Mark A. Adelman

The cause of perioperative stroke after carotid endarterectomy

PURPOSE The purpose of this study was to examine the cause of perioperative stroke after carotid endarterectomy. METHODS The records of 2365 patients undergoing 3062 carotid endarterectomies from 1965 through 1991 were reviewed. Sixty-six (2.2%) operations were associated with a perioperative stroke. The mechanism of stroke was determined in 63 of 66 cases. Patient risk factors and surgeon-dependent factors were analyzed. RESULTS More than 20 different mechanisms of perioperative stroke were identified, but most could be grouped into broad categories of ischemia during carotid artery clamping (n = 10), postoperative thrombosis and embolism (n = 25), intracerebral hemorrhage (n = 12), strokes from other mechanisms associated with the surgery (n = 8), and stroke unrelated to the reconstructed artery (n = 8). Dividing the operative experience approximately into thirds, during the years 1965 to 1979, 1980 to 1985, and 1986 to 1991 the perioperative stroke rates were 2.7%, 2.2%, and 1.5%, respectively. This, in part, is associated with a better selection of patients (more symptom free, fewer with neurologic deficits). There has been a notable decrease in perioperative stroke caused by ischemia during clamping and intracerebral hemorrhage, but postoperative thrombosis and embolism remain the major cause of neurologic complications. CONCLUSIONS Although patient selection seems to play a role, most perioperative strokes were due to technical errors made during carotid endarterectomy or reconstruction and were preventable.

The surgical management of carotid artery stenosis in patients with previous neck irradiation

BACKGROUND A history of therapeutic irradiation to the neck complicates the management of carotid artery occlusive disease. Serious surgical concerns are raised regarding alternative incisions, difficult dissections, and adequate wound closure. Pathology may be typical atherosclerotic occlusive disease or radiation-induced arteritis. In order to establish guidelines for the treatment of these patients, we have reviewed our operative experience. PATIENTS AND METHODS A review of our operative experience over the past 15 years revealed 10 patients with a history of prior irradiation to the neck who underwent 14 carotid operations. RESULTS The indications for radiation included laryngeal carcinoma and lymphoma. Five patients had undergone previous radical neck dissections, and four patients had permanent tracheostomies. The surgical indications were asymptomatic high-grade stenosis in 7 cases, transient ischemic attack in 4 cases, stroke in 2 cases, and a pseudoaneurysm in 1 case. Conventional carotid endarterectomy with patch angioplasty was used in 10 of the 14 operations. In the remaining four operations, saphenous vein interposition grafting was utilized to replace the diseased segment of carotid artery secondary to a panarteritis. Wound closure required dermal grafting in two of five cases where surgery was performed ipsilateral to a prior radical neck dissection. One perioperative cerebral infarction occurred; there were no other neurologic or non-neurologic complications. All patients are doing well in one- to five-year follow-up, with serial postoperative duplex scans demonstrating no signs of recurrent stenosis. CONCLUSIONS Patients with a history of irradiation to the neck should be screened for the presence of carotid disease. Carotid occlusive disease should be treated surgically in these patients with the usual indications. Intraoperative surgical management is similar to that of non-irradiated patients. Concerns about difficulty in achieving an adequate endarterectomy plane and about problems with wound closure have generally been unfounded.

Dexmedetomidine for awake carotid endarterectomy: efficacy, hemodynamic profile, and side effects.

