Midazolam Nasal Spray May Reduce Seizures (CME/CE)

Action Points
A nasal spray formulation of midazolam may diminish repeated seizures and lower the risk of
generalized tonic-clonic seizures in hospitalized epilepsy patients.Note that only four of 75 patients
had an adverse event; there were no serious adverse events and the treatment was generally welltolerated.
A nasal spray formulation of midazolam may diminish repeated seizures and lower the risk of
generalized tonic-clonic seizures in hospitalized epilepsy patients, researchers found.

In a retrospective analysis of data from a

German university epilepsy center, those
given intranasal midazolam during or
right after a seizure remained free of
seizures longer than those not given the
drug (5.83 hours versus 2.37 hours),
according to Lara Kay, a doctoral
candidate at Philipps University in
Marburg in Germany, and colleagues.
Those who didn't get the drug also had a
higher risk of generalized tonic-clonic
seizures over the next 24 hours (odds
ratio 4.67, 95% CI 1.06 to 2.12), they reported online in Epilepsia.
The researchers noted that it's important to give anticonvulsants quickly, easily, and safely when
managing repetitive and prolonged seizures, both in the hospital and in the community setting.
The gold standard treatment in such cases is intravenous lorazepam, but getting venous access may
be a challenge during a seizure, and it may not be possible for a caregiver to do so outside of a
hospital in an emergency situation.
Other formulations for home use have included rectal diazepam, which hasn't had good uptake for a
number of reasons, including stigma and shame, the researchers said. There's also buccal
midazolam, which has been approved in Europe.
Intranasal midazolam is an emerging technique for periprocedural sedation and for acute seizure
control. The idea is to have a formulation that allows for rapid and easy administration. It's been
studied in home use, with no differences in efficacy or complications when compared with
intravenous diazepam.
Now the researchers are looking at its in-hospital effects. Since 2008, the hospital's epilepsy center
has used intranasal midazolam to treat seizures and prevent seizure clusters and tonic-clonic

seizures.
Kay and colleagues reviewed the records of 75 patients, mean age 35, who were treated with
intranasal midazolam at their center, during or right after an epileptic seizure from 2008 to 2014.
The nasal spray was manufactured by the hospital's pharmacy, and http://80grados.net/bullies/ it
delivered a dose of 2.5 mg midazolam per puff. The average dose per patient was 5 mg, or two
sprays. It took a median time of 2.17 minutes to give intranasal midazolam.
They found that over the next 12 hours, the number of seizures was significantly lower for those who
took intranasal midazolam. The median seizure-free interval was significantly longer for those who
had the nasal spray than for those who didn't (P=0.015).
They noted that the likelihood of a patient developing a subsequent seizure was four higher in first
hour and fell gradually after 12 hours (OR 4.33, 95% CI 1.30-14.47 and OR 1.5, 95% CI 1.06-2.12,
respectively).
Patients who didn't receive intranasal midazolam had a much higher likelihood of experiencing a
generalized tonic-clonic seizure during a 24-hour observation period than those who didn't get the
drug (P=0.009).
Only four patients (5.3%) had an adverse event. Three patients had nasal irritation, while in the
fourth, administration was delayed by the patient's ictal automatisms and head turning.
There were no serious adverse events and the treatment was generally well-tolerated, the
researchers said.
"This study provides evidence that ictal and immediate postictal administration of intranasal
midazolam is a well-tolerated procedure and prevents subsequent seizures for a 12-hour period and
especially generalized http://www.health.com/health/dental-care tonic-clonic seizures for a 24-hour
period," they concluded.
They added that intranasal midazolam is "easy to employ, and it can be delivered from any position.
Even during a seizure, it takes little time to administer the dose, and patients do not need to be
restrained."
The study was limited by its retrospective, observational nature and lack of randomization, and the
results need to be confirmed in larger randomized trials, the researchers said.
Another challenge is that there's no commercial preparation available, but it still may be an
inexpensive way to reduce the costs of morbidity and mortality associated with seizure activity, they
concluded.
Kay disclosed no relevant relationships with industry. Some co-authors disclosed relevant
relationships with Desitin Arzneimittel GmbH, UCB Pharma, Desitin Pharma, Novartis, Medtronic,
Cerbomed, the European Union, Deutsche Forschungsgemeinschaft, ViroPharma, Bayer HealthCare,
Boehring Ingelheim, and Eisai.

Reviewed by

Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco
and Dorothy Caputo, MA, BSN, RN, Nurse Planner
last updated 07.30.2015
http://www.medpagetoday.com/Neurology/Seizures/52830