Hypertensive Encephalopathy After Bilateral Carotid Endarterectomy
Background Hypertension occurs frequently after carotid endarterectomy and may lead to cerebral vascular complications and myocardial infarction. Its pathophysiology has recently been related to surgically induced damage of carotid baroreceptors.
Case Description A 45-year-old normotensive man with no history of epilepsy was admitted 3 weeks after bilateral carotid endarterectomy for severe repetitive paroxysmal headaches, vomiting, and agitation that were closely associated with attacks of marked hypertension. During one of these attacks, he had a grand mal seizure. Plasma catecholamine levels during hypertensive attacks were highly elevated despite the absence of pheochromocytoma, reflecting abnormalities in baroreceptor sensitivity that lead to unrestrained activation of the central sympathetic nervous system. Heart rate response to Valsalva maneuver showed suppression of the usual tachycardia, indicating baroreceptor reflex insensitivity.
Conclusions We report the first case of hypertensive encephalopathy associated with baroreflex failure syndrome after bilateral carotid endarterectomy. The role of blood pressure monitoring may be critical in revealing carotid baroreceptor insensitivity in such clinical settings.
Approximately 21% of normotensive patients may have increased arterial pressure after carotid endarterectomy.1 2 The pathophysiology of this usually episodic hypertension may be related to surgically induced abnormalities of carotid baroreceptor sensitivity.3 4 We describe a patient who, after bilateral carotid endarterectomy, developed daily severe paroxysmal headaches, vomiting, and agitation related to hypertensive attacks, suggesting hypertensive encephalopathy. This paroxysmal hypertension was related to carotid baroreceptor dysfunction, and its pathophysiology was investigated.
A normotensive 45-year-old white man with familial hypercholesterolemia and no history of epilepsy or alcohol or drug addiction was investigated for a right amaurosis fugax. Angiography revealed a 90% atherosclerotic stenosis of both carotid bifurcations, without any intracranial abnormality. Findings of cerebral computed tomography (CT), electrocardiography, transthoracic echocardiography, effort thallium scintigraphy, and aortic abdominal echography were normal. Carotid endarterectomy was performed initially on the right side. Before and after the first endarterectomy, blood pressure level was 140/80 mm Hg. A second intervention was performed on the left side 3 weeks later. The patient underwent general anesthesia, and the vertical incision involving both common and internal carotid arteries was 4 cm long.
Four hours after the second operation, unstable blood pressure levels, including hypertensive (240 to 146 mm Hg) and hypotensive (88 to 47 mm Hg) attacks, were noticed but tended to disappear over the following days. The patient was discharged with aspirin treatment. He was admitted 10 days later because of daily paroxysmal headaches, nausea, vomiting, and agitation. On physical examination, his temperature was 37°C, pulse was 100 beats per minute (bpm), blood pressure was 223/110 mm Hg at both arms, and he showed no confusion, somnolence, or focal deficits. Ten minutes later, the patient had a grand mal seizure lasting (tonic and clonic phases) about 30 seconds and followed by a 30-minute obnubilation period. After treatment with intravenous clonazepam and nicardipine, seizures did not recur. No predisposing factors, including hyponatremia or centrally acting drug withdrawal, were found.
The next day, the patient’s condition was good, physical and neurological examinations were normal, and blood pressure was 135/75 mm Hg on administration of intravenous nicardipine. Optic fundi were normal. Blood counts, cerebrospinal fluid, and blood and urine chemistry values were normal, as were cerebral CT scan and cervical and transcranial Doppler ultrasonography. Electroencephalogram showed 2- to 5-Hz waves on both posterior temporal regions, without any seizurelike activity.
