Abstract
Although carotid endarterectomy (CEA) is now widely accepted as the surgical therapy for carotid stenosis, the role of and indications and evidence for many pharmacologic agents that are used adjunctively in the perioperative setting have not been conclusively established. Aspirin (acetylsalicylic acid) is the pharmaceutical agent that has been studied most extensively in conjunction with CEA; other than aspirin and dextran, the use of many agents before, during, and after CEA has not been standardized. Prospective randomized trials are still needed to demonstrate efficacy, predict outcome, and determine the optimal use of these medications in their adjunctive use during CEA to improve patient care and obtain optimal surgical outcomes.
Carotid endarterectomy (CEA) has been widely performed since the early 1950s. However, the role of and indications and evidence for many pharmacologic agents that are used perioperatively have not been conclusively established. The lack of evidence for adjunctive medications is not surprising as randomized clinical studies have provided level I evidence for only the surgery itself. In fact, CEA was widely accepted within the general medical community only within the last decade. 1
Aspirin (acetylsalicylic acid) is the pharmaceutical agent that has been studied most extensively in conjunction with CEA. Other agents routinely used during CEA have little or no evidence that conclusively documents their utility for this particular surgical procedure. This article reviews the available literature on several medications that are commonly used adjunctively during CEA.
Antiplatelet Agents
Aspirin
Aspirin was developed by the Bayer Corporation in 1897 2 and was used exclusively as an analgesic until 1971, when it was demonstrated to have additional utility in preventing several different types of cancer. 3 The mechanism of aspirin action includes both central and peripheral mechanisms. The primary mechanism of action is to block the production of prostaglandins in injured peripheral tissues, which accounts for its analgesic effect. In addition, the salicylate and acetate moieties each cross into the brain and spinal cord to inhibit central prostaglandin receptors, preventing activation of these central receptors by diffusible peripheral prostaglandins. Aspirin also inhibits cyclooxygenase within platelets by binding to it in an irreversible fashion; since platelets do not have nuclei and thus cannot synthesize additional cyclooxygenase during their short 8-day life, aspirin effectively permanently inhibits platelet function (Figure 1). However, aspirin affects only one of multiple pathways that regulate coagulation; thus, it is not surprising that aspirin decreases the relative risk of thromboembolic stroke by only 20 to 25% 4 and that patients can still suffer from a stroke while taking aspirin.
Mechanism of antiplatelet action. Downstream inhibitory effects are shown in half-tone. ADP = adenosine diphosphate; ASA = acetylsalicylic acid; GP = glycoprotein.
Aspirin is the only drug that has been extensively studied in patients undergoing CEA. Historically, aspirin has been the most commonly used adjunctive medication during CEA and is used to prevent thrombus formation both at the site and distally to the area of endarterectomy. In various studies, aspirin doses have been examined in the range of 75 to 1,300 mg/d. Although a wide range of doses has been found to be effective in clinical studies, the ideal dose has not been established.
The use of aspirin in several of the landmark CEA studies is reviewed in Table 1. Since aspirin was only an adjunctive medication and its evaluation was not the primary goal of these studies, there is difficulty in assessing the specific role of aspirin in determining the outcome of these trials. However, the North American Symptomatic Carotid Endarterectomy Trial (NASCET) reported a dose-dependent effect in preventing stroke in patients receiving high- versus low-dose aspirin. Cox regression analysis identified high-dose aspirin (650 mg/d) as one of four characteristics associated with greater long-term benefit of surgery; this benefit was decreased for those taking less aspirin or none. 5,6
Use of Aspirin in Landmark Carotid Endarterectomy Trials
ACAS = Asymptomatic Carotid Atherosclerosis Study; ACST = Asymtomatic Carotid Surgery Trial; CEA = carotid endarterectomy; ECST = European Carotid Surgery Trialists' Collaborative Group; NASCET = North American Symptomatic Carotid Endarterectomy Trial; NOS = not otherwise specified; VA = Veterans Affairs.
A smaller randomized trial examining the effect of a single preoperative dose of aspirin, 120 mg, found no benefit to this low dose. 7 Other studies examining low-dose aspirin (75–120 mg) administration have reported both positive and negative outcomes. 8,9 Therefore, we interpret these studies to recommend a perioperative dose of 650 mg, or possibly 1,300 mg, if tolerated by the patient 10 ; however, these higher doses place the patient at risk of temporary medication discontinuation owing to adverse events.
