Intranasal midazolam as first-line inhospital treatment for status epilepticus: a pharmaco-EEG cohort study

Abstract

Objective: We sought to evaluate the efficacy and tolerability of intranasal midazolam (in-MDZ) as first-line inhospital therapy in patients with status epilepticus (SE) during continuous EEG recording. Methods: Data on medical history, etiology and semiology of SE, anticonvulsive medication usage, efficacy and safety of in-MDZ were retrospectively reviewed between 2015 and 2018. Time to end of SE regarding the administration of in-MDZ and ß-band effects were analyzed on EEG and with frequency analysis. Results: In total, 42 patients (mean age: 52.7 ± 22.7 years; 23 females) were treated with a median dose of 5 mg of in-MDZ (range: 2.5–15 mg, mean: 6.4 mg, SD: 2.6) for SE. The majority of the patients suffered from nonconvulsive SE (n = 24; 55.8%). In total, 24 (57.1%) patients were responders, as SE stopped following the administration of in-MDZ without any other drugs being given. On average, SE ceased on EEG at 05:05 (minutes:seconds) after the application of in-MDZ (median: 04:56; range: 00:29–14:53; SD:03:13). Frequency analysis showed an increased ß-band on EEG after the application of in-MDZ at 04:07 on average (median: 03:50; range: 02:20–05:40; SD: 01:09). Adverse events were recorded in six patients (14.3%), with nasal irritations present in five (11.9%) and prolonged sedation occurring in one (2.6%) patient. Conclusions: This pharmaco-EEG–based study showed that in-MDZ is effective and well-tolerated for the acute treatment of SE. EEG and clinical effects of in-MDZ administration occurred within 04:07 and 5:05 on average. Intranasal midazolam appears to be an easily applicable and rapidly effective alternative to buccal or intramuscular application as first-line treatment if an intravenous route is not available.