Over the following days, the patient had repetitive pulsating paroxysmal headaches, heralded by a sensation he described as a “faraway rumble preceding the storm.” There were associated photophobia, nausea, sweating, and erythema of the palms, without any visual signs. Each cephalalgic episode was closely associated with marked hypertension. During these hypertensive attacks, systolic and diastolic pressure values increased by 50% and 30%, respectively, reaching a maximum of 230/120 mm Hg in about 10 minutes, while pulse was 100 to 110 bpm (Fig 1⇓). Although these attacks lasted about 2 hours and occurred once or twice each day, the daily mean arterial pressure and heart rate values recorded by a noninvasive method were normal (automatic nonambulatory blood pressure monitor, Dinamap SX/SXP 1846 Critikon). During hospitalization the blood pressure variance was 120.7±3.5/75.2±2.3, the mean blood pressure was 106.4±2.4, and heart rate always varied parallel to blood pressure fluctuations but never exceeded 110 bpm during hypertensive attacks. No precipitating factor was found. Episodes of asymptomatic low blood pressure without orthostatic hypotension were also recorded. Hypertensive encephalopathy was diagnosed; dysfunction of carotid baroreceptors after bilateral endarterectomy or pheochromocytoma were considered as possible causes.
Baroreceptor reflex function was assessed by heart rate response to Valsalva maneuver (electrocardiogram recorded within the 40 seconds after the subject blows at a pressure of 40 mm Hg for 15 seconds into a mouthpiece attached to a pressure gauge). Heart rate responses to active standing and to progressive upright tilt testing were also investigated to assess autonomic cardiovascular function. A 47-year-old healthy control subject was also examined.
During the Valsalva maneuver, performed without nicardipine, persistent bradycardia was recorded; after release, tachycardia occurred rather than the expected bradycardia (Fig 2⇓). Results of the active standing test are shown in Fig 2⇓. Upright tilt testing, performed with administration of nicardipine, induced slight tachycardia. Blood pressure was 115/57 mm Hg supine and 120/60 mm Hg standing. Heart rate was 81 bpm supine and 102 bpm standing.
Plasma catecholamine levels, which were normal when the patient was normotensive, became highly elevated during hypertensive attacks (Fig 3⇓). A 24-hour urine collection yielded normal values for catecholamine, vanillylmandelic acid, metanephrine, and 5-hydroxyindole acetic acid. Abdominal CT scan and [131I]metaiodobenzylguanidine (MIBG) scintigraphy showed no pheochromocytoma. There was no primary hyperaldosteronism, and Doppler ultrasonography of renal arteries was unremarkable. Cerebral magnetic resonance imaging, performed 6 months after discharge, was normal.
The hypertensive attacks, which were not prevented by nicardipine, were eventually controlled by an association of guanfacine, a clonidinelike centrally acting antihypertensive agent, and acebutolol, a β-blocking agent. Eight months after discharge, the patient was in good physical condition, and blood pressure was stable with guanfacine treatment alone (mean blood pressure was 130/80). An attempt to taper out guanfacine was unsuccessful because of recidivism.
Hypertensive encephalopathy is characterized by high blood pressure associated with agitation, severe headaches, and convulsions.5 6 Visual symptoms are frequently reported as well as optic disc swelling and fundal hemorrhages and exudates.5 6 According to one theory, these clinical features could result from cerebral vasospasm in response to acute hypertension (ie, overregulation), inducing ischemia and cytotoxic edema.7 A second theory emphasizes the role of a breakthrough of cerebral autoregulation leading to focal vasogenic edema.8 Absence of ophthalmologic signs in our patient may have been due to the brevity of hypertensive attacks. This may also explain why radiological findings were normal, contrasting with the decreased density in the white matter already reported.8 9 Nevertheless, in this case, even short periods of high blood pressure led to hypertensive encephalopathy, thus emphasizing the critical role of a rapid rise in blood pressure in the development of this syndrome.6
Carotid baroreceptors play a major role in maintaining normal arterial pressure by buffering its fluctuations.10 Glossopharyngeal nerves transmit baroreceptor input to the sympathoexcitatory neurons within the rostral ventrolateral medulla. Abnormal input from damaged baroreceptors inadequately modulating these neurons may lead to an enhanced sympathetic activity expressed by excessive release of catecholamines (norepinephrine).4 11 12 13 This in turn may result in paroxysmal hypertension. Data from our patient support this hypothesis. Indeed, excessive release of norepinephrine was found during all hypertensive attacks, contrasting with normal plasma levels during normotensive periods. Paroxysmal release of catecholamines was not sufficiently strong and prolonged to increase the 24-hour urinary concentrations, as it does in pheochromocytoma. Hence, this finding may be of interest in differentiating carotid baroreceptor dysfunction from pheochromocytoma.4 11 Elevation of epinephrine, which is not secreted by sympathetic nerves, was probably related to stress-induced release by the medullosurrenal gland.
