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Factors Associated with Refractory Status Epilepticus Termination Following Ketamine Initiation: A Multivariable Analysis Model

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Abstract

Background

In this study, we identify factors associated with ketamine success in the treatment of refractory status epilepticus (SE). We also evaluate for adverse events including systemic and cerebral hemodynamic stability and fluid volume overload.

Methods

In this retrospective, large, single-center, observational study over a 10-year period, 879 consecutive patients receiving intravenous (IV) ketamine were reviewed, and 81 patients were identified as receiving IV ketamine for the treatment of SE. Descriptive analysis was done to determine treatment response and adverse events in patients receiving IV ketamine for SE. Multivariable logistic regression analyses were fitted to determine prediction models for seizure cessation.

Results

Permanent cessation of SE was achieved in 49 of 81 (60.5%) of patients for whom ketamine was part of the treatment plan. Of those, 36 (44.4%) were attributed to ketamine as the last drug used (ketamine-associated cessation [AC]). Prior history of epilepsy had an odds ratio of 3.19 (confidence interval 0.83–12.67, p = 0.09) associated with efficacious medication response. Increased latency to ketamine was associated with cessation of SE specifically in patients in the AC group (p = 0.077). Longer SE duration (p = 0.04), administration of ketamine loading dose (bolus; p = 0.03), and anoxia (p = 0.007) were negatively associated with AC. Administration of ketamine loading dose (p = 0.02) and anoxia (p = 0.009) were negatively associated with overall SE cessation. There was no significant impact of ketamine on cerebral hemodynamics, but evidence of fluid volume overload was seen (28.4% of patients).

Conclusions

Our cohort is a large observational study showing a high success rate of permanent cessation of SE after the addition of ketamine. Using multivariable analysis, we demonstrate a significant association with seizure cessation in patients with prior history of epilepsy and those with prolonged latency to ketamine initiation. Furthermore, we describe the impact of fluid volume overload as an anticipated complication with ketamine use.

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Authors and Affiliations

  1. Department of Neurology, Wayne State University School of Medicine, Detroit, MI, USA

    Meghana Srinivas, Rohit Marawar, Deepti Zutshi & Maysaa M. Basha

  2. Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI, USA

    Dennis Parker

  3. Department of Neurology and Department of Physical Medicine and Rehabilitation, Wayne State University School of Medicine, Detroit, MI, USA

    Scott Millis

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  1. Meghana Srinivas
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  2. Dennis Parker
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  5. Deepti Zutshi
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Contributions

MS: data collection, formatting, literature review, article writing. DP: expert pharmacological opinion, literature review, article editing. SM: interpretation of data and statistical analysis, article editing. RM: literature review, article editing. DZ: literature review, article editing. MMB: conceptualization of idea, data collection and review, literature review, article writing. The authors have read and approved the final manuscript.

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Correspondence to Maysaa M. Basha.

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On behalf of all the authors, I confirm that the manuscript complies with all the instructions to authors, authorship requirements have been met and the final manuscript was approved by all authors. The manuscript has not been published in part of full elsewhere and is not under consideration by another journal. The authors have adhered to ethical guidelines and sought IRB approval prior to the initiation of study.

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Srinivas, M., Parker, D., Millis, S. et al. Factors Associated with Refractory Status Epilepticus Termination Following Ketamine Initiation: A Multivariable Analysis Model. Neurocrit Care 38, 235–241 (2023). https://doi.org/10.1007/s12028-022-01578-0

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  • DOI: https://doi.org/10.1007/s12028-022-01578-0

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