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Ischemic Cerebrovascular Disease

Patients presenting for carotid endarterectomy (CEA) are often elderly, have advanced cerebrovascular disease, and frequently have significant coexisting diseases involving other organ systems. Anesthetic management of these patients requires both an understanding of the physiologic stress imposed by the surgical procedure (disruption of the major cerebral hemispheric blood supply) and an appreciation of the physiologic constraints imposed by the coexisting diseases.

I. Guidelines for performing CEA

Several prospective, randomized studies have reported superior outcome for medically stable patients who have symptomatic, high-grade carotid stenoses (70% to 99%) after CEA combined with best medical therapy compared to medical treatment alone.
On the basis of these studies, both the American Heart Association and the Canadian Neurosurgical Society have formulated guidelines for performing CEA (Table -1).
Subgroup analyses of the results of these multicenter trials have expanded the selection criteria for patients likely to benefit from CEA to include older patients and those who have complex carotid disease (e.g., tandem extracranial-intracranial stenoses). As a result, anesthesiologists can expect to care more frequently for older patients and those at increased risk for complications.
Endovascular treatment for carotid stenosis ”carotid angioplasty and stenting (CAS)” has been developed over the past several years. Although CAS are increasingly used in clinical practice, the utility and durability are still undergoing clinical trials which will better define indications.
CEA remains the preferred surgical intervention for the prevention of stroke among patients who have extracranial cerebrovascular disease.

II. Physiologic considerations

Cerebral blood flow (CBF) and metabolism
The brain is highly active metabolically but is essentially devoid of oxygen and glucose reserves, making it dependent on the continuous delivery of oxygen and glucose by cerebral circulation.

Table -1. Surgery guidelines for carotid endarterectomy

Appropriate candidate for CEA
  Symptomatic 70-99% stenosis with
    TIA(s) or nondisabling stroke
    Surgically accessible stenosis
    Stable medical and neurologic condition
Uncertain candidate for CEAa
  Symptomatic <70% stenosis withb
    TIA(s) or nondisabling stroke
    Surgically accessible stenosis
    Stable medical and neurologic condition
  Asymptomatic >60% stenosis with
    Surgically accessible stenosis
    Stable medical condition
Inappropriate candidate for CEA
  Asymptomatic <60% stenosis
  Symptomatic or asymptomatic with
    Intracranial stenoses more severe than the extracranial stenosis
    Uncontrolled diabetes mellitus, hypertension, congestive heart failure, or unstable angina pectoris
    A major neurologic deficit or decreased level of consciousness

The percentage stenosis should be defined by cerebral angiography and the NASCET method. The surgeon's rate of surgical complications (stroke or death) should be <6% for CEA in cases of symptomatic stenoses (appropriate or uncertain candidates), and <3% in cases of asymptomatic stenoses (uncertain candidates).
aGuidelines uncertain = insufficient evidence to support a definitive recommendation.
bGuideline for symptomatic <70% stenosis expected to be clarified this year with publication of NASCET results for this group of patients.
TIA, transient ischemic attack; CEA, carotid endarterectomy; NASCET, North American Symptomatic Carotid Endarterectomy Trial.

