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Combined Ketamine and Midazolam Versus Midazolam Alone for Initial Treatment of Pediatric Generalized Convulsive

Amr A Othman1, Abdelrahim A Sadek1, Esraa A Ahmed2

  • 1Neuropsychiatry Unit, Department of Pediatrics, Faculty of Medicine, Sohag University, Sohag, Egypt.

Pediatric Neurology
|April 5, 2025
PubMed

Insights

Adding ketamine to midazolam significantly improved seizure cessation in children with generalized convulsive status epilepticus (GCSE). This combination therapy offers a promising alternative for first-line treatment of pediatric GCSE.

Area of Science:

  • Pediatric Neurology
  • Emergency Medicine
  • Clinical Pharmacology

Background:

  • Generalized convulsive status epilepticus (GCSE) in children often proves refractory to initial benzodiazepine treatment.
  • Approximately one-third of pediatric GCSE cases require alternative or additional therapies beyond standard benzodiazepines.
  • Investigating novel therapeutic combinations is crucial for improving outcomes in pediatric GCSE.

Purpose of the Study:

  • To evaluate the efficacy of ketamine as an adjunct to midazolam for the first-line management of pediatric GCSE.
  • To compare the seizure cessation rates and safety profiles of ketamine-midazolam versus midazolam-placebo in pediatric GCSE.

Main Methods:

  • A randomized controlled trial involving 144 pediatric patients (6 months to 16 years) diagnosed with GCSE.
  • Patients were randomized to receive either ketamine plus midazolam (Ket-Mid group) or placebo plus midazolam (Pla-Mid group).
  • Primary outcome was seizure cessation at 5 minutes; secondary outcomes included seizure control at later timepoints and adverse events.

Main Results:

  • The ketamine-midazolam group achieved significantly higher seizure cessation rates at 5 minutes (76% vs 21%) compared to the placebo-midazolam group.
  • The Ket-Mid group demonstrated superior seizure control at 15, 35, and 55 minutes, with reduced need for repeat midazolam boluses and endotracheal intubation.
  • While statistically significant, differences in other measured outcomes between the groups were not substantial.

Conclusions:

  • The combination of ketamine and midazolam appears more effective than midazolam alone for the initial treatment of pediatric GCSE.
  • Further research is warranted to confirm these findings and establish the definitive role of ketamine in pediatric GCSE management.
  • This study suggests a potential improvement in first-line treatment strategies for pediatric status epilepticus.
Abstract

Keywords:
Antiseizure medicationsBenzodiazepinesKetaminePolytherapyStatus epilepticus

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