Postoperative prophylactic anticonvulsant therapy in cerebral gliomas.

A retrospective study was performed to evaluate the efficacy of prophylactic anticonvulsants in preventing seizures in 68 patients with supratentorial astrocytomas who had been treated with operation and irradiation and who had no previous history of convulsions. Thirty-three patients received prophylactic anticonvulsants and 38 patients did not. The incidence of all types of seizures (generalized convulsions or partial) was lower in patients receiving anticonvulsants. No seizures with an impairment of consciousness occurred in the patients with documented therapeutic anticonvulsant blood levels. The overall incidence of seizures was 39% in untreated patients and 21% in treated patients. The incidence of major seizures including tonic/clonic or partial complex seizures with impairment of consciousness was zero in patients with therapeutic anticonvulsant levels and 18% in untreated patients. Regarding the overall incidence of seizures in both groups, there tend to be fewer seizures in older patients, females, patients with a higher grade of malignancy, and patients who had a more radical resection of the tumor. This study suggests that seizures are a frequent occurrence after operation and irradiation for supratentorial glioma and that anticonvulsants may be effective in reducing the incidence of those seizures.

Effects of naloxone during high dose barbiturate anesthesia.

This experiment was performed to investigate the ability of naloxone to reverse high dose barbiturate anesthesia or produce cerebrovasodilation or changes in cerebral metabolism in dogs neuronally depressed by high doses of barbiturate. Six dogs were deeply anesthetized with sufficiently high doses of sodium pentobarbital to produce and then maintain isoelectric activity or cerebral silence on the electroencephalogram (EEG). Blood flows were determined using the radioactive microsphere technique both before and after the intravenous bolus injection of naloxone (10 mg/kg), which failed to produce any significant changes in cerebral blood flow, the cerebral metabolic rate of oxygen, cerebrovascular resistance, or EEG activity. Cardiovascular parameters were also essentially unchanged. Naloxone in a dose of 10 mg/kg i.v. produced no changes in the cerebral or systemic circulations or in brain metabolism during high dose sodium pentobarbital anesthesia.

Adenosine triphosphate-induced arterial hypotension in the dog.

This study was designed to investigate the potential use of adenosine triphosphate (ATP), a naturally occurring vasodilator, for producing profound intraoperative hypotension. Six mongrel dogs were anesthetized with morphine, nitrous oxide, and oxygen, paralyzed with pancuronium, and ventilated to a PaCO2 of 40. The mean arterial pressure was lowered to 40 mm Hg with an intravenous infusion of ATP (10.6 +/- 3.5 (SE) mg/kg/minute). Blood flow was determined using the radioactive microsphere technique. Measurements were made before and 20, 40, and 60 minutes after the induction of hypotension and after a 40-minute recovery. Infusion of ATP to lower the mean arterial pressure to 40 mm Hg resulted in a reduction of mean arterial pressure of 64% and an increase in heart rate of 11% accompanied by frequent cardiac arrhythmias. However, cardiac output decreased only 8%. Myocardial flow increased 137%, kidney flow decreased 71%, and masseter muscle flow increased 333%. A severe metabolic acidosis developed with a reduction in pH from control values of 7.39 +/- 0.03 to 7.16 +/- 0.03 after 60 minutes of hypotension. The cerebral metabolic rate of oxygen, determined using the oxygen content of the sagittal sinus, was not affected. Cerebral hemisphere blood flow decreased 21%, caudate nucleus flow decreased 31%, and corpus callosum flow decreased 43%. Blood flow to the brain stem and cerebellum was unchanged. Hypotension was readily induced, maintained, and reversed using ATP, without apparent tachyphylaxis. However, the profound metabolic acidosis and cardiac arrhythmias that occurred may be serious contraindications to the use of this agent clinically.

Comparison of systemic and cerebrovascular effects of isoflurane and halothane.

