Efficacy of Ketamine Infusion Compared With Traditional Anti-epileptic Agents in Refractory Status Epilepticus

The traditional treatment for refractory status epilepticus includes diazepam, midazolam,
valproic acid, thiopental and propofol. These medications fail to control seizure activity in
20-40% of patients. This is attributed to decrease in activity of gamma-aminobutyric acid
receptors along with reciprocal up regulation of N-Methyl-D-aspartate receptors. Glutamate
activation of N-methyl-D-aspartate receptors promotes calcium influx and excitotoxicity.
Ketamine, an intravenous anesthetic agent which is a non-competitive antagonist of
N-methyl-D-aspartate receptors can block the flow of Ca and Na and by combining with
phencyclidine binding sites inside the ion channel of N-methyl-D-aspartate receptors, reduce
the epileptiform burst discharges and after potential. Therefore, targeting the
N-methyl-D-aspartate receptors with ketamine may provide a novel approach to control
refractory seizures. Moreover, by blocking glutamate mediated N-methyl-D-aspartate receptor
induced neurotoxicity, ketamine may render neuroprotection. Ketamine also provides additional
advantage of hemodynamic stability. Currently, ketamine is used as a last resort drug in the
treatment of refractory status epilepticus.

The specific aim is to determine whether continuous infusion of ketamine as a first line
agent for refractory status epilepticus is effective in controlling seizures.

The central hypothesis of our proposal is that early treatment with ketamine will be much
more efficacious in controlling refractory status compared to the traditional treatment.

Inclusion Criteria:

- Patients more than 18 years of age with a diagnosis of status epilepticus

- Considered for burst suppression therapy after failing 2 or 3 anti-epileptic
medications

Exclusion Criteria:

- Post anoxic status epilepticus

- Pregnant women, as confirmed by urine, or blood human chorionic gonadotropin,
ultrasound or physical exam

- Prisoners

- Age less than 18 years

- Allergy or sensitivity to the drug in question