Embolism from aortic plaque: Thromboembolism".)

Carotid thrombosis and restenosis — Acute and subacute in-stent thrombosis has been reported in 0.5 to 2 percent of patients with CAS [57,58]. Some cases may be related to inadequate or discontinued antiplatelet therapy [59-61].

Beyond 30 days, early restenosis after carotid revascularization procedures is mainly due to neointimal hyperplasia [62,63]. Reported rates of early restenosis after CAS vary widely. In a systematic review that analyzed 34 carotid stenting studies involving 3814 arteries, angiographic restenosis, defined as ≥50 to 70 percent stenosis (a lower threshold), occurred in about 6 percent of arteries after one year [64]. This compares favorably with reported rates of restenosis in the first 12 to 18 months after carotid endarterectomy, which range from 5.2 to 11.4 percent [65-67].

Stent fracture — Stent fracture may be a common complication of CAS, but its clinical significance is unknown. In a retrospective report of 48 carotid stents in 43 patients, stent fracture was detected at a mean radiologic follow-up of 18 months in 29 percent [71]. The risk of stent fracture was associated with the presence of arterial calcification in the region of the deployed stent (odds ratio 7.7, 95% CI 1.9-32.0). Restenosis >50 percent was present in 3 of the 14 fractured stents and 3 of 34 stents without fracture. Larger prospective studies are needed to determine whether carotid stent fracture is associated with an increased risk of restenosis or ischemic events.

 

INTRODUCTION — Treatment aimed at carotid atherosclerotic lesions may be beneficial for symptomatic or asymptomatic patients. This topic will review the preoperative evaluation and surgical technique of carotid endarterectomy (CEA). The indications for carotid revascularization and perioperative stroke risk assessment for patients with carotid atherosclerosis are discussed elsewhere. (See "Management of asymptomatic carotid atherosclerotic disease" and "Management of symptomatic carotid atherosclerotic disease".)

Carotid artery stenting is also discussed separately. (See "Carotid artery stenting and its complications".)

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INDICATIONS — Carotid endarterectomy (CEA) is most commonly performed for symptomatic or asymptomatic high-grade (>60, 70 percent, respectively) internal carotid artery stenosis. The effectiveness of CEA has been established by large randomized clinical trials. The indications for CEA in patients with significant carotid atherosclerosis are discussed in detail elsewhere. (See "Management of symptomatic carotid atherosclerotic disease", section on 'Carotid endarterectomy' and "Management of asymptomatic carotid atherosclerotic disease", section on 'Carotid endarterectomy'.)

Special considerations

Bilateral carotid stenosis — Some patients have varying degrees of bilateral carotid disease. No randomized clinical trials have evaluated the effectiveness of bilateral CEA for such patients. However, bilateral carotid occlusive disease appears to increase the risk for complications during and after unilateral CEA [1-4]. As an example, in one study of 700 patients undergoing CEA, 15.4 percent had contralateral disease [2]. The combined death and stroke rates in these patients were almost twice that of matched patients with unilateral disease (5.6 versus 2.4 percent).

The impact of severe contralateral carotid artery stenosis or occlusion on the benefit and risk of unilateral CEA in patients with symptomatic and asymptomatic disease is discussed separately in the appropriate topic reviews. (See "Management of symptomatic carotid atherosclerotic disease", section on 'Contralateral carotid stenosis or occlusion' and "Management of asymptomatic carotid atherosclerotic disease", section on 'Contralateral carotid stenosis or occlusion'.)

When the extent of contralateral carotid disease is significant enough to warrant bilateral CEA, most surgeons stage the approach, with a delay of at least one to two weeks between operations.

The risk of respiratory compromise secondary to neck hematomas or laryngeal nerve injury, frequent difficulty with blood pressure control after manipulation of the carotid sinus, concerns about cerebral hyperperfusion syndrome and the unknown effect of bilateral cerebral ischemia (although temporary) generally contraindicates a combined approach. (See 'Complications' below.)

Prophylactic carotid endarterectomy — Prophylactic carotid intervention in patients with severe carotid artery stenosis prior to another surgery is rarely needed and a decision to proceed should be individualized depending upon the risk of perioperative stroke.

Coronary artery bypass surgery — Neurologic complications are second only to heart failure as a cause of morbidity and mortality following cardiac surgery. New stroke or transient ischemic attack occurs in about 3 percent of patients following CABG. As a result, carotid endarterectomy (CEA) is often considered in conjunction with coronary artery bypass grafting (CABG) in patients with significant carotid stenosis. However, there have been no trials examining the use of CEA in patients having CABG. In addition, it is not clear if CABG should be combined with CEA or should be staged (ie, performed before or after CEA). Whether to offer prophylactic CEA before or after CABG is discussed in detail elsewhere. (See "Coronary artery bypass grafting in patients with cerebrovascular disease", section on 'Prophylactic carotid intervention'.)  

General surgery — The incidence of stroke appears to be lower following general (nonvascular) surgical procedures than following cardiac surgery, with a reported incidence in patients undergoing general anesthesia of less than 0.5 percent [5-7]. The risk may be slightly higher (1 percent) in asymptomatic patients with a carotid bruit who undergo general surgery [8].

There have been no randomized trials examining the use of prophylactic CEA in patients with carotid stenosis prior to general surgery. A retrospective review suggests that prophylactic CEA is probably not warranted in most patients with asymptomatic carotid disease [9]. This study was a chart review of 284 patients who had undergone nonvascular surgery requiring general anesthesia and had preoperative carotid ultrasound. While a previous history of stroke or TIA, a carotid bruit, or both were present in 250 patients, all were considered to have asymptomatic carotid stenosis [10]. Ten of 284 patients (3.5 percent) had perioperative ischemic strokes within 30 days of the index procedure, and 8 of 224 (3.6 percent) with >50 percent carotid stenosis had an ipsilateral perioperative stroke (bilateral lesions were present in three patients). While this stroke risk exceeds that of the general population and of patients with carotid bruits, the increased risk appears to be insufficient to mandate prophylactic CEA for asymptomatic carotid stenosis in the general surgical population.

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Vascular procedures — Although there are no trials of prophylactic CEA prior to abdominal aortic aneurysm repair or other major peripheral vascular procedures, many vascular surgeons support performing prophylactic CEA in anticipation of a major vascular procedure that may involve significant hemodynamic fluctuations.

Endarterectomy in patients with intracranial aneurysm — Ipsilateral intracranial aneurysms that are distal to a cervical internal carotid artery stenosis may be susceptible to sudden hemodynamic changes associated with CEA leading to aneurysm rupture. On the other hand, surgical clipping of an aneurysm distal to a severe internal carotid stenosis may increase the risk of ischemic stroke.

Unfortunately, data are too sparse to allow firm conclusions as to which problem should be treated first. However, caution is advised if CEA is performed in this setting, especially if the ipsilateral aneurysm is ≥7 mm in diameter or if there is a history of subarachnoid hemorrhage from another aneurysm. (See "Unruptured intracranial aneurysms".)

Contraindications — The only absolute contraindication to carotid endarterectomy is asymptomatic complete carotid occlusion. Whether it is appropriate to perform carotid revascularization for acute symptomatic carotid occlusion is discussed elsewhere. (See "Management of symptomatic carotid atherosclerotic disease".)  

Relative contraindications — The following conditions may increase the risk of local or systemic complications and may support the use of alternative treatments such as medical management and/or carotid angioplasty and stenting [11].

 

History of prior neck irradiation resulting in “woody fibrosis” of the skin and subcutaneous tissues.

Concurrent tracheostomy Prior radical neck dissection with or without radiation Contralateral vocal cord paralysis from prior endarterectomy Atypical lesion location, either high or low that is surgically inaccessible Severe recurrent carotid stenosis Unacceptably high medical risk (eg, unstable cardiac status) (see 'Perioperative risk

assessment' below)

 

Patients with these conditions may be candidates for carotid artery stenting. (See "Carotid artery stenting and its complications".)

PREOPERATIVE EVALUATION — A thorough vascular history and physical examination are essential components of the evaluation of a patient being considered for CEA. A search should be made for evidence of atherosclerotic disease elsewhere, including abdominal aortic aneurysm and peripheral artery disease. (See "Screening for abdominal aortic aneurysm" and "Noninvasive diagnosis of arterial disease".)

