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E C Haley

Publications and source records attributed to E C Haley.

At least 37 records · Page 2Linked to original sources
PubMed1997

A randomized, double-blind, vehicle-controlled trial of tirilazad mesylate in patients with aneurysmal subarachnoid hemorrhage: a cooperative study in North America.

To test the safety and efficacy of tirilazad mesylate, a nonglucocorticoid 21-aminosteroid, in improving the outcome of patients with aneurysmal subarachnoid hemorrhage (SAH), 902 patients were enrolled in a prospective randomized, double-blind, vehicle-controlled trial at 54 North American neurosurgical centers. Five patients were excluded prior to receiving any study drug. Of 897 patients who received at least one dose of study medication, 300 received a placebo containing a citrate vehicle, 298 received 2 mg/kg per day tirilazad, and 299 received 6 mg/kg per day tirilazad, all administered intravenously beginning within 48 hours of the SAH and continuing through 10 days posthemorrhage. All patients were also treated with orally administered nimodipine. At 3 months post-SAH, there were no significant differences (p < 0.025) among the groups with regard to mortality rate, favorable outcome on the Glasgow Outcome Scale, or employment status. During the first 14 days after the SAH, there were no significant differences among the groups in the incidence or severity of clinically symptomatic or angiographically identifiable cerebral vasospasm. Mortality data stratified by gender and neurological grade on admission (assessed according to a modified World Federation of Neurological Surgeons scale) demonstrated that the men with Grades IV to V had a 33% mortality rate in the vehicle group, 52% in the 2 mg/kg per day tirilazad group (p = 0.29), and 5% in the 6 mg/kg per day tirilazad group (p = 0.03). Tirilazad was well tolerated at both dose levels. Tirilazad mesylate at dosage levels of up to 6 mg/kg per day for 8 to 10 days following SAH did not improve the overall outcome in patients with aneurysmal SAH in this trial. The differences in the efficacy of tirilazad in this trial and a previously reported trial in Europe, Australia, and New Zealand, in which dosage levels of tirilazad of 6 mg/kg per day reduced mortality rates and increased good recovery, may be a result of differences in admission characteristics of the patients and/or differences in management protocols, including the use of anticonvulsant medications.

Administration, Oral↗
PubMed1996

Randomized, double-blind, vehicle-controlled trial of tirilazad mesylate in patients with aneurysmal subarachnoid hemorrhage: a cooperative study in Europe, Australia, and New Zealand.

Tirilazad mesylate, a nonglucocorticoid 21-aminosteroid, has been shown in experimental models to reduce vasospasm following subarachnoid hemorrhage (SAH) and to reduce infarct size from focal cerebral ischemia. To test whether treatment with tirilazad would reduce ischemic symptoms from vasospasm and improve overall outcome in patients with ruptured aneurysms, a prospective randomized, double-blind, vehicle-controlled trial was conducted at 41 neurosurgical centers in Europe, Australia, and New Zealand. One thousand twenty-three patients were randomly assigned to receive 0.6, 2, or 6 mg/kg per day of intravenously administered tirilazad or a placebo containing the citrate vehicle. All patients were also treated with intravenously administered nimodipine. Patients receiving 6 mg/kg per day of tirilazad had reduced mortality (p = 0.01) and a greater frequency of good recovery on the Glasgow Outcome Scale 3 months after SAH (p = 0.01) than similar patients treated with vehicle. There was a reduction in symptomatic vasospasm in the group that received 6 mg/kg per day tirilazad; however, the difference was not statistically significant (p = 0.048). The benefits of treatment with tirilazad were predominantly shown in men rather than in women. There were no material differences between the outcomes in the groups treated with 0.6 and 2 mg/kg tirilazad per day and the group treated with vehicle. Tirilazad was well tolerated at all three dose levels. These observations suggest that tirilazad mesylate, at a dosage of 6 mg/kg per day, is safe and improves overall outcome in patients (especially in men) who have experienced an aneurysmal SAH.

Adult↗
PubMed1996

Prognostic value of the hyperdense middle cerebral artery sign and stroke scale score before ultraearly thrombolytic therapy.

