We review recent advances in our understanding and treatment of
status epilepticus (SE). Repeated
seizures cause an internalization of
gamma-aminobutyric acid (
GABA)(A) receptors, together with a movement of
N-methyl-d-aspartate (
NMDA) receptors to the synapse. As a result, the response of experimental SE to treatment with GABAergic drugs (but not with
NMDA antagonists) fades with increasing seizure duration. Prehospital treatment, which acts before these changes are established, is finding increased acceptance, and solid evidence of its efficacy is available, particularly in children. Rational
polypharmacy aims at multiple receptors or
ion channels to increase inhibition and simultaneously reduce excitation. Combining
GABA(A) agonists with
NMDA antagonists and with agents acting at other sites is successful in treating experimental SE, and in reducing SE-induced brain damage and epileptogenesis. The relevance of these experimental data to clinical SE is actively debated.
Valproate and
levetiracetam have recently become available for intravenous use, and the use of
ketamine and of other agents (
topiramate,
felbamate, etc.) have seen renewed interest. A rapidly increasing but largely anecdotal body of literature reports success in seizure control at the price of relatively few complications with the clinical use of those agents in refractory SE.