This study was carried out to compare the cerebral and systemic circulatory effect of halothane and isoflurane. Six mongrel dogs were anesthetized with 1.3 minimal alveolar concentration (MAC) (1%) halothane and were compared with six mongrel dogs anesthetized with 1.3 MAC (1.5%) isoflurane. Likewise, 6 dogs anesthetized with 1.7 MAC (1.3%) halothane were compared with 6 dogs anesthetized with 1.7 MAC (2%) isoflurane. Blood flow (using the radioactive microsphere technique) and cardiovascular measurements were obtained 2 hours after the induction of anesthesia and were repeated 5 more times at hourly intervals. The heart rate was similar in all groups of dogs, except that it was significantly lower with 1.7 MAC halothane. The mean arterial pressure was statistically higher with isoflurane at both concentrations than with halothane. The cardiac index was similar in all groups, except with 1.7 MAC isoflurane, when it was higher. At the early measurements, total cerebral blood flow (CBF) was above "normal" levels in all groups. At 1.3 MAC, the total CBF tended to be lower with isoflurane, but did not reach statistically significant levels. Blood flow decreased over time in all groups. The cerebral vascular resistance (CVR) mirrored the changes in blood flow, showing no difference between agents at 1.7 MAC, but the CVR with isoflurane was significantly higher at 1.3 MAC than it was with halothane. Regional cerebral blood flow showed marked differences. Regional flow to the hemispheres and the cortical gray matter showed that isoflurane tended to produce lower blood flow, particularly at the 1.3 MAC concentration. The reverse was true in the posterior fossa structures, with the brain stem and cerebellum showing higher blood flows with isoflurane, particularly at 1.7 MAC. Isoflurane may have several advantages over halothane for neurosurgical procedures.

Unruptured fusiform aneurysms of the posterior circulation with thalamic infarction.

Three patients with unruptured fusiform aneurysms of the posterior circulation presented with nonhemorrhagic thalamic infarctions. All of the aneurysms were seen on enhanced computed tomographic (CT) scans preangiographically. Although unruptured fusiform aneurysms are probably a rare cause of nonhemorrhagic thalamic infarction, their importance lies in the therapeutic implications of this diagnosis. In patients with nonhemorrhagic thalamic infarction, we suggest careful scrutiny of the blood vessels on enhanced CT scans.

Treatment of ischemic deficits from cerebral vasospasm with high dose barbiturate therapy.

In 12 patients with life-threatening neurological deficits from vasospasm refractory to other measures, high dose barbiturate therapy was used in an attempt to prevent permanent changes in the brain. In each case angiography was performed and intracranial pressure was measured. Dexamethasone, a low molecular weight dextran, and mannitol were administered. If intracranial pressure (ICP) was elevated, drainage of cerebrospinal fluid and hyperventilation were used. Arterial pressure was maintained at not less than 140/90 preoperatively and 180/100 postoperatively. Barbiturate therapy was continued until vasospasm decreased angiographically and ICP was normal. Eleven of the 12 patients perished. One had a fatal rebleed. One died of an iatrogenic hemothorax. Four died from uncontrollable intracranial hypertension. One improved slightly and then died from a cardiac arrhythmia. One died of increased ICP when her ventriculostomy malfunctioned. One improved and was responding purposefully to pain, only to die suddenly with a low ICP. Two patients became awake and responsive to verbal commands; 1 of these died from Klebsiella meningitis and the other died from an intracerebral hematoma. In the 3 patients in whom hypothermia was also used, profound alterations in acid-base and fluid electrolyte balance occurred. These discouraging results are most likely a reflection of the severity of the patients' condition at the beginning of therapy. There may be some benefit of barbiturates in the management of vasospasm, and the potential effectiveness of barbiturates may be more obvious if therapy is started at an earlier stage. However, until further evidence of the usefulness of this modality becomes manifest, it should be limited to patients with life-threatening impairments unresponsive to all other measures.

Effect of dimethyl sulfoxide on the cerebral and systemic circulations of the dog.

