The Effect of Nimodipine Monotherapy and Combined Treatment with Ketamine and Lignocaine in Aneurysmal Subarachnoid Haemorrhage

Abstract

The clinical effects of nimodipine monotherapy were compared with the effects of nimodipine combined with ketamine and lignocaine (combination therapy) in a single-centre, one investigator, open study in patients with proven aneurysmal subarachnoid haemorrhage (aSAH). After clipping of the aneurysm, nimodipine was administered intravenously until day 5 – 7 after clipping. Thereafter the intravenous nimodipine was substituted by oral doses of nimodipine. These were decreased gradually and then discontinued within the following 6 days. For combination therapy, nimodipine was given together with both a bolus injection of 1 μg/kg ketamine followed by an infusion of the drug at a rate of 3 μg/kg/min and a bolus injection of 1.5 mg/kg lignocaine followed by an infusion of the drug at a rate of 12 μg/kg/min. During the study period, 173 patients were admitted to the hospital with subarachnoid haemorrhage (SAH). Of these patients, 115 with a proven aneurysm were operated on and evaluated: 66 patients received nimodipine monotherapy and 49 were given nimodipine combined with ketamine and lignocaine. These subgroups were comparable in terms of the baseline characteristics (age, Hunt and Hess score). The (baseline corrected) Hunt and Hess scores after surgery and a 0 – 5 clinical outcome score were applied as indices for clinical effects. Patients receiving nimodipine monotherapy and combined therapy showed a significant clinical improvement compared to baseline (P = 0.001 and P = 0.006, respectively). The beneficial effect of nimodipine monotherapy is in line with previous double-blind, placebo-controlled studies. Although nimodipine monotherapy seems to be more effective than combined treatment, this was not statistically significant. Our data indicate that combined treatment with ketamine and lignocaine is not more effective than nimodipine monotherapy in patients with mild aSAH, but this does not rule out an effect in severe cases. There was no indication of a pharmacodynamic interaction between nimodipine and co-medication. No serious or clinically relevant adverse reactions were noted during the study.