1 Early carotid endarterectomy in patients with small, fixed neurologic deficits Anthony D. Whittemore, M.D., Steven T. Ruby, M.D., Nathan P. Couch, M.D., and John A. Mannick, M.D., Boston, Mass. Patients who have sustained a large hemispheric stroke are not candidates for early carotid endarterectomy, but there is less agreement regarding the role of carotid endarterectomy in patients with small, fixed neurologic deficits. Accepted practice in many centers is to wait 4 to 6 weeks after the onset of the deficit before proceeding with carotid endarterectomy because of the fear that early revascularization will increase the size of the infarct. Earlier endarterectomy, however, in patients with significant residual ipsilateral carotid territory at risk may prevent repeated infarctions. For the past 5 years our approach to patients with a small stable stroke and significant stenosis (>75%) has been prompt ipsilateral endarterectomy. Of the 337 carotid endarterectomies at our institution since 1979, a subset of 28 patients with hemodynamicauy significant carotid lesions presented with a small, fixed stroke. The period of time between the appearance of the stroke and carotid endarterectomy averaged 11 days, but 53% of patients were operated on within 7 days of the onset of symptoms. Selective shunting based on intraoperative EEG monitoring was utilized and 40% of the 28 patients required shunts. Operative mortality consisted of one death from a pulmonary embolus, and no patient sustained a new postoperative deficit. Long-term follow-up was available for 96% of patients over a mean of 2 years. During this time two new neurologic events occurred: one fatal stroke and one transient deficit. This experience indicates that patients with small, fixed neurologic deficits who continue to have carotid territory at risk may safely undergo carotid endarterectomy without waiting 4 to 6 weeks. (J VASC SURG 1984; 1: ) Carotid endarterectomy is most clearly indicated for appropriate lesions in patients with transient ischemic attacks (TIAs) to reduce both the frequency of these episodes and the likelihood of major stroke. Far more controversial is the role of surgical intervention in patients with evolving or fluctuating strokes, or small, fixed deficits. While a 1% incidence of mortality and neurologic morbidity is anticipated with endartcrectomy for TIAs and asymptomatic lesions, 1 a higher rate of serious complications has been reported for patients with fixed deficits, especially if carried out prior to a 4- to 6-week period of stabilizationy -4 In selected patients with high-grade stenoses, however, subsequent total occlusion with extension of cerebral infarction during this 4- to &week period may represent more of a risk than the reported neurologic morbidity resulting from prompt endarterectomy. In addition to the controversy surrounding acute management of these pa- From the Department of Surgery, Brigham & Women's Hospital/Harvard Medical School. Presented at the Thirty-eighth Annual Meeting of the Society for Vascular Surgery, Atlanta, Ga., June 7-8, Reprint requests: Anthony D. Whittemore, M.D., Brigham & Women's Hospital, 75 Francis St., Boston, MA tients, recent evidence suggests that the subsequent incidence of stroke in patients endarterectomized for small, fixed deficits may not be significantly altered from the unoperated natural history of the disease. 5 This retrospective clinical study represents our limited experience with endarterectomy in a small group of pa6ents operated on within an average of 11 days following the onset of a small, fixed neurologic deficit. PATIENT POPULATION The records of 337 patients who have undergone carotid endarterectomy at this institution during the 5 years since 1979 were reviewed retrospectively. Twenty-eight of these patients were operated on within 30 days of the occurrence of a limited, stable stroke associated with an ipsilateral hemodynarnically significant carotid lesion (> 75 % stenosis). There were 15 men and 13 women in the group, whose average age was 65 years. At the time of endarterectomy all patients had unequivocal clinical evidence of a fixed neurologic deficit. In most cases the deficit consisted of a mild aphasia/dysarthria, weakness of an extremity, or both, indicating significant residual carotid territory at risk (Table I). 795
