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 retrospectively SRSE patients who were treated with ketamine. Additionally, we 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 SRSE patients who were admitted between 2009 and 2018, were 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 old, 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 (OR 1.39, 95% CI 1.38-1.40), and with decreased in vasopressor requirements over time. We found no effect on intracranial pressure, cerebral blood flow, and 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.

Isoflurane in (Super-) Refractory Status Epilepticus: A Multicenter Evaluation

“…Considering the previously reported data, the responder rate of isoflurane (sustainable termination of SE) in our cohort was below that of midazolam (78%), propofol (68%), and thiopental (64%) [16]. Ketamine in combination with other anesthetics has also been used as a salvage therapy in RSE/SRSE, with promising permanent seizure control rates from 57 to 91% [20][21][22]. However, it must be mentioned that comparing current isoflurane data to the efficacy of other anesthetics is a delicate task given the marked heterogeneity in terms of patients and methods across all studies.…”

“…The study was approved by the Cologne University Ethics Committee (18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29). Because of the retrospective study design, written informed consent was waived.…”

Pearls and Pitfalls of Introducing Ketogenic Diet in Adult Status Epilepticus: A Practical Guide for the Intensivist

“…Earlier attainment of burst suppression may allow for a more rapid anesthetic wean [ 23 ], and it is important to frequently monitor the EEG and titrate anesthetic dose as appropriate. The goal of anesthetic use in RSE is the resolution of epileptiform activity in order to avoid physiologic effects while the underlying cause is identified and treated [ 24 , 25 ].…”

Review and Updates on the Treatment of Refractory and Super Refractory Status Epilepticus

“…Another attractive continuous anesthetic is ketamine due to its NMDA antagonism and its favorable side effect profile [ 41 , 42 ]. NMDA receptors are increasingly expressed during sustained seizure activity, offering a pathophysiological basis for the efficacy of ketamine in RSE and SRSE.…”

“…NMDA receptors are increasingly expressed during sustained seizure activity, offering a pathophysiological basis for the efficacy of ketamine in RSE and SRSE. In SRSE, ketamine has been studied retrospectively with a wide range of reported efficacy between 28–91% [ 41 , 43 , 44 , 45 , 46 ].…”