PURPOSE: To determine the relationship between the hyperdense middle cerebral artery sign (HMCAS) and neurologic deficit, as evidenced by the National Institutes of Health (NIH) stroke scale score, and to determine the relationship of the HMCAS and the NIH stroke scale score to arteriographic findings after thrombolytic therapy. METHODS: Fifty-five patients with acute ischemic stroke were rated on the NIH stroke scale, were examined with CT, and were treated with intravenous alteplase within 90 minutes of symptom onset. Presence of the HMCAS was determined on the baseline CT scan by a neuroradiologist blinded to the patient's neurologic deficit. Patients with the HMCAS were compared with those without HMCAS with regard to baseline NIH stroke scale score, 2-hour NIH stroke scale score, findings at posttreatment arteriography, 3-month residual neurologic deficit, and 3-month ischemia volumes as evidenced on CT scans. RESULTS: Eighteen patients (33%) had the HMCAS. These patients had a median baseline NIH stroke scale score of 19.5 compared with a median score of 10 for the patients lacking the HMCAS sign. At 3 months, one (6%) of the HMCAS-positive patients was completely improved neurologically compared with 17 (47%) of the HMCAS-negative patients. Restricting analysis to those patients with a stroke scale score of 10 or greater (n = 37), 18 HMCAS-positive patients showed less early neurologic improvement, were less likely to be completely improved at 3 months, and had larger infarcts compared with the 19 HMCAS-negative patients. Compared with the HMCAS-positive and HMCAS-negative patients with a stroke scale score of 10 or greater, patients with a stroke scale score of less than 10 had fewer occlusive changes of the internal carotid and middle cerebral arteries on posttreatment arteriograms and had a better neurologic recovery at 3 months. CONCLUSION: The presence of the HMCAS on CT scans obtained within 90 minutes of stroke onset is associated with a major neurologic deficit, and in this study it predicted a poor clinical and radiologic outcome after intravenous thrombolytic therapy. However, a major neurologic deficit, defined as a stroke scale score of 10 or more, was better than a positive HMCAS as a predictor of poor neurologic outcome after thrombolytic therapy. Patients with a low stroke scale score (< 10) may benefit from ultraearly intravenous alteplase therapy.

Adult↗
PubMed1995

Medical complications of aneurysmal subarachnoid hemorrhage: a report of the multicenter, cooperative aneurysm study. Participants of the Multicenter Cooperative Aneurysm Study.

OBJECTIVES: This report examines the frequency, type, and prognostic factors of medical (nonneurologic) complications after subarachnoid hemorrhage in a large, prospective study. The influences of contemporary neurosurgical, neurological, and critical care practice on mortality and morbidity rates after aneurysmal subarachnoid hemorrhage are evaluated. DESIGN: A study of medical complications observed in the placebo limb of a large, randomized, controlled trial of the calcium antagonist, nicardipine, after subarachnoid hemorrhage. SETTING: Patients were recruited from 50 hospitals in 41 neurosurgical centers in the United States and Canada. PATIENTS: A total of 457 patients with subarachnoid hemorrhage, > or = 18 yrs of age, were randomly assigned to the placebo group. All patients arrived at the participating center within 7 days (mean 1.0 +/- 1.8 [SD] days) of rupture of an angiographically documented saccular aneurysm. MEASUREMENTS AND MAIN RESULTS: The frequency rates of symptomatic vasospasm, rebleeding, and total mortality rate after subarachnoid hemorrhage at 3-month follow-up were 46%, 7%, and 19%, respectively. The frequency of having at least one severe (life-threatening) medical complication was 40%. The proportion of deaths from medical complications was 23%. This value was comparable with the proportion of deaths attributed to the direct effects of the initial hemorrhage (19%), rebleeding (22%), and vasospasm (23%) after aneurysmal rupture. The frequency of life-threatening cardiac arrhythmias was 5%; less ominous rhythm disturbances occurred in 30% of the patients. There was an increased frequency of cardiac arrhythmias on the day of, or day after, aneurysm surgery. Pulmonary edema occurred in 23% of the patients, with a 6% occurrence rate incidence of severe pulmonary edema. There was a wide variation from center to center, with the greatest frequency on days 3 through 7. There was a nonsignificant association of pulmonary edema with the use of hypertensive hypervolemic therapy (p = .10), and a significant association with the timing of surgery (p < .05). Some degree of hepatic dysfunction was noted in 24% of patients, the majority with only mild abnormalities of hepatic enzymes with no clinical accompaniment (4% frequency of severe hepatic dysfunction). Thrombocytopenia occurred in 4% of patients, usually in the setting of sepsis. Renal dysfunction was reported in 7% of the patients, with 15% of that figure deemed to be of life-threatening severity. There was an association (p = .001) with antibiotic therapy. CONCLUSIONS: Potentially preventable medical complications after ruptured cerebral aneurysm add to the total mortality rate of patients, and may increase length of hospital stay in the critical care setting. The proportion of deaths after subarachnoid hemorrhage from medical complications equals those deaths from either direct effects, rebleeding, or vasospasm individually. Pulmonary complications are the most common nonneurologic cause of death. Cardiac arrhythmia, although frequent, was not associated with significant mortality. The frequency of cardiac arrhythmia and pulmonary edema increased on the day of, or day after, aneurysm surgery. Renal and hepatic dysfunction, and blood dyscrasias, were also observed, underscoring the need for meticulous monitoring for metabolic and hematologic derangements.