Baroreceptor function is usually assessed by heart rate response to arterial fluctuations induced by (1) the Valsalva maneuver, (2) vasopressor (phenylephrine) or vasodilator (nitroglycerin) agents, and (3) externally applied neck pressure or suction.14 The average intercorrelation among these techniques was shown to be statistically significant.14 During the Valsalva maneuver the usual hypotension-induced tachycardia was not observed, and after release, which normally leads to hypertension and stimulation of carotid baroreceptors, the expected bradycardia was not recorded.
During these explorations, we unfortunately could not record continuous blood pressure variations with a Finapres, which allows continuous and noninvasive blood pressure monitoring.15 Even though active standing and upright tilt testing are thought to be less specific in revealing baroreceptor dysfunction, the heart rate response during these tests, without any cardiac abnormality or orthostatic hypotension, indicates partial adaptation of baroreceptors and/or compensation from aortic baroreceptors. One may hypothesize that these compensatory mechanisms played a role in preventing our patient from having symptomatic orthostatic hypotension.
Dysfunction of carotid baroreceptors was found to be related to surgical damage during endarterectomy.3 16 Particular attention during dissection of the common carotid artery to avoid damaging the vagus nerve, the carotid sinus, and the hypoglossal nerve during dissection of the carotid bifurcation could be important to prevent carotid baroreceptor dysfunction.17 Unstable blood pressure occurs in 73.5% of these patients during the first 24 hours after carotid endarterectomy.1 This is usually a short-lived phenomenon, and persistence of chronic hypertension is quite unusual, but an increase in the pulsatile component of blood pressure and its variability 12 weeks after operation has recently been demonstrated.17 In our patient, who 6 months after surgery presumably has normal thoracic baroreceptor activity (normal active standing, tilt testing, and echocardiography), withdrawal of guanfacine was followed by recurrence of hypertension. This suggests that chronic high blood pressure may be a potential complication in this case of baroreflex failure syndrome, as recently characterized in other pathological settings.11 Occurrence of this syndrome after carotid endarterectomy was associated with bilateral surgical procedures. Because baroreceptor insensitivity has been found in hypertensive patients,18 baroreflex failure syndrome may be a potential complication in hypertensive patients with severe bilateral atherosclerotic lesions, even after unilateral carotid endarterectomy.
We used nicardipine to treat the initial hypertensive paroxysms with good results, but later the drug proved to be ineffective in controlling blood pressure levels; therefore, guanfacine, a clonidinelike centrally acting antihypertensive agent, was chosen to reduce sympathoneural outflow because it has been recently shown that patients with baroreflex failure usually respond to clonidine.11 Guanfacine may be added to the list of antihypertensive drugs already proved beneficial in treating post–carotid endarterectomy hypertension.4 12 13
Even though hypertension is the most dramatic blood pressure change following carotid endarterectomy, it should be remembered that hypotension, possibly related to recanalization and readjustment of baroreceptor sensitivity, is nevertheless the most frequent.16 18
This case report underlines the critical importance of blood pressure monitoring in detecting paroxysmal hypertension associated with baroreflex dysfunction after carotid endarterectomy. Uncontrolled hypertension may lead to severe cerebral complications such as encephalopathy.
Reprint requests to Olivier Ille, MD, Service de Neurologie, Hôpital Lariboisiere, 2 rue Ambroise-Paré, 75010, Paris, France.
- Received July 12, 1994.
- Revision received November 21, 1994.
- Accepted November 21, 1994.
- Copyright © 1995 by American Heart Association
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