Cardiac evaluation should be considered selectively since patients undergoing CEA are most likely to have morbidity that is related to coronary heart disease. This evaluation may be performed with exercise stress testing, dobutamine echocardiography, dipyridamole imaging, or, when warranted, coronary catheterization [12]. However, there is no evidence that immediate cardiac intervention alone reduces perioperative procedural risk of stroke or death for carotid endarterectomy. (See "Estimation of cardiac risk prior to noncardiac surgery", section on 'Noninvasive cardiac testing'.)

Preoperative chest radiography is generally not warranted for most patients undergoing elective surgery. However, we obtain a chest radiograph for most patients prior to carotid endarterectomy due to the association of carotid atherosclerosis with smoking and coronary heart disease [13]. (See "Preoperative medical evaluation of the healthy patient", section on 'Chest radiograph' and "Overview of the risk equivalents and established risk factors for cardiovascular disease".)

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Perioperative risk assessment — Identification of risk factors for morbidity and mortality associated with CEA is important in order to avoid surgery in patients who may face unacceptably high risk for endarterectomy.

Data are conflicting regarding risk factors for morbidity following CEA. One or more of the following characteristics have been associated with an increased risk of poor outcome (stroke, myocardial infarction, or death) at 30 days after CEA in some [14-20], but not all [21-25] studies:

 

Age 80 years or older Severe heart disease Severe pulmonary dysfunction Renal insufficiency or failure Stroke as the indication for endarterectomy Anatomic issues, including limited surgical access, prior cervical irradiation, prior ipsilateral

CEA, and contralateral carotid occlusion (see 'Relative contraindications' above)

 

As already noted, a number of reports have NOT confirmed the independent association of these proposed risk factors with poor outcome after CEA [21,22,24,26,27]:

 

One of the largest studies queried the database of the National Surgical Quality Improvement Program of the American College of Surgeons and analyzed a sample of 3949 patients who had CEA as the primary procedure in 2005 and 2006 [27]. Patients with one or more "high risk" factors (age >80 years, major cardiac disease or chronic obstructive pulmonary disease) made up 30 percent of the population. Neither the indication for CEA (symptomatic versus asymptomatic disease) nor anatomic risk factor status (eg, prior neck radiation therapy) was available in the database. The following observations were reported [27]:

 

 

The 30-day stroke rate was similar for patients with and without "high risk" criteria (1.4 versus 1.7 percent). In contrast, the 30-day mortality was significantly higher for patients with "high risk" criteria (1.3 versus 0.4 percent). However, when individual "high risk" criteria were analyzed, only major cardiac disease was associated with a higher 30-day mortality; age >80 was not.

In multivariate analysis, independent risk factors for stroke at 30 days were intraoperative transfusion, baseline hemiplegia, longer intraoperative anesthesia time, and shorter height (likely a surrogate for smaller artery size). However, from other studies, there is no convincing evidence that female gender is a significant risk factor for adverse outcomes [28-32]. Independent risk factors for 30-day mortality were baseline critical limb ischemia and poor functional status.

 

 

A retrospective review of 625 patients compared patients with high-risk (anatomic and pathophysiologic) with normal risk patients and found no differences in perioperative outcomes [11]. Two-year survival was worse in high-risk patients.

A single center series of 2236 consecutive isolated CEA operations reported a 30-day stroke and death rate of 1.4 percent [26]. No single clinical variable was significantly associated with perioperative complications.

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Another single center study of 1370 consecutive CEAs found that patients with two or more risk factors had significantly higher mortality compared with those who had no risk factors [16].

 

Advances in perioperative management have led at least some surgeons to conclude that the proportion of patients with unacceptable risk is extremely small and continues to shrink [21,33]. Others have challenged the concept of a high-risk group of patients for CEA [24]. Modifications in surgical practice, refinement of anesthetic techniques, refinement and use of vasoactive medications in the perioperative period and the declining use of routine preoperative contrast angiography may all be driving a reduction in the perioperative complication rates for CEA [26]. In the series of 2236 CEAs discussed above, the investigators noted that morbidity and mortality in the last five years of the study compared with the previous five years had declined by 36 percent [26].

Patients deemed unfit for general anesthesia can undergo CEA with regional anesthesia, a technique that has shown equally good perioperative outcomes after CEA in patients with and without risk factors such as advanced age, diabetes, coronary artery disease, and contralateral internal carotid occlusion [34]. (See 'Choice of anesthesia' below.)

Preoperative imaging — Patients suspected of having carotid atherosclerosis are typically evaluated with carotid duplex ultrasound as the initial test to assess the severity and extent of carotid stenosis. Other useful noninvasive methods to assess the degree of stenosis of the internal carotid artery include computed tomography angiography, magnetic resonance angiography (MRA) and contrast enhanced magnetic resonance angiography. The utility of these noninvasive methods and cerebral angiography in the initial evaluation of carotid stenosis is discussed in detail separately. (See "Evaluation of carotid artery stenosis".)

In patients with a hemodynamically significant atherosclerotic lesion identified on duplex ultrasound, it remains controversial if further imaging is needed prior to endarterectomy in asymptomatic patients to verify the degree of stenosis or further evaluate arterial anatomy.

Carotid duplex — Prior to performing carotid endarterectomy in asymptomatic patients, we obtain a duplex ultrasound within one to two weeks of elective carotid endarterectomy to be certain that the carotid artery has not occluded, which contraindicates carotid endarterectomy.

Some surgeons may feel the sensitivity of carotid duplex at their institution is not sufficient to reliably determine the degree of internal carotid artery stenosis or to rule out occlusion [35,36]. In support of this point of view is a lack of uniformly applied, prospectively-validated criteria in some settings for quantifying the degree of internal carotid artery stenosis with duplex ultrasound. Against this point of view are the disadvantages, risks and costs associated with other imaging modalities such as catheter-based angiography; magnetic resonance angiography, which tends to overestimate the degree of stenosis; and computed tomographic angiography, which may underestimate the degree of stenosis [37-39]. (See "Evaluation of carotid artery stenosis".)

Experts in carotid ultrasound addressed this issue and developed recommendations for using duplex-derived velocity and imaging parameters to quantify internal carotid artery stenosis with duplex ultrasound [40]. The recommendations are by consensus and further state that the utility of the recommendations should be verified in individual vascular laboratories, and the suggested parameters should not replace duplex parameters that are locally well documented as providing accurate assessment of carotid stenosis. As such, it may be reasonable for the surgeon who has access to a certified vascular laboratory with ongoing quality assurance programs and staffed by registered vascular technologists to use duplex ultrasound as a sole imaging modality of the cervical internal carotid artery prior to performing carotid endarterectomy.

Brain imaging — In the symptomatic patient, the preoperative evaluation should also include computed tomography (CT) or magnetic resonance imaging (MRI) of the brain to assess the degree of cerebral infarction, if any, and to exclude other disorders that might be responsible for symptoms (eg, subdural hematoma, tumor).

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The added risk and costs of catheter-based arteriography probably outweigh the benefit of obtaining more anatomic detail. The Asymptomatic Carotid Atherosclerosis Study (ACAS) found a 1.6 percent incidence of stroke associated with routine arteriography, although the risk was less in other reports [41]. However, arteriography is the gold standard for evaluating intracranial atherosclerotic disease, which is present, to some degree, in 20 to 50 percent of patients with stenosis of the extracranial internal carotid artery.

In an analysis of a subset of patients from NASCET, the relative risk of stroke associated with intracranial atherosclerotic disease in medically-treated patients was 1.3 for extracranial stenosis <50 percent, and 1.8 for extracranial stenosis 85 to 99 percent [42]. CEA reduced this risk, suggesting that detection of intracranial atherosclerotic disease, particularly in those with moderate extracranial carotid stenosis, may help stratify patients into a group that is more likely to achieve benefit from CEA. Of the available noninvasive tests (ie, transcranial Doppler, CTA, MRA), CTA may be more accurate for identifying intracranial large artery stenosis. The diagnosis of intracranial stenosis is discussed elsewhere. (See "Intracranial large artery atherosclerosis", section on 'Diagnosis'.)

Laryngoscopy — Otolaryngologic examination, which may include laryngoscopy, should be performed in patients who have a residual vocal disturbance (tone change, hoarseness) after a prior neck surgery (eg, CEA, thyroid surgery). (See "Hoarseness in adults", section on 'Neurologic dysfunction'.)

PREOPERATIVE PREPARATION

Medication management

Aspirin — Antiplatelet therapy with aspirin reduces the risk of stroke of any cause in patients undergoing carotid endarterectomy (CEA) [43,44]. In addition, lower-dose aspirin (81 to 325 mg daily) is more effective than higher-dose aspirin (650 to 1300 mg daily).

