Abstracts

RATIONALE: Diazepam rectal solutions are widely used as treatment for early status epilepticus. An acute treatment with a benzodiazepine can prevent evolution into refractory status epilepticus in most cases. However, application of a rectal solution is not always social acceptable, or may encounter physically insurmountable problems. A nasal spray may overcome some of these limitations. In a previous study in healthy volunteers we have proven that midazolam nasal spray has high social acceptance and is absorbed fast with a bioavailability of 70% of intravenous administration. By using a concentrated nasal spray, the midazolam is absorbed topically, and no first pass effect could be demonstrated.
METHODS: Twelve patients with medically refractory epilepsy using enzyme-inducing anticonvulsants were randomly assigned to application of either 5 or 10 mg midazolam nasal spray. A nasal spray was used which delivered 2,5 mg pro 0,09 ml pif, about five times as concentrated as the commercially available parenteral solution. The clinical effect and side effects were evaluated, including monitoring of oxygenation; EEG samples were taken at regular intervals during two hours for analysis of the power spectra; an indwelling venous catheter was placed during eight hours for frequent blood sampling in order to calculate the AUC.
RESULTS: Twelve patients fulfilled inclusion criteria and gave informed consent. Application of the nasal spray was accompanied with nasal pain and watery eyes. These complaints subsided within a few minutes in all patients. After five minutes the patients became sedated, especially when 10 mg was administrated. No other generalized side effects were noticed. We will present the results of plasma level monitoring and of EEG powerspectra.
CONCLUSIONS: Midazolam concentrated nasal spray is well tolerated, has good social acceptance and is rapidly absorbed also in persons using anticonvulsant medication. Midazolam nasal spray may have potential for intervention in early status epilepticus. A study is in preparation to compare the efficacy and side effects of midazolam nasal spray with those of diazepam rectal solutions in beginning status epilepticus.
[Supported by: Dutch epilepsy fund NEF.]