Ketamine to treat super-refractory status epilepticus

Abstract

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

Methods: We studied a consecutive series of 68 patients with SRSE who were admitted between 2009 and 2018, treated with ketamine, and monitored with scalp EEG. Eleven of these patients underwent MMM at the time of ketamine administration. We compared patients who had seizure cessation after ketamine initiation to those who did not.

Results: Mean age was 53 ± 18 years and 46% of patients were female. Seizure burden decreased by at least 50% within 24 hours of starting ketamine in 55 (81%) patients, with complete cessation in 43 (63%). Average dose of ketamine infusion was 2.2 ± 1.8 mg/kg/h, with median duration of 2 (1-4) days. 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. Using a generalized linear mixed effect model, ketamine was associated with stable mean arterial pressure (odds ratio 1.39, 95% confidence interval 1.38-1.40) and with decreased vasopressor requirements over time. We found no effect on intracranial pressure, cerebral blood flow, or cerebral perfusion pressure.

Conclusion: 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.

Classification of evidence: This study provides Class IV evidence that ketamine decreases seizures in patients with SRSE.

Figure 1. Treatment response of patients with super-refractory status epilepticus (SRSE) with ketamine infusion

Ketamine efficacy in the treatment of SRSE. The figure demonstrates treatment response within 24 hours after initiation of ketamine and after ketamine discontinuation.

Figure 2. Average mean arterial pressure (MAP) over time in 68 patients with super-refractory status epilepticus (SRSE) on ketamine infusion

(A) Average MAP (y-axis) over time (x-axis) (blue line) in patients with SRSE on ketamine infusion for SRSE treatment. No correlation was found, with Pearson r value of 0.051 (black line). (B) Percentage of patients on vasopressors for hemodynamic support from ketamine. Day 1 represents the date of ketamine initiation.

Figure 3. Effect of ketamine infusion on cerebral multimodal monitoring in 11 patients with super-refractory status epilepticus

(A) Boxplots show the relationship of increasing ketamine doses (x-axis) and mean cerebral blood flow (CBF), cerebral perfusion pressure (CPP), and intracranial pressure (ICP) measurements (y-axis). (B) Average CBF, CPP, and ICP for each patient presented in different colors (x-axis) over time (y-axis) of ketamine administration. Data were computed from 11 patients with ICP monitors and 6 patients with CBF monitors.