Diazepam (Valium, Diastat) is a very common first treatment for SE, but conservative management would restrict it to patients with continuing convulsions or those having another convulsion during infusion of a maintenance medication. Reported efficacy rates in SE have varied widely, from 38% to 83%. Diazepam can interrupt convulsive SE rapidly but should not be used alone.
The usual practice is to administer 10 mg (0.15 mg/kg) intravenously over a few minutes, repeating if necessary. Rectal administration has been effective, particularly in children, and a gel suitable for rectal administration (Diastat) is available. Doses of the rectal gel necessary to terminate seizures are somewhat higher and vary by weight and age. A buccal formulation (Diazapam Intensol) is less well studied but widely considered effective as well. Both rectal and buccal formulations bypass first-pass hepatic metabolism and thus result in reasonable levels within about 30 minutes. In contrast, both intramuscular and oral diazepam are absorbed slowly and should not be used when acute seizure control is necessary.
Diazepam is very lipid-soluble, enters the brain rapidly, and may have an anticonvulsant effect within a minute after intravenous administration. Nevertheless, it redistributes to many tissues and its CNS effect declines in 20 to 30 minutes, so longer-acting anticonvulsants should be used concomitantly to prevent recurrent seizures or SE. Repeated doses may lose effectiveness but produce metabolites with prolonged elimination half-lives and potential toxicity, including prolonged coma.
Continuous infusion of diazepam (generally 4 to 8 mg/h) is often discussed for the management of SE but is rarely practiced, probably because the optimal doses have not been clearly established and rapid acute tolerance may develop. Continuous infusion should be used in intensive care units only. Iatrogenic apnea (often ascribed to seizures or to "tongue swallowing") can occur suddenly.
Reviewed and revised February 2004 by Thaddeus Walczak, MD, MINCEP® Epilepsy Care, Minneapolis, MN
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