CBF is provided by the internal carotid arteries (approximately 80%) and the vertebral arteries (approximately 20%), which anastomose at the base of the brain to form the circle of Willis.
Patients who have advanced occlusive cerebrovascular disease may be dependent on other collateral channels to maintain adequate CBF.
Normally, CBF is autoregulated to match the brain's metabolic requirements and maintain normal neuronal function.
Cerebral perfusion
CBF is related to cerebral perfusion pressure (CPP) and cerebrovascular resistance (CVR) according to the equation CBF = CPP/CVR.
The following factors affect CBF:
1. CPP equals mean arterial blood pressure (MAP) minus intracranial pressure or central venous pressure, whichever is higher.
2. CVR is a function of blood viscosity and the diameter of the cerebral resistance vessels.
Optimization of CBF during CEA is hampered by the fact that the only factors readily amenable to intraoperative manipulation are arterial blood pressure and arterial carbon dioxide tension (Paco2), which impact on CPP and CVR, respectively.
Carbon dioxide tension Paco2
Within the range of Paco2 from 20 to 80 mm Hg, CBF changes by 1 to 2 mL/100 g/minute for every 1 mm Hg change in Paco2.
The most common approach to ventilatory management during CEA is to maintain normocapnia. This is achieved by ventilation to a Paco2 that produces a normal pH in the absence of coexisting metabolic acidosis.
Blood pressure
CBF remains remarkably constant within the range of MAP from 50 to 150 mm Hg. Beyond this range, the limit of vasomotor activity is exceeded and CBF directly depends on changes in CPP.
In patients who have preexisting chronic hypertension, both the upper and lower limits of autoregulation are shifted to higher pressures.
In patients who have cerebrovascular disease, the CBF response to changes in Paco2 during carotid cross-clamping is impaired. Under these conditions, improvement in CBF is likely to depend largely on increases in CPP, emphasizing the relatively greater importance of blood pressure control during CEA surgery.
During CEA, blood pressure should be maintained within the normal preoperative range. Mild increases in systolic blood pressure of up to 20% above normal at the time of cross-clamping are acceptable, but hypotension and severe hypertension should be avoided.

III. Preanesthetic assessment

The patient's state of health is determined from the medical history, pertinent physical examination, and chart review.
Coexisting diseases are assessed and optimized. Common coexisting diseases include coronary artery disease, arterial hypertension, peripheral vascular disease, chronic obstructive pulmonary disease, diabetes mellitus, and renal insufficiency.
For patients who have diabetes, perioperative blood glucose should be carefully managed to avoid both hypo- and hyperglycemia. Current evidence suggests that hyperglycemia adversely affects outcome after temporary focal or global cerebral ischemia.
Cardiac complications are a major source of mortality after CEA. Preoperative factors reported to correlate with increased perioperative cardiac morbidity include poorly controlled hypertension, congestive heart failure, and recent myocardial infarction.
Cerebral angiograms should also be reviewed to identify patients at increased risk from the presence of significant contralateral carotid artery disease or poor collateral circulation.
A risk stratification scheme for perioperative complications has been proposed for patients undergoing CEA (Table -2).

IV. Anesthetic management

CEA can be safely performed under general anesthesia, regional anesthesia, or local anesthetic infiltration. Experienced centers report similar morbidity and mortality, and available evidence is insufficient to establish the definitive superiority of any one technique.
Regional anesthesia
Superficial and deep cervical plexus blocks are the most commonly used regional anesthetic techniques for CEA.
1. A superficial cervical plexus block is performed by injecting a local anesthetic subcutaneously along the posterior border of the sternocleidomastoid muscle where the cutaneous branches of the plexus fan out to innervate the skin of the lateral neck.
2. A deep cervical plexus block is a paravertebral block of the C2-4 nerve roots. This technique involves injecting local anesthetic at the vertebral foramina (transverse processes) of the C2-4 vertebrae to block the neck muscles, fascia, and greater occipital nerve.
3. Many regional anesthesia textbooks describe the techniques in detail and should be reviewed before performing the blocks.
Intraoperative monitors include the following:
1. Intra-arterial cannula for blood pressure measurement
2. Continuous electrocardiogram (ECG)
3. Pulse oximetry
4. Capnography sampled via nasal prongs for monitoring respiratory rate
Supplemental oxygen should be provided through a mask or nasal prongs positioned to avoid the site of surgery.
Carefully titrated sedation using small, repeated, intravenous doses of fentanyl, 10 to 25 mcg, and/or midazolam, 0.5 to 2 mg, should render the patient comfortable and cooperative during the operation. Propofol is a reasonable alternative administered as intermittent intravenous bolus doses, 0.3 to 0.5 mg/kg, or as a low-dose continuous infusion, 10-50 mg/kg/hr. The potential advantages of using dexmedetomidine, an alpha2-agonist, include supplemental sedation, modest analgesia, minimal respiratory depression, and preserved cognitive function. Careful attention is necessary during administration to avoid hemodynamic instability (i.e., transient hypertension, hypotension, and bradycardia).