Abstract: A randomized, double-masked, placebo-controlled study was designed to compare dexmedetomidine as a primary sedative agent with a commonly used drug combination in patients undergoing awake carotid endarterectomy (CEA). Sixty-six patients undergoing CEA (ASA II–IV) were randomly assigned to receive either dexmedetomidine (total dose of 97.5 ± 54.7 mcg) or normal saline (control). Supplemental doses of midazolam, fentanyl, and/or propofol were administered as deemed necessary by the anesthesiologist. An observer blinded to the study drug assessed sedation level (Observer’s Assessment of Alertness-Sedation [OAA/S] scale). The primary outcomes were defined as the number of patients with an OAA/S score of 4 intraoperatively and an OAA/S score of 5 postoperatively. The authors also compared cardiorespiratory parameters, intra- and postoperative side effects, and complications. Chi-square tests were used to analyze the primary endpoints. All secondary parameters were analyzed using the Wilcoxon rank sum test. Three patients in the dexmedetomidine group (10%) had an OAA/S score of 4 at all four time points assessed intraoperatively, while no patient in the control group had a score of 4 at all the time points considered. Thirteen patients in the dexmedetomidine group had a score of 4 at three or more time points (42%) compared with six patients (19%) in the control group. Four patients in the control group (13%) and one patient in the dexmedetomidine group (3%) did not achieve a score of 4 at any of the four critical intraoperative time points (χ2 for association = 9.9, P < 0.05; χ2 for a trend = 8.6, P < 0.004, with the trend favoring dexmedetomidine). More patients in the control group required treatment with metoprolol (26% vs. 6%, P = 0.04) and labetalol (48% vs/ 6%, P < 0.01). Plasma levels of norepinephrine were significantly lower in the dexmedetomidine group during and after surgery compared with the control group. Six patients (19%) in the dexmedetomidine group required intra-arterial shunts, while only two patients (6%) required shunts in the control group (P = 0.16). These data show that the use of dexmedetomidine in patients undergoing awake CEA resulted in fewer fluctuations from the desired sedation level. Patients receiving dexmedetomidine required less antihypertensive therapy compared with the midazolam/fentanyl/propofol combination. The effect of dexmedetomidine on cerebrovascular circulation in the study population needs further investigation.

Natural history and management of the asymptomatic, moderately stenotic internal carotid artery

PURPOSE Although it has been widely accepted as the evidence supporting prophylactic carotid endarterectomy, aspects of the Asymptomatic Carotid Atherosclerosis Study have left unease among clinicians who must decide which individuals without symptoms should undergo surgery. Additional confusion has been created by the fact that the several large randomized trials investigating the efficacy of carotid endarterectomy have classified and analyzed different categories of carotid stenosis. In an effort to provide more information on the natural history of asymptomatic, moderate carotid artery stenosis (50% to 79%), we have reviewed data on approximately 500 arteries. METHODS Records of our vascular laboratory from 1990 to 1992 were reviewed. We identified 425 patients with asymptomatic, moderate carotid artery stenosis; 71 patients had bilateral stenoses in this category, resulting in 496 arteries for study. RESULTS The mean length of follow-up was 38 +/- 18 months. New ipsilateral strokes occurred in 16 (3.8%) patients. New ipsilateral transient ischemic attacks occurred in 25 (5.9%) patients. Documented progression of stenosis occurred in 48 (17%) of the 282 arteries for which a repeat duplex examination was available. Arteries that progressed to > 80% stenosis were significantly more likely to have caused strokes than those that remained in the 50% to 79% range (10.4% vs 2.1%, p < 0.02). Conversely, arteries that remained stable in the degree of stenosis were significantly more likely to have remained asymptomatic than those that progressed (92.7% vs 62.5%, p < 0.001). With life-table analysis the estimated cumulative ipsilateral stroke rate was 0.85% at 1 year, 3.6% at 3 years, and 5.4% at 5 years. The respective estimated cumulative transient ischemic attack rates were 1.9%, 5.5%, and 6.3%. The respective estimated cumulative rates for progression of stenosis were 4.9%, 16.7%, and 26.5%. Life-table comparison of ipsilateral stroke revealed a significantly higher cumulative rate among arteries that progressed in the degree of stenosis than among those that remained stable (p < 0.001). CONCLUSIONS Based on the low rate of permanent neurologic events in these cases, prophylactic carotid endarterectomy for the asymptomatic, moderately stenotic internal carotid artery cannot currently be recommended. The only factor that appears to predict increased risk for future stroke is progression of stenosis. Careful follow-up with serial repeat duplex examinations must be performed in these patients. Until there are widely accepted duplex parameters that can provide all clinicians with accurate identification of arteries with narrowing corresponding to 60% stenosis as defined by the Asymptomatic Carotid Atherosclerosis Study, all surgeons will need to be aware of specifically how their noninvasive laboratories are deriving their results. For the many laboratories that continue to use the University of Washington criteria, 80% should remain the level above which prophylactic carotid endarterectomy is warranted.

