Neal F. Kassell

Treatment of Ischemic Deficits from Vasospasm with Intravascular Volume Expansion and Induced Arterial Hypertension

In 58 patients with progressive neurological deterioration from angiographically confirmed cerebral vasospasm after spontaneous subarachnoid hemorrhage, arterial hypertension was induced in an attempt to improve their deficits. The most effective regimen consisted of intravascular volume expansion, blockade of the vagal depressor response, and the administration of antidiuretics and vasopressor agents. With this protocol, arterial blood pressure could be sustained at high levels for prolonged periods. Neurological deterioration was reversed in 47 patients, transiently in 4; permanent improvement occurred in 43. Complications experienced during therapy included pulmonary edema, dilutional hyponatremia, aneurysmal rebleeding, coagulopathy, hemothorax, and myocardial infarction. Elevating systemic arterial pressure in states of cerebrovascular insufficiency resulting from vasospasm is safe if meticulous attention is paid to physiological, biochemical, and hematological parameters, with the exception that it may be hazardous in the presence of an untreated ruptured or intact aneurysm. Intravascular volume expansion and induced hypertension are effective in reversing ischemic deficits from vasospasm provided that treatment commences before cerebral infarction and that adequate pressures are maintained for a sufficient period. The production of a hypervolemic state by the use of colloid and crystalloid infusion accompanied by atropine blockade of the vagal depressor response and blunting of the diuresis with vasopressin enables arterial pressure to be elevated for longer than 1 week.

Aneurysmal rebleeding: a preliminary report from the Cooperative Aneurysm Study.

It is generally considered that the peak incidence of rebleeding after aneurysmal subarachnoid hemorrhage is at the end of the 1st or the beginning of the 2nd week after the initial rupture. However, in a series of 2265 patients admitted within 3 days of their first subarachnoid hemorrhage, the peak of rebleeding occurred on the same day as the initial hemorrhage and there was no later peak. These data suggest that new management strategies for minimizing rebleeding must be considered for patients admitted soon after aneurysm rupture.

Preoperative prognostic factors for rebleeding and survival in aneurysm patients receiving antifibrinolytic therapy: report of the Cooperative Aneurysm Study.

Prognostic factors for mortality and recurrent hemorrhage in the preoperative, 2-week period were determined in 1114 patients who participated in the antifibrinolytic therapy investigations of the Cooperative Aneurysm Study between 1970 and 1977. Factors significantly related to mortality were admission neurological status, diastolic blood pressure, interval to treatment, degree of vasospasm, and medical condition. Factors associated with the likelihood of recurrent hemorrhage were interval to treatment, patients sex, and admission neurological status. These factors need to be considered in the analysis of clinical data in the management of ruptured intracranial aneurysms.

Intracranial saccular aneurysm and moyamoya disease.

Moyamoya disease is a rare but well described entity which has been found in the angiographic investigation of subarachnoid hemorrhage, its most common symptom in adults. We present 4 patients in whom moyamoya disease and an intracranial saccular aneurysm were discovered. In 2 of the 3 patients suffering a hemorrhage, the aneurysm was the source of bleeding. Three of the aneurysms were located at the basilar artery bifurcation. We recommend a careful search for a concomitant aneurysm in all patients with subarachnoid hemorrhage in whom moyamoya disease is found. We believe these patients should be treated as though the aneurysm were the source of bleeding.

Influence of timing of admission after aneurysmal subarachnoid hemorrhage on overall outcome. Report of the cooperative aneurysm study.

The overall management results after aneurysmal rupture were studied in 158 patients admitted to the hospital on day 0-3 and 175 patients admitted on day 4-7 following subarachnoid hemorrhage. In this series surgery was planned no sooner than 12 days following the ictus. Despite effective medical and surgical therapy overall results were disappointing: 3 months following the initial hemorrhage only 43% of patients in the 0-3 day group and 53% of patients in the 4-7 day group were capable of independent functional living. Patients admitted on days 4-7 also had a lower mortality rate, re-bled less frequently, and had lower postoperative mortality and morbidity than those admitted on days 0-3. For reasons not well defined, time of admission following aneurysmal SAH has an important influence on outcome. Accordingly, in evaluating outcome for patients with ruptured aneurysms treated with different therapeutic modalities, time of admission must be carefully controlled.

The patient with transient ischemic attacks--is this the time for a new therapeutic approach?

Current and future improvements in treatment to prevent cerebral infarction among patients with transient ischemic attacks may reduce neurological morbidity but may not lead to a proportional improvement in life expectancy. Because the long-term primary cause of death in these patients is myocardial infarction, it is most likely that the most important way to prolong survival may be the vigorous investigation of their cardiac status and the treatment of their coronary artery disease, even if asymptomatic.