 

In a randomized trial involving 232 patients, aspirin (75 mg daily) or placebo treatment was started preoperatively and continued for six months [45]. Patients assigned to aspirin had significantly fewer strokes at one month and six months compared with those assigned to placebo. However, this study was likely underpowered [46].

The ACE trial randomly assigned 2849 patients scheduled for endarterectomy to aspirin at doses of 81, 325, 650, or 1300 mg daily [47]. Aspirin was started before surgery and continued for three months. At three-month follow-up, the primary end point (stroke, myocardial infarction, vascular death) was significantly reduced in the lower-dose (81 or 325 mg daily) aspirin group compared with the higher-dose group (6.2 versus 8.4 percent).

 

Consensus guidelines from the American Academy of Neurology (AAN) and the American College of Chest Physicians (ACCP) recommend aspirin for symptomatic and asymptomatic patients undergoing CEA [46,48]. We recommend starting aspirin (81 to 325 mg daily) prior to CEA and continuing indefinitely in the absence of contraindications. Although other agents are available, aspirin is the best studied antiplatelet agent following carotid endarterectomy, and aspirin alone is generally deemed adequate for postoperative management given that the carotid plaque has been removed. However, for those patients with atherosclerotic plaque elsewhere (eg, lower extremity), other agents or combinations may be favored for long-term secondary prevention of cardiovascular events. (See "Secondary prevention of cardiovascular disease" and "Antiplatelet therapy for secondary prevention of stroke".)

For patients who are allergic or sensitive to aspirin, clopidogrel can be used as an alternative agent. (See "Benefits and risks of aspirin in secondary and primary prevention of cardiovascular disease", section on 'Aspirin sensitivity' and "Antiplatelet therapy for secondary prevention of stroke".)

Any decision to use another agent or to add additional antithrombotic agents needs to be individualized based upon the indications for dual antiplatelet therapy or triple antithrombotic therapy. It may be reasonable to allow patients who are placed on dual antiplatelet therapy for other indications to continue these throughout the perioperative period. In one study of 102 patients undergoing CEA,

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no significant difference in perioperative bleeding was found in patients taking dipyridamole/ASA (n = 39), dipyridamole/ASA plus dextran (n = 30) or dipyridamole/ASA plus clopidogrel (n = 33) [49]. There was also no difference in the number of postoperative microembolic signals as detected by transcranial Doppler. The management of warfarin in the perioperative period is individualized based upon the original indication for long-term anticoagulation. (See "Management of anticoagulation before and after elective surgery" and "Triple antithrombotic therapy in patients with cardiovascular disease".)

Statins — The use of statins in symptomatic patients undergoing CEA may be associated with improved outcomes. In a retrospective observational study of 3360 CEAs, statin use was associated with reduced in-hospital mortality and combined in-hospital ischemic stroke or death (adjusted odds ratio 0.25, 95% CI 0.07-0.90 and 0.55, 95% CI 0.32-0.95, respectively), but in-hospital cardiac outcomes were not significantly improved [50]. In contrast, statin use by patients with asymptomatic carotid stenosis was not associated with significantly different outcomes.

Similar results were reported in another retrospective study involving 1566 patients with symptomatic and asymptomatic disease who received statins for at least one week before CEA [51]. These findings require confirmation in randomized clinical trials.

Evidence is also emerging that statins may be of benefit in the perioperative period, and that this benefit might be lost if statins are discontinued. This issue is discussed elsewhere. (See "Perioperative medication management", section on 'Non-statin hypolipidemic agents'.)

Sedative-analgesic medications — Certain sedative-analgesic medications may be warranted to relieve preoperative anxiety. When an anxiolytic is chosen, a short-acting agent should be used, and it should be administered only after the patient’s neurologic examination has been documented.

Prophylactic antibiotics — We recommend administration of antibiotics prior to carotid endarterectomy to control surgical site infection due to the frequent use of prosthetic material (table 1) [52]. (See "Antimicrobial prophylaxis for prevention of surgical site infection in adults", section on 'Vascular surgery'.)

SURGICAL ANATOMY AND PHYSIOLOGY

Carotid artery — The left common carotid artery (CCA) originates from the aortic arch, whereas the right CCA originates from the innominate artery (figure 1). The CCA divides into the internal carotid artery (ICA) and external carotid artery (ECA) at the level of the superior border of the thyroid cartilage corresponding to the C3/C4 disc space. The vagus nerve is located posteriorly to the common carotid artery in most individuals, although it may be located anteriorly in 5 to 10 percent of cases.

External carotid artery — The ECA has multiple branches that supply the face and scalp and provide collateral circulation to the brain (figure 2). These branches include (caudal to cranial) the superior thyroid, lingual, facial, ascending pharyngeal, occipital, posterior auricular, maxillary, and superficial temporal arteries. The ascending pharyngeal artery arises very near the bifurcation of the carotid artery. In one anatomic study, the ascending pharyngeal artery originated from the ECA in 80 percent of specimens (56 percent medially, 44 percent posteriorly) [53]. In the other 20 percent, the ascending pharyngeal artery originated from the internal carotid artery (5 percent), carotid bifurcation (5 percent), occipital artery (5 percent), and a trunk common to the lingual and facial arteries (5 percent).

Internal carotid artery — The ICA normally has no branches in the neck (figure 3). The cervical segment of the internal carotid extends from the carotid bifurcation until it enters the carotid canal anterior to the jugular foramen. The internal carotid artery runs cranially within the carotid sheath and lies posterior and lateral to the external carotid artery beneath the medial border of the sternocleidomastoid muscle. In its distal (cranial) course, it passes beneath the hypoglossal nerve, the digastric muscle, the stylohyoid muscle, the occipital artery and the posterior auricular artery. More cranially, the styloglossus and stylopharyngeus muscles, the tip of the styloid process and the stylohyoid ligament, the glossopharyngeal nerve and the pharyngeal branch of the vagus nerve separate the internal from the external carotid artery.

Carotid baroreceptor — Baroreceptors are stretch-sensitive mechanoreceptors that respond to alterations in blood pressure. The carotid sinus baroreceptors are located within the adventitia of the origin of the internal carotid artery and are innervated by the sinus nerve of Hering, which is a branch

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of glossopharyngeal nerve. In response to low blood pressure, the nerve fibers decrease their firing rates stimulating the sympathetic nervous system and inhibiting of the parasympathetic nervous system via a centrally-acting mechanism. Carotid sinus reactivity may be altered in patients with carotid atherosclerosis. (See "Pathophysiology of symptoms from carotid atherosclerosis", section on 'Impaired vasoreactivity'.)

Patients display varying degrees of heart rate or blood pressure alterations during manipulation of the carotid bifurcation, carotid clamping, or postoperatively following CEA [54]. Endarterectomy, removal of atheromatous debris, and reconstruction of the carotid artery may increase tension on the carotid sinus baroreceptor, increasing its activity [55]. The opposite is also possible if damage to the carotid sinus or sinus nerve occurs. As an example, eversion endarterectomy requires division of the carotid artery, and as a result, the longitudinal fibers of the carotid sinus nerve are transected. A study that measured baroreceptor sensitivity following CEA found increased sensitivity with conventional CEA and decreased sensitivity with an eversion technique [56]. Correspondingly, postoperative blood pressures were significantly increased for eversion compared with conventional CEA (systolic: 127, diastolic: 64, mean: 86, versus systolic: 111, diastolic: 55, mean: 75). Compensation over time occurs due to intact baroreceptor mechanisms from the contralateral side and aortic arch. (See 'Conventional versus eversion endarterectomy' below.)

CHOICE OF ANESTHESIA — The use of general anesthesia for CEA or performing awake carotid surgery with local anesthesia (with or without cervical block) is generally determined by surgeon preference and patient characteristics and preference. Ideally, surgical and anaesthetic teams should be competent in both techniques because a patient might prefer, or there might be a medical reason to choose, one anesthetic technique rather than another [57]. An analysis of 26,070 cases in the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) database identified the use of general anesthesia in 84.6 percent and regional anesthesia in 15.4 percent of cases [58].

The available evidence suggests that the choice of anesthetic technique has no significant impact on clinically important outcomes after CEA [57,59-61]. Blood pressure in the perioperative period is affected by the method of anesthesia. General anesthesia reduces blood pressure during anesthesia induction and may require the use of pressor agents. Overall, the use of local anesthesia appears to be associated with fewer alterations in blood pressure compared with general anesthesia. (See 'Labile blood pressure' below.)

