A multicenter trial of the efficacy of nimodipine on outcome after severe head injury. The European Study Group on Nimodipine in Severe Head Injury. Traumatic subarachnoid hemorrhage and its treatment with nimodipine. German tSAH Study Group. Cerebral arterial spasm--a controlled trial of nimodipine in patients with subarachnoid hemorrhage. Prevention of vasospasm in subarachnoid haemorrhage. A controlled study with nimodipine.
Between January 1, 1989, and June 30, 1991, 852 severely head-injured patients were entered into a prospective placebo-controlled trial of the efficacy of nimodipine administration. The patients could not obey commands at the time of entry into the trial, which was within 12 hours after the start of the inability to obey commands and within 24 hours of injury. The main hypothesis that nimodipine would increase the percentage of patients with a favorable outcome (moderate disability or good recovery) from 50% to 60% was rejected. A trend toward a favorable effect was seen in patients who exhibited traumatic subarachnoid hemorrhage (SAH) on the computerized tomography (CT) scan obtained prior to entry into the study. The effect was statistically significant in those patients who complied with all protocol requirements. This finding is consistent with the effect of nimodipine on secondary ischemia following spontaneous SAH. The results of the study warrant a clinical trial of the efficacy of nimodipine in severely head-injured patients who show traumatic SAH on the initial CT scan. A prospective, randomized, double-blind, placebo-controlled study of nimodipine used to treat traumatic subarachnoid hemorrhage (tSAH) was conducted in 21 German neurosurgical centers between January 1994 and April 1995. One hundred twenty-three patients with tSAH appearing on initial computerized tomography (CT) scanning were entered into the study. Requirements for inclusion included age between 16 and 70 and admission into the study within 12 hours after head injury, regardless of the patient's level of consciousness. Eligible patients received either a sequential course of intravenous and oral nimodipine or placebo treatment for 3 weeks. Patients were closely monitored using clinical neurology, computerized tomography, laboratory, and transcranial Doppler ultrasound parameters. Patients treated with nimodipine had a significantly less unfavorable outcome (death, vegetative survival, or severe disability) at 6 months than placebo-treated patients (25% vs. 46%, p = 0.02). The relative reduction in unfavorable outcome in the nimodipine-treated group was even higher (55%, p = 0.002) when only patients who complied with the protocol were considered. We enrolled 125 neurologically normal patients with intracranial aneurysms in a multi-institution, prospective, double-blind, randomized, placebo-controlled trial within 96 hours of their subarachnoid hemorrhage, to determine whether treatment with the calcium blocker nimodipine would prevent or reduce the severity of ischemic neurologic deficits from arterial spasm. A deficit from cerebral arterial spasm that persisted and was severe or caused death by the end of the 21-day treatment period occurred in 8 of 60 patients given placebo and in 1 of 56 given nimodipine (P = 0.03, Fisher's exact test). Analysis of the amount of basal subarachnoid blood on pre-entry CAT scans in patients with deficits from spasm showed that an increase in subarachnoid blood was not associated with a worse neurologic outcome among patients who received nimodipine, unlike the situation in patients given a placebo. There were no side effects from nimodipine. We conclude that nimodipine should be given to patients who are neurologically normal after subarachnoid hemorrhage in order to reduce the occurrence of severe neurologic deficits due to cerebral arterial spasm. A prospective randomized double blind study was conducted in 70 patients suffering from subarachnoid haemorrhage, due to aneurysm rupture, to determine if the use of nimodipine reduces the severity of ischaemic deficits secondary to vasospasm. At the end of the study, two patients had severe deficit or died in the treated group, while 10 had a bad outcome in the placebo group. Angiographic vasospasm was not significantly different in its frequency or its severity between the two groups. However, the association of extensive and diffuse vasospasm was less frequent in the nimodipine group. This study confirms the effectiveness of Nimodipine in reducing the occurrence of neurological deficit due to vasospasm, even if this action is not observed in all cases.
This systematic review of randomised controlled trials of calcium channel blockers in acute traumatic head injury patients shows that considerable uncertainty remains over their effects. The effect of nimodipine in a subgroup of brain injury patients with subarachnoid haemorrhage shows a beneficial effect, though the increase in adverse reactions suffered by the intervention group may mean that the drug is harmful for some patients.