2 796 Whittemore et al. Journal of VASCULAR SURGERY Table I. Distribution of small, fixed deficits Clinical deficit No. ofpatients Isolated speech deficit 6 Isolated paresis Upper extremity 10 Lower extremity 0 Isolated arnaurosis 0 Hemiparesis 6 Combination speech deficit and paresis 6 Table II. Shunt requirement Clinical No. of patients Patients requiring shunt presentation at risk No. % Asymptomatic/TIA Unilateral stenosis Bilateral stenosis Small, fixed deficit Unilateral stenosis Bilateral stenosis *p = " * Patients with a dense hemiplegia or profound aphasia were not managed surgically. The period of time between the onset of symptoms and endarterectomy averaged 11 days (range 2 to 30 days). However, 53% of patients underwent surgery within 7 days of appearance of the stroke. Evidence of cerebral infarction was clearly documented in 62% of the 21 patients who had preoperative CT scans. All 28 patients had at least a 75% stenosis of the appropriate internal carotid artery demonstrated by arteriography, and 50% of the group had a lesion resulting in more than 90% stenosis. In nine patients the status of the contralateral carotid could not be precisely determined because of limited contrast studies. Of the remaining 18 patients, the contralateral carotid was characterized by a nonstenotic ulcerated atheroma in six, 95% stenosis in three, and total occlusion in three. No significant contralateral lesion was found in seven patients. Endarterectomy was carried out under general anesthesia with standard techniques as outlined in a prior report? Continuous EEG monitoring was used in all patients, and the necessity for an indwelling shunt was selectively determined on the basis of EEG changes after carotid clamping. RESULTS Following intraoperative carotid clamping, 11 patients (40%) demonstrated EEG changes requiring insertion of a shunt, Of these 11, seven had no significant contralateral carotid lesion, whereas three had significant contralateral stenosis, and one had contralateral occlusion (Table II). The 30-day operative mortality consisted of one death (3.5%) resulting from a massive pulmonary embolus on the second postoperative day. There were no new neurologic deficits, and no patient sustained a clinical extension of the antecedent preoperative infarct. Of the 27 patients discharged, follow-up information was available for 26 (96%) over a period ranging from 6 to 108 months (mean 2 years). During this period, only two new neurologic events occurred: one transient, affecting the contralateral hemisphere, and a second fatal. The. second cerebrovascular accident was responsible for one of the three late deaths. DISCUSSION Carotid endarterectomy for patients experiencing TIAs is generally well accepted in patients with significant lesions. Several investigators have demonstrated that this operation can be carried out with a minimal mortality rate and with a low incidence of postoperative stroke in properly selected patients. Endarterectomy in the setting of an established neurologic deficit, however, remains significantly controversial. The role and timing of surgery following a small stroke have yet to be resolved. It has been generally accepted that patients who sustain a large neurologic deficit should not be subjected to early endarterectomy. This was first established in 1964 by Wylie et al.,2 who performed carotid endarterectomies in patients with profou~ acute strokes. Fifty-five percent of patients died within 3 days postoperatively. This substantial mortality rate was subsequently confirmed in studies reported by Rob 3 and Bauer et al.4 These findings were in accordance with experimental data suggesting that restoration of normal blood flow could convert an ischemic cerebral infarction into a hemorrhagic infarct with further destruction of cerebral tissue. 6 Other investigators have taken issue with this hypothesis and conclude that systemic hypertension is the only factor capable of converting a "white" infarct into a hemorrhagic infarct, z The usefulness of carotid endarterectomy in patients with fluctuating neurologic deficits has been the subject of several retrospective studies. Gold-
3 Volume 1 Number 6 November 1984 Carotid endarterectomy for small fixed deficits 797 stone and Moore 8 reported no operative fatality or morbidity in a group of 26 patients undergoing emergency endarterectomy for crescendo TIAs or stroke in evolution. They caution against operating on patients with a profound stroke and recommend not opening a carotid occlusion. The findings of Mentzer et al. 9 are in agreement with this point of view and suggest an increased chance of survival for patients undergoing endarterectomy for fluctuating deficits. Opinions vary about the performance and especially the timing of carotid endarterectomy in patients with small, completed strokes. Arguments favoring endarterectomy include the fact that patients who have sustained a small stroke have residual brain tissue at high risk for the occurrence of subsequent neurologic insult. Bardin et al. 5 have 'emonstrated a 5-year cumulative stroke rate of 20% fbr patients who already have a permanent neurologic deficit. As a result, they recommended that prophylactic carotid endarterectomy be performed after the occurrence of a small stroke in patients with a carotid lesion appropriate to the deficit. Takolander et al. ~0 concluded that minor stroke is not a contraindication to carotid endarterectomy but recommended that it should not be performed until at least 4 weeks following the occurrence of a small stroke. The desire to postpone endarterectomy following the occurrence of a permanent neurologic event is based in part on pathologic