Local/regional anesthesia may be more beneficial for some patients, but mandates a “dedicated” anesthesiologist with refined skills in regional anesthetic techniques. Anesthetic techniques are discussed in detail elsewhere. (See "Overview of anesthesia and anesthetic choices", section on 'Types of anesthesia' and "Peripheral nerve block: Techniques", section on 'Superficial cervical plexus block'.)

A systematic review and meta-analysis of randomized trials comparing locoregional with general anesthesia identified ten trials that included 4335 operations of which 3526 were from the General Anesthesia versus Local Anesthesia (GALA) trial [57]. The primary outcome measure of the GALA trial was a composite of stroke (including retinal infarction), myocardial infarction (MI), or death between randomization and 30 days after surgery.

 

There was no significant difference in the primary outcome between the local and general anesthesia groups (4.4 versus 4.8 percent). However, 9.5 percent of patients randomized to one arm received the opposite treatment. An as-treated analysis was performed removing the crossovers for the composite outcome (no differences) but individual outcomes (stroke, death, MI) were not assessed.

There was no difference between the groups (intention-to-treat analysis) in the risk of postoperative stroke within 30 days of surgery, but locoregional anesthesia was associated with a trend towards decreased mortality, odds ratio (OR) 0.62 (95% CI 0.36-1.07). No significant differences were found for other measures, including myocardial infarction, postoperative bleeding, pulmonary complications, or length of stay. In the NSQIP study above, adjusted analysis identified general anesthesia as a risk factor for postoperative myocardial infarction (odds ratio 2.18, 95% CI 1.17-4.04) [58].

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A post-hoc analysis of the GALA trial found that local anesthesia may be more cost-effective than general anesthesia [62]. The difference in cost was primarily due to differences in the length of intensive care unit stay and the use of consumables, with a mean cost difference of ₤178 ($285 US). Two other nonrandomized studies have similarly suggested a cost difference between the two anesthesia techniques [60,63]. The larger of these evaluated 24,716 patients from National Surgery Quality Improvement Program (NSQIP) database finding modestly shorter operative and anesthesia times, and a larger proportion of patients discharged on the first postoperative day in the local compared with general anesthesia groups (77 versus 64 percent) [60]. We do not feel that these modest differences translate into any meaningful clinical advantage.

 

SURGICAL TECHNIQUE

Endarterectomy procedure — Carotid endarterectomy (CEA) is performed through a neck incision, either bordering the sternocleidomastoid muscle, or with a transverse incision in a skin crease at the level of carotid bulb. For the latter incision, preoperative imaging and palpation of the neck will guide the surgeon to the optimal placement of the incision. No significant differences between these approaches have been identified in terms of stroke, wound complications, or nerve complications [64].

The underlying platysma muscle and subcutaneous tissues are divided, the carotid sheath exposed, and the internal carotid artery (ICA) is carefully identified and dissected. The extent of exposure of the artery is dependent upon the distribution of disease determined by intraoperative findings. Typically, dissection is needed from the common carotid artery (CCA) to a point distal to the bifurcation of the ICA and ECA that is beyond palpable ICA plaque to allow for clamping of normal soft artery.

After proximal and distal control of the artery is obtained, the patient is given a bolus of heparin, intravenously. Monitoring of the activated clotting time (ACT) is not usually needed owing to the short duration of carotid clamping, typically less than an hour. The internal, common, and external arteries are then clamped sequentially; the internal carotid artery is usually clamped first to prevent embolization. A longitudinal arteriotomy is performed below the level of the bifurcation and extended proximally and distally.

With general anesthesia and mandatory shunting, the shunt is placed after the vessel is opened and prior to the endarterectomy. For patients who are undergoing general anesthesia, some surgeons routinely place a carotid shunt while others use cerebral perfusion monitoring to guide the need for selective shunt placement. For these patients and those undergoing awake carotid endarterectomy using local anesthesia (with or without cervical block), the endarterectomy is often completed prior to the need to place a shunt, as indicated by brain monitoring. (See 'Carotid shunting' below and 'Assessing brain perfusion' below.)

The carotid plaque, which is consistently found at the carotid bifurcation and the origin of the internal carotid artery, is then freed and removed through a dissection plane developed in the layers of the deep media. Great care is taken to create a smoothly tapered transition between the endarterectomized portion of the artery and its normal distal extent. This maneuver avoids intimal flaps that might lead to arterial dissection after flow is reestablished.

After meticulous inspection of the endarterectomized surface to remove any residual plaque or debris, attention is directed at repair. Some surgeons choose to repair primarily, while others patch the artery with saphenous vein or prosthetic material such as polyester (eg, Dacron), polytetrafluoroethylene (PTFE, eg, Gore-Tex) or bovine pericardium. (See 'Patch angioplasty versus primary closure' below.)

Just prior to completion of the arterial closure, the carotid clamps are sequentially briefly released and re-clamped to back bleed (ECA, ICA) and forward flush (CCA) the vessel which is then irrigated with heparinized saline and suctioned of any residual debris. After the suture line is completed, flow is restored first to the ECA, then to the ICA.

A topical hemostatic agent may be used over the suture line to slow any oozing of blood. In a retrospective analysis of 4587 patients in a regional registry, reversal of heparin with protamine was associated with a lower incidence of serious bleeding requiring reoperation (0.64 versus 1.7 percent)

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compared with no reversal, without increasing the risk of MI, stroke, or death [65]. Although a small Jackson Pratt drain can be placed, drains are generally not required if heparin is reversed. The platysma and skin are closed and the wound dressed.

A completion study to assess integrity of the repair can be performed using duplex ultrasound, contrast arteriogram or angioscopy, depending upon resources and operator preference [66-78]. A retrospective review that categorized surgeons as rarely, selectively, or routinely using completion imaging found no significant differences in perioperative stroke or death after adjustment for patient characteristics [70]. A small but significant reduction in restenosis (>70 percent) was found for surgeons who performed completion imaging.

High access — More distal (cranial) access may be needed. As the internal carotid artery is dissected, the hypoglossal nerve will be seen to cross anteriorly. The nerve is isolated and gently retracted.

The ansa hypoglossus nerve, which innervates the strap muscles of the neck, is typically seen coursing along the carotid sheath. The ansa can be divided without clinically significant consequence when dissection needs to be carried more cranially. The posterior belly of the digastric muscle can also be divided. Subluxation of the jaw is rarely warranted.

Conventional versus eversion endarterectomy — Eversion endarterectomy is a variant of carotid endarterectomy. The internal carotid artery is transected horizontally at its origin at the carotid bulb and then the artery is everted, or turned inside-out, which creates an exposure not seen with vertical arteriotomy. Eversion endarterectomy is particularly appealing in small arteries and in patients with significant carotid redundancy as a means to eliminate carotid kinks and coils. However, in our opinion, the bulk of the evidence does not favor one technique over the other.

The largest and best designed trial comparing eversion endarterectomy with conventional endarterectomy (EVEREST trial) was a multicenter trial that included 1342 patients [79]. No significant differences were found for the primary endpoints (perioperative stroke and death, carotid occlusion) or secondary endpoints (any stroke, ipsilateral stroke, transient ischemic attack, cranial nerve injury, neck hematoma, myocardial infarction). For eversion CEA compared with conventional CEA, the odds ratio for a combined endpoint of perioperative major stroke or death was 1.0 (95% CI 0.4-2.9), and for any perioperative stroke, 1.2 (95% CI 0.5-2.7). Compared with CEA performed without a patch, eversion CEA and conventional patched CEA each had a lower risk of carotid restenosis (hazard ratio [HR] 0.3, 95% CI 0.2-0.6, and HR 0.2, 95% CI 0.07-0.6, respectively). A metaanalysis that included the EVEREST trial and five other smaller trials [79-85] identified a trend toward a reduced risk of perioperative (30-day) stroke for eversion CEA compared with conventional CEA (OR 0.56, 95% CI 0.33-0.96) [86]. Among the included randomized trials, one single center trial found a significantly reduced risk for perioperative stroke [82]; the other trials found no significant differences between the techniques. In this trial, perioperative stroke occurred in 2.9 percent of patients undergoing conventional CEA and no patient undergoing eversion endarterectomy [82]. Two of the four strokes involved the contralateral hemisphere, not necessarily related to endarterectomy technique, and the other two strokes were related to angulation at the interface of the artery and the patch material.