Adult↗
PubMed1995

Phase II trial of tirilazad in aneurysmal subarachnoid hemorrhage. A report of the Cooperative Aneurysm Study.

Tirilazad mesylate, a 21-aminosteroid free-radical scavenger, has been shown to ameliorate cerebral vasospasm and reduce infarct size in animal models of subarachnoid hemorrhage (SAH) and focal cerebral ischemia. In preparation for performing large-scale clinical trials in humans with aneurysmal SAH, the safety of varying doses of tirilazad was tested in a randomized, double-blind, vehicle-controlled, sequential dose-escalation study at 12 Canadian neurosurgical centers. Two hundred forty-five patients with an aneurysmal SAH documented by angiography were enrolled in the study sequentially within 72 hours of hemorrhage. The patients were assigned to one of three dosage tiers: receiving 0.6 mg/kg, 2 mg/kg, or 6 mg/kg tirilazad or vehicle per day intravenously in divided doses through Day 10 following the SAH. All patients also received oral nimodipine. No serious side effects of tirilazad treatment were identified at any of the three doses, despite close monitoring of hepatic and cardiac toxicity. A trend toward improvement in overall 3-month patient outcome was seen in the 2 mg/kg per day tirilazad-treated group compared to the outcomes in the vehicle-treated groups. We conclude that tirilazad mesylate is safe in SAH patients at doses up to 6 mg/kg per day for up to 10 days and is a promising drug for the treatment of patients with aneurysmal SAH.

Adult↗
PubMed1995

A randomized trial of intraoperative, intracisternal tissue plasminogen activator for the prevention of vasospasm.

A multicenter, randomized, blinded, placebo-controlled trial was conducted to study the possible role of intracisternally administered fibrinolytic agent recombinant tissue plasminogen activator (rt-PA) in preventing delayed onset cerebral vasospasm following aneurysmal subarachnoid hemorrhage (SAH). The target population was patients with ruptured saccular aneurysms causing severe SAH, placing them at high risk for vasospasm. Treatment consisted of a single 10 ml intraoperative injection of either vehicle buffer solution or rt-PA (1 mg/ml) into the opened basal subarachnoid cisterns immediately following aneurysm clipping. The major efficacy endpoint in this trial was angiographic vasospasm, and the major safety concern was intracranial hemorrhage. One hundred patients were randomized, 49 to placebo and 51 to rt-PA treatment. Baseline population characteristics were similar between the two groups. Severity of intracranial hemorrhage on computed tomographic scans was also similar between groups: 87.2% of both placebo and rt-PA treated patients had thick subarachnoid clots, and the rates for intracerebral and intraventricular hemorrhage were, respectively, 16.3% and 22.5% for placebo and 23.5% and 21.6% for rt-PA. Nine randomized patients did not receive treatment in the operating room, and in 8 this was due to conditions felt unsafe for the administration of a fibrinolytic agent. The overall incidence of angiographic vasospasm measured between the seventh and eleventh day following SAH was similar between the two groups, with arterial narrowing detected in 74.4% of dosed placebo patients and 64.6% of rt-PA treated patients. However, there was a trend toward lesser degrees of vasospasm in the rt-PA treated group. The rates for no or mild, moderate, and severe vasospasm were 69%, 16% and 15% in the rt-PA treated group, versus 42%, 35% and 23% in the placebo group (P = 0.07). When only those patients with thick subarachnoid clots were considered at the treating centers, there was a 56% relative risk reduction of severe vasospasm in the rt-PA treated group, which was significant (P = 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Urgent therapy for acute stroke. Effects of a stroke trial on untreated patients.

