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October 20, 2020; 95 (16) Article

Ketamine to treat super-refractory status epilepticus

View ORCID ProfileAyham Alkhachroum, Caroline A. Der-Nigoghossian, Elizabeth Mathews, Nina Massad, Riva Letchinger, Kevin Doyle, Wei-Ting Chiu, Julie Kromm, Clio Rubinos, Angela Velazquez, David Roh, Sachin Agarwal, Soojin Park, View ORCID ProfileE. Sander Connolly, View ORCID ProfileJan Claassen
First published September 1, 2020, DOI: https://doi.org/10.1212/WNL.0000000000010611
Ayham Alkhachroum
From the Departments of Neurology (A.A., C.A.D.-N., E.M., N.M., R.L., K.D., W.-T.C., C.R., A.V., D.R., S.A., S.P., J.C.) and Neurosurgery (E.S.C.), Columbia University, New York, NY; and Departments of Critical Care Medicine and Clinical Neurosciences (J.K.), University of Calgary, Canada.
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Caroline A. Der-Nigoghossian
From the Departments of Neurology (A.A., C.A.D.-N., E.M., N.M., R.L., K.D., W.-T.C., C.R., A.V., D.R., S.A., S.P., J.C.) and Neurosurgery (E.S.C.), Columbia University, New York, NY; and Departments of Critical Care Medicine and Clinical Neurosciences (J.K.), University of Calgary, Canada.
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Elizabeth Mathews
From the Departments of Neurology (A.A., C.A.D.-N., E.M., N.M., R.L., K.D., W.-T.C., C.R., A.V., D.R., S.A., S.P., J.C.) and Neurosurgery (E.S.C.), Columbia University, New York, NY; and Departments of Critical Care Medicine and Clinical Neurosciences (J.K.), University of Calgary, Canada.
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Nina Massad
From the Departments of Neurology (A.A., C.A.D.-N., E.M., N.M., R.L., K.D., W.-T.C., C.R., A.V., D.R., S.A., S.P., J.C.) and Neurosurgery (E.S.C.), Columbia University, New York, NY; and Departments of Critical Care Medicine and Clinical Neurosciences (J.K.), University of Calgary, Canada.
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Riva Letchinger
From the Departments of Neurology (A.A., C.A.D.-N., E.M., N.M., R.L., K.D., W.-T.C., C.R., A.V., D.R., S.A., S.P., J.C.) and Neurosurgery (E.S.C.), Columbia University, New York, NY; and Departments of Critical Care Medicine and Clinical Neurosciences (J.K.), University of Calgary, Canada.
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Kevin Doyle
From the Departments of Neurology (A.A., C.A.D.-N., E.M., N.M., R.L., K.D., W.-T.C., C.R., A.V., D.R., S.A., S.P., J.C.) and Neurosurgery (E.S.C.), Columbia University, New York, NY; and Departments of Critical Care Medicine and Clinical Neurosciences (J.K.), University of Calgary, Canada.
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Wei-Ting Chiu
From the Departments of Neurology (A.A., C.A.D.-N., E.M., N.M., R.L., K.D., W.-T.C., C.R., A.V., D.R., S.A., S.P., J.C.) and Neurosurgery (E.S.C.), Columbia University, New York, NY; and Departments of Critical Care Medicine and Clinical Neurosciences (J.K.), University of Calgary, Canada.
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Julie Kromm
From the Departments of Neurology (A.A., C.A.D.-N., E.M., N.M., R.L., K.D., W.-T.C., C.R., A.V., D.R., S.A., S.P., J.C.) and Neurosurgery (E.S.C.), Columbia University, New York, NY; and Departments of Critical Care Medicine and Clinical Neurosciences (J.K.), University of Calgary, Canada.
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Clio Rubinos
From the Departments of Neurology (A.A., C.A.D.-N., E.M., N.M., R.L., K.D., W.-T.C., C.R., A.V., D.R., S.A., S.P., J.C.) and Neurosurgery (E.S.C.), Columbia University, New York, NY; and Departments of Critical Care Medicine and Clinical Neurosciences (J.K.), University of Calgary, Canada.
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Angela Velazquez
From the Departments of Neurology (A.A., C.A.D.-N., E.M., N.M., R.L., K.D., W.-T.C., C.R., A.V., D.R., S.A., S.P., J.C.) and Neurosurgery (E.S.C.), Columbia University, New York, NY; and Departments of Critical Care Medicine and Clinical Neurosciences (J.K.), University of Calgary, Canada.
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David Roh
From the Departments of Neurology (A.A., C.A.D.-N., E.M., N.M., R.L., K.D., W.-T.C., C.R., A.V., D.R., S.A., S.P., J.C.) and Neurosurgery (E.S.C.), Columbia University, New York, NY; and Departments of Critical Care Medicine and Clinical Neurosciences (J.K.), University of Calgary, Canada.
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Sachin Agarwal
From the Departments of Neurology (A.A., C.A.D.-N., E.M., N.M., R.L., K.D., W.-T.C., C.R., A.V., D.R., S.A., S.P., J.C.) and Neurosurgery (E.S.C.), Columbia University, New York, NY; and Departments of Critical Care Medicine and Clinical Neurosciences (J.K.), University of Calgary, Canada.
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Soojin Park
From the Departments of Neurology (A.A., C.A.D.-N., E.M., N.M., R.L., K.D., W.-T.C., C.R., A.V., D.R., S.A., S.P., J.C.) and Neurosurgery (E.S.C.), Columbia University, New York, NY; and Departments of Critical Care Medicine and Clinical Neurosciences (J.K.), University of Calgary, Canada.
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E. Sander Connolly
From the Departments of Neurology (A.A., C.A.D.-N., E.M., N.M., R.L., K.D., W.-T.C., C.R., A.V., D.R., S.A., S.P., J.C.) and Neurosurgery (E.S.C.), Columbia University, New York, NY; and Departments of Critical Care Medicine and Clinical Neurosciences (J.K.), University of Calgary, Canada.
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Jan Claassen
From the Departments of Neurology (A.A., C.A.D.-N., E.M., N.M., R.L., K.D., W.-T.C., C.R., A.V., D.R., S.A., S.P., J.C.) and Neurosurgery (E.S.C.), Columbia University, New York, NY; and Departments of Critical Care Medicine and Clinical Neurosciences (J.K.), University of Calgary, Canada.
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Citation
Ketamine to treat super-refractory status epilepticus
Ayham Alkhachroum, Caroline A. Der-Nigoghossian, Elizabeth Mathews, Nina Massad, Riva Letchinger, Kevin Doyle, Wei-Ting Chiu, Julie Kromm, Clio Rubinos, Angela Velazquez, David Roh, Sachin Agarwal, Soojin Park, E. Sander Connolly, Jan Claassen
Neurology Oct 2020, 95 (16) e2286-e2294; DOI: 10.1212/WNL.0000000000010611

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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.

Glossary

AED=
antiepileptic drug;
CBF=
cerebral blood flow;
CI=
confidence interval;
CPP=
cerebral perfusion pressure;
GABAA=
γ-aminobutyric acid;
ICP=
intracranial pressure;
MAP=
mean arterial pressure;
MMM=
multimodality monitoring;
OR=
odds ratio;
RSE=
refractory status epilepticus;
SRSE=
super-refractory status epilepticus

Footnotes

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Class of Evidence: NPub.org/coe

  • Received December 29, 2019.
  • Accepted in final form May 14, 2020.
  • © 2020 American Academy of Neurology
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