Table-2. Preoperative risk stratification for patients undergoing CEA

Risk Group Characteristics Total Morbidity and Mortality (%)
1 Neurologically stable, no major medical or angiographic risk 1
2 Neurologically stable, significant angiographic risk, no major medical risk 2
3 Neurologically stable, major medical risk, ± major angiographic risk 7
4 Neurologically unstable, ± major medical or angiographic risk 10
Type of Risk Risk Factors
Medical risk Angina
Myocardial infarction (<6 mo)
Congestive heart failure
Severe hypertension (>180/110 mm Hg)
Chronic obstructive pulmonary disease
Age >70 y
Severe obesity
Neurologic risk Progressing deficit
New deficit (<24 hr)
Frequent daily TIA(s)
Multiple cerebral infarcts
Angiographic risk Contralateral ICA occlusion
ICA siphon stenosis
Proximal or distal plaque extension
High carotid bifurcation
Presence of soft thrombus

TIA, transient ischemic attack; ICA, internal carotid artery.

Equipment should be immediately available to convert to a general anesthetic if intraoperative conditions warrant.
Advantages of regional anesthesia include the following:
1. Superior neurologic monitoring associated with an awake patient
2. Potential to minimize interventions such as shunt insertion based on the presence or absence of neurologic symptoms at cross-clamping
3. Less expensive
4. Reports of more rapid recovery and shorter hospitalization
Disadvantages of regional anesthesia include the following:
1. Requirement of an operating room staff committed to working with patients under regional anesthesia, which necessitates patience, gentle technique, and reinforcement of the block as needed
2. Lack of airway and ventilatory control
3. Potential need to deal with complications in an awake patient: stroke or transient cerebral ischemia, cross-clamp intolerance, seizure, airway obstruction, hypoventilation, confusion, agitation, and angina
4. Complications associated with cervical plexus blocks: local anesthetic toxicity, inadvertent injection into either the subarachnoid space or the vertebral artery, and phrenic or recurrent laryngeal nerve block
General anesthesia
General anesthesia represents the most common anesthetic technique for CEA.
Intraoperative monitors are the same as for regional anesthesia.
1. Monitoring central venous and pulmonary artery pressure is used infrequently. A central venous catheter facilitates the management of intraoperative fluid administration and provides central access for drug administration or resuscitation. A pulmonary artery catheter may be helpful in patients who have high-risk cardiovascular disease (e.g., unstable angina, poor left ventricular function, recent myocardial infarction). Care should be exercised to avoid carotid puncture when inserting these catheters into the jugular vein.
The key consideration during the induction of anesthesia is the maintenance of stable hemodynamic conditions during intubation, positioning, and draping.
Thiopental, midazolam, propofol, and etomidate are all appropriate induction drugs and should be supplemented with opioid.
All of the nondepolarizing neuromuscular-blocking drugs facilitate tracheal intubation. Succinylcholine is a reasonable alternative. However, its use is contraindicated in patients who have had a recent paretic cerebral infarct.
General anesthesia is usually maintained with a combination of volatile anesthetic (typically isoflurane, desflurane, or sevoflurane) and opioid. Neuromuscular blockade is maintained throughout the procedure. Propofol infusion is a reasonable alternative. The use of remifentanil, an ultrashort-acting opioid, has also become popular as an adjunct to general anesthesia for CEA. Its short duration of action facilitates titration of anesthesia and promotes early emergence, particularly when used in combination with short-acting volatile anesthetic drugs such as desflurane and sevoflurane.
