Early Ketamine to Treat Refractory Status Epilepticus

Abstract

Management of refractory status epilepticus (SE) involves administration of intravenous γ-aminobutyric acid (GABA(A)) receptor agonists, such as benzodiazepines, barbiturates, or propofol. Animal models suggest that reductions in synaptic GABA(A) receptors may cause these drugs to become less effective as the duration of SE increases. This may explain the large doses that are commonly required to control seizures, which in turn contributes to a high incidence of complications, including hypotension and the need for vasopressors. In contrast, expression of excitatory N-methyl-D-aspartate (NMDA) receptors increases with prolonged SE and their stimulation by glutamate may propagate seizure activity. Ketamine is a NMDA-receptor antagonist that is considered promising as treatment for refractory SE. Compared with other anaesthetic drugs, ketamine produces less hypotension. This report describes a patient who developed worsening hypotension with escalating doses of midazolam and propofol in the context of non-convulsive SE. He was therefore treated with ketamine within hours of being diagnosed. Ketamine was immediately efficacious at reducing the frequency, amplitude, and duration of seizures. The dose was rapidly titrated upwards using quantitative continuous EEG monitoring, until seizures were completely abolished. SE did not recur with weaning of sedatives and he went on to have an excellent recovery. A small number of previous reports have found ketamine to abort late SE. In most cases, ketamine was administered several days into the course, and outcomes were poor even though seizures were controlled. Larger series and phase I clinical trial(s) of ketamine for treatment of refractory SE seem warranted.