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Epilepsia. 2015 Sep;56(9):1408-14. doi: 10.1111/epi.13088. Epub 2015 Jul 27.

Intranasal midazolam during presurgical epilepsy monitoring is well tolerated, delays seizure recurrence, and protects from generalized tonic-clonic seizures.

Author information

1
Epilepsy Center Hessen and Department of Neurology, Philipps-University, Marburg, Germany.
2
Epilepsy Center Frankfurt Rhine-Main, Department of Neurology, Johann Wolfgang Goethe University, Frankfurt am Main, Germany.
3
Central Pharmacy, University Hospitals Giessen and Marburg, Marburg, Germany.

Abstract

OBJECTIVE:

To evaluate the tolerability and efficacy of the ictal and immediate postictal application of intranasal midazolam (in-MDZ) in adolescents and adults during video-electroencephalography (EEG) monitoring.

METHODS:

Medical records of all patients treated with in-MDZ between 2008 and 2014 were reviewed retrospectively. For each single patient, the time span until recurrence of seizures was analyzed after an index seizure with and without in-MDZ application. To prevent potential bias, we defined the first seizure with application of in-MDZ as the in-MDZ index seizure. The control index seizure was the preceding, alternatively the next successive seizure without application of in-MDZ.

RESULTS:

In total, 75 epilepsy patients (mean age 34 ± 14.7 years; 42 male, 33 female) were treated with in-MDZ (mean dose 5.1 mg). Adverse events were observed in four patients (5.3%), and no serious adverse events occurred. The median time after EEG seizure onset before administration of in-MDZ was 2.17 min (interquartile range [IQR] 03.82; range 0.13-15.0 min). Over the next 12 h after in-MDZ, the number of seizures was significantly lower (p = 0.031). The median seizure-free interval was significantly longer following treatment with in-MDZ (5.83 h; IQR 6.83, range 0.4-23.87) than it was for those with no in-MDZ treatment (2.37 h; IQR 4.87, range 0.03-21.87; p = 0.015). Conversely, the likelihood of the patient developing a subsequent seizure was four times higher (odds ratio [OR] 4.33, 95% confidence interval [CI] 1.30-14.47) in the first hour and decreased gradually after 12 h (OR 1.5, 95% CI 1.06-2.12). The occurrence of generalized tonic-clonic seizures was lower in the in-MDZ group in the 24-h observation period (OR 4.67, 95% CI 1.41-15.45; p = 0.009).

SIGNIFICANCE:

Ictal and immediate postictal administration of in-MDZ was well tolerated and not associated with serious adverse events. We demonstrated a significant reduction of subsequent seizures (all seizure types) for a 12 h period and of generalized tonic-clonic seizures for 24 h following in-MDZ.

KEYWORDS:

Benzodiazepine; Emergency; Epilepsy; Intranasal; Midazolam; Seizure control

PMID:
26216711
DOI:
10.1111/epi.13088
[Indexed for MEDLINE]
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