Randomized trials and other observational studies that have evaluated conventional versus eversion CEA have included patients with asymptomatic and symptomatic disease. A post hoc analysis of data from the Stent-Protected Angioplasty versus Carotid Endarterectomy in Symptomatic Patients (SPACE-1) trial found no overall difference between the techniques; however, perioperative outcomes were better for conventional CEA, while later outcomes favored eversion CEA [87]. Ipsilateral stroke or death ≤30 days was significantly reduced for conventional versus eversion CEA (9 versus 3 percent), but the risk of ipsilateral stroke >30 days was significantly lower for eversion compared with conventional CEA (3 versus 0 percent). Interestingly, eversion CEA was not found to have a significantly lower incidence of restenosis in contrast to other studies [86,88].

Proponents of eversion CEA feel that once the technique has been mastered, it may be easier to perform than conventional CEA. Although this may be so, advocates of conventional CEA point out that shunt insertion during eversion CEA can be more difficult since the plaque must be completely removed before the shunt can be inserted. In addition, eversion CEA is less commonly introduced during vascular surgery training, and for those who adopt it later the technique may be associated with a learning curve. A retrospective review at an academic medical center compared the outcomes of the first 100 patients on whom they performed eversion endarterectomy with 100 patients who underwent conventional endarterectomy [89]. The rate of perioperative neurologic deficits and deaths

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were not significantly different. One case of amaurosis occurred after eversion CEA, and one case each of transient cerebral ischemia and retinal infarction after conventional CEA; one cardiac death occurred with each. No significant differences were seen in the rate of critical (>80 percent) residual or recurrent stenosis, late stroke, or late carotid occlusion at 36 months follow-up. However, eversion endarterectomy had a higher rate of >50 percent recurrent stenosis (38 versus 6 percent) compared with conventional CEA in spite of similar residual stenosis rates. The significance of this late mild to moderate stenosis is unknown.

Patch angioplasty versus primary closure — As noted above, some surgeons choose to repair to the carotid artery primarily, while others patch the artery with saphenous vein or material (eg, polytetrafluoroethylene, Dacron, bovine pericardium) [90-93]. We recommend patch closure for all patients undergoing carotid endarterectomy (non-eversion).

The trials that have been performed suggest two benefits from use of a patch: a marked reduction in the frequency of ≥50 percent restenosis and a lower rate of ipsilateral stroke [94,95]. A systematic review of patch angioplasty versus primary closure during CEA identified ten eligible randomized controlled trials involving 1967 patients undergoing 2157 operations [95]. Many of the trials were limited by significant methodological flaws; most were small, and none could be analyzed on a true intention-to-treat basis because of losses to follow-up. The use of a patch is associated with:

 

A reduction in the risk of ipsilateral stroke in the perioperative period (odds ratio (OR) 0.31, 95% CI 0.1-0.63 and long-term OR 0.32, 95% CI 0.16-0.63).

A reduced risk of perioperative arterial occlusion (OR 0.18, 95% CI 0.08-0.41). Decreased restenosis during long-term follow-up in eight trials (OR 0.24, 95% CI 0.17-0.34).

These results are more certain than those of the previous review since the number of operations and events have increased. However, the sample sizes are still relatively small, data were not available from all trials, and there was significant loss to follow-up.

No significant correlation was found between use of patch angioplasty and the risk of either perioperative or long-term all-cause death rates.

 

A separate systematic review identified 13 trials involving 2083 operations [93]. Seven trials compared vein closure with PTFE closure and six trials compared Dacron with other synthetic materials. No significant differences were found comparing synthetic grafts versus vein graft for stroke, stroke or death, arterial occlusion, arterial rupture, nerve palsy, wound infection or recurrent arterial stenosis during perioperative or one-year follow-up. The review identified one high-quality trial that compared Dacron with PTFE and found that Dacron was associated with an increased risk for perioperative stroke and an increased risk for both perioperative and late, recurrent carotid stenosis [90,91]. Using a synthetic patch was found to decrease the risk of pseudoaneurysm relative to using a vein patch (odds ratio 0.09, 95% CI, 0.02-0.49). However, the studies that examined pseudoaneurysm outcomes were older [96-98], using saphenous vein, jugular vein or other vein sites; the technical aspects of vein handling were not included. In one of these studies, the incidence of pseudoaneurysm was 17 percent using jugular vein, 9 percent using saphenous vein or PTFE, and 5 percent with primary closure [96]. The use of vein during initial open carotid endarterectomy has declined, but when vein is needed (eg, graft infection, re-do carotid surgery), we prefer to use proximal saphenous vein harvested from the groin.

Very few arterial complications, including hemorrhage, infection, cranial nerve palsies and pseudo-aneurysm formation have been evaluated with patch compared with primary closure but the available data suggest no significant differences [99].

Assessing brain perfusion — The benefit derived from CEA is partially dependent upon low perioperative morbidity. Although 80 to 85 percent of patients tolerate clamping of the carotid artery without consequence, assessment of the ability of the collateral circulation via the circle of Willis should be performed in all patients who do not undergo mandatory shunting. Assessing cerebral perfusion in selectively shunted patients can be accomplished with a variety of methods that are determined in part by the type of anesthesia chosen. Methods that have been studied include awake monitoring, transcranial Doppler, somatosensory evoked potentials, raw electroencephalographic

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(EEG) monitoring, processed EEG monitoring, carotid stump pressure, jugular venous oxygen saturation and others. The most commonly used methods are discussed below. The author prefers EEG monitoring. (See 'Choice of anesthesia' above and 'Carotid shunting' below.)

Data from randomized trials on which neurologic monitoring method should be used to select patients for shunting are limited. A trial comparing EEG to carotid stump pressure monitoring showed a benefit to EEG monitoring [100]. A trial that randomly assigned 200 patients undergoing CEA under general anesthesia to routine or selective shunting (carotid systolic blood pressure <40 mmHg), found no significant difference in perioperative stroke rate between the groups [101]. Other methods of assessing brain perfusion have not been evaluated in randomized trials.

A review of the literature reported mean perioperative stroke rates for CEAs using the various techniques [102]. These are tabulated below and the more commonly used techniques are discussed in the next sections.

 

Routine shunting – 1.4 percent, Routine non-shunting – 2 percent Selecting shunting – 1.6 percent

 

 

Cervical block anesthesia (awake endarterectomy) – 1.1 percent Electroencephalogram – 1.6 percent Stump pressure – 1.6 percent Somatosensory evoked potentials – 1.8 percent Transcranial Doppler – 4.8 percent

 

Awake endarterectomy — Patients who undergo local/regional anesthesia can be followed clinically throughout the procedure by monitoring mental status, speech and extremity function. A disadvantage of awake surgery is that it is frequently uncomfortable for the patient and may necessitate urgent conversion to general anesthesia or urgent shunt placement.

A neurologic assessment is performed at the beginning of the procedure and repeated every ten to fifteen minutes during carotid dissection, immediately prior to carotid clamping and continuously during carotid clamping. Agitation, slurred speech, disorientation, and extremity weakness are indications for shunt placement. (See 'Carotid shunting' below.)

Clinical assessment of the patient undergoing awake carotid endarterectomy is consistently associated with the lower rates of shunt use. With awake carotid endarterectomy, a carotid shunt is needed in <5 percent of patients. In a metaanalysis of ten trials, five evaluated shunt use and found significantly less use for local anesthesia compared with general anesthesia (odds ratio 0.27, 95% CI 0.23-0.31) [59]. However, there were no significant differences in the rates of stroke or death.

EEG monitoring — When general anesthesia is used, raw EEG monitoring is more commonly used. A neurologist monitors the tracings during the course of the procedure for cerebral ischemia as indicated by the presence of theta and delta waves or disorganized rhythms that indicate the need for shunting [103]. (See 'Carotid shunting' below.)

Processed EEG monitoring (eg, bispectral index) has been used to correlate cerebral ischaemia with processed EEG monitor values [104-106]. Bispectral index monitoring for depth of anesthesia and normal BIS values during general anesthesia are presented elsewhere (table 2). (See "Awareness with recall following general anesthesia", section on 'Brain monitoring'.)

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In one study, bispectral index (BIS) monitoring used during awake carotid endarterectomy found that the percent reduction in BIS values from baseline was significantly greater in patients shunted on the basis of clinical neurologic status compared with non-shunted patients (14 versus 4 percent). No trials are available using processed EEG prospectively in patients undergoing general anesthesia.

Stump pressure — Although stump pressures have been used to determine the need for carotid shunting in the past, EEG monitoring is more commonly used in patients undergoing general anesthesia when mandatory shunting is not chosen.