studies that show that more than 8 days are required before an area of infarction is sufficiently stabilized to withstand the reestablishment of normal blood flow. :~ However, reperfusion probably does not occur since the infarct is usually the result of an embolus to an end vessel without sufficient collateral. Graber et al. 12 _ 7iewed the course of patients who had undergone CT scan prior to endarterectomy and found a significantly higher incidence of new postoperative permanent neurologic deficits in patients with infarctions seen on the preoperative CT scan. The reasons for this association, however, remain unclear and appear to be at variance with our own data. Our experience indicates that patients with small, fixed neurologic deficits can be safely operated on soon after the onset of the deficit. We have not had any stroke-related operative deaths, extensions of prior deficits, or new deficits following endarterectomy performed as early as 2 days after a small :~ stroke Thirteen of 28 patients had preoperative evidence of infarction on CT scan. This did not influence their postoperative course. Selective shunting based on EEG monitoring was used and rcsultcd in shunt insertion in 40% of patients (Table II). This represents a significant difference (p = 0.032) from 18% of patients requiring a shunt overall in our simultaneous series of carotid endarterectomies undertaken for all indications. Brain tissue that has already sustained an insult may be more sensitive to hypoxia and/or low flow and as a resuk may require continuous perfusion via an intraktminal shunt. Based on the present evidence it is our belief that patients with significant carotid stenosis who have sustained a small stroke are at risk for further neurologic insult and therefore should undergo prompt endarterectomy. We have demonstrated in this small group of patients that early operation can be accomplished safely and suspect that other surgeons have also adopted a similar approach to these patients who were formerly believed to require a 4- to &week period of stabilization bcfore carotid surgery. REFERENCES 1. Whittemore AID, Kauffman IL, Kohler TR, Marmick JA. Routine electroencephalographic (EEG) monitoring during carotid endarterectomy. Ann Surg 1983; 197: Wylie EJ, Hein MF, Adams JE. Intracranial hemorrhage following surgical rcvascularization for treatment of acute strokes. J Ncurosurg 1964; 21: Rob CG, Operation for acute completed stroke due to thrombosis of the internal carotid artery. Surgery 1969; 65: Bauer RB, Neyer JS, Fields WS, Remington R, Macdonald MC, Callen P. Joint study of extracranial arterial occlusion. III. Progress reports of controlled study of long-term survival in patients with and without operation. JAMA 1969; 208: Bardin JA, Berstein EF, Humber PB, Collins GM, Delly RB, Devon JB, Stuart SH. Is carotid endarterectomy beneficial in prevention of recurrent stroke? Arch Surg 1982; 117: Meyer JS. Importance ofischemic damage to small vessels in experimental cerebral infarction. J Neuropathol Exp Neurol 1958; 17: Paulson OB, Cerebral apoplexy (stroke): Pathogenesis, pathophysiology, and therapy as illustrated by regional blood flow measurements in the brain. Stroke 1970; 2: Goldstone J, Moore WS. Emergency carotid artery surgery in neurologically unstable patients. Arch Surg 1976; 111: Mentzer Jr RM, Funkelmeier BA, Crosby IK, Wellons HA. Emergency carotid endarterectomy for fluctuating neurological deficits. Surgery 1980; 89: Takolander KJ, Bergentz SE, Ericson BF. Carotid artery surgery in patients with minor strokes. Br J Surg 1983; 70: Clanss RH, Sanoudos GM, Ray III JF, Moallein S. Carotid
4 798 Whittemore et al. Journal of VASCULAR SURGERY endarterectomy for cerebrovascular ischemia. Surg Gynecol Obstet 1973; 136: Graber JN, Vollman RW, Lcvine H, Scott RM, Nabseth DC. Stroke following carotid endarterectomy: Ri~k predicted by preoperative CT scan (Abstract). Presented at the New England Vascular Society Meeting, October DISCUSSION Dr. John I. Ricotta (Rochester, N.Y.). We have looked at a similar group of patients at the University of Rochester as a subset of a larger group of patients with what we have defined as unstable carotid lesions. Since 1976 we have performed early endarterectomy on 12 patients with fixed deficits. These patients are somewhat different from the group presented in that all patients had a greater than 90% stenosis and they were all operated on within 10 days of the onset of their deficit. Of this group of 12 patients, two patients died, both of whom were operated on within 24 hours of their neurologic deficit. One patient died of a cerebral infarct, the other of a myocardial infarction. The other patients in the group were maintained on heparin and operated on between 4 and 10 days later. We had CT scans done on Ii of the 12 patients. Six patients with normal CT scans showed neurologic improvement and eventually were completely normal at follow-up. However, of the five patients with abnormal CT scans, only two