Additional evidence of the efficacy of aspirin in preventing perioperative stroke is obtained from extrapolating the results of aspirin's efficacy in other similar cardiovascular studies. The Antiplatelet Trialists' Collaboration meta-analysis examined patients with transient ischemic attack or minor ischemic stroke. A component of this trial examined the difference between groups of patients receiving 300 and 1,200 mg of aspirin over a 4-year period but failed to show clear-cut differences between these groups. 11
Another meta-analysis was performed more recently and reported that aspirin was protective in most types of patients at increased risk of occlusive vascular events. 12 This study reported that lower-dose aspirin (75–150 mg daily) over a long term was effective in the treatment of acute myocardial infarction or ischemic stroke, unstable or stable angina, previous myocardial infarction, stroke or cerebral ischemia, peripheral arterial disease, or arterial fibrillation, but in an acute situation, benefit was observed only when a dose of at least 150 mg aspirin was used. Patients undergoing CEA were included in this study but only as part of a “high-risk” group.
Two large, international, randomized, placebo-controlled trials demonstrated reduced mortality following the short-term administration of aspirin in acute stroke. In the Chinese Acute Stroke Trial (CAST), a one-third reduction in recurrent ischemic stroke was observed when patients were given 160 mg/d of aspirin within 48 hours of the onset of stroke symptoms and continued administration for up to 4 weeks. 13 The International Stroke Trial treated patients with 300 mg of aspirin “as soon as possible” following symptoms of stroke and for up to 14 days after a stroke and demonstrated a significant reduction in the combined end point of baseline prognosis-adjusted death and disability 6 months post-stroke. 14 These shorter-term data may imply that a period of preoperative administration followed by postoperative administration of medium-dose aspirin may have a translatable protective effect in patients undergoing CEA.
In addition to dose, the perioperative details of administration, especially timing of aspirin administration relative to CEA surgery, are not established, possibly owing to the irreversible action of aspirin on platelets and therefore leading to the thought that these studies have not been necessary. The daily administration of 81 or 325 mg of aspirin for approximately 1 week prior to surgery and indefinitely following surgery is practical and could lead to a lesser incidence of stroke while minimizing adverse events. However, since aspirin inhibits only one of several coagulation pathways, even when larger doses of aspirin are used, stroke may still occur. 15
Lower-dose aspirin has been shown to be as effective as high-dose aspirin in the prevention of general stroke, with fewer adverse bleeding events. Higher doses of aspirin have been known to induce bleeding complications and gastrointestinal irritation over the long term. 16,17 Low-dose aspirin therapy is as effective as higher-dose therapy in the prevention of initial and recurrent stroke and offers fewer adverse events 18 ; these data agree with the more limited data available on CEA surgery, but the possibility for bleeding to occur in these patients still exists.
Limited amounts of data are available regarding aspirin compared with other antithrombotic compounds in CEA surgery, but aspirin can be effective in the prevention of thrombus formation. In a large trial involving noncardioembolic ischemic stroke (N = 2,206), 325 mg of aspirin was shown to be as effective as warfarin in preventing recurrent ischemic stroke or death, with fewer bleeding complications (20.8% vs 12.9%), 19 but it is unknown if these data are translatable to patients undergoing CEA.
Clopidogrel (Plavix)
Clopidogrel is an adenosine diphosphate (ADP) receptor antagonist and thus inhibits platelet function by a different mechanism of action than aspirin (see Figure 1). Accordingly, the combination of aspirin and clopidogrel would be expected to provide synergistic platelet inhibition. However, clopidogrel has been associated with excessive intraoperative bleeding and thus is often stopped, usually for approximately 1 week, prior to CEA; patients treated with clopidogrel alone are often switched to aspirin alone during the perioperative period. Thus, there are limited data regarding the use of clopidogrel in patients undergoing CEA.
One study examined the administration of a single preoperative 75 mg dose of clopidogrel or placebo in addition to 150 mg of aspirin. In comparison with patients receiving aspirin alone, clopidogrel produced a 10-fold reduction in the relative risk of those patients with > 20 emboli detected on transcranial Doppler (TCD) ultrasonography in the postoperative period (p < .01). In this study, clopidogrel was not associated with an increased incidence of either bleeding complications or the need for blood transfusions. 20 Therefore, use of clopidogrel in combination with moderately low doses of aspirin may be a reasonable therapeutic strategy for patients thought to be at higher risk of postoperative microemboli, especially if dextran is not used perioperatively (see below).