The administration of nitrous oxide is controversial as a result of reports of potential adverse effects on cerebral metabolism and increased risk of postoperative vomiting.
Blood pressure is maintained at preoperative levels. Small bolus doses of vasopressor (e.g., phenylephrine, 40 to 60 mcg, or ephedrine, 5 to 7.5 mg) can be administered to support blood pressure if necessary. Some anesthesiologists use infusions of phenylephrine to maintain or increase blood pressure, especially during cross-clamping. However, evidence suggests that this practice may be associated with an increased risk of myocardial ischemia.
Ventilation is adjusted to maintain normocapnia.
Advantages of general anesthesia include the following:
1. Is potentially more comfortable for patients and operating room staff
2. Facilitates intraoperative control of ventilation, airway, and sympathetic responses
3. Facilitates management of complications (e.g., cross-clamp intolerance and transient cerebral ischemia) through the use of induced hypertension or pharmacologic suppression of electroencephalographic (EEG) activity
4. Reduces the need for expedience in performing surgery because patient tolerance is not a factor
5. May provide some cerebral protection
Disadvantages of general anesthesia include the following:
1. There is the need for an alternate method for monitoring cerebral function.
2. In the absence of a completely reliable cerebral function monitor, it is possible that some remediable complications will not be detected before the occurrence of irreversible neuronal injury (e.g., cross-clamp intolerance, kink in carotid shunt).
3. Prolonged emergence might confuse postoperative evaluation.
4. It is more expensive.
Carotid cross-clamping
Before cross-clamping, heparin, 75 to 100 U/kg, is administered intravenously.
Carotid cross-clamping is often associated with an increase in blood pressure of up to approximately 20% above preoperative levels. Excessive increases can reflect cerebral ischemia. This should be considered before controlling the increase in blood pressure pharmacologically.
Neurologic monitoring
1. The purpose of neurologic monitoring is to identify patients at risk for adverse neurologic outcome owing to the development of cerebral ischemia, particularly during carotid cross-clamping.
2. An awake patient represents the least expensive and most sensitive neurologic function monitoring during CEA.
3. Because patients are not awake during general anesthesia, various other techniques are available to monitor neurologic function. EEG, carotid stump pressure measurements, transcranial Doppler (TCD), cerebral oximetry, and CBF measurements are used most commonly, either individually or in combination (i.e., EEG and TCD). The use of SEP with carotid protocol is helpful in detecting early shifts in latency and amplitude.
4. Each of these techniques can identify significant reductions in cerebral perfusion. However, controversy continues regarding the reliability of these techniques, individually or in combination, to predict outcome accurately.
5. Interventions available but unproven in clinical trials in response to evidence of cerebral ischemia include the following:
(1) Increasing CPP by administering systemic vasopressor drugs (e.g., phenylephrine)
(2) Reducing the risk of ischemia by pharmacologic suppression of cerebral metabolic requirements (e.g., thiopental, propofol)
(3) Restoring internal carotid artery blood flow by inserting a carotid shunt
Emergence
Emergence should be designed to avoid excessive coughing or straining and surges in systemic blood pressure, which might open the freshly closed arteriotomy.
Heparin is usually partially reversed at the time of wound closure.
Many surgeons prefer patients to be awake and their tracheas extubated at the conclusion of the procedure to facilitate neurologic examination in the early postoperative period.

