Assessment of First-line Therapy With Midazolam for Prehospital Seizures in Children

This cohort study assesses the effectiveness of midazolam treatment in terminating pediatric seizures in the prehospital setting.


Introduction
In the prehospital setting, pediatric patients are sometimes actively seizing when emergency medical services (EMS) arrive at the scene or during transport, and if they are not effectively treated, the potential morbidity of these patients can be substantial. 1The National Association of State EMS Officials (NASEMSO) guideline 2 recommends the use of intravenous midazolam in a dose of 0.1 mg/kg or intranasal or intramuscular midazolam in a dose of 0.2 mg/kg as first-line therapy for pediatric seizures.However, there are limited data on the effectiveness of this treatment.In this cohort study, we assessed the effectiveness of midazolam treatment in terminating pediatric seizures in the prehospital setting.

Methods
This study was approved by the institutional review board of the Israel National EMS (INEMS) system and Rambam Medical Center.Informed consent was not required due to the observational and  We conducted a retrospective analysis of all patients aged 0 to 18 years for whom a mobile intensive care unit was dispatched due to a seizure between January 1, 2017, and December 31, 2019.We used the database of the INEMS system, which includes a log of dispatched calls, vehicles, paramedics' records, and the diagnosis and treatment of all patients treated by paramedics. 3The primary outcome was the administration of rescue therapy, defined as an additional dose of midazolam following the first midazolam administration during the prehospital encounter. 4Univariable and multivariable analyses were used to identify factors associated with rescue therapy.The adjusted odds ratio (aOR) for rescue therapy was determined with a 95% CI.Data were analyzed from September 2021 to March 2022 with SPSS statistical software version 21 (SPSS-IBM).

Results
Overall  In univariable analysis, age, glucose level, route of administration, and chronic disease were significant for inclusion in the multivariable model.In multivariable analysis, only the route of administration was a significant independent factor associated with rescue therapy.Initial treatment by the intranasal and intramuscular routes had an aOR for rescue therapy of 1.65 (95% CI 1.13-2.42)and 0.97 (95% CI 0.62-1.53),respectively, compared with the intravenous route.

Discussion
The major finding of this cohort study is the high proportion of patients (39.16%) who required rescue therapy.First-line treatment by the intranasal route was associated with a higher risk for rescue therapy, and almost half the patients (48.46%) who were initially treated by the intranasal route required rescue therapy.High proportions of patients who received first-line treatment by the intravenous (31.93%) and intramuscular route (35.58%) also required rescue therapy.Rescue therapy failed in 153 patients (13.05%).Taken together, these findings suggest that the effectiveness of midazolam to terminate prehospital pediatric seizures was suboptimal.Previous adult studies [4][5][6] reported similar observations.A possible explanation for the inferior performance of midazolam in the prehospital setting could be the long period from the onset of seizures to the time of starting therapy.Another important finding is the substantial number of patients who needed respiratory support among those who received rescue therapy (Figure ).
This study has limitations inherent to a retrospective medical record review.We did not have information on the timing of treatment regarding seizure onset and the rate of unsuccessful venous cannulation.Our results may not be generalizable to populations where home rescue treatment for seizures is common.

Table .
Baseline Characteristics of Children Treated With Midazolam for Prehospital Seizures, by Number of Doses Assessment of First-line Therapy With Midazolam for Prehospital Seizures in Children Rescue therapy failed in 153 of 1172 patients (13.05%), who required a third dose of midazolam or more to terminate the seizures (Figure and Table).