Is intranasal midazolam an effective rescue medication in adolescents and adults with severe epilepsy?

Abstract

The aim of this study was to determine whether intranasal midazolam is a safe and effective rescue medication in adolescent and adult patients with severe epilepsy. This field trial was designed to test the feasibility of the use of intranasal midazolam as an alternative to rectal diazepam in a cohort of patients with severe epilepsy who require rescue medication as part of their treatment. A dose of intranasal midazolam (5 mg if the patient weighed less than 50 kg and 10 mg if the patient weighed over 50 kilograms) was prescribed for those who had previously responded to other rescue medication. Midazolam was prescribed buccally if excessive head movement accompanied seizures. The protocol reverted to the usual rescue medication if there was no response to midazolam within 10 minutes. Vital signs were monitored for half an hour following the administration of the treatment. Twenty-two patients received 84 treatment episodes and 79 of these were considered clinically effective. Five treatment failures were recorded, three due to poor technique in delivering the midazolam. Two patients were successfully retried on midazolam and a third is awaiting a retrial of this drug. The two other treatment failures received the drug buccally. In the first patient the