Carotid stump pressures are obtained after clamping the proximal common and external carotid arteries. A needle attached to a transducer is introduced into the common carotid artery to obtain a waveform. Mean pressures greater than 30 to 50 mmHg imply adequate collateralization via the circle of Willis down the ipsilateral carotid artery. Lower stump pressures are an indication for shunt placement and higher pressures are associated with stroke rates <0.5 percent [107].

Critics of this technique caution that pressures are only obtained after initial clamping, and, therefore, represent a "snapshot" in time. In addition, the above criteria should be used with caution in patients who have suffered prior ipsilateral strokes since there is a poor correlation between adequate perfusion pressures and outcomes in this setting. The accuracy of the pressure in the face of a preocclusive (string) lesion may also be questionable.

Carotid shunting — For any patient who demonstrates evidence of cerebral ischemia by any of the monitoring techniques discussed above, shunting should be performed expeditiously. A temporary shunt is placed beyond the proximal and distal extent of the arteriotomy from the common to the internal carotid artery. Blood flows through the shunt providing continuous cerebral perfusion during the procedure. Neurologic reassessment is then performed.

Studies targeted at defining the best approach (mandatory shunting, selective shunting) have been equivocal with respect to demonstrating any difference in important clinical outcomes, and given that there is no consensus, neurologic monitoring with selective shunting versus routine shunting has been largely a matter of surgeon preference [108-111]. A key question is whether shunting results in lower overall rates of perioperative stroke or other morbidity. A systematic review that identified three trials involving 686 patients found no significant differences in the rates of all stroke, ipsilateral stroke or death up to 30 days for patients that were routinely shunting compared with no shunting [111]. Similarly, there are insufficient data to support one type of carotid shunt over another [110]. Many shunts are available for use (Argyle™, Pruitt-Inahara, Brenner, Burbank, Sundt) and each have their advantages and disadvantages. The features (stiff versus flexible, inline Doppler, balloons for occlusion), and use of these shunts can be found on proprietary websites. The selection of a particular shunt by a vascular surgeon is based on their experience. Most vascular surgeons become comfortable using one particular shunt.

Although some surgeons prefer to use carotid shunts routinely to avoid the need for intraoperative neurologic monitoring, it should be recognized that shunting is unnecessary in approximately 90 percent of patients and exposes patients to the risks of shunting that may include the following:  

 

Formation of an intimal flap during shunt insertion, resulting in arterial dissection Dislodgement of plaque emboli during vessel manipulation Air embolism due to bubbles in the shunt

 

Surgeons who routinely shunt feel that shunt complications are less likely to occur if shunting is routinely performed. The advantages of routine shunting may include:

 

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Familiarity of the surgeon and surgical team with the technique. Data from the Vascular Study Group of New England (VSGNE) database found that surgeons who routinely shunted had lower stroke rates during carotid endarterectomy in patients with contralateral carotid occlusion compared with those who selectively shunted [112]. The higher rate of stroke amongst practitioners who selectively shunted may be attributable to a lack of familiarity with the procedure. Other groups have also reported a higher rate of shunting in patients with contralateral carotid occlusion [113,114].

Cerebral flow is assured with a properly placed shunt without need for neurological monitoring (EEG, stump pressure, awake neurological examination).

 

POSTOPERATIVE CARE — Upon recovering from anesthesia, a neurologic assessment is performed and repeated every hour during recovery.

Because blood pressure lability is common in the first 12 to 24 hours postoperatively, it is standard care for CEA patients to be placed in a monitored setting with an arterial line in place.

Labile blood pressure — Manipulation of the carotid bulb during carotid endarterectomy not infrequently results in hemodynamic instability intraoperatively and in the early postoperative period [115]. Adequate cerebral perfusion pressure should be maintained during periods of hemodynamic instability to avoid low cerebral blood flow and cerebral ischemia.

Systolic blood pressure should be maintained between 100 to 150 mmHg in the postoperative period. Hypertension may increase the likelihood of neck hematoma or suture line disruption, while relative hypotension compared with the patient's baseline value will increase the likelihood of inadequate cerebral perfusion and potential thrombosis of the endarterectomy site. Hypotension is more likely to result in cerebral ischemia and neurologic deficits in those patients who also have intracerebral small vessel disease. Patients may require pressor or antihypertensive drips to maintain the target blood pressure. (See "Drug treatment of hypertensive emergencies", section on 'Nitroglycerin'.)

A systematic review identified nine trials that recorded blood pressure during and after carotid endarterectomy. Blood pressure dropped significantly in the general anesthesia group after induction of anesthesia and in one trial, more patients in the general anesthesia group had significant hypotension during or after the operation (25 versus 7 percent) [111]. The GALA trial found that more patients undergoing general anesthesia required manipulation of blood pressure compared with patients receiving local anesthetic (72 versus 54 percent) [57]. However, blood pressure responses intraoperatively and postoperatively are highly variable with hypertension and hypotension reported for local and general anesthesia.

Bleeding — Postoperative bleeding, resulting in neck hematoma, occasionally occurs after CEA. It is easy to underestimate the size of a neck hematoma and the patient can rapidly lose their airway. There must be a low threshold to reexplore the neck and search for a surgically correctable source of bleeding.

Close observation and judgment are critical in deciding when to open a neck wound and drain a hematoma. The airway may be lost if clinical signs such as hoarseness and stridor are relied upon. Diagnostic studies are generally not helpful in making this clinical decision. If there is any question about the significance of a hematoma, the patient should be returned to the OR for re-exploration

COMPLICATIONS — While a number of controlled trials have highlighted the patient population most likely to benefit from carotid endarterectomy (CEA), this operation is not without risk [116]. The perioperative mortality associated with CEA ranges from <0.5 to 3 percent. Mortality rates may be higher when this procedure is performed at non-tertiary care centers [117-119]. Surgeons are encouraged to keep accurate records of their individual stroke rates to ensure that standards are upheld. Low patient volume (<3 CEAs performed every two years) and a greater number of years since licensure of the surgeon are associated with worse outcomes following CEA [120].

The American Heart Association (AHA) consensus statement states that indications for surgery are proven in symptomatic patients in whom morbidity and mortality rates associated with CEA are less than 6 percent and in the asymptomatic patient when the rates are less than 3 percent [121,122].

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These recommendations are, however, more than 10 years old and based upon data that are up to 20 years old. The AHA recommendations are under revision. Two large randomized trials likely reflect more accurately the contemporary risk of stroke or death following carotid endarterectomy:

 

The European trial (International Carotid Stenting Study [ICSS]) randomly assigned patients to receive carotid endarterectomy or carotid stenting for treatment of symptomatic carotid stenosis [123]. The 120 day all-cause mortality for the 857 symptomatic patients in the endarterectomy group was 0.8 percent. The 120 day combined any stroke or procedural death rate was 4.2 percent.

In North America, the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) reported combined results for symptomatic and asymptomatic patients [124]. In 1240 patients assigned to endarterectomy (47.3 percent asymptomatic), the 30-day death rate was 0.3 percent and the rate of any periprocedural (30-day) stroke or death or postprocedural ipsilateral stroke was 2.3 percent.

 

Myocardial infarction — The majority of deaths following CEA are due to cardiac events, placing emphasis on the appropriate cardiac workup and perioperative management in these patients. (See 'Perioperative risk assessment' above and "Perioperative myocardial infarction after noncardiac surgery".)

Postoperative stroke — Stroke is the second most common cause of death following CEA. The rate of perioperative stroke (30 day) associated with CEA ranges from less than 0.25 to more than 3 percent, with the experience of the surgeon again being important.

Multiple factors can contribute to postoperative stroke in patients who have undergone CEA. These include:

 

Plaque emboli Platelet aggregates Improper flushing Poor cerebral protection Relative hypotension

 

However, neurologic changes in the patient after CEA must be considered secondary to thrombosis at the operative site until proven otherwise. Technical errors must be ruled out.

Evaluation and treatment — Evaluation of the CEA patient with new neurologic deficits varies among surgeons. Some advocate recovery room or intraoperative ultrasound to assess potential thrombosis, while others immediately return to the operating room and open the endarterectomy site for direct visual inspection.

The optimal time to heparinize the symptomatic postoperative patient is also controversial [125]. Some surgeons heparinize immediately upon suspicion of the diagnosis, while others first obtain a head CT to rule out hemorrhagic stroke. Head CT performed immediately after an embolic event is frequently normal; follow-up CT in a few days may reveal injury.