Dimethyl sulfoxide (DMSO) has a variety of properties suggesting that it may be a useful agent in the management of central nervous system trauma and stroke. The purpose of this investigation was to determine the systemic and cerebrovascular effects of varying doses of DMSO in a normal animal. Five mongrel dogs were subjected to a constant infusion of 100% DMSO at a rate of 4 g/kg/hour. Using the radioactive microsphere technique, we measured blood flow before giving DMSO and after 2, 4, 6, and 8 g of DMSO per kg had been infused. After 2 g/kg had been given, hemolysis was evident and the intravascular volume increased, resulting in a lowered hematocrit. The cerebral metabolic rate of oxygen remained stable throughout the study. The total cerebral blood flow increased over 20% after a cumulative dose of 6 g/kg. Blood flow to the cerebellum and brain stem was unchanged, while flow to the caudate nuclei and cerebral hemispheres increased. There was a reduction in flow to the corpus callosum and spinal cord. DMSO caused an increase in the cardiac index accompanied by a large increase in the right and left ventricular blood flows, but a reduction in kidney flow. The relationship of this redistribution of blood flow, especially within the cerebrospinal axis, to the therapeutic effects of DMSO bears further investigation.

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.

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.

High dose naloxone produces cerebral vasodilation.

In this study, 12 dogs were anesthetized with sodium pentobarbital, and blood flows were determined using the radioactive microsphere technique. Ten dogs were first made acutely hypertensive by the infusion of norepinephrine and demonstrated preserved cerebral autoregulation. The administration of naloxone, 10 mg/kg i.v., in these animals produced a significant increase in cerebral blood flow and a proportional drop in cerebrovascular resistance with no change in the cerebral metabolic rate of oxygen or the electroencephalogram. Two additional spontaneously hypertensive dogs demonstrated a similar response to naloxone. These results suggest that high dose naloxone produces cerebrovasodilation either directly or through the inhibition of cerebral autoregulation.

Spontaneous subarachnoid hemorrhage in young adults.

We evaluated 95 hospitalized patients (50 women and 45 men) aged 15 to 45 who had nontraumatic subarachnoid hemorrhage (SAH). Aneurysmal SAH was identified in 75 patients. Other causes for SAH were ruptured arteriovenous malformations (2 cases), amphetamine arteritis (1 case), and leptomeningeal melanoma (1 case). The cause of SAH was undetermined in 16 (17%) patients. Thirteen patients had histories of hypertension, 5 used oral contraceptives, and 4 had consumed large quantities of alcohol during the day before SAH. Only 1 patient had Type I diabetes mellitus. Diagnosis was delayed in 21 patients. Operation was performed in 71 patients, with only 3 (4.2%) deaths. The overall mortality was 8.4% (8 of 95), with all deaths due to neurological causes. Our data suggest that the overall management and surgical results of treatment of ruptured aneurysms in young adults are excellent, diabetes is rare among young adults with SAH, recent alcohol consumption does not seem to be a major factor predisposing to SAH in young adults, and misinterpretation of the early symptoms of SAH continues to be a serious problem.

Overall management of ruptured aneurysm: comparison of early and late operation.

The overall management results with 61 consecutive patients admitted within 3 days of subarachnoid hemorrhage from a ruptured intracranial aneurysm were analyzed. During the course of this study, the preferred method of management shifted from late surgery (planned at least 7 days after the last hemorrhage) to early surgery (within 4 days of the last hemorrhage). Ten moribund patients were excluded from analysis, leaving 24 in the late group and 27 in the early group. Both groups had comparable patient demographic characteristics and neurological conditions, and their care was supervised by one neurosurgeon (N.F.K.). A microsurgical intracranial operation was performed on all patients who survived long enough to have surgery. The intraoperative conditions and complications were similar for the two groups. The average length of follow-up was 11 months in the late and 9 months in the early group. The overall management results for the late group showed a 42% favorable outcome, a 17% unfavorable outcome, and a 42% mortality. The early group had an 81% favorable outcome, a 7% unfavorable outcome, and an 11% mortality. Patients in both good and poor conditions fared better in the early group. Seven late group patients rebled, compared to none in the early group. The number of medical complications, the length of hospitalization, and the occurrence of symptomatic vasospasm were all greater in the late group. Vasospasm in the early group occurred only postoperatively and, with the aneurysms secured, was treated more aggressively and successfully with hypertensive/hypervolemic therapy than the predominantly operative vasospasm in the late group.