BACKGROUND AND PURPOSE: As part of the recruitment efforts for the National Institutes of Health Tissue Plasminogen Activator Pilot Study, public education and awareness campaigns were conducted to encourage early hospital arrival. We evaluated the change in arrival times during the course of the study for all stroke patients, including those who were not entered into study. METHODS: Data were gathered on all patients presenting within 24 hours of stroke onset to all of the study hospitals. Coincident with the start of the study, educational and promotional programs, which stressed signs and symptoms of stroke and the need to call 911, were presented to physicians, paramedical personnel, and the public. The study was divided into four quartiles to analyze differences in time to hospital arrival and use of 911. RESULTS: Of 2099 patients screened, time data were available on 1116. During the course of the study, the mean time from symptom onset to hospital arrival declined significantly (3.2 hours versus 1.5 hours). Patients arrived for treatment sooner at community hospitals than at university/teaching hospitals. The use of 911 increased from 39% in the first quartile of the study to 60% in the fourth quartile. This was a consistent finding in all study sites. Increased use of 911 was seen almost exclusively in patients with nonhemorrhagic stroke. CONCLUSIONS: Times from stroke onset to hospital arrival decreased significantly during the course of the National Institutes of Health Tissue Plasminogen Activator Pilot Study. Significantly increased use of 911 was the likely major explanation for the shortened arrival times. The decrease in arrival times may be a consequence of the public and professional education programs conducted at all study sites.

Acute Disease↗
PubMed1994

Improved reliability of the NIH Stroke Scale using video training. NINDS TPA Stroke Study Group.

BACKGROUND AND PURPOSE: Despite the frequent use of clinical rating scales in multicenter therapeutic stroke trials, no generally acceptable method exists to train and certify investigators to use the instrument consistently. We desired to train investigators to use the National Institutes of Health Stroke Scale in a study of acute stroke therapy so that all examiners rated patients comparably. METHODS: We devised a two-camera videotape method that optimizes the visual presentation of examination findings. We then measured the effectiveness of the training by asking each investigator to evaluate a set of 11 patients, also on videotape. We tabulated the evaluations, devised a scoring system, and calculated measures of interobserver agreement among the participants in this study. RESULTS: We trained and certified 162 investigators. We found moderate to excellent agreement on most Stroke Scale items (unweighted kappa > 0.60). Two items, facial paresis and ataxia, exhibited poor agreement (unweighted kappa < 0.40) and should be revised in future editions of the scale. Performance improved with video training compared with previous studies. Inclusion of the motor rating of the unaffected limbs in the total score did not affect reliability. CONCLUSIONS: Video training and certification is a practical and effective method to standardize the use of examination scales. Two cameras must be used during the taping of patients to accurately present the clinical findings. This method is easily adapted to any study in which a large number of investigators will be enrolling patients at multiple clinical centers.

Cerebrovascular Disorders↗
PubMed1994

Factors related to intracranial hematoma formation in patients receiving tissue-type plasminogen activator for acute ischemic stroke.

BACKGROUND AND PURPOSE: Several studies are currently evaluating tissue-type plasminogen activator (TPA) as a potential therapy in acute ischemic stroke. The possibility of inducing intracranial hematomas, however, introduces an important concern into ultimate evaluation of risk and benefit. This retrospective analysis sought to identify factors associated with intracranial hematoma formation in a pilot phase 1 study of TPA for stroke. METHODS: Ninety-four patients received TPA within 3 hours of the onset of an acute ischemic stroke. Five of these patients developed a symptomatic intracerebral hematoma: 3 of 74 (4%) among patients treated within 90 minutes of stroke onset and 2 of 20 (10%) among those treated at 91 to 180 minutes. Three of the 5 died within 2 weeks. The analysis investigated associations between clinical factors and intracerebral hematomas. RESULTS: Factors significantly related to the development of an intracerebral hematoma were TPA dose and diastolic hypertension. Intracerebral hematomas developed in 4 (18%) of 22 patients given a TPA dose of at least 0.90 mg/kg versus only 1 hematoma in the remaining 72 patients (1%; P < .02, Fisher's exact test). Four (18%) of 22 patients who had initial diastolic blood pressures of at least 100 mm Hg suffered an intracerebral hematoma versus only 1 (1%) of 72 patients (P < .02) with lower initial diastolic pressures. CONCLUSIONS: Since the study was not designed to test specific safety hypotheses, results must not be overinterpreted. Nonetheless, these data emphasize the need for caution in both patient and dose selection for further studies of thrombolytic agents in stroke.