Percutaneous transluminal carotid angioplasty with stenting is an alternative therapy for elective treatment of carotid artery disease. Carotid stenting may also be effective for managing perioperative stroke after CEA, particularly if the cause is a flow-limiting dissection. As an example, one study evaluated 13 patients with major or minor neurologic complications after CEA who underwent emergency carotid angiography and stent placement [126]. The angiographic success was 100 percent and 11 patients had complete resolution of neurologic symptoms. In contrast, only one of five patients

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undergoing surgical reexploration had neurologic recovery. Stenting, however, is not considered standard for treatment of acute complications of carotid endarterectomy. (See "Carotid artery stenting and its complications".)

Intraarterial thrombolytic therapy, in highly selected cases, may be another treatment option in patients with a postoperative stroke proven by arteriography to be due to distal emboli that, presumably, occurred during the course of the endarterectomy. The rationale for the administration of tissue-type plasminogen activator (alteplase) in this setting is based upon trials in acute stroke in which benefit has been demonstrated if therapy is initiated within 4.5 hours in highly selected patients. (See "Reperfusion therapy for acute ischemic stroke".)

However, the incidence of intracranial hemorrhage in patients treated with thrombolytic therapy for acute stroke has been in the range of 6 percent [127]. Furthermore, it is not known if the results obtained from the intravenous systemic administration of alteplase can be extrapolated to localized intraarterial therapy.

Intraarterial thrombolysis for patients with postoperative stroke has only been described in case reports and retrospective studies and is, currently, experimental. There are, as yet, no controlled trials. Some neurologists advocate searching for distal thrombosis via arteriogram and, if found, proceeding with intraarterial thrombolytic therapy.

Hyperperfusion syndrome — The cerebral hyperperfusion syndrome is probably the cause of most postoperative intracerebral hemorrhages and seizures in the first two weeks after CEA. The clinical manifestations of hyperperfusion occur in only a small percentage of patients after carotid revascularization (from less than 1 to as high as 3 percent in various reports) [128-131].

The mechanism of hyperperfusion is related to changes that occur in the ischemic or low-flow carotid vascular bed. To maintain sufficient cerebral blood flow, small vessels compensate with chronic maximal dilatation.

After surgical correction of the carotid stenosis, blood flow is restored to a normal or elevated perfusion pressure within the previously hypoperfused hemisphere. The dilated vessels are thought to be unable to vasoconstrict sufficiently to protect the capillary bed because of a loss of cerebral blood flow autoregulation. Breakthrough perfusion pressure then causes edema and hemorrhage, which in turn results in the clinical manifestations.

The hyperperfusion syndrome is characterized by the following clinical features:

 

Headache ipsilateral to the revascularized internal carotid, typically improved in upright posture, may herald the syndrome in the first week after endarterectomy.

Focal motor seizures are common, sometimes with postictal Todd's paralysis mimicking post-endarterectomy stroke from carotid thrombosis.

Intracerebral hemorrhage is the most feared complication, occurring in about 0.6 percent of patients after CEA, usually within two weeks of surgery [132].

 

Neuroimaging studies, including head CT and MRI with T2 or FLAIR sequences, typically show cerebral edema, petechial hemorrhages, or frank intracerebral hemorrhage. Post-revascularization ipsilateral cerebral blood flow (CBF) is markedly increased compared with preprocedure flow [133]. Ipsilateral CBF after revascularization may be two to three times that of homologous regions in the contralateral hemisphere [134]. However, hyperperfusion syndrome may develop in the presence of only moderate (20 to 44 percent) increases in ipsilateral cerebral blood flow, as measured by perfusion magnetic resonance imaging, and in the absence of increases in middle cerebral artery flow velocity, as measured by transcranial Doppler (TCD) [135].

The hyperperfusion syndrome appears to be more likely with revascularization of a high-grade (80 percent or greater stenosis) carotid lesion, and it may be more likely when CEA is performed after

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recent cerebral infarction [136]. Reduced CBF or cerebral vasoreactivity prior to CEA may also be a risk factor for postoperative hyperperfusion [137].

Transcranial Doppler techniques have been used to monitor flow velocities of the middle cerebral artery in order to predict the occurrence of hyperperfusion syndrome [138-140], but the utility of these methods for this indication is not clearly established.

Treatment — The best remedy for cerebral hyperperfusion is prevention. Strict control of postoperative hypertension is paramount. Systolic blood pressure must be maintained at or below 150 mmHg. Aggressive measures including intravenous labetalol, nitroprusside, and nitroglycerin may be necessary to achieve this goal. Therapy should begin at the time of restoration of internal carotid flow and be maintained vigilantly during the hospital stay and for the first 10 to 14 days postprocedure. Fortunately, most postoperative blood pressure lability resolves in the first 24 hours. (See 'Labile blood pressure' above.)

Seizures related to hyperperfusion are usually successfully treated with standard antiepileptic drugs such as phenytoin [141].

Intracerebral hemorrhage from hyperperfusion is often devastating. Hypertension must be strictly controlled and anticoagulant and antithrombotic drugs should be discontinued. For patients on aspirin, platelet transfusions may be useful to reverse the antiplatelet effect. (See "Clinical and laboratory aspects of platelet transfusion therapy", section on 'Platelet function defects'.)

Nerve injury — A number of nerve injuries can complicate CEA:

 

The vagus nerve, which usually lays posterolaterally in the carotid sheath, is identified during dissection of the carotid from the internal jugular vein and is at risk for injury.

The recurrent laryngeal nerve branches of the vagus are distal to the area of carotid artery dissection; injury to this nerve may result in unilateral vocal cord paralysis. The occasionally nonrecurrent nerve places this branch at even higher risk.

The facial nerve exits the stylomastoid foramen and courses along the inferior portion of the ear. The most common branch affected during CEA is the marginal mandibular branch, which may be damaged during improper or prolonged retraction. The resulting paresis of the lateral aspect of the orbicularis oris muscle may be exacerbated during bedside examination with a revealing asymmetric smile.

The glossopharyngeal nerve is more cephalad than the extent of the typical neck dissection during CEA. A branch of this nerve, the nerve of Hering, has great clinical significance since it innervates the carotid sinus and is responsible for the bradycardic and hypotensive responses that may be seen with manipulation of this structure. Some surgeons anesthetize the carotid sinus with lidocaine to avoid this complication, which is typically manifested intraoperatively.

Damage to the hypoglossal nerve, also identified routinely during a CEA, is the complication with which most are familiar. Injury to this nerve may result from inadvertent retraction or, rarely, transection; it results in tongue deviation to the side of injury.

Branches of the trigeminal nerve may be transected during dissection, resulting in sensory loss in the area of distribution

The ansa hypoglossus nerve innervates the strap muscles of the neck and is typically seen coursing along the carotid sheath. Unlike the other nerves, this nerve may be divided without clinically significant consequence.

The superior laryngeal nerve is rarely injured during CEA. The internal branch supplies sensation to the larynx, while the external branch innervates the cricopharyngeal muscle. Changes in voice quality may result from nerve injury.

 

The vast majority of cranial nerve injuries associated with CEA resolve over the first few months after surgery, and the risk of permanent cranial nerve deficit is very low. Among the 1739 patients who had CEA in the European Carotid Surgery Trial (ECST), immediate motor cranial nerve injury occurred in 5.1 percent, all ipsilateral to the side of the operation [142]. By hospital discharge, the cranial nerve injury rate had declined to 3.7 percent, and the involved cranial nerves included hypoglossal (n = 27),

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marginal mandibular (n = 17), recurrent laryngeal (n = 17), accessory (n = 1), and Horner syndrome (n = 3). The rate of persistent cranial nerve injury at four-month follow-up declined to 0.5 percent. Duration of surgery longer than two hours was the only independent risk factor for cranial nerve injury.

Parotitis — Parotitis is an unusual complication after CEA that results from manipulation of the parotid gland during the procedure. For this reason, most surgeons use this landmark as the cephalad extent of their dissection. The evaluation and management of parotitis is discussed elsewhere. (See "Suppurative parotitis in adults".)

FOLLOW-UP CARE — Following carotid endarterectomy, patients are typically discharged within one to three days. The most common delay in discharge is due to difficulties controlling blood pressure.

Wound care — The postoperative dressing is removed on the first postoperative day. If a drain has been placed, it should be removed as soon as possible in the postoperative period (day one or two) to decrease the potential for wound infection provided there is no significant drainage. Antibiotics are limited to perioperative prophylaxis. (See 'Prophylactic antibiotics' above.)

Duplex surveillance — Repeat duplex ultrasonography should be obtained three to six weeks following carotid endarterectomy to establish a new baseline for future comparison. Duplex surveillance is performed at six months and annually. More frequent intervals may be warranted if a contralateral stenosis is being observed.  