V. Postanesthetic management

The intra-arterial cannula is maintained during the initial postoperative period to permit continuous blood pressure monitoring.
All patients receive supplemental oxygen postoperatively. Pulse oximetry monitors the adequacy of oxygenation. Bilateral CEA is associated with the abolition of the ventilatory and cardiovascular responses to hypoxemia. Providing supplemental oxygen and closely monitoring ventilatory status are particularly important in these patients.
Postoperative hemodynamic instability occurs in >40% of patients after CEA and is postulated to be related to carotid baroreceptor dysfunction.
CEA performed using a carotid sinus nerve-sparing technique is associated with a higher incidence of postoperative hypotension, most likely because of increased exposure of the carotid sinus after removal of the atheromatous plaque. Associated with a marked decrease in systemic vascular resistance, hypotension can be prevented or treated with local anesthetic blockade of the carotid sinus nerve, the administration of intravenous fluid or, if necessary, the administration of vasopressor drugs such as phenylephrine.
Hypertension after CEA is less well understood and has been reported to be more common in patients who have preoperative hypertension and in patients who undergo CEA with denervation of the carotid sinus. Mild increases in postoperative blood pressure of up to 20% above preoperative levels are acceptable, but marked increases are treated with antihypertensive drugs.
Other causes of hemodynamic instability after CEA include myocardial ischemia or infarction, arrhythmias such as atrial fibrillation, hypoxia, hypercarbia, pneumothorax, pain, confusion, and distention of the urinary bladder.
In most hospitals, patients are discharged from the postanesthetic care unit to an environment in which intensive neurologic and cardiovascular monitoring is available (e.g., intensive care unit or neurosurgical observation unit).

VI. Complications

Major postoperative complications after CEA include stroke, myocardial infarction, and hyperperfusion syndrome.
Stroke
Approximately two-thirds of strokes associated with CEA occur in the postoperative period. Most of these appear to be related to surgical factors resulting in either carotid occlusion (e.g., thrombosis, intimal flap) or emboli originating at the surgical site.
Intraoperative strokes represent approximately one-third of strokes that occur in the perioperative period. Most intraoperative strokes happen at the time of carotid cross-clamping and are either technical (i.e., shunt malfunction) or embolic, rather than hemodynamic, in origin.
Monitoring intraoperative neurophysiologic function is directed to identifying a relatively small group of patients who develop hemodynamically induced ischemia, which is potentially reversible with early recognition and intervention.
It is likely that, beyond using current anesthetic and monitoring techniques and meticulously manipulating hemodynamic and ventilatory parameters, the anesthesiologist has little ability, at present, to affect the incidence of stroke and the outcome during CEA.
Myocardial infarction
Myocardial infarction represents the major cause of mortality after CEA. The incidence of fatal postoperative myocardial infarction is 0.5% to 4%, and the proportion of total perioperative mortality (within 30 days of operation) attributed to cardiac causes is estimated to be at least 40%.
On the basis of the high incidence of coronary artery disease among patients undergoing CEA, routine coronary angiography has been advocated. However, little evidence supports the premise that routine preoperative coronary angiography improves cardiac outcome after CEA. It seems more reasonable to assume that all patients presenting for CEA have atherosclerotic disease involving the coronary arteries and to gauge perioperative risk in relation to the patient's functional status.
High-risk patients including those who have unstable angina, recent myocardial infarction, or recent heart failure may be considered more appropriate candidates for CEA staged or combined with a coronary artery bypass graft (CABG) procedure.
Existing evidence is insufficient to formulate firm recommendations regarding the staging of CEA with CABG surgery. The risk of stroke is similar if CEA precedes or is combined with CABG. This risk is lower than when CABG is performed before CEA. However, the incidence of myocardial infarction and death is higher when CEA precedes CABG. Pending results from well-designed prospective studies, recommendations from the Canadian Neurosurgical Society suggest that CEA should precede CABG if possible. When the patient's cardiac condition is too unstable to permit a prior CEA, combined surgery should be considered.
Death
Stroke and myocardial infarction represent the major causes of perioperative mortality associated with CEA.
Patient selection, the experience of the surgeon, and the institution where the surgery is performed affect operative risk.
On the basis of these considerations, the American Heart Association Stroke Council has recommended that the combined risk for either death or stroke associated with CEA should not exceed 3% for asymptomatic patients, 5% for symptomatic (transient cerebral ischemia) patients, 7% for patients who have suffered a previous stroke, and 10% for patients undergoing reoperation for recurrent carotid stenosis.
Hyperperfusion syndrome
An increase in CBF occurs frequently after CEA. Typically the magnitude of this increase is relatively small (<35%). However, in severe cases, increases in CBF can exceed 200% of preoperative levels and are associated with an increase in morbidity and mortality.
Clinical features of this hyperperfusion syndrome include headache (usually unilateral), face and eye pain, cerebral edema, seizures, and intracerebral hemorrhage.
Patients at greatest risk include those who already have a preoperative reduction in hemispheric CBF owing to bilateral high-grade carotid stenoses, unilateral high-grade carotid stenosis with poor collateral cross-flow, or unilateral carotid occlusion with contralateral high-grade stenosis.
The syndrome is thought to result from restoration of perfusion to an area of the brain that has lost its ability to autoregulate as the result of a chronic decrease in CBF. The restoration of CBF leads to a state of hyperperfusion that persists until autoregulation is reestablished, usually over a period of days.
Patients at risk for this syndrome should be monitored closely in the perioperative period, and blood pressure should be meticulously controlled.
Other complications. Other complications associated with CEA include hematoma formation and cranial nerve palsies. Hematoma formation can lead to airway compromise owing to mass effect, which might require opening the wound acutely to reestablish the airway before emergent reoperation. Cranial nerve palsies are typically temporary and could manifest themselves as vocal cord paralysis and altered gag reflex.