Comparison of sodium thiopental and methohexital for high-dose barbiturate anesthesia.

High-dose sodium thiopental is frequently used in neuroanesthesia. The authors performed a study to compare a shorter-acting barbiturate, methohexital, to sodium thiopental in producing high-dose barbiturate anesthesia. In two groups of five mongrel dogs each, regional cerebral blood flow (CBF) was determined using the radioactive-microsphere technique, and cardiovascular parameters were measured before, during, and 1 hour after a 1 1/2-hour period of deep barbiturate anesthesia with either sodium thiopental or methohexital. Doses of the barbiturates were adjusted to produce electroencephalogram burst suppression of greater than 30 seconds. Both agents produced a similar degree of cardiac depression, reduction in CBF, and decrease in cerebral metabolic rate of oxygen (CMRO2). Changes in cerebral and peripheral vascular resistance indicated that methohexital caused less vasoconstriction than sodium thiopental. When the barbiturate infusions were discontinued, CMRO2 and CBF returned more rapidly toward control values in the methohexital group than in the thiopental group. The more rapid recovery time and decrease in cerebral vascular resistance with methohexital suggest that it may have some advantage over sodium thiopental during certain neurosurgical procedures.

Systemic and cerebral effects of prostacyclin-induced arterial hypotension in the dog.

Prostacyclin has strong vasodilating and antiplatelet properties. This study was performed to investigate its potential for producing profound intraoperative hypotension. Five dogs were anesthetized with morphine, nitrous oxide, and oxygen, paralyzed with pancuronium, and ventilated to a PaCO2 of 40 torr. Mean arterial blood pressure (MABP) was lowered to 40 mm Hg with an intravenous infusion of prostacyclin in 0.05 M Tris buffer (average rate of infusion 3 +/- 1 micrograms/kg/min). Blood flow was determined using the radioactive microsphere technique. Measurements were made before and after 20, 40, and 60 minutes of hypotension; and after a 40-minute recovery period. Infusion of prostacyclin reduced MABP 63% while increasing heart rate 51%. Tachyarrhythmias occurred in all dogs, and cardiac index decreased 18%. Myocardial blood flow decreased an average of 29%, cerebral blood flow decreased 30%, cerebellar blood flow decreased 18%, and blood flow in the brain stem and spinal cord was unchanged. Cerebral metabolic rate of oxygen, determined by measuring the oxygen content of the sagittal sinus, was unchanged. Hypotension was easily induced and maintained using prostacyclin, without apparent tachyphylaxis. However, the cardiac changes caused by this drug are more severe than those accompanying hypotension induced by most other agents, and may represent a serious contraindication to its clinical use.

Cerebrovascular effects of hypocapnia during adenosine-induced arterial hypotension.

Profound arterial hypotension is a commonly used adjunct in surgery for aneurysms and arteriovenous malformations. Hyperventilation with hypocapnia is also used in these patients to increase brain slackness. Both measures reduce cerebral blood flow (CBF). Of concern is whether CBF is reduced below ischemic thresholds when both techniques are employed together. To determine this, 12 mongrel dogs were anesthetized with morphine, nitrous oxide, and oxygen, and then paralyzed with pancuronium and hyperventilated. Arterial pCO2 was controlled by adding CO2 to the inspired gas mixture. Cerebral blood flow was measured at arterial pCO2 levels of 40 and 20 mm Hg both before and after mean arterial pressure was lowered to 40 mm Hg with adenosine enhanced by dipyridamole. In animals where PaCO2 was reduced to 20 mm Hg and mean arterial pressure was reduced to 40 mm Hg, cardiac index decreased 42% from control and total brain blood flow decreased 45% from control while the cerebral metabolic rate of oxygen was unchanged. Hypocapnia with hypotension resulted in small but statistically significant reductions in all regional blood flows, most notably in the brain stem. The reported effects of hypocapnia on CBF during arterial hypotension vary depending on the hypotensive agents used. Profound hypotension induced with adenosine does not eliminate CO2 reactivity, nor does it lower blood flow to ischemic levels in this model, even in the presence of severe hypocapnia.

