A multicenter, randomized placebo-controlled double-blind trial of nimodipine in poor-grade aneurysm patients was carried out in 17 Canadian hospitals. Of 188 patients enrolled in the trial, 32 were excluded for protocol violations and two were excluded due to statistical considerations, leaving 154 patients for valid outcome analysis. Nimodipine treatment was associated with a significantly better outcome (p less than 0.001): 21 (29.2%) of 72 nimodipine-treated patients had a good outcome at 3 months after subarachnoid hemorrhage (SAH) compared to eight (9.8%) of 82 placebo-treated patients. Delayed ischemic deficits from vasospasm alone were significantly less frequent in the nimodipine group (p less than 0.05) with permanent deficits occurring in five nimodipine-treated patients (6.9%) and in 22 placebo-treated patients (26.8%). Improvement in the good outcome rate and reduction in delayed ischemic deficits from vasospasm alone occurred in both Grade 3 and 4 patients, with no difference between nimodipine- and placebo-treated patients being found in Grade 5 patients. Repeat angiography after Day 4 was carried out in 124 patients. There was no significant difference in the incidence of moderate or severe diffuse spasm, which was seen in 64.3% of nimodipine-treated patients and 66.2% of placebo-treated patients. The authors conclude that nimodipine treatment in poor-grade patients with SAH results in an increase in the number of good outcomes and a reduction in the incidence of delayed neurological deterioration due to vasospasm. This effect occurs by a mechanism other than prevention of large-vessel spasm as visualized on angiography.

When is the outlook hopeless after rupture of an intracranial aneurysm? Some data bearing on the answer to this important question were obtained in a prospective, multicenter trial of 184 poor grade patients in a study of the calcium antagonist nimodipine. Entry was within 3 days of subarachnoid hemorrhage (SAH). The admission work-up included angiography of the anterior and posterior circulations and computed tomographic (CT) scans. The angiograms were repeated as close to Day 8 post-SAH as possible, and the CT scans were repeated at 3 months at the time of follow-up neurological assessment. Radiological assessment was performed independently of knowledge of drug treatment or patient outcome. A discriminant function analysis indicated that the relative importance of factors prognostic for outcome was, in order of importance: whether the patient was treated surgically, neurological grade on admission, age, initial systolic blood pressure, and aneurysm size. The discriminant function analysis correctly classified 80% of our cases. A constellation of poor prognostic features will aid the neurosurgeon in treating a patient conservatively and appropriately advising relatives. The ultimate decision on how to treat a given patient continues to depend partly on clinical judgement, which remains intuitive and subject to influences not studied here.

Fifteen patients undergoing surgery within 48 hours of aneurysm rupture were administered recombinant tissue plasminogen activator (rt-PA) directly into the basal subarachnoid cisterns after minimal surgical clot removal and aneurysm clipping. Preoperatively, 13 patients had diffuse or localized thick subarachnoid blood clots on computerized tomography (CT), and two had diffuse thin clots. The rt-PA was given as a single intraoperative injection of 7.5 mg (one patient), 10 mg (nine patients), or 15 mg (five patients). Postoperative cisternal drainage was employed in three patients. All patients except one demonstrated partial to complete cisternal clot clearance on CT scans within 24 hours after surgery. The patient who showed no clot reduction was the only patient in this series to develop symptomatic vasospasm and was the only fatality, dying 8 days after rupture. No vasospasm was seen on follow-up cerebral angiography in six of the 14 responding patients, and mild-to-moderate arterial narrowing was seen in at least one major cerebral artery in the remaining eight patients. Severe angiographic vasospasm was not seen, although the patient who died did not undergo repeat angiography. There was one major complication early in the series which seemed clearly related to treatment, and that was a large extradural hematoma occurring within several hours of craniotomy. Intrathecal fibrinolytic treatment appears effective in clearing subarachnoid clot and reducing vasospasm, and may be associated with acceptable risks if given to patients with large-volume subarachnoid hemorrhages at high risk for severe vasospasm.

A retrospective analysis of the cases of 173 patients operated on for aneurysms and admitted to a neurosurgical service early after subarachnoid hemorrhage was conducted with respect to white blood cell (WBC) count and highest daily temperature. Daily trends for the development of clinically significant vasospasm (VSP) as well as mortality during the hospitalization were analyzed. An admission WBC count greater than 15 x 10(9)/l was associated with 55% mortality as opposed to 25% mortality for those with a lower WBC count. The mortality of those with a temperature greater than 37.5 degrees C on Day 0 was 60%, compared with 35% for those with a lower temperature. A WBC count greater than 15 x 10(9)/l on Day 0 was associated with a VSP rate of 40%; a lower WBC count was associated with a VSP rate of 30% Day 0 temperatures greater than 37.5 degrees C were associated with a VSP rate of 40%, while patients with lower temperature had a VSP rate of 30%. By Day 6, the patients with temperatures greater than 37.5 degrees C had a VSP rate of 60%, double that of the VSP rate of those with temperatures less than 37.5 degrees C. WBC count was apparently more closely linked to the chance of dying than the chance of developing VSP. The development of fever after a few days is related to both increased mortality and increased chance of developing VSP.

A retrospective analysis of the cases of 173 patients operated on for aneurysms and admitted to a neurosurgical service early after subarachnoid hemorrhage was conducted with respect to white blood cell (WBC) count and highest daily temperature. Daily trends for the development of clinically significant vasospasm (VSP) as well as mortality during the hospitalization were analyzed. An admission WBC count greater than 15 × 109/I was associated with 55% mortality as opposed to 25% mortality for those with a lower WBC count. The mortality of those with a temperature greater than 37.5°C on Day 0 was 60%, compared with 35% for those with a lower temperature. A WBC count greater than 15 × 109/1 on Day 0 was associated with a VSP rate of 40%; a lower WBC count was associated with a VSP rate of 30%. Day 0 temperatures >37.5°C were associated with a VSP rate of 40%, while patients with lower temperature had a VSP rate of 30%. By Day 6, the patients with temperatures >37.5°C had a VSP rate of 60%, double that of the VSP rate of those with temperatures <37.5°C. WBC count was apparently more closely linked to the chance of dying than the chance of developing VSP. The development of fever after a few days is related to both increased mortality and increased chance of developing VSP.