Long-term follow-up of patients undergoing reoperation for recurrent carotid artery disease

PURPOSE We examined the perioperative course and long-term fate of individuals who required reoperation for recurrent carotid artery disease. METHODS The records of 2289 patients undergoing 2961 consecutive operations during a 22-year period were reviewed. Forty-two patients (1.8%) who underwent reoperations were studied. Forty-seven redo carotid artery reconstructions were performed on these 42 patients for neurologic symptoms or asymptomatic high-grade stenosis. Long-term follow-up was obtained on 41 of 42 patients (mean 54 months; range 9 to 202 months). RESULTS The forty-seven reoperations consisted of endarterectomy with patch angioplasty (n = 36), saphenous vein or polytetrafluoroethylene interposition graft (n = 7), or simply vein or polytetrafluoroethylene patch angioplasty (n = 4). There were no perioperative strokes or deaths. Three patients had perioperative transient ischemic attacks and two had cranial nerve injuries. The incidence of late failure after secondary surgery was 19.5% (8/41 patients). These failures consisted of one stroke, three transient ischemic attacks, and four asymptomatic occlusions. One tertiary carotid artery reconstruction was performed for a restenosis at the site of the secondary reconstruction. CONCLUSION The factors responsible for the high incidence of late failures after secondary carotid artery reconstruction are unclear. Reoperation for recurrent carotid artery disease appears less durable than primary carotid endarterectomy. Close postoperative surveillance is recommended after carotid artery reoperation.

Association between advanced age and vascular disease in different arterial territories: a population database of over 3.6 million subjects.

OBJECTIVES This study sought to determine the relationship between vascular disease in different arterial territories and advanced age. BACKGROUND Vascular disease in the peripheral circulation is associated with significant morbidity and mortality. There is little data to assess the prevalence of different phenotypes of vascular disease in the very elderly. METHODS Over 3.6 million self-referred participants from 2003 to 2008 who completed a medical and lifestyle questionnaire in the United States were evaluated by screening ankle brachial indices <0.9 for peripheral artery disease (PAD), and ultrasound imaging for carotid artery stenosis (CAS) >50% and abdominal aortic aneurysm (AAA) >3 cm. Participants were stratified by decade of life. Multivariate logistic regression analysis was used to estimate odds of disease in different age categories. RESULTS Overall, the prevalence of PAD, CAS, and AAA, was 3.7%, 3.9%, and 0.9%, respectively. Prevalence of any vascular disease increased with age (40 to 50 years: 2%, 51 to 60 years: 3.5%, 61 to 70 years: 7.1%, 71 to 80 years: 13.0%, 81 to 90 years: 22.3%, 91 to 100 years: 32.5%; p < 0.0001). Prevalence of disease in each vascular territory increased with age. After adjustment for sex, race/ethnicity, body mass index, family history of cardiovascular disease, smoking, diabetes, hypertension, hypercholesterolemia, and exercise, the odds of PAD (odds ratio [OR]: 2.14; 95% confidence interval [CI]: 2.12 to 2.15), CAS (OR: 1.80; 95% CI: 1.79 to 1.81), and AAA (OR: 2.33; 95% CI: 2.30 to 2.36) increased with every decade of life. CONCLUSIONS There is a dramatic increase in the prevalence of PAD, CAS, and AAA with advanced age. More than 20% and 30% of octogenarians and nonagenarians, respectively, have vascular disease in at least 1 arterial territory.

A comparison of regional and general anesthesia in patients undergoing carotid endarterectomy

