Nimodipine treatment in poor-grade aneurysm patients

Abstract

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.

The effect of nimodipine on autoregulation of cerebral blood flow after subarachnoid haemorrhage in rat

“…The present study indicates that there is no direct correlation between vasospasm in large intracranial arteries and impaired CBF autoregulation, as the incidence of angiographically demonstrable vasospasm is not influenced by nimodipine treatment 4,8,17,22,27 It should be underlined, that even if nimodipine treatment might improve CBF autoregulation in SAH patients, it is still dangerous to allow extensive MABP fluctuations, especially because the shape of the autoregulation curve in every single patient is unknown. From experimental results it seems reasonable to expect a more pronounced effect on CBF autoregulation if treatment with nimodipine is initiated early after the onset of SAH 7.…”

Management problems in acute hydrocephalus after subarachnoid hemorrhage.

“…Although the risk of rebleeding can be diminished by long-term antifibrinolytic treatment, the benefit is negated by an increased frequency of delayed cerebral ischemia. 12 To improve outcome, it might be necessary to combine antifibrinolytic agents with plasma volume expansion 29 or calcium antagonists, 30 but even if this treatment combination is effective, it remains to be seen whether such a combined regimen would be effective after ventricular drainage. An alternative could be to have treatment of hydrocephalus by ventricular drainage soon followed by, or simultaneously performed with, clipping of the aneurysm.…”

Differing calcium sensitivities of human cerebral and digital arteries, human metatarsal veins, and rat aorta.

“…Nifedipine is known to cause headaches as a side effect, presumably as a result of its cerebral vasodilatory action. It is also likely that spasm of cerebral vessels resulting from subarachnoid haemorrhage may respond to dihydropyridine calcium antagonists (Petruk et al, 1988), depending on the mechanism of the spasm and whether calcium entry through voltage operated channels is at least partly responsible for the abnormal vascular contraction. The mixed resistance and capacitance effects of nifedipine also lends weight to its use in angina and hypertension, where mixed vasodilators achieve optimal reduction in myocardial workload.…”