CAROTID RESTENOSIS — Historical rates of carotid artery restenosis after CEA were as high as 20 percent [143]. Lower values (2.6 to 10 percent at five years) are reported in more contemporary series [1,144,145].

Pathology — The pathology of the restenotic lesion is related to the time of presentation after initial surgery [146].

"Early" restenosis is that which occurs within two to three years after CEA. Patients with early restenosis frequently have highly cellular and minimally ulcerated intimal hyperplasia, similar to that which occurs after angioplasty or with stent placement. As a result, there is a low likelihood of symptomatic embolization.

"Late" restenosis occurs more than two to three years after CEA and generally results from progression of atherosclerotic disease. It is frequently associated with irregular plaques that may serve as an embolic source.

Risk factors — Patients at increased risk for restenosis include those below age 65, smokers, and women, probably due to the smaller size of their carotid arteries [146,147]. Elevated creatinine has been associated with the development of early restenosis, and elevated serum cholesterol with late restenosis [144]. Lipid lowering drugs may be protective for both early and late restenosis [144], although this finding requires confirmation.

The cellular features of the atheroma at the time of CEA may predict the occurrence of restenosis. In a prospective study of 500 patients that examined target lesion atherosclerotic plaque composition from specimens obtained at carotid endarterectomy, both low macrophage infiltration and a small or absent lipid core were associated with an increased risk of restenosis at one year [148]. In another study of 150 patients, an abundance of smooth muscle cells and a scarcity of macrophages were seen in the primary lesion of those who had neointima development six months after surgery; in those who did not develop neointima, the lesions were rich in lymphocytes and macrophages [149].

Patch angioplasty appears to be associated with a decreased risk of long-term recurrent stenosis compared with primary closure (see 'Patch angioplasty versus primary closure' above) [150].

Reoperation — Once the diagnosis of restenosis has been made, a decision has to be made about the need for reoperation. This decision is not one to be made lightly since reoperative CEA may be associated with a significant incidence of complications, although the evidence is retrospective and conflicting. The following studies illustrate the range of perioperative complications reported for redo CEA:

 

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An earlier series described 69 patients (48 percent men, 66 percent symptomatic) who had 82 reoperative CEA procedures [151]. Nine patients had two reoperative CEAs and two patients had three reoperative CEAs for either bilateral recurrence or a second recurrence on the same side. The average time to presentation with recurrent carotid stenosis was 6.5 years. The incidence of postoperative stroke (4.8 percent), transient ischemic attack (7.3 percent), and hematomas (7.3 percent) was nearly twice as high as reported for a first CEA [151].

In a series of 401 reoperative CEAs in 10 states in the United States, the 30-day combined risk of stroke or death from mid-1998 to mid-1999 was 5.7 percent [152].

A subsequent series described 145 patients (56 percent men, 36 percent symptomatic) who had 153 reoperative CEA procedures [153]. The incidence of perioperative stroke (1.9 percent) and death (O) was very low. While the average time from primary to reoperative CEA was 6.1 years in this series, 41 percent of the cohort were patients with early (<2 years) restenosis, which is typically due to intimal hyperplasia and carries a low risk of symptomatic disease compared with late restenosis (see 'Pathology' above).

A study of 31 patients who underwent carotid surgery for a secondary recurrent carotid stenosis required resection of the carotid and placement of an interposition graft in about 30 percent of the patients. No perioperative strokes were reported and peripheral nerve injury occurred in 10 percent of the patients [154]

 

An additional major concern is that there are no controlled studies establishing the efficacy of reoperative CEA in patients with restenosis. The presumed benefits of surgery in this group of patients are an extrapolation of the results of trials performed on patients at initial presentation.

PREDICTORS OF LONG-TERM OUTCOME — The predictors of long-term outcome after surgical therapy for atherosclerotic occlusive disease of the carotids were evaluated in one study of 1982 patients who underwent surgery at a single center and were followed for ≥25 years. Predictors of mortality included [155]:

 

Age, with a relative risk of 1.51 for each 10 year increase in age Male sex, relative risk 1.58 Diabetes mellitus, relative risk 1.48 Systemic hypertension, relative risk 1.31 Cigarette smoking, relative risk 1.13

 

Predictors of recurrence of symptoms or progression of disease were established by analysis of a subset of 886 patients who underwent one or more postoperative angiograms; these included [155]:

 

Total cholesterol, with a relative risk of 1.13 for each 50 mg/dL (1.3 mmol/L) increase Systemic hypertension, relative risk 1.42 Cigarette smoking, relative risk 1.47

 

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, “The Basics” and “Beyond the Basics.” The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

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Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on “patient info” and the keyword(s) of interest.)

 

Basics topics (see "Patient information: Carotid artery disease (The Basics)")

 

SUMMARY AND RECOMMENDATIONS

 

The effectiveness of carotid endarterectomy (CEA) for moderate to severe asymptomatic or symptomatic carotid artery stenosis has been established in large randomized trials. Prophylactic carotid endarterectomy in patients with asymptomatic carotid stenosis prior to cardiac or general surgery has no demonstrated benefit. For patients with indications for bilateral carotid endarterectomy, a staged rather than combined procedure is performed. (See "Management of symptomatic carotid atherosclerotic disease" and "Management of asymptomatic carotid atherosclerotic disease" and 'Introduction' above and 'Indications' above.)

Prior to carotid endarterectomy for asymptomatic carotid stenosis, duplex ultrasound may be sufficient to reliably determine the degree of internal carotid artery stenosis and assess local anatomy when performed in a certified vascular laboratory using validated criteria. If these standards cannot be met, additional imaging to verify the degree of stenosis should be performed. (See 'Carotid duplex' above.)

Prior to carotid endarterectomy, we recommend starting aspirin (81 to 325 mg daily) and continuing treatment indefinitely (Grade 1B). For patients who are sensitive to aspirin, clopidogrel is an alternative agent. (See 'Aspirin' above.)

For patients with symptomatic carotid stenosis, we suggest initiation of statin therapy prior to carotid endarterectomy (or maintenance in patients already being treated) (Grade 2B). The use of statins in symptomatic patients is associated with reduced morbidity and mortality following CEA. For patients with asymptomatic carotid stenosis undergoing CEA, statin therapy has not shown the same benefit but may be indicated for other medical reasons. (See 'Statins' above.)

We recommend antibiotic prophylaxis prior to carotid endarterectomy to reduce the risk of surgical site infection due to the frequent use of prosthetic material (Grade 1B). Antibiotics should be discontinued within 24 hours. (See 'Prophylactic antibiotics' above.)

Carotid endarterectomy can be performed using general anesthesia or local anesthesia (with or without cervical block). Statistically significant differences for major endpoints (perioperative stroke, myocardial infarction, and death) have not been consistently shown for differing anesthetic approaches. The choice of anesthesia technique is largely dependent on the preferences of the patient, the anesthesiologist and the surgeon. (See 'Choice of anesthesia' above.)

No one technique for plaque removal has been found to be superior over another with respect to the incidence of stroke, death or other morbidity. As with many surgical techniques, one technique may be preferable to another for specific circumstances and the choice of technique is largely dependent on the preferences and experience of the surgeon. (See 'Endarterectomy procedure' above.)

Prior to carotid artery clamping, the patient is systemically anticoagulated. At the completion of the procedure, we suggest reversal of heparin with protamine over no reversal (Grade 2B). (See 'Endarterectomy procedure' above.)

Following carotid plaque removal, we recommend patch closure of the carotid artery over no patch (non-eversion technique) (Grade 1B). With conventional CEA, carotid patch techniques are associated with decreased rates of stroke and carotid restenosis. No one patch material (synthetic, vein, bovine pericardium) has been shown to be superior over another.

After the completion of the procedure, the patient’s neurologic status and blood pressure are carefully monitored. We keep the systolic blood pressure between 100 and 150 mmHg.

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Hypotension and hypertension are both associated with adverse outcomes. (See 'Postoperative care' above.)

Complications following CEA include perioperative stroke, myocardial infarction, cerebral hyperperfusion syndrome, cranial nerve injury and parotitis. The cerebral hyperperfusion syndrome is probably the cause of most postoperative intracerebral hemorrhages and seizures in the first two weeks after CEA. The mechanism of hyperperfusion is related to loss of cerebral autoregulation. Patients complaining of severe ipsilateral headache (same side as CEA) within two weeks of CEA should be evaluated for hyperperfusion syndrome. (See 'Complications' above.)