of these patients showed neurologic improvement, and two other patients, although they recovered from surgery well, did not show any resolution of their deficit One patient in this group died. I would like to ask the following questions: First, in your patients, how many actually improved neurologically after surgery? And did neurologic improvement correlate with CT findings? Second, do you use noninvasive testing early in the clinical course in these patients to decide which patients with a stroke have a tight stenosis and might benefit by early angiography and surgery? Third, do you maintain these patients on heparin prior to surgery, and what clinical criterion do you use to decide when to intervene surgically? Dr. William H. Baker (Maywood, Ill.). During the past 5 or 6 years we have had experience with a total of 23 patients who had carotid endarterectomy within 30 days of the onset of stroke: 18 patients were operated on within 14 days and eight of these, within 4 days. Our results are similar to those reported by Dr. Whittemore. Sixteen of these patients improved, five were unchanged, one became transiently worse, and one died of an extension of his stroke. My first question concerns the selection of patients for this operation. You mentioned a small, fixed neurologic deficit, then proceeded to tell us that you operated on patients who had hemiparesis, which is not exactly a small, fixed deficit in my experience. How would you define such a &fidt? Second, 60% of your patients had abnormal CT scans, which is exactly the same percentage as in our series. In our experience the one man that died of an extension of his stroke had a normal preoperative CT scan, and all those with abnormal scans did very well. Where do you think we ought to draw the line in using the CT scan as a point of judgment? Finally, I would like to caution that in the past years vascular surgeons have achieved good results with delayed carotid endarterectomy in patients with neurologic die cits. How then does early operation play a role? Itch, experience it plays a role in those few patients in heparin does not control symptoms, those who have ~. total occlusions, or those who have angiographically demonstrated intraluminal thrombi. These patients would be few in number, and I urge continued caution. Dr. Rudolph W. Vollman (Boston, Mass.) I congratulate Dr. Whittemore and his colleagues for addressing an issue that may affect our surgical approach to that subset of carotid patients with a mild frank stroke. They have shown that this group of patients, if selected properly, can be operated on safely with minimal perioperative morbidity and possible long-term neurologic benefit. In addition, they have shown that early operation (average of 11 days after stroke) in this small group did not result in extension or aggravation of the stroke, and more important, did not result in hemorrhage into the infarct that has been a feared complication traditionally accepted for years. This aggressive approach is a significant change in philosophy However, I urge caution in the selection of these frank stroke panents for early surgery as well a~ ~n the interpretation of the results until larger numbers o~ patients are studied. My questions for the authors are twofold. First, did your patients presented have fixed, stable strokes, or were they in reality reversible ischemic neurologic deficits (RIND)? Fifteen patients (over 50%) in the series had either negative CT scans (eight) for infarct or no CT scans (seven) performed, and many had improving neurologic ~ deficits at the time of their operation (2 to 30 days). If this is true, then they would have been more accurately classified as having RIND rather than fixed stroke. In our experience this RIND group of patients is similar to the transient ischemic attack (TIA) category and would, by detinition, carry a much better surgical as well as long; term prognosis since there is no preoperative evidence for permanent cerebral infarction. Second, how does one define a small stroke, by clinical assessment or by infarct size on CT scan? In our recent
5 Voiurne 1 Number 6 November 1984 Carotid endarterectomy for small fixed deficits 799 published review from the Boston Veterans Administration Medical Center (Am J Surg 1984; 147:492-7), we found that patients with a positive preoperative CT scan, although they may have been asymptomatic or having only TIA, RIND or mild stroke, had a surprisingly high risk for postoperative neurologic deficits regardless of CT infarct size. This morbidity occurred despite EEG monitoring and liberal use of shunting. Dr. Joseph M. Giordano (Washington, D.C.). We at the George Washington University Medical Center have also been interested in the timing of carotid endarterectomy following a stroke. We have reviewed 352 endarterectomies: 49 were done following a stroke and 303 were performed for TIAs or hemodynamically significant asymptomatic stenoses. Twenty-seven endarterectomies were performed within 5 weeks of