Clopidogrel may have some benefit over aspirin in preventing thrombosis in those patients with aspirin resistance or intolerance, but clopidogrel has not been shown to be superior to aspirin in patients undergoing CEA. Based on the available information in trials involving ischemic stroke syndromes, the combination of routine doses of clopidogrel and aspirin may be more effective than aspirin alone, but with a greater number of bleeding complications. 21
Anticoagulant Agents
Heparin
Heparin was first discovered by a second-year medical student in 1916, who named the “hep” in heparin after the liver from which it was first extracted. 22,23 Heparin is now a very well-established anticoagulant, with its main anticoagulant effect likely mediated by its binding to antithrombin III, accelerating the inhibition of thrombin-mediated conversion of fibrinogen to fibrin and preventing additional thrombus accumulation. The precise mechanism by which heparin exerts its anticoagulant action has not been completely elucidated; however, heparin likely exerts its effects primarily via the intrinsic clotting cascade and heparin cofactor II. 24
Heparin is the anticoagulant of choice to prevent thrombosis distally to the clamped internal carotid artery during CEA owing to heparin's rapid onset of action, its short effective half-life (approximately 90–120 minutes), and its ability to be neutralized by protamine. In spite of their high anti–factor Xa to anti–factor IIa activity ratio, and thus the potential to inhibit thrombosis with fewer bleeding side effects, low-molecular-weight heparins are not typically used as an adjunct to CEA owing to their increased cost, longer half-life, and poor response to reversal by protamine.
Heparin may be administered during CEA as either a fixed dose or using a weight-based nomogram. Fixed heparin dosing achieves safe and efficacious anticoagulation in the great majority of patients having CEA, with typical doses of heparin (5,000 U for a 70 kg patient) expected to result in adequate anticoagulation. However, weight-based nomograms to guide heparin dosing may reduce the incidence of complications, such as hematoma formation, and may result in more predictable anticoagulation. During routine surgical cases, either nomogram-based or fixed-dosing schedules may be adequate. Although lower doses of heparin are advocated during aneurysm repair by some groups to reduce hemorrhagic side effects, there is no evidence that this is problematic during CEA. 25
Protamine sulfate–mediated neutralization of heparin given during CEA has been associated with an increased postoperative stroke rate in some studies, but the use of subcutaneous low-dose heparin may eliminate the need for protamine. 25 The use of protamine has been identified as a process of care that may improve outcome after CEA, 26 although the use of protamine is not universal among vascular surgeons. The evidence guiding the use of protamine during CEA is not conclusive to adequately guide its use.
Heparin-induced thrombocytopenia (HIT) has been reported to occur in patients receiving heparin, with an incidence of 0 to 30%. Although often mild and of no obvious clinical significance, thrombocytopenia can be accompanied by severe thromboembolic complications, such as skin necrosis, gangrene, myocardial infarction, stroke, and even death. 27 An important mechanism in avoiding any type of HIT is to limit a subject's exposure to heparin; if HIT is diagnosed or suspected and an anticoagulant is indicated, an anticoagulant with a different mechanism of action than heparin is often substituted, although lower-molecular-weight heparin has reportedly been used as well. 28 Additional substitutes available in the United States include the direct thrombin inhibitors lepirudin, bivalirudin, and argatroban. 29 Few data exist regarding the use of alternate anticoagulants for patients with a history of HIT needing surgical procedures. A single clinical report exists describing the use of argatroban in a patient with a history of HIT undergoing CEA. In this case report, a bolus of argatroban (150 μg/kg) followed by an infusion (5 μg/kg/min) was given, and adequate anticoagulation was demonstrated with multiple laboratory tests; the patient recovered uneventfully. 30 As awareness and detection of HIT increase and patients with a history of HIT require CEA, we expect that reports of the management of intraoperative anticoagulation will continue to guide safe use in general practice.
Warfarin
Warfarin's discovery dates back prior to 1940 31 and is named for the Wisconsin Alumni Research Foundation, which patented and licensed this oral anticoagulant as both a rat poison and a treatment for cardiovascular disease. Warfarin interferes with the synthesis of the vitamin K–dependent factors II, VII, IX, and X, as well as proteins C and S, and prevents reduction of vitamin K once it has functioned in the liver as a cofactor in the γ-carboxylation, and thus activation, of these factors. The action of warfarin can thus be easily reversed with the administration of subcutaneous vitamin K. The long half-life of factor II, 100 hours, compared with the other vitamin K–dependent or warfarin-sensitive factors, contributes to the long therapeutic action of warfarin.
