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

Abstract

ObjectiveWe 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.MethodsData 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.ResultsIn 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.ConclusionsThis 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.

Efficacy, Tolerability, and Safety of Concentrated Intranasal Midazolam Spray as Emergency Medication in Epilepsy Patients During Video-EEG Monitoring

“…In comparison, intranasal midazolam (in-MDZ) may be a more favorable option as it can be administered in a significantly shorter interval without the need for an intravenous route [15] and has been shown to be reliable and efficient [8,[14][15][16][17][18][19]. Furthermore, as compared with rectal diazepam, it is at least as effective in its anticonvulsive action [14,20,21] and is preferred by caregivers [20,22].…”

Using quality improvement to implement the CNS/AAN quality measure on rescue medication for seizures

“…In July of that same year, Nationwide Children's Hospital began utilizing 5 mg/ mL prefilled syringes of midazolam that were calibrated to provide standardized dosing. [16][17][18][19] The combination of those three interventions led to the first centerline shift in August of 2017 to 2.8%. In January of 2018, this project was established as the Neurology Division's Quality Improvement goal, which had a direct influence on physician bonus incentives.…”

“…16 Of the 723 caregivers that participated, 21% did not pass the exam. 16 Moreover, 94% of the 427 caregivers that provided feedback mentioned felt that the test made patents with epilepsy safer. 16 These results show the importance of education and training given from providers to caregivers in order to effectively utilize rescue medications.…”

“…14,15 Considering these drawbacks, in addition to commercially available rectal diazepam, our institution was able to source 5 mg/mL prefilled syringes of midazolam that were calibrated to provide standardized dosing and availability of commercial products. [16][17][18][19] The recommended intranasal midazolam dosing was based on a review of the medical literature. [14][15][16][17][18][19][20][21][22] Dosing for rectal diazepam was based on recommendations provided with the commercial product, Diastat.…”

“…Yet, dosing for the rectal diazepam product is cumbersome and complicated for the providers, given that dose adjustments occur in small increments after accounting for the patient's age and weight 14,15 . Considering these drawbacks, in addition to commercially available rectal diazepam, our institution was able to source 5 mg/mL prefilled syringes of midazolam that were calibrated to provide standardized dosing and availability of commercial products 16–19 . The recommended intranasal midazolam dosing was based on a review of the medical literature 14–22 .…”