a stroke. Five of these 27 patients developed a new postoperative stroke, for a morbidity rate of 18.5%. In 22 patients, endarterectomy was performed more tnan 5 weeks after the stroke. None of these had a new postoperative stroke. The postoperative stroke rate for the 303 endarterectomies performed for indications other than stroke was 2.3%. The initial deficits of the five patients who developed a new stroke postoperatively were stable and relativdy small. Only two of five had positive CT scans, and in all cases there was substantial clinical improvement in their symptoms by the time of their operation. In view of all the variables, our conclusion is that the early timing of the operation was the major reason for the high operative stroke rate in this particular group. Perhaps the difference in our series and the one presented by Dr. Whittemore is the concept of a small stroke. What is a small stroke? Is it a neurologic deficit with a negative CT scan? Is it a deficit that completely clears within a short period of time? Or is it a deficit that involves a small part of the anatomy? Until this is better defined or until we have a good method to determine the stability of cerebral infarcts, our wn data at least suggest that caution should be exercised in performing an endarterectomy within 5 weeks following a stroke. Dr. Anthony M. Imparato (New York, N.Y.). One of the important variables in the outcome of this type of approach has been the question or absence of hypertension. Would you comment on the measures taken to control postoperatively blood pressure? Dr. Whittemore (closing). I would like to thank the discussants for their constructive comments and address at the outset the common theme that each has brought to light. This common theme relates to our definition of a "small stroke" and therefore to our method of patient selection. The key point to bear in mind is that each patient had residual ipsilateral carotid territory at risk for further infarction that might result in a more profound disability. Thus, Dr. Ricotta, we listed two patients with hemiparesis, not hemiplegia, who nevertheless remained at risk for hemiplegia in the event of reinfarction. Most patients, however, had mild clinical deficits defined on the basis of the small area of anatomy involved. Dr. Baker, we are reassured that your data in essence confirm our findings. I have addressed the issue of patient selection, and I certainly echo your words of caution in proceeding with endarterectomy only in a limited number of appropriate patients selected on the basis oft he criteria outlined. Both Drs. Vollman and Baker pointed out the fact that only 50% of the CT scans in our patient population were positive. There were several reasons for this. Early in our experience CT scans were not routinely available. Second, they were not always carried out with contrast studies and, third, in some cases CT scans were not obtained at the most opportune time for visualization of defects following the onset of clinical symptoms. Although we routinely obtain CT scans in all such patients now, the findings bore no significance to the operative results, as has been pointed out previously by Dr. Vollman's group. In their previously published series, the size of defect demonstrated by CT scan did not correlate with their operative results. Thus our criteria are based on the area of anatomy clinically involved~ rather than on preoperative CT scanning. With respect to the timing of surgical intervention, endarterectomy was undertaken as soon as arteriography confirmed the presence of a significantly stenotic lesion in a patient with a clearly stable small deficit. We would concur wholeheartedly with Dr. Ricotta's words of caution in excluding patients with embolic occlusion of the internal carotid artery. This represents an entirely different situation than the group of individuals in our series, which is limited to those with antecedent atherosclerotic stenosis as the cause of the cerebrovascular insult. Finally, President-Elect Imparato has raised an extremely important issue with regard to the management of blood pressure, particularly in the very early postoperative period in the recovery room. Approximately one third of our patients were hypertensive preoperatively, and about the same proportion developed transient hypertension postoperatively, as is true in most series. The presence of antecedent hypertension, however, did not necessarily correlate with eventual postoperative hypertension. Nevertheless, we maintain an indwelling arterial line for continuous blood pressure monitoring in these individuals until they are clearly stable at normotensive levels. This not infrequently requires intravenous antihypertensive therapy directed at maintaining a patient's blood pressure in a reasonably normal range in an effort to prevent cerebral ischemia on the basis of hypertension. With this policy of very careful and continuous monitoring, we did not notice extension of neurologic morbidity.