Ketamine decreases seizure burden in super-refractory status epilepticus

Super-refractory status epilepticus (SRSE) is specified by ongoing or recurring clinical or electroencephalographic seizure activity 24 h or more after initiation of anesthetic treatment. Ketamine (KET) has a strong antagonistic effect on the NMDA–glutamate receptor. Its half-life is 2–3 h, and KET undergoes extensive hepatic metabolism. Animal models (hippocampal electrical stimulation or pilocarpine animal models) have demonstrated the efficacy of KET in refractory status epilepticus (RSE) in rats, even in late stages, when GABA-ergic drugs have failed. The most significant adverse effects of KET are hallucinations and sympathetic adrenergic effects. To test ketamine infusion efficacy in the treatment of super-refractory status epilepticus (SRSE), researchers evaluated the patients with SRSE who were treated with ketamine. They further assessed the effect of high doses of ketamine on brain physiology as reflected by invasive multimodality monitoring (MMM).

Researchers studied a series of 68 patients with SRSE who were admitted between 2009 and 2018, treated with ketamine, and monitored with scalp EEG. Among 68 patient,s 11 underwent MMM at the time of ketamine administration. They compared patients who had seizure cessation after ketamine initiation to those who did not. The mean age of patients enrolled was 53 ± 18 years, among which 46% were female. The average dose of ketamine infusion was 2.2 ± 1.8 mg/kg/h, with median duration of 2 (1–4) days and the average dose of midazolam was 1.0 ± 0.8 mg/kg/h at the time of ketamine initiation and was started at a median of 0.4 (0.1–1.0) days before ketamine.

Researchers noted that the seizure burden was decreased by at least 50% within 24 hours of starting ketamine in 55 (81%) patients, with complete cessation in 43 (63%). Upon generalized linear mixed effect model, they found that ketamine was associated with stable mean arterial pressure (odds ratio 1.39) and with decreased vasopressor requirements over time. They found no effect on intracranial pressure, cerebral blood flow, or cerebral perfusion pressure.

The authors concluded, "Ketamine treatment was associated with a decrease in seizure burden in patients with SRSE. Our data support the notion that high-dose ketamine infusions are associated with decreased vasopressor requirements without increased intracranial pressure".

For further information:

https://n.neurology.org/content/95/16/e2286