Warfarin is usually stopped prior to elective surgery to prevent hemorrhage. An analogous study that reported a randomized, double-blind comparison of warfarin and aspirin (325 mg/d) in 2,206 patients with previous noncardioembolic ischemic stroke demonstrated no benefit of warfarin over aspirin in the prevention of recurrent ischemic stroke or death. 32 The incidence of minor hemorrhage was higher in the group treated with warfarin compared with aspirin (20.8% vs 12.9%; p < .001); major bleeding was also higher in the group treated with warfarin, but this difference was not statistically different.
The protocol to discontinue warfarin prior to surgery depends on its indication. Patients using warfarin as an anticoagulant for atrial fibrillation may choose to omit therapy for a few days, whereas patients using warfarin for a mechanical prosthetic valve would likely need a substitute anticoagulant, such as heparin, in warfarin's absence. No prospective trials exist examining the discontinuation of warfarin in patients undergoing CEA, nor are they likely to be performed. Since warfarin is a potent anticoagulant, its routine use is associated with a higher number of hemorrhagic adverse events, and its routine discontinuation is likely warranted prior to elective CEA. However, the exact time of discontinuation prior to CEA is not clearly established and is based on general perioperative guidelines, along with recommendations for substitute anticoagulant therapy. Warfarin is difficult to dose, increases the risk of minor bleeding, and has not been shown to be superior to standard-dose aspirin for preventing stroke in patients undergoing CEA.
Dextran
The anticoagulant utility of dextran sulfate was established in 1945, 33 although it is mostly used as a plasma volume expander, which is still its only US Food and Drug Administration–approved indication today. Dextran is thought to exert its anticoagulant effect by multiple mechanisms, including decreasing platelet adhesion via von Willebrand's factor, by causing defective fibrin polymerization, and by improving circulation via volume expansion, but its exact mechanism of action has not been completely determined. 34 Dextran's anticoagulant effect can be monitored via the activated partial thromboplastin time, the prothrombin time, or the thrombin time.
Dextran has less anticoagulant activity compared with heparin. The high-molecular-weight form, dextran 70, has greater potential for anticoagulation compared with the low-molecular-weight form, dextran 40. 35 However, this may be due to the failure to infuse sufficient dextran 40 because dextran 40 is excreted more rapidly than dextran 70. 36 One study reported the relationship of the dose of dextran to blood flow in the shunt placed during CEA; the administration of 100 mL of dextran 40 solution was found not to improve the shunt blood flow, whereas 500 mL of dextran significantly decreased blood viscosity. 37
An interesting placebo-controlled study examining 150 patients within 3 hours of CEA reported that 10% dextran 40 decreased cerebral emboli detected by TCD ultrasonography. The overall embolic signal counts were 46% fewer for the dextran group after 1 hour postoperatively (p = .052) and 64% fewer after 2 to 3 hours postoperatively (p = .04). 38 In a large (N = 600) prospective study, dextran 40 at 20 mL/h was effective in decreasing the stroke rate from 4 to 0.2%. 39 This group also reported that using TCD ultrasonography to direct dextran therapy for 3 hours postoperatively was as effective as 6 hours in the prevention of postoperative carotid thrombosis. 40
Dextran is commonly used after endarterectomy to prevent platelet adherence to the endarterectomy site. Although dextran has been demonstrated to reduce emboli detected on TCD ultrasonography after CEA, its routine use in preventing clinically important emboli is not clear. Postoperative TCD ultrasonographic monitoring and selective administration of dextran 40 have also been successful in reducing embolization and progression to stroke. 41
β-Blockers
Antagonists to β-adrenergic receptors are often prescribed in patients with cardiac disease. Selective β1 antagonists are less likely than nonselective agents to provoke unopposed alpha vasoconstriction in the peripheral or central circulation or in the airway. However, at higher doses, β1 selective antagonists may also have a mixed β1-β2 effect, provoking airway spasm. It is important to control blood pressure and heart rate during CEA surgery; however, it may be beneficial to allow temporary rises in blood pressure, maximizing collateral blood flow to the brain, until shunt placement occurs. For this reason, long-acting β-blockade is not routinely recommended.