PURPOSE The optimal anesthetic for use during carotid endarterectomy is controversial. Advocates of regional anesthesia suggest that it may reduce the incidence of perioperative complications in addition to decreasing operative time and hospital costs. To determine whether the anesthetic method correlated with the outcome of the operation, a retrospective review of 3975 carotid operations performed over a 32-year period was performed. METHODS The records of all patients who underwent carotid endarterectomy at our institution from 1962 to 1994 were retrospectively reviewed. Operations performed with the patient under regional anesthesia were compared with those performed with the patient under general anesthesia with respect to preoperative risk factors and perioperative complications. RESULTS Regional anesthesia was used in 3382 operations (85.1%). There were no significant differences in the age, gender ratio, or the rates of concomitant medical illness between the two patient populations. The frequency of perioperative stroke in the series was 2.2%; that of myocardial infarction, 1.7%; and that of perioperative death, 1.5%. There were no statistically significant differences in the frequency of perioperative stroke, myocardial infarction, or death on the basis of anesthetic technique. A trend toward higher frequencies of perioperative stroke (3.2% vs 2.0%) and perioperative death (2.0% vs 1.4%) in the general anesthesia group was noted. In examining operative indications, however, there was a significant increase in the percentage of patients receiving general anesthesia who had sustained preoperative strokes when compared with the regional anesthesia patients (36.1% vs 26.4%; p < 0.01). There was also a statistically significant higher frequency of contralateral total occlusion in the general anesthesia group (21.8% vs 15.4%; p = 0.001). The trend toward increased perioperative strokes in the general anesthesia group may be explicable either by the above differences in the patient populations or by actual differences based on anesthetic technique that favor regional anesthesia. CONCLUSIONS In a retrospective review of a large series of carotid operations, regional anesthesia was shown to be applicable to the vast majority of patients with good clinical outcome. Although the advantages over general anesthesia are perhaps small, the versatility and safety of the technique is sufficient reason for vascular surgeons to include it in their armamentarium of surgical skills. Considering that carotid endarterectomy is a procedure in which complication rates are exceedingly low, a rigidly controlled, prospective randomized trial may be required to accurately assess these differences.

Initial successful management of type I endoleak after endovascular aortic aneurysm repair with n-butyl cyanoacrylate adhesive

OBJECTIVE Transcatheter embolization with coils and other agents has been described as a treatment method for type II endoleak after endovascular aortic aneurysm repair (EVAR). Type I endoleak has not been treated commonly with such therapies, although most investigators believe they warrant definitive intervention. The liquid adhesive n-butyl 2-cyanoacrylate (n-BCA) is often used to treat congenital arteriovenous malformations. The objective of this study is to report our initial experience in treating type I endoleak with n-BCA and with a variety of other interventions. METHODS A retrospective review was performed of 270 patients who underwent EVAR at our institution between January 1994 and December 2002. Of these, 24 patients had type I endoleak (8.9%), diagnosed either intraoperatively (n = 13, 52%) or during follow-up (n = 12, 48%). Among these 24 patients, 17 had proximal leaks and the remaining 8 patients had distal leaks. These cases form the focus of this study. RESULTS Twenty-two leaks required endovascular intervention, with the following success rate: n-BCA, 12 of 13 cases (92.3%); extender cuffs, 4 of 5 cases (80%); coils with or without thrombin, 3 of 4 cases (75%). In one patient with persistent endoleak despite attempted endovascular intervention the device ultimately was surgically explanted, and the patient did well. Of six patients with endoleak initially managed expectantly, two eventually underwent attempts at definitive intervention, both with n-BCA. Three sealed spontaneously before definitive intervention could be performed; and in one 97-year-old patient who refused intervention, the aneurysm subsequently ruptured and the patient died. In total, 13 patients with type I endoleak underwent n-BCA transcatheter embolotherapy. No serious complications were directly related to this therapy. Colon ischemia developed in one patient, and was believed to be a result of thromboembolism during wire and catheter manipulation rather than n-BCA treatment. Twelve of these 13 leaks remain sealed at mean follow-up of 5.9 months (range, 0-19 months). CONCLUSION Our initial use of n-BCA occlusion suggests that it may be an effective and safe method of treatment of type I endoleak after EVAR. In particular, n-BCA embolotherapy may be especially useful in treating type I endoleak not amenable to placement of extender cuffs. Larger case series and longer follow-up are needed before this treatment is more broadly recommended. Type I endoleak after EVAR can be treated successfully with a variety of endovascular methods, and surgical explantation is rarely required.