Adult↗
PubMed1994

A randomized trial of two doses of nicardipine in aneurysmal subarachnoid hemorrhage. A report of the Cooperative Aneurysm Study.

High-dose intravenous nicardipine has been shown to reduce the incidence of angiographic and symptomatic vasospasm in patients with aneurysmal subarachnoid hemorrhage (SAH), but treatment may be complicated by side effects, including hypotension or pulmonary edema/azotemia. From August, 1989, to January, 1991, 365 patients at 21 neurosurgical centers were entered into a randomized double-blind trial comparing high-dose (0.15 mg/kg/hr) nicardipine with a 50% lower dose (0.075 mg/kg/hr) administered by continuous intravenous infusion for up to 14 days following SAH. Patients in all neurological grades were eligible for the study. During the study period, 184 patients were randomly assigned to receive high-dose nicardipine and 181 to receive the low dose. There were no significant differences in patient age, admission neurological condition, or amount and distribution of blood clot on initial computerized tomography scan. Patients in the high-dose group received a significantly smaller proportion of the planned dose than those in the low-dose group (80% +/- 0.2% vs. 86% +/- 0.2%, p < 0.05), largely because of premature treatment termination after adverse medical events. The incidence of symptomatic vasospasm was 31% in both groups, and the overall 3-month outcomes were nearly identical. These data suggest that, from a clinical standpoint, the results of high-dose and low-dose nicardipine treatment are virtually equivalent, but administration of low-dose nicardipine is attended by fewer side effects.

Adult↗
PubMed1993

Time of hospital presentation in patients with acute stroke.

BACKGROUND: Stroke is a leading cause of death and disability in the United States. Although new treatments are being studied, most must be given early in the course of stroke to be effective. This study was performed to identify factors associated with early hospital arrival in patients with stroke. METHODS: As part of the National Institute of Neurologic Disorders and Stroke Tissue-Type Plasminogen Activator Pilot Study, information from patients, patients' families, or, most commonly, the medical record was gathered on all patients presenting to the hospital within 24 hours of the onset of stroke. A total of 14 hospitals participated. Three were university hospitals, and 11 were community hospitals with and without university affiliation. The main outcome measure was the time from stroke onset to hospital arrival. RESULTS: Of 2099 patients screened, adequate time data were available in 1159. Thirty-nine percent presented to the hospital 90 minutes or less after symptom onset and 59% within 3 hours. Early hospital arrival after stroke was greatly influenced by the type of first medical contact and, to a lesser degree, by the patient's location at the time of the stroke and the time of the day at which the stroke occurred. Hospital arrival was fastest in patients using 911 as their first medical contact (mean, 155 minutes; median, 84 minutes) vs their personal physician (mean, 379 minutes; median, 270 minutes; P < .0001) or a study hospital (mean, 333 minutes; median, 212 minutes; P < .0001). Time from symptom onset to arrival was longer for patients having the stroke at night compared with patients having a stroke in the morning (P < .05), in the afternoon (P < .01), or in the evening (P < .0001). Time to hospital arrival was significantly longer for patients having the stroke at home than for patients having the stroke at work (P < .01) or in an unknown place (P < .05). Gender, age, race, and presence of brain hemorrhage had no significant effect. CONCLUSIONS: As many as 50% of patients with stroke arrive at the hospital within 3 hours of symptom onset. Our data indicate that strategies to increase the use of 911 systems may have a high yield with regard to recruitment into urgent treatment protocols for stroke.

Acute Disease↗
PubMed1993

Blood pressure during the first minutes of focal cerebral ischemia.

