Seizures are a critical medical emergency requiring prompt intervention to improve patient outcomes and prevent complications. Intranasal (IN) midazolam has emerged as a promising treatment due to its ease of administration and rapid onset. However, there is a lack of comprehensive systematic reviews assessing its effectiveness, particularly in prehospital settings compared to other treatments. This study aimed to systematically evaluate and compare the efficacy of intranasal midazolam in acute seizure management and patient outcomes in prehospital care and emergency departments. A comprehensive search was conducted, using the PICOS framework, including clinical trials and observational studies published between August 2014 and August 2024. Data were extracted using Covidence and organized into summary tables for analysis. Three out of 489 studies included 5,062 patients, all under 18 years, and 4,957 in prehospital settings. One study was a clinical trial and two were cohort studies. The main indicator of medication success was seizure termination within ten minutes. One study reported the success rate of 88.2%. The second indicator was the reduction of seizure recurrence. Two studies noted the need for redosing, with the intranasal route with a risk difference of 11% and 95% CI. Despite the higher frequency of redosing, intranasal midazolam showed comparable efficacy to other routes. Adverse effects included respiratory depression, nasal irritation, somnolence and vomiting. The majority of the studies reported that intranasal midazolam might be an effective, safe, and easily applicable treatment for acute seizures in adolescent and pediatric populations. However, it might require redosing compared to other routes.

Keywords: Emergency healthcare providers include paramedics, ER nurses, ER physicians, ER consultants, EMS specialists, and emergency technicians. Seizures: Various terms describing seizure types and conditions, including epileptic seizures, generalized tonic‒clonic seizures, myoclonic seizures, partial seizures, convulsions, complex partial seizures, and tonic‒clonic seizures, were used. Emergency Care: The terms used included prehospital emergency care, eme