A model for predicting occult carotid artery stenosis: screening is justified in a selected population

OBJECTIVES The diagnosis and treatment of carotid artery disease is an integral part of stroke prevention. However, a population of patients who would benefit from screening for carotid artery stenosis has not been well defined. As part of an institutional stroke-screening program, a modified, rapid duplex scan was developed to evaluate patients for occult carotid stenosis. The goal of this study was to evaluate risk factors predictive of carotid stenosis in a selected population, and to identify patients who would benefit from carotid screening. METHODS Patients were eligible for the study if they were >60 years of age and had a history of hypertension, heart disease, current smoking, or family history of stroke. A modified carotid duplex scan that had been previously validated against formal duplex scanning was utilized; this involved visualization of the carotid bulb and proximal internal carotid artery where Doppler flow velocities were obtained and recorded. RESULTS Screening was performed on 394 patients. Thirty-eight patients (9.6%) had either unilateral or bilateral carotid stenosis of > or =50%. Risk factors evaluated included smoking, hypertension, cardiac disease, or hypercholesterolemia. If none of these risk factors was present, the incidence of carotid stenosis was 1.8%. This increased to 5.8% with one risk factor, 13.5% with two risk factors, and 16.7% with three risk factors. Two of three patients with all four risk factors had carotid stenosis (66.7%). Logistic regression and prespecified contrast statements for multiple comparisons were used to assess the relationship between the presence of risk factors and occult carotid artery stenosis. The presence of any one of these risk factors was associated with a statistically significant increase in the presence of occult carotid stenosis (P <.01). This was also statistically significant for the presence of any two risk factors (P <.01) or three risk factors (P <.05). CONCLUSION The prevalence of carotid stenosis significantly increases with the presence of one or more identifiable demographic risk factors in a selected population. Assuming the diagnosis and treatment of carotid stenosis are fundamental to stroke prevention, screening for carotid artery disease is justified in this group of patients.

Temporal expression and activation of matrix metalloproteinases-2, -9, and membrane type 1-matrix metalloproteinase following acute hindlimb ischemia.

OBJECTIVE Matrix metalloproteinase (MMP) activity is essential for remodeling of ischemic tissue. The murine hindlimb ischemia model exhibits tissue remodeling including revascularization in part due to angiogenesis. MMP-2 and -9 are type IV collagenases necessary for basement membrane degradation as a part of extracellular matrix remodeling and angiogenesis. Polymorphonuclear leukocytes (PMNs) contain MMP-9, and in the presence of membrane type 1 (MT1)-MMP, are able to activate proMMP-2 in vitro. Activation of MMP-2 and -9 may be essential in ischemic limbs both for tissue remodeling and revascularization via angiogenesis. We hypothesized that MMP-2 and -9 would be activated following acute hindlimb ischemia (HI), and this activation would be temporally related to PMN infiltration. DESIGN OF STUDY HI was achieved by unilateral femoral artery ligation in 20 FVB/N mice. Five mice underwent sham operation without hindlimb ischemia. Gastrocnemius muscle was harvested from both hindlimbs at 1, 3, 14, and 30 days following ligation and assayed for MMP-2, -9 (gelatin zymography), and MT1-MMP (Western blotting). MMP-2 and -9 expression and activation were analyzed by gelatin zymography and quantified by densitometry with NIH Image Analysis software. Neutrophils per high power field were counted. The results were expressed as a ratio of ischemic to nonischemic limbs and compared at each time point using ANOVA. RESULTS Zymographic analysis revealed a 212% increase in active MMP-2 3 days postligation (P <.05). Active MMP-9 reached its maximum level (800% over baseline) on postoperative day 3 and continued to be elevated on day 14 (737% over baseline) (P <.05). The increase in active MMP-2 and -9 levels paralleled PMN infiltration that also peaked 3 days postligation (1184% over baseline) (P <.05). PMN count, MMP-2, and -9 all returned to baseline levels by postoperative Day 30. MT1-MMP was present in tissue samples from all time points as confirmed by Western blot. CONCLUSIONS Limb ischemia causes an early activation of MMP-2 and -9 in temporal relation to PMN infiltration. HI may prime PMNs, leading to their sequestration in ischemic tissue. Primed PMNs, along with constitutively expressed MT1-MMP, may activate MMPs-2 and -9 and enable tissue remodeling essential for limb revascularization and angiogenesis.