The Nose Knows: Intranasal Midazolam To Treat Acute Seizures During Inpatient Epilepsy Monitoring

Efficacy, Tolerability, and Safety of Concentrated Intranasal Midazolam Spray as Emergency Medication in Epilepsy Patients During Video-EEG Monitoring von Blomberg A, Kay L, Knake S, Fuest S, Zöllner JP, Reif PS, Herrmann E, Balaban Ü, Schubert-Bast S, Rosenow F, Strzelczyk A. CNS Drugs. 2020;34(5):545-553. doi: 10.1007/s40263-020-00720-wBackground:An efficient, well tolerated, and safe emergency treatment with a rapid onset of action is needed to prevent seizure clusters and to terminate prolonged seizures and status epilepticus. Objectives: This study aimed to examine the efficacy, tolerability, and safety of intranasal midazolam (in-MDZ) spray in clinical practice.Methods:In this retrospective, multicenter observational study, we evaluated all patients with peri-ictal application of in-MDZ during video-electroencephalography (EEG) monitoring at the epilepsy centers in Frankfurt and Marburg between 2 014 and 2017. For every patient, we analyzed the recurrence of any seizure or generalized tonic-clonic seizures after index seizures with and without in-MDZ administration. Treatment-emergent adverse events were also evaluated.Results:Intranasal MDZ was used in 243 patients with epilepsy (mean age 35.5 years; range 5-76 years; 46.5% female) for treatment of 459 seizures. A median dose of in-MDZ 5 mg (ie, 2 puffs; range 2.5-15 mg) was administered within a median time from EEG seizure onset until in-MDZ application of 1.18 minutes (interquartile range [IQR] 1.27), while median time from clinical seizure onset until in-MDZ administration was 1.08 minutes (IQR 1.19). Intranasal MDZ was given within 1 minute after EEG seizure onset in 171 seizures. An intraindividual comparison of seizures with and without application of in-MDZ was feasible in 171 patients, demonstrating that in-MDZ reduced the occurrence of any (Cox proportional-hazard model P < .001) and generalized tonic-clonic seizure (Cox proportional-hazard model P = .0167) over a period of 24 hours. The seizure-free time span was doubled from a median of 5.0 hours in controls to a median of 10.67 hours after in-MDZ administration. We additionally clustered in-MDZ administrations for the 119 patients who received in-MDZ more than once, comparing them with the index cases without in-MDZ. Even when considering subsequent seizures with in-MDZ administration, a patient receiving in-MDZ is still half as likely to incur another seizure in the upcoming 24 hours as compared with when the same patient does not receive in-MDZ (hazard ratio 0.50; 95% CI: 0.42-0.60; P < .01). Intranasal MDZ was well tolerated without major adverse events. The most common side effects were irritation of the nasal mucosa (37 cases [8.1%]), prolonged sedation (26 cases [5.7%]), and nausea and vomiting (12 cases [2.6%]). A decline in oxygen saturation was measured after 78 seizures (17%).Conclusion:We conclude that in-MDZ is a safe and efficient treatment option to prevent short-term recurrence of seizures. Intranasal MDZ can be administered very quickly by trained staff within 1 to 2 minutes after seizure onset. No major cardiocirculatory or respiratory adverse events were observed.