VII. Neuroradiology-Carotid Angioplastic Stenting

General considerations
Carotid angioplasty with or without the use of endovascular stenting is a relatively new technique for the treatment of carotid stenosis. Its safety and efficacy relative to CEA, particularly with respect to perioperative and long-term neurologic outcome, are currently the subject of several multicenter studies.
CAS techniques have been progressively modified as new technologies become available to include self-expanding stents and cerebral-protection devices.
Advocates suggest that the technique offers advantages in patients who have high-risk medical conditions and those who have surgically inaccessible carotid disease (e.g., previous neck irradiation, intracranial stenosis).
Anesthetic technique
CAS can be performed under either general anesthesia or sedation. No evidence is available to recommend one technique over the other.
Advantages of general anesthesia include the following:
(1) Provides better airway control
(2) Provides better quality of the images
(3) Facilitates control of blood pressure, Paco2
(4) Facilitates treatment of neurologic emergencies
Advantages of an awake, sedated patient include the following:
(1) Awake cerebral function monitoring
(2) Identification of intraoperative complications
(3) Rapid emergence and postoperative neurologic assessment
(4) Less expensive
Anesthetic considerations
Preoperative assessment is the same as for patients scheduled for CEA.
For patients undergoing CAS, factors affecting the selection of the awake (sedation) technique include the presence of gastroesophageal reflux and evidence of orthopnea.
Monitoring should be consistent with operating room standards including intra-arterial blood pressure measurement, pulse oximetry, ECG, and capnography. Central venous access is optional depending on the patient's medical condition.
Hemodynamic changes typically associated with carotid distension at the time of angioplasty or stent expansion, especially bradycardia and asystole, can be profound. A small dose of atropine or glycopyrrolate is often administered to attenuate this response. The immediate availability of external pacing equipment is prudent.

VIII. Summary

Here, we are focusing on the anesthetic management of patients undergoing CEA. It also includes a brief overview of the current status of CAS. Physiologic concepts that form the basis for current recommendations regarding the choice of anesthetic technique, drugs, monitoring, and hemodynamic and ventilatory management are discussed. Newer anesthetic drugs facilitate the titration of anesthesia in relation to the patient's responses to changing intraoperative conditions and promote rapid emergence and early assessment after CEA. Expanded criteria defining appropriate candidates for CEA suggest that the anesthesiologist will increasingly be called upon to care for patients who are older and present with significant complex needs. The management of coexisting disease, particularly the risk of cardiac complications, continues to represent important perioperative challenges for the anesthesiologist.


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