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Early ketamine plus midazolam therapy and clinical outcomes in pediatric refractory convulsive status epilepticus: A
1Gaziantep City Hospital, Department of Pediatric Neurology, Gaziantep, Turkey.
Insights
Ketamine combined with midazolam showed promising results for treating pediatric refractory convulsive status epilepticus (RCSE), leading to faster seizure control. However, further research is needed to confirm its effectiveness as an initial anesthetic strategy.
Area of Science:
- Pediatric Neurology
- Anesthesiology
- Critical Care Medicine
Background:
- Refractory convulsive status epilepticus (RCSE) in children presents significant morbidity and mortality risks.
- Ketamine, an NMDA receptor antagonist, is explored as an adjunctive therapy due to its mechanism complementing GABAergic agents.
Purpose of the Study:
- To evaluate the efficacy of ketamine plus midazolam versus midazolam alone as an initial anesthetic strategy for pediatric RCSE.
- To compare clinical outcomes, including sustained seizure cessation, between the two treatment groups.
Main Methods:
- Retrospective single-center cohort study involving pediatric patients with RCSE.
- Patients received either continuous midazolam infusion or ketamine plus midazolam infusion.
- Propensity score overlap weighting was utilized to control for baseline differences.
Main Results:
- Unadjusted analysis showed higher treatment success rates (73.0% vs. 40.0%) and shorter seizure control times with ketamine plus midazolam.
- Adjusted analyses indicated a trend towards higher treatment success with combination therapy, though not statistically significant (aOR, 4.16; p=0.052).
- No significant treatment-limiting adverse events were reported.
Conclusions:
- Early ketamine plus midazolam therapy demonstrated favorable unadjusted outcomes and faster seizure control in pediatric RCSE.
- Adjusted analyses were inconclusive, highlighting the need for further investigation.
- Prospective, multicenter studies are recommended to definitively establish ketamine's role in initial pediatric RCSE management.
Background:
Refractory convulsive status epilepticus (RCSE) in children is associated with substantial morbidity and mortality. Ketamine has emerged as a potential adjunctive therapy because of its NMDA receptor antagonism and complementary mechanism to GABAergic agents. This study aimed to evaluate the association of concomitant ketamine plus midazolam therapy with clinical outcomes, compared with midazolam alone, as the initial anesthetic strategy in pediatric RCSE.
Methods:
In this retrospective single-center cohort study, pediatric patients with RCSE received either continuous midazolam infusion alone or concomitant ketamine plus midazolam infusion as the initial anesthetic strategy. The primary outcome was sustained seizure cessation within 24 h without the need for an additional continuous anesthetic agent. Propensity score overlap weighting was used to adjust for baseline differences between treatment groups.
Results:
Seventy-seven patients were included (midazolam, n = 40; ketamine plus midazolam, n = 37). In unadjusted analyses, the combination therapy group demonstrated higher rates of primary treatment success (73.0%vs 40.0%, p = 0.006), lower requirement for a second anesthetic agent (24.3%vs 60.0%, p = 0.003), and shorter time to seizure control (p = 0.010). After overlap weighting, ketamine plus midazolam remained associated with higher odds of treatment success, although the association did not reach statistical significance (adjusted OR, 4.16; 95% CI, 0.99-17.44; p = 0.052). No serious treatment-limiting adverse events were observed.
Conclusions:
Early ketamine plus midazolam therapy was associated with favorable unadjusted clinical outcomes and faster seizure control in pediatric RCSE; however, adjusted analyses were inconclusive. Prospective multicenter studies are needed to further clarify the role of ketamine as part of the initial anesthetic strategy in pediatric RCSE.
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