The administration of β-blockers has been shown to be independently associated with reduced perioperative mortality and nonfatal myocardial infarction in patients undergoing noncardiac surgery, particularly in high-risk patients. 42–44 Only two studies examined the administration of β-blockers specifically in conjunction with CEA. One double-blind, prospective study examined premedication with 50 mg of atenolol prior to CEA surgery, performed in 20 patients under cervical plexus block. A sustained tachycardia of 3 minutes or more occurred in 13 patients in the placebo group but only 2 patients in the atenolol group (p < .01); there was no difference in the occurrence of bradycardia, hypotension, or hypertension between the two groups. The authors concluded that atenolol pretreatment was an effective method of reducing tachycardia during CEA performed under cervical plexus blockade. 45
Similarly, another study explored the double-blind, placebo-controlled administration of esmolol in 62 patients undergoing CEA using general anesthesia. 46 Patients were premedicated with intravenous esmolol over a period of 12 minutes (500 μg/kg/min for 4 minutes and 300 μg/kg/min for 8 minutes). Esmolol was found to decrease the maximum increases in heart rate and blood pressure from baseline when compared with placebo (p < .01). Thus, β-blockers also reduce tachycardia during CEA performed under general surgery.
Although no conclusive evidence remains that β-blockers reduce cardiac complications after CEA specifically, the reduction in tachycardia demonstrated in these studies, as well as the effects in patients undergoing other types of high-risk surgery, suggests that routine use of β-blockade is warranted. It remains to be determined whether alternate agents are available for those patients in whom routine β-blockade is contraindicated or not tolerated.
3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibitors (Statins)
The statins are a class of agents that are competitive inhibitors of the enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase). Inhibition of this enzyme results in lowering of plasma cholesterol levels by inhibiting the body's synthesis of cholesterol to a small extent, and, more importantly, increasing the number of low-density lipoprotein (LDL) receptors expressed on both hepatic and extrahepatic tissues. An increasing body of evidence suggests that in addition to lowering LDL, statins also reduce inflammation, reverse endothelial dysfunction, and decrease thrombogenicity. 47 It is now recognized that atherosclerosis has a strong inflammatory component and that macrophages contribute to plaque formation and subsequent rupture; statins have been shown to decrease cholesterol synthesis within macrophages, which may reduce macrophage activation and plaque rupture.
Several landmark studies have demonstrated that in individuals with carotid artery disease and/or coronary artery disease with moderately elevated LDL cholesterol levels, aggressive LDL cholesterol lowering with statins can reduce cardiovascular events and overall mortality. 48–51 Statins have been shown to significantly reduce the arterial wall thickness of the common carotid artery and vessel wall stiffness of the common femoral artery in patients with familial hypercholesterolemia, suggesting a beneficial role in the prevention of atherosclerosis. 47
One provocative study reported the use of pravastatin as an adjunct to CEA, treating patients with pravastatin to stabilize plaque preoperatively and then analyzing these plaques after they were surgically removed. 52 Patients with symptomatic carotid artery stenosis received 40 mg/d pravastatin (n = 11) or no lipid-lowering therapy (n = 13) for 3 months prior to scheduled CEA. Pravastatin decreased lipids, lipid oxidation, inflammation, matrix metalloproteinase 2, and cell death and increased tissue inhibitor of metalloproteinase 1 and collagen content in these excised symptomatic carotid plaques, consistent with a proposed plaque-stabilizing effect.
There have been some recent reports regarding the use of statins in patients undergoing CEA. One study retrospectively examined the effect of statins on several noncardiac vascular surgeries, including CEA. 53 Adverse events were 9.9% fewer in patients receiving statins than in those not receiving statins (p = .001), even accounting for the effects of age, gender, type of surgery, emergent surgery, left ventricular dysfunction, and diabetes mellitus.
Another larger study examined the outcome of symptomatic (n = 815) and asymptomatic (n = 665) patients undergoing CEA. Statin use by symptomatic patients was associated with reduced in-hospital mortality and in-hospital ischemic stroke or death but not in-hospital cardiac outcomes. Curiously, this association was not seen in asymptomatic patients on statins. 54 These results were recently confirmed in a large series of patients at Johns Hopkins Hospital, with reduced perioperative mortality and stroke in patients receiving statin therapy. 55
It is believed that long-term administration of statins provides plaque stability. The group from the Massachusetts General Hospital recently reported that long-term use of lipid-lowering agents was five- to eightfold protective of restenosis after CEA. 56 Although the precise dose, particular statin, and length of statin therapy have not been established, the data suggest that both perioperative and long-term use of a statin after CEA is indicated.
