Conference Coverage

Intranasal midazolam as first line for status epilepticus



Intranasal midazolam is a legitimate first-line option for treatment of status epilepticus in patients who don’t already have an intravenous line in place, Lara Kay, MD, said at the International Epilepsy Congress.

Dr. Lara Kay, a neurologist at University Hospital Frankfurt. Bruce Jancin/MDedge News

Dr. Lara Kay

Why? Because status epilepticus is a major medical emergency. It’s associated with substantial morbidity and mortality. And of the various factors that influence outcome in status epilepticus – including age, underlying etiology, and level of consciousness – only one is potentially within physician control: time to treatment, she noted at the congress sponsored by the International League Against Epilepsy.

“Time is brain,” observed Dr. Kay, a neurologist at the epilepsy center at University Hospital Frankfurt.

While intravenous benzodiazepines – for example, lorazepam at 2-4 mg – are widely accepted as the time-honored first-line treatment for status epilepticus, trying to place a line in a patient experiencing this emergency can be a tricky, time-consuming business. Multiple studies have demonstrated that various nonintravenous formulations of benzodiazepines, such as rectal diazepam or buccal or intramuscular midazolam, can be administered much faster and are as effective as intravenous benzodiazepines. But buccal midazolam is quite expensive in Germany, and the ready-to-use intramuscular midazolam applicator that’s available in the United States isn’t marketed in Germany. So several years ago Dr. Kay and her fellow neurologists started having their university hospital pharmacy manufacture intranasal midazolam.

Dr. Kay presented an observational study of 42 consecutive patients with status epilepticus who received intranasal midazolam as first-line treatment. The patients had a mean age of nearly 53 years and 23 were women. The starting dose was 2.5 mg per nostril, moving up to 5 mg per nostril after waiting 5 minutes in initial nonresponders.

Status epilepticus ceased both clinically and by EEG in 24 of the 42 patients, or 57%, in an average of 5 minutes after administration of the intranasal medication at a mean dose of 5.6 mg. Nonresponders received a mean dose of 7.5 mg. There were no significant differences between responders and nonresponders in terms of the proportion presenting with preexisting epilepsy or the epilepsy etiology. However, responders presented at a mean of 54 minutes in status epilepticus, while nonresponders had been in status for 17 minutes.

The 57% response rate with intranasal midazolam is comparable with other investigators’ reported success rates using other benzodiazepines and routes of administration, she noted.

Session cochair Gregory Krauss, MD, commented that he thought the Frankfurt neurologists may have been too cautious in their dosing of intranasal midazolam for status epilepticus.

“Often in the U.S. 5 mg is initially used in each nostril,” according to Dr. Krauss, professor of neurology at Johns Hopkins University, Baltimore.

Dr. Kay reported having no financial conflicts of interest regarding her study.

SOURCE: Kay L et al. IEC 2019, Abstract P029.

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