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A Comparison of Ketamine and Midazolam as First-Line Anesthetic Infusions for Pediatric Status Epilepticus

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An Invited Commentary to this article was published on 02 November 2023

Abstract

Background

Pediatric refractory status epilepticus (RSE) often requires management with anesthetic infusions, but few data compare first-line anesthetics. This study aimed to compare the efficacy and adverse effects of midazolam and ketamine infusions as first-line anesthetics for pediatric RSE.

Methods

Retrospective single-center study of consecutive study participants treated with ketamine or midazolam as the first-line anesthetic infusions for RSE at a quaternary care children’s hospital from December 1, 2017, until September 15, 2021.

Results

We identified 117 study participants (28 neonates), including 79 (68%) who received midazolam and 38 (32%) who received ketamine as the first-line anesthetic infusions. Seizures terminated more often in study participants administered ketamine (61%, 23/38) than midazolam (28%, 22/79; odds ratio [OR] 3.97, 95% confidence interval [CI] 1.76–8.98; P < 0.01). Adverse effects occurred more often in study participants administered midazolam (24%, 20/79) than ketamine (3%, 1/38; OR 12.54, 95% CI 1.61–97.43; P = 0.016). Study participants administered ketamine were younger, ketamine was used more often for children with acute symptomatic seizures, and midazolam was used more often for children with epilepsy. Multivariable logistic regression of seizure termination by first-line anesthetic infusion (ketamine or midazolam) including age at SE onset, SE etiology category, and individual seizure duration at anesthetic infusion initiation indicated seizures were more likely to terminate following ketamine than midazolam (OR 4.00, 95% CI 1.69–9.49; P = 0.002) and adverse effects were more likely following midazolam than ketamine (OR 13.41, 95% CI 1.61–111.04; P = 0.016). Survival to discharge was higher among study participants who received midazolam (82%, 65/79) than ketamine (55%, 21/38; P = 0.002), although treating clinicians did not attribute any deaths to ketamine or midazolam.

Conclusions

Among children and neonates with RSE, ketamine was more often followed by seizure termination and less often associated with adverse effects than midazolam when administered as the first-line anesthetic infusion. Further prospective data are needed to compare first-line anesthetics for RSE.

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Funding

N. Abend was supported by the Wolfson Family Foundation. I. Helbig was supported by The Hartwell Foundation through an Individual Biomedical Research Award and by the NORSE Foundation. This work was also supported by the National Institute for Neurological Disorders and Stroke (K02 NS112600), including support through the Center Without Walls on channel function in epilepsy (Channelopathy-associated Research Center, U54 NS108874), the Eunice Kennedy Shriver National Institute of Child Health and Human Development through the Intellectual and Developmental Disabilities Research Center at Children’s Hospital of Philadelphia and the University of Pennsylvania (U54 HD086984), and by intramural funds of the Children’s Hospital of Philadelphia through the Epilepsy NeuroGenetics Initiative. Research reported in this publication was also supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under Award Number UL1TR001878. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. This project was also supported in part by the Institute for Translational Medicine and Therapeutics Transdisciplinary Program in Translational Medicine and Therapeutics at the Perelman School of Medicine of the University of Pennsylvania.

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Authors and Affiliations

  1. Division of Neurology, Department of Pediatrics, Children’s Hospital of Philadelphia, 34th and Civic Center Blvd, Philadelphia, PA, 19104, USA

    Marin Jacobwitz, Caitlyn Mulvihill, Michael C. Kaufman, Alexander K. Gonzalez, Ingo Helbig & Nicholas S. Abend

  2. The Epilepsy NeuroGenetics Initiative, Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Michael C. Kaufman, Alexander K. Gonzalez & Ingo Helbig

  3. Department of Biomedical and Health Informatics, Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Michael C. Kaufman, Alexander K. Gonzalez & Ingo Helbig

  4. Department of Anesthesia and Critical Care Medicine, Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Karla Resendiz & Alexis A. Topjian

  5. Division of Critical Care, Québec, QC, Canada

    Conall Francoeur

  6. Department of Pediatrics, Centre Hospitalier Universitaire de Québec–University of Laval Research Center, Québec, QC, Canada

    Conall Francoeur

  7. Departments of Neurology and Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA

    Ingo Helbig & Nicholas S. Abend

  8. Department of Anesthesia and Critical Care, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA

    Alexis A. Topjian & Nicholas S. Abend

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  1. Marin Jacobwitz
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Contributions

Study Conception: Dr. MJ and Dr. NS.A. Study Design: Dr. MJ, KR, Dr. CF, Dr. AA.T, Dr. NS.A. Major Role in Acquisition of Data: Dr. MJ, CM. MC.K, AK.G, Dr. IH. Data Analysis and Interpretation of Results: Dr. MJ and Dr. NS.A. Draft Preparation of the Manuscript: Dr. MJ. Critical Revision of Manuscript for Important Intellectual Content: Dr. MJ, CM, MC.K, AK.G, KR, Dr. CF, Dr. IH, Dr. AA.T, Dr. NS.A. All authors reviewed the results and approved the final version of the manuscript.

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Correspondence to Marin Jacobwitz.

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Jacobwitz, M., Mulvihill, C., Kaufman, M.C. et al. A Comparison of Ketamine and Midazolam as First-Line Anesthetic Infusions for Pediatric Status Epilepticus. Neurocrit Care (2023). https://doi.org/10.1007/s12028-023-01859-2

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