Effects of Naloxone on Canine Cerebral Vascular Smooth Muscle

The pharmacological effects of naloxone on cerebral arterial smooth muscle in vitro were examined using canine basilar arterial strips. Naloxone exerted two different effects on canine basilar artery: (1) at a high concentration (3 × 10−4 M) it produced nonspecific vasodilation, and (2) at lower concentrations (3 × 10−7, 3 × 10−6, and 3 × 10−5 M) it inhibited the vasoconstrictor effects of norepinephrine without altering KCl-, serotonin-, or hemoglobin-induced constriction. Morphine (2 × 10−5 or 2 × 10−4 M) did not reverse the specific vasodilating effect of naloxone (3 × 10−5 M) on norepinephrine-induced constriction. Rather, morphine and naloxone together produced a greater vasodilating effect on norepinephrine-induced constriction than either agent alone. Naloxone (3 × 10−5M) failed to alter either phenylephrine-induced constriction or clonidine-induced constriction. The vasodilating effect of naloxone (3 × 10−5 M) on 10−3 M norepinephrine-induced constriction was not reduced with 10−6 M propranolol. These results suggest that the vasodilating effect of naloxone on norepinephrine-induced constriction does not result from an antagonistic action on opiate receptors, direct inhibition of α-adrenoreceptors, or direct stimulation of β-adrenoreceptors in canine cerebral arterial smooth muscle. The vasodilating effect of naloxone on norepinephrine-induced constriction may influence the CBF changes following naloxone administration.

Time-dependent Changes in Cerebral and Cardiovascular Parameters in Isoflurane-Nitrous Oxide-anesthetized Dogs

The purpose of this study was to examine the time-dependent effects of isoflurane-nitrous oxide anesthesia on cerebral blood flow and metabolism and on cardiovascular parameters. Eleven 15-kg mongrel dogs were anesthetized with 0.8% isoflurane (approximately 1.3 MAC (minimal anesthetic concentration], 70% nitrous oxide, and 30% O2 and were paralyzed with pancuronium. Blood flow (using the radioactive microsphere technique) and cerebrovascular and cardiovascular parameters were measured 6 times at 30-minute intervals beginning 2 hours after the induction of anesthesia. In this experiment, cerebral blood flow was markedly elevated at 2 hours after the induction of anesthesia, but then declined progressively by 40 to 50% over the 2 1/2-hour time period investigated, approaching values for normal awake dogs. The decline was accompanied by a progressive decrease in the cerebral metabolic rate of oxygen and a constant rise in cerebrovascular resistance. Blood flow to organs outside the central nervous system declined progressively, but with more variability between tissues. The mean arterial pressure increased slightly, and the peripheral vascular resistance almost doubled, but cardiac index, cardiac work, and stroke volume all decreased gradually. We conclude that isoflurane-nitrous oxide anesthesia produces significant cerebral vasodilatation in dogs, but that this effect diminishes over time. These time-dependent circulatory changes merit further investigation in humans.

Effects of naloxone on cerebral blood flow and metabolism in isoflurane/nitrous oxide-anesthetized dogs.

The purpose of this study was to document the changes in the cerebral and systemic circulations that result from various doses of naloxone. Twenty-four dogs were anesthetized with 0.8% isoflurane and 70% nitrous oxide (1.3 minimal anesthetic concentration). Thirteen of the dogs received bolus injections of naloxone at logarithmically increasing doses 30 minutes apart. Blood flow to the brain and other organs was determined using the radioactive microsphere technique. Electrical activity was measured by electroencephalography (EEG). High dose naloxone increased both cerebral blood flow (CBF) and cerebral metabolism. The changes in CBF were most pronounced in structures containing a large amount of gray matter, particularly the cerebral cortex, brain stem, and cervical spinal cord. The increase in blood flow was proportionately greater than the increase in the cerebral metabolic rate of oxygen, and EEG activity was unchanged. Naloxone did not produce any significant cardiovascular changes or alterations in myocardial, renal, hepatic, stomach, jejunum, or temporalis and paraspinous muscle flow. Accordingly, it seems that naloxone may have direct cerebral vasodilator properties.

Unilateral Nasal Hemianopia as a Sign of Intracranial Optic Nerve Compression

A 52-year-old woman complained of progressive loss of vision in the right eye. Although the visual acuity was normal, there was a relative afferent pupillary defect, and a mild decrease in color vision, mild optic disk pallor, and a nasal field defect along the central vertical meridian. The left eye was normal. Craniotomy disclosed a giant right-sided carotid-ophthalmic artery aneurysm.