STUDY OBJECTIVE: To determine whether blood pressure declines spontaneously during the first minutes and hours of focal cerebral ischemia. DESIGN: Multiple blood pressure measurements as part of an urgent stroke therapy trial (treatment within 90 minutes of stroke onset). SETTING: Thirteen hospitals in three metropolitan communities. PARTICIPANTS: Sixty-nine patients (mean age, 65 +/- 9 years) with acute ischemic stroke who were participants in a phase I urgent stroke therapy trial of recombinant tissue plasminogen activator. MAIN OUTCOME MEASURE: Blood pressures recorded at the scene of stroke by life-squad personnel, in the emergency department, and in the ICU. RESULTS: The mean time from stroke onset to the time of first blood pressure measurement was 19 +/- 13 minutes. Twenty-four of the 69 patients in the urgent stroke therapy trial had an initial systolic blood pressure of at least 160 mm Hg. Of these, 23 had a significant decline in systolic and diastolic blood pressure during the first 90 minutes after the onset of stroke (mean change in systolic pressure, -29 +/- 22 mm Hg, P < .001; mean change in diastolic pressure, -10 +/- 14 mm Hg, P < .01). No patients received antihypertensive therapy during the time in which the decline in blood pressure was noted. CONCLUSION: Mildly or moderately elevated blood pressure frequently declines spontaneously during the first minutes and hours of focal cerebral ischemia and generally does not require urgent pharmacologic treatment.

Acute Disease↗
PubMed1993

Thrombolytic therapy for acute ischemic stroke.

Emergency treatment of acute thromboembolic stroke by lysis of the occlusive arterial clot has received increasing attention in recent years. Development of newer thrombolytic agents combined with an enhanced appreciation of the time course of reversible cerebral ischemia have led to further clinical and laboratory exploration of this approach to stroke treatment, which had previously been believed to be unsafe. Recent studies suggest that very early recanalization of cerebral arteries can be achieved with acceptable risks using either local arterial or intravenously administered thrombolytic agents. While most published reports have suggested clinical benefit, definitive proof of sustained clinical efficacy, as measured by overall functional outcome and compared to concurrent controls, remains to be established.

Acute Disease↗
PubMed1993

Pilot randomized trial of tissue plasminogen activator in acute ischemic stroke. The TPA Bridging Study Group.

BACKGROUND AND PURPOSE: Early thrombolytic therapy with recombinant tissue-type plasminogen activator is a theoretically attractive approach to the treatment of acute focal cerebral ischemia. In preparation for a larger multicenter trial, three centers piloted a protocol for a randomized, double-blind, placebo-controlled trial of intravenous recombinant tissue-type plasminogen activator begun within 3 hours of the onset of symptoms of acute stroke to test its feasibility and to explore trends. METHODS: Eligible patients had pretreatment computed tomographic scanning, gave informed consent, and began treatment with either 0.85 mg/kg recombinant tissue-type plasminogen activator or placebo as soon as possible, but no later than 180 minutes after stroke onset. Patients were stratified by whether treatment was begun within 90 minutes or 91 to 180 minutes from onset. The primary end point was the proportion of patients in each group who improved by 4 or more points on the National Institutes of Health Stroke Scale at 24 hours, as determined by a separate blinded evaluator. RESULTS: Twenty-seven patients were randomized: 20 (10 recombinant tissue-type plasminogen activator, 10 placebo) within 90 minutes, and 7 (4 recombinant tissue-type plasminogen activator, 3 placebo) from 91 to 180 minutes. Median baseline Stroke Scale scores were 16 (minimum = 5, maximum = 26) for the recombinant tissue-type plasminogen activator-treated group and 11 (minimum = 3, maximum = 21) for the control subjects in the group treated within 90 minutes. Six patients treated with recombinant tissue-type plasminogen activator within 90 minutes improved by 4 or more points at 24 hours compared with 1 patient in the placebo group (P < .05, Fisher's Exact Test). Two patients in each group in the 91- to 180-minute arm improved. One fatal intracerebral hemorrhage occurred in the placebo group. CONCLUSIONS: A randomized, double-blind, placebo-controlled trial of recombinant tissue-type plasminogen activator very early in acute stroke is feasible. Preliminary observations suggest that recombinant tissue-type plasminogen activator treatment within 90 minutes may be associated with early neurological improvement. Larger studies are needed so that the potentially serious short-term risks of this treatment can be assessed in relation to meaningful long-term benefit.