Angiotensin-Converting Enzyme Inhibitors
Angiotensin-converting enzyme inhibitors (ACEIs) have an established role as antihypertensive agents affecting the renin-angiotensin axis but have also been shown to have alternative modes of action. Microvascular endothelial dysfunction associated with atherosclerosis may be improved by the administration of ACEI therapy. A study examining 43 patients with coronary atherosclerosis who received an infusion of enalaprilat showed the potentiation of bradykinin- and acetylcholine- but not nitroprusside-induced vasodilator responses. 57 This result suggests that this ACEI selectively improves endothelium-dependent but not endothelium-independent vasodilation; in addition, this potentiation may be mediated by increased nitric oxide activity. 58
ACEIs were also implicated in decreasing atheroprogression in animal models and decreasing reinfarction rates in humans. 59 Additionally, ACEI receptor expression has been found in the intimal layer of human carotid artery plaques. In uncomplicated lesions, angiotensin-converting enzyme (ACE) staining was modest, as well as in some clusters of macrophages and on the luminal side of carotid artery vascular endothelium. Smooth muscle cells did not show this expression. 59
These data suggest an important mechanism by which increased ACE expression may play a role in carotid atherosclerosis. However, more clinical and basic science studies are needed to explore the exact mechanism and clinical implications prior to advocating routine use of ACEIs as an adjunct to CEA, a procedure that removes the endothelium from the carotid bulb. In particular, as imaging techniques improve, it may be possible to more accurately determine the rates of re-endothelialization and restenosis after CEA and the effect of ACEIs on this process.
Local Anesthetics
Local anesthetics block conduction by preventing the initiation and transmission of nerve impulses by altering the permeability of the cell membrane to sodium ions. Bupivacaine is a long-acting local anesthesic with a long duration of action, 3 to 7 hours. 60 Lidocaine is used as a short-acting local anesthetic and as an antiarrhythmic agent, with a shorter half-life of 10 to 20 minutes; epinephrine is often added to promote retention in the injected tissue, promoting its effective duration of action. 61
Hemodynamic changes such as hypertension, hypotension, or bradycardia are commonly seen in patients undergoing CEA owing to the proximity of the carotid sinus baroreceptor to the area of the endarterectomy procedure (ie, the carotid bulb). Lidocaine has been suggested to relieve perioperative hemodynamic instability during CEA surgery. Several randomized studies examined the injection of lidocaine or a derivative thereof into the carotid sinus nerve but found no differences in the incidences of hemodynamic changes or the need for vasoactive medications in the operating room following restoration of carotid artery blood flow up to 1 day following surgery. 61 For this use, lidocaine preparations should not contain epinephrine.
Two double-blind studies, with 99 and 92 subjects, respectively, using both short- and long-term derivatives of lidocaine showed no difference in hypotension, hypertension, or bradycardia either during or after surgery between groups given lidocaine and control. 62,63 However, another double-blind study (N = 34) examining the use of lidocaine showed that patients had a lower pulse rate and lower systolic and mean blood pressures than those receiving placebo, with a relationship to clamp application and shunt removal. 64 Although these studies examined different end points, the difference in these outcomes suggests the need for further study.
Local anesthetics can also be used for general procedural analgesia and thus avoiding the use of general anesthesia. A combined block using lidocaine or bupivacaine as a cervical plexus block can have a rapid peak, which potentially may 65 or may not 66 exhibit a systemic effect. To avoid this, additional doses of local anesthetics must be injected carefully and at least 40 minutes after the initial block to avoid the peak concentrations. CEA may be performed by using either superficial or a combined superficial-deep block, and the perioperative lidocaine requirements will typically be the same regardless of which block is used. 67 Several studies have demonstrated an excellent outcome after CEA was performed under locoregional anesthesia and that this technique may contribute to an excellent outcome. 68
Conclusions
With the possible exception of aspirin and dextran, the use of many pharmacologic agents before, during, and after CEA has not been standardized. Prospective randomized trials are still needed to demonstrate efficacy, predict outcome, and determine the optimal use of these medications in their adjunctive use during CEA.
The prospective testing of these agents is an important aspect of improving outcomes in patients undergoing CEA. Vascular surgeons hope to obtain superior results with CEA compared with other surgical specialties. It is, therefore, imperative to understand the additional underlying adjuncts in care that vascular surgeons use because these adjuncts may contribute to improved outcomes. 25,69–71
Footnotes
Acknowledgments
The authors would like to recognize and thank Dr. Kert Shuster, PharmD, and Lyn Crispino, MLS, AHIP, for their expertise, efforts, and contribution.
Presented in part at the 32nd annual VEITHsymposium, New York, NY, November 17–20, 2005.