Efficacy and usability of buccal midazolam in controlling acute prolonged convulsive seizures in children.

A Prolonged convulsive seizure is the most common neurological medical emergency with poor outcome. An ideal anticonvulsant should be easy-to-use, effective, and safe, and it should also have a long-lasting effect. Benzodiazepines, give via the intravenous or rectal route have generally been used as first-line drugs. In small children, IV access can be difficult and time consuming. Midazolam is a potent anticonvulsant and is rapidly absorbed from the rectal, nasal, and buccal mucosa. Our aim was to evaluate the efficacy and usability of buccal midazolam in controlling seizures in children with acute prolonged seizures, by comparing it with rectal diazepam. Ninety-eight patients were enrolled, with 49 patients in each treatment group. In the buccal midazolam group, 42 (88%) patients were controlled in less than 4 min of drug administration, and all of the patients were controlled within 5 min of drug administration. In the rectal diazepam group, 24 (49%) patients were controlled in less than 4 min and 40 (82%) patients were controlled within 5 min of drug administration. The time for drug administration and drug effect was significantly less with buccal midazolam than with rectal diazepam (p value<0.001). In the buccal midazolam group, 46 (94%) parents were satisfied with their child's treatment and route of drug administration while in the rectal diazepam group, 7 (14%) parents were satisfied. Buccal midazolam was significantly more acceptable than rectal diazepam (p value<0.001). In conclusion, buccal midazolam may be as effective as rectal diazepam but more convenient to use in the controlling acute prolonged seizures in children, especially in situations in which there is a difficulty in gaining IV access, for example, in infants.

Neuroprotective effects of diazoxide and its antagonism by glibenclamide in pyramidal neurons of rat hippocampus subjected to ischemia-reperfusion-induced injury.

Mitochondrial ATP-sensitive potassium channel opener, diazoxide, is shown to have protective effect on the heart and brain following ischemia-reperfusion-induced injury (IR/II). However, the detailed effect of diazoxide and its antagonist on neuronal death, mitochondrial changes, and apoptosis in cerebral IR/II has not fully studied. IR/II was induced in rats by the 4-vessel occlusion model. Neuronal cell death and mitochondrial changes in CA1-CA4 pyramidal cells of the hippocampus were studied by light and electron microscopy, respectively. Apoptosis was assessed by measuring the amount of protein expressed by Bax and Bcl-2 genes. In light microscopy studies, the number of total and normal cells were increased only following 18 mg/kg of diazoxide. Lower doses (2 and 6 mg/kg) failed to change the cell numbers. All three doses of glibenclamide (1, 5, and 25 mg/kg) decreased the number of total and normal cell populations. In electron microscopy studies, different doses of diazoxide and glibenclamide prevented and aggravated the IR-induced morphological changes, respectively. Western blot analysis showed that diazoxide and glibenclamide inhibited and enhanced Bax protein expression respectively. Regarding Bcl-2 expression, only diazoxide showed a significant enhancement of gene expression. In conclusion, the results show that diazoxide can exhibit neuroprotective effects against IR/II in hippocampal regions, possibly through the opening of mitochondrial ATP-sensitive K(+) channels.