Aged↗
PubMed1993

A randomized controlled trial of high-dose intravenous nicardipine in aneurysmal subarachnoid hemorrhage. A report of the Cooperative Aneurysm Study.

Because of their action as cerebral vasodilators, dihydropyridine calcium antagonists have received intense scrutiny for their potential benefit in ameliorating the devastating consequences of delayed cerebral vasospasm following aneurysmal subarachnoid hemorrhage (SAH). From October, 1987, to September, 1989, 41 North American neurosurgical centers in the Cooperative Aneurysm Study accrued 906 patients with recent (Days 0 to 7) aneurysmal SAH into a prospective randomized double-blind placebo-controlled trial of high-dose intravenous nicardipine to test whether treatment with this agent improved overall outcome. Eligible patients received 0.15 mg/kg/hr of either nicardipine or placebo by continuous infusion for up to 14 days following hemorrhage. The 449 patients randomly assigned to the nicardipine-treated group and the 457 patients assigned to the placebo-treated group were balanced with regard to prognostic factors for ischemic deficits from vasospasm and for overall outcome. Other medical and surgical interventions were used with similar frequency in both groups, except that antihypertensive agents were used less frequently in the nicardipine-treated patients (26% of the nicardipine-treated group vs. 43% of the placebo-treated group, p < 0.001), and more patients in the placebo-treated group had intentional hypervolemia, induced hypertension, and/or hemodilution administered therapeutically for symptomatic vasospasm (38% of the placebo-treated group vs. 25% of the nicardipine-treated group, p < 0.001). The incidence of symptomatic vasospasm during the treatment period was higher in the placebo-treated group (46%) than in the nicardipine-treated group (32%) (p < 0.001). Despite the reduction in symptomatic vasospasm in the nicardipine-treated group, overall outcome at 3 months was similar between the two groups. Fifty-five percent of nicardipine-treated patients were rated as having a good recovery according to the Glasgow Outcome Scale at follow-up review and 17% were dead, compared to 56% and 18%, respectively, in the placebo-treated group (not statistically significant). These data suggest that high-dose intravenous nicardipine treatment is associated with a reduced incidence of symptomatic vasospasm in patients with recent aneurysmal SAH, but not with an improvement in overall outcome at 3 months when compared to standard management in North America. It is postulated that, while nicardipine prevents vasospasm, hypertensive/hypervolemic therapy may be effective in reversing ischemic deficits from vasospasm once they occur.

Adult↗
PubMed1993

A randomized trial of nicardipine in subarachnoid hemorrhage: angiographic and transcranial Doppler ultrasound results. A report of the Cooperative Aneurysm Study.

Calcium antagonist drugs were proposed for use in patients with recent aneurysmal subarachnoid hemorrhage (SAH) because of their ability to block the effects of a wide variety of vasoconstrictor substances on cerebral arteries in vitro. It was suggested that these agents might, therefore, be useful in ameliorating cerebral vasospasm and its ischemic consequences which frequently complicate SAH. This hypothesis was tested in an arm of a randomized double-blind placebo-controlled trial of high-dose intravenous nicardipine in patients with recently ruptured aneurysms. Participating investigators were required to send selected copies of all admission and follow-up angiograms obtained between Days 7 and 11 following hemorrhage (the peak period of risk for vasospasm) to the Central Registry of the Cooperative Aneurysm Study for blinded interpretation and review for the presence and severity of angiographic vasospasm. In centers with transcranial Doppler ultrasound (TCD) capabilities, middle cerebral artery (MCA) mean flow velocities were measured and recorded. Angiograms obtained between Days 7 and 11 were available for 103 (23%) of 449 patients receiving nicardipine and 121 (26%) of 457 receiving placebo. There was a balance of prognostic factors for vasospasm between the groups. Fifty-one percent of placebo-treated patients had moderate or severe vasospasm on "Day 7-11 angiograms" compared to 33% of nicardipine-treated patients. This difference is statistically significant (p < 0.01). Sixty-seven (49%) of 137 placebo-treated patients examined with TCD between Days 7 and 11 had mean MCA flow velocities exceeding 120 cm/sec compared to 26 (23%) of 112 nicardipine-treated patients (significant difference, p < 0.001). These data suggest that high-dose intravenous nicardipine reduces the incidence and severity of delayed cerebral arterial narrowing in patients following aneurysmal SAH.

Adult↗