[A controlled, double-blind, randomized pilot clinical trial of nicardipine as compared with a placebo in patients with moderate or severe head injury]. Traumatic subarachnoid hemorrhage and its treatment with nimodipine. German tSAH Study Group. A double blind placebo controlled trial of the calcium entry blocking drug, nicardipine, in the treatment of vasospasm following severe head injury. A multicenter trial of the efficacy of nimodipine on outcome after severe head injury. The European Study Group on Nimodipine in Severe Head Injury.
One of the factors involved in the occurrence of ischemic cerebral lesions following head injury is cerebral vasospasm. We analyze the effect of intravenous nicardipine on the prevention and treatment of posttraumatic cerebral vasospasm.
                We made a placebo-controlled, randomised, double-blind pilot study of the effect of nicardipine (intravenously 5 mg/hour for one week) on patients with moderate or severe head injury who presented with cerebral vasospasm, defined as an average Doppler flow velocity (DFV) of 100 cm/second or more. The main variable assessed was the evolution of the DFV and the secondary criteria were the evolution of the arterial blood pressure, coma scales, the findings on the Glasgow Coma Scale and the safety of the drug.
                Eleven patients were included in each homogeneous group. The DFV was found to have become normal on the first day of treatment with nicardipine and on the third day with the placebo (p = 0.023). During the first day of treatment the percentage of cerebral hemispheres diagnosed as having suspected spasm was 11.1% for nicardipine and 64.3% for the placebo (p = 0.02881). The average time for recovery (DFV < 100 cm/second) was 3.33 days with the placebo and 1.22 days with nicardipine (p = 0.0039). The patients treated with nicardipine had 8.89 times more chance of recovery from vasospasm. The incidence of adverse effects was greater with the placebo (p = 0.014).
                Nicardipine is effective in the reversal and prevention of increased Doppler flow velocity in patients with moderate or severe head injury. 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. A double blind, placebo controlled trial of nicardipine in the treatment of high Doppler Flow Velocity (DFV) following severe head injury (Glasgow Coma Score (GSC) less than or equal to 8) was performed. Thirty patients with high DFV (greater than or equal to 100 cm/s for 6 h duration) on transcranial Doppler ultrasound, were treated with nicardipine or placebo for 24 h (2.5 mg/h, increasing in steps of 2.5 mg/h at 2 h intervals (maximum rate 7.5 mg/h) depending on response of DFV). DFV was measured hourly for 24 h and then every 12 h for 2 days. Nicardipine significantly reduced DFV below the threshold of 100 cm/s (16/19 cf placebo 3/11, chi-square p less than 0.001). In the nicardipine treated group maximum DFV was significantly reduced (p less than 0.001) and time with DFV below 100 was significantly longer. Rises in DFV were significantly reduced by the drug if the DFV was normal at the time of entry. High DFV returned on cessation of the infusion. No unexpected or adverse side effects were seen. No clinical benefit was demonstrable. 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.
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.