Intranasal Midazolam vs Rectal Diazepam for the Home Treatment of Acute Seizures in Pediatric Patients With Epilepsy

Abstract

Objective: To compare intranasal midazolam, using a Mucosal Atomization Device (IN-MMAD), with rectal diazepam (RD) for the home treatment of seizures in children with epilepsy.Design: Prospective randomized study.Setting: Patients' homes and a freestanding children's hospital that serves as a referral center for 5 states.Patients: A total of 358 pediatric patients who visited a pediatric neurology clinic from July 2006 through September 2008 and were prescribed a home rescue medication for their next seizure.Intervention: Caretakers were randomized to use either 0.2 mg/kg of IN-MMAD (maximum, 10 mg) or 0.3 to 0.5 mg/kg of RD (maximum, 20 mg) at home for their child's next seizure if it lasted more than 5 minutes.Outcome Measures: The primary outcome measure was total seizure time after medication administration. Our secondary outcome measures were total seizure time, time to medication administration, respiratory complications, emergency medical service support, emergency department visits, hospitalizations, and caretakers' ease of administration and satisfaction with the medication.Results: A total of 92 caretakers gave the study medication during a child's seizure (50 IN-MMAD, 42 RD). The median time from medication administration to seizure cessation for IN-MMAD was 1.3 minutes less than for RD (95% confidence interval, 0.0-3.5 minutes; P=.09). The median time to medication administration was 5.0 minutes for each group. No differences in complications were found between treatment groups. Caretakers were more satisfied with IN-MMAD and report that it was easier to give than RD. Conclusions:There was no detectable difference in efficacy between IN-MMAD and RD as a rescue medication for terminating seizures at home in pediatric patients with epilepsy. Ease of administration and overall satisfaction was higher with IN-MMAD compared with RD.

Treatment of Acute Seizures: Is Intranasal Midazolam a Viable Option?

“…No one trial has focused solely on comparing the adverse drug reactions of intranasal midazolam to rectal diazepam, but useful information can be extrapolated from several past studies. 1,8,12,16,17 A prospective, randomized trial by Holsti and colleagues 1 found no detectable difference in the number of adverse drug reactions among the intranasal midazolam and rectal diazepam groups. Occurrence of repeated seizure within 12 hours, need for ED services, and respiratory depression rates were similar.…”

“…Prospective and retrospective evidence shows that intranasal midazolam terminates seizures at least as fast as rectal diazepam. 1,5,8,[12][13][14][15] Most clinical studies have used a 5 mg/mL midazolam solution dosed at 0.2 mg/ kg (divided into each nostril) administered via an intranasal mucosal atomization (IN-MADD) device or nasal dropper as suggested by Kyrkou and colleagues. 16 Three open-labeled studies prospectively evaluated the time to seizure cessation with a dose of nasal midazolam (Table).…”

“…Of those 13 (Table). 1,8,12,13 Bhattacharyya and colleagues 12 compared intranasal midazolam to rectal diazepam in 46 children who presented to the ED with febrile or afebrile seizures. Baseline characteristics were similar between the 2 groups.…”

“…19 Generic diazepam rectal gel is $334, whereas a dose of intranasal midazolam is a mere $12. 1,19 One study determined that at about 10% of the cost of rectal diazepam, intranasal midazolam is a cost-effective and likely more convenient alternative medication for rapid seizure termination. 16 A limitation of intranasal midazolam use is the lack of availability from retail pharmacies.…”

“…1 Most seizures self-terminate within 5 minutes, but those lasting longer warrant medication administration for seizure cessation and status epilepticus avoidance. 2 Although the time period for diagnosing status epilepticus is controversial, traditional classification is defined as either one continuous seizure lasting 30 minutes, or a series of seizures that recurs in which the patient did not regain full consciousness between seizures.…”