Cerebral and systemic circulatory effects of arterial hypotension induced by adenosine.

In six dogs anesthetized with halothane and nitrous oxide, mean arterial pressure (MAP) was lowered to 40 mm Hg for an average of 90 minutes by intravenous infusion of adenosine. The hypotensive effect of the adenosine was potentiated by administering dipyridamole to block its intravascular inactivation. Blood flow to the brain, spinal cord, heart, kidneys, and skeletal muscle was measured six times in each animal using the radioactive microsphere technique. Determinations were made before, during, and 30 minutes after the hypotensive period. During the hypotensive period, MAP was decreased 61% and was related to a proportional decrease in peripheral vascular resistance. Cardiac index decreased 14%. Total cerebral blood flow (CBF) decreased an average of 28% and cerebral vascular resistance decreased 53%. The reduction in CBF was heterogeneous; the cerebral cortex and corpus callosum were most affected and the brain stem least affected. No change occurred in the cerebral metabolic rate of oxygen usage (CMRO2). Left ventricle flow increased 147% and right ventricle flow increased 271%. Blood flow to the kidneys decreased 70%, and to the liver decreased to 6% of control. Jejunum blood flow increased 138% during recovery, while stomach flow varied but showed no statistical change. There was no tachyphylaxis, rebound hypertension, or toxicity associated with the adenosine-induced hypotension. These properties suggest that adenosine may be a useful agent for inducing arterial hypotension in neurosurgical patients.

Dose-escalation study of intravenous nicardipine in patients with aneurysmal subarachnoid hemorrhage.

A dose-escalation study of the calcium ion entry blocking drug nicardipine was performed using large dose infusions in 67 patients with recent aneurysmal subarachnoid hemorrhage (SAH). A safe, potentially therapeutic dose of the drug was determined. Patients admitted within 7 days of SAH from a documented cerebral aneurysm were entered into the study if no spasm was present on the initial angiogram. Nicardipine was administered as a continuous intravenous infusion throughout the 14-day period after SAH, regardless of the timing of surgery. To determine the safest possible dose, nicardipine was administered at seven dose levels from 0.01 to 0.15 mg/kg/hr. The total daily doses ranged from 27.7 mg to 375.0 mg. A follow-up angiogram was carried out on all 67 patients 7 to 10 days after SAH. Computerized tomography and neurological examinations were used to determine the presence of cerebral infarction. No major adverse effects, unexpected reactions, or permanent sequelae could be attributed to nicardipine. A decline in blood pressure was noted following administration of the drug. This occurred more frequently among patients given the largest dose but did not produce clinical problems or require discontinuation of the drug. Favorable outcomes were noted in 52 patients (78%). Vasospasm was found by arteriography in 31 patients (46%). A dose-related trend was noted: only eight (24%) of 33 patients treated at the highest dose level (approximately 10 mg/hr) developed arteriographic evidence of vasospasm. Symptomatic vasospasm was diagnosed in only two (6%) of 33 patients treated with this dose. Of the 34 patients receiving the lower dose levels, angiographic spasm was observed in 68% and symptomatic vasospasm in 27%. No deaths due to vasospasm occurred. Nicardipine appears to prevent both vasospasm and cerebral ischemia after SAH. A multicenter randomized double-blind trial to test this hypothesis is planned.

Surgical treatment of giant aneurysm of vertebral-basilar junction.

A giant aneurysm of the vertebro-basilar junction is reported. It was successfully treated by ligation of the left vertebral artery, temporary occlusion of the right vertebral and basilar arteries, and evacuation of the aneurysm, following which the neck of the aneurysm was clipped.