Ketamine reduces seizure burden in patients with super-refractory status epilepticus

Ketamine successfully reduced seizure burden among patients with super-refractory status epilepticus with no impact on intracranial pressure, cerebral blood flow or cerebral perfusion pressure, according to findings published in Neurology.

Status epilepticus refers to ongoing seizure activity, or two or more seizures without regaining of consciousness, lasting for more than 30 minutes. Super-refractory status epilepticus has been described as status epilepticus that continues or recurs despite administration of third-line antiepileptic drugs. The condition is associated with high morbidity and mortality rates.

“To test ketamine infusion efficacy in the treatment of super-refractory status epilepticus (SRSE), we studied retrospectively SRSE patients who were treated with ketamine,” the researchers wrote. “Additionally, we studied the effect of high doses of ketamine on brain physiology as reflected by invasive multimodality monitoring (MMM).”

Ayham Alkhachroum, MD, an assistant professor of neurology at the University of Miami who was a fellow in the department of neurology at Columbia University at the time the research was conducted, and colleagues reviewed a consecutive series of 68 patients who received ketamine for SRSE between 2009 and 2018. They monitored all participants with scalp EEG and 11 patients underwent MMM at the time of ketamine administration. The researchers compared rates of seizure cessation between patients who received ketamine compared with those who did not.

The mean age of the cohort was 53 years (± 18 years) and 46% were women. The average dose of ketamine infusion was 2.2 ± 1.8 mg/kg per hour, with a median duration of 2 days (range, 1 to 4 days). The average dose of midazolam was 1.0 ± 0.8 mg/kg per hour at the time of ketamine initiation and was started at a median of 0.4 days (range, 0.1 to 1.0 days) prior to ketamine initiation.

The researchers found that seizure burden decreased by at least 50% within 24 hours of ketamine administration in 55 patients (81%), with complete cessation in 43 patients (63%). A generalized linear mixed effect model demonstrated that ketamine correlated with stable mean arterial pressure (OR = 1.39; 95% CI, 1.38-1.4) and a reduction in vasopressor requirements over time. Alkhachroum and colleagues observed no effect on intracranial pressure, cerebral blood flow and cerebral perfusion pressure.

“This study provides class IV evidence that ketamine decreases seizures in patients with SRSE,” the researchers wrote.

References:

• Lee A, et al. Neurology. 2017;88(16 Suppl.).
• Nelson SE, et al. Continuum. 2018;doi:10.1212/CON.0000000000000668.