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

Marin Jacobwitz; Caitlyn Mulvihill; Michael C Kaufman; Alexander K Gonzalez; Karla Resendiz; Conall Francoeur; Ingo Helbig; Alexis A Topjian; Nicholas S Abend

doi:10.1007/s12028-023-01859-2

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

Neurocrit Care. 2023 Oct 2. doi: 10.1007/s12028-023-01859-2. Online ahead of print.

Authors

Marin Jacobwitz¹, Caitlyn Mulvihill², Michael C Kaufman^{2

3

4}, Alexander K Gonzalez^{2

3

4}, Karla Resendiz⁵, Conall Francoeur^{6

7}, Ingo Helbig^{2

3

4

8}, Alexis A Topjian^{5

9}, Nicholas S Abend^{2

8

9}

Affiliations

¹ Division of Neurology, Department of Pediatrics, Children's Hospital of Philadelphia, 34th and Civic Center Blvd, Philadelphia, PA, 19104, USA. jacobwitzm@chop.edu.
² Division of Neurology, Department of Pediatrics, Children's Hospital of Philadelphia, 34th and Civic Center Blvd, Philadelphia, PA, 19104, USA.
³ The Epilepsy NeuroGenetics Initiative, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
⁴ Department of Biomedical and Health Informatics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
⁵ Department of Anesthesia and Critical Care Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
⁶ Division of Critical Care, Québec, QC, Canada.
⁷ Department of Pediatrics, Centre Hospitalier Universitaire de Québec-University of Laval Research Center, Québec, QC, Canada.
⁸ Departments of Neurology and Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
⁹ Department of Anesthesia and Critical Care, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.

PMID: 37783824
DOI: 10.1007/s12028-023-01859-2

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.

Keywords: Pediatric neurocritical care; Pediatric refractory status epilepticus; Pediatric status epilepticus; Pediatric superrefractory status epilepticus.