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Ketamine reduces seizure and interictal continuum activity in refractory status epilepticus: a multicenter in-person and teleneurocritical care study

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Abstract

Background

There is not a preferred medication for treating refractory status epilepticus (RSE) and intravenous ketamine is increasingly used. Ketamine efficacy, safety, dosage, and influence of other variables on seizure cessation while on ketamine infusions are not well studied. We aimed to characterize ketamine effect on RSE, including interictal activity on electroencephalogram (EEG) and when done by Teleneurocritical care (TNCC).

Methods

We conducted a multicenter, retrospective study from August 2017 to October 2022. Patients 18 years or older who had RSE and received ketamine were included. The primary outcome was effect of ketamine on RSE including interictal activity; secondary outcomes were effect of other variables on RSE, care by TNCC, ketamine infusion dynamics, adverse events, and discharge outcomes. Logistic regression was used.

Results

Fifty-one patients from five hospitals met inclusion criteria; 30 patients had RSE and interictal activity on EEG. Median age was 56.8 years (IQR 18.2) and 26% had previously diagnosed epilepsy. Sixteen (31%) patients were treated virtually by TNCC. In those with RSE on EEG, ketamine was added as the fourth antiseizure medication (mean 4.4, SD 1.6). An initial bolus of ketamine was used in 24% of patients (95 mg, IQR 47.5), the median infusion rate was 30.8 mcg/kg/min (IQR 40.4), and median infusion duration was 40 h (IQR 37). Ketamine was associated with 50% cessation of RSE and interictal activity at 24 h in 84% of patients, and complete seizure cessation in 43% of patients. In linear regression, ASMs prior to ketamine were associated with seizure cessation (OR 2.6, 95% CI 0.9–6.9, p = 0.05), while the inverse was seen with propofol infusions (OR 0.02, 95% CI 0.001–0.43, p = 0.01). RSE management by in-person NCC versus virtual by TNCC did not affect rates of seizure cessation.

Conclusions

Ketamine infusions for RSE were associated with reduced seizure burden at 24 h, with 84% of patients having 50% seizure reduction. Similar efficacy and safety was observed irrespective of underlying RSE etiology or when done via TNCC vs in-person NCC.

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Data Availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Author notes

  1. Brittany Harnicher and Nick M. Murray contributed equally to manuscript, co-primary authors.

Authors and Affiliations

  1. Intermountain Medical Center Department of Pharmacy, 5121 Cottonwood Street, Murray, UT, 84107, USA

    Brittany Harnicher, Jena Dresbach, Breyanna Reachi, Jeremy Bair, Quang Hoang & Gabriel V. Fontaine

  2. Intermountain Medical Center Department of Neurology, Division of Neurocritical Care, 5121 Cottonwood Street, Murray, UT, 84107, USA

    Nick M. Murray

  3. Intermountain Medical Center Department of Research Analytics, Murray, UT, USA, 5121 Cottonwood Street, 84107

    Dave S. Collingridge

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  1. Brittany Harnicher
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  7. Quang Hoang
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  8. Gabriel V. Fontaine
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Contributions

BH, NM, JD, and GF developed study conception and design, data acquisition, data analysis, and manuscript writing. DC led data analysis, and also assisted study conception and manuscript writing. BR, JD, and QH assisted with study design and manuscript writing.

Corresponding author

Correspondence to Nick M. Murray.

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Harnicher, B., Murray, N.M., Dresbach, J. et al. Ketamine reduces seizure and interictal continuum activity in refractory status epilepticus: a multicenter in-person and teleneurocritical care study. Neurol Sci (2024). https://doi.org/10.1007/s10072-024-07635-0

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