Intravenous ketamine may be effective for the treatment of super-refractory status epilepticus (SRSE), as most patients treated with ketamine infusion had a significant decrease in seizure burden within 24 hours of treatment, according to study results published in Neurology.

Limited data are available on the optimal management of SRSE, defined as status epilepticus that continues despite anesthetic agents. The aim of the current study was to assess the efficacy of ketamine infusion for the treatment of SRSE, and to investigate the effect of high dose ketamine on brain physiology.

This retrospective study included 68 (68% women, mean age 53 years) patients with SRSE, admitted to the neurological intensive care unit at Columbia University Medical Center between January 1, 2009 and December 31, 2018. Status epilepticus was defined by continuous seizure activity for a minimum of 5 minutes. All 68 patients were treated with ketamine infusions and midazolam. Study researchers reviewed all electroencephalogram (EEG) reports, including the day before starting ketamine, the day of ketamine infusion, the day after ketamine infusion initiation, and the day after termination of ketamine. They utilized a generalized linear mixed effect model accounting for repeated measures to determine the effect of ketamine on blood pressure and cerebral multimodality physiologic measures. Additionally, they compared patients who had seizure cessation after ketamine initiation to those who did not.

The average infusion rate of ketamine was 2.2 mg/kg/h (±1.8 mg/kg/h) and the median duration of infusion was 2 days.


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Findings indicated at least a 50 percent reduction of seizure burden within 24 hours of ketamine initiation in 55 participants (81%), with complete seizure cessation in 43 patients (63%).

Study researchers reviewed mean arterial pressure in all patients. Higher ketamine infusion dose (odds ratio [OR], 1.39; 95% CI, 1.38-1.40) and longer administration time (OR, 0.9; 95% CI, 0.8-1.0) were associated with stable mean arterial pressure and with decreased vasopressor requirements over time. High dose ketamine had no significant effect on intracranial pressure, cerebral blood flow, and cerebral perfusion pressure.

The study had several limitations, including its retrospective, single center design, lack of a control group of patients not treated with ketamine, and potential selection bias as ketamine was initiated at the discretion of the treating physician.

Researchers concluded that “this study supports the use of ketamine infusions for the treatment of SRSE and suggests that high doses of ketamine are associated with improved hemodynamics without an increase in intracranial pressure.”

Reference

Alkhachroum A, Der-Nigoghossian CA, Mathews E, et al. Ketamine to treat super-refractory status epilepticus. Neurology. Published online September 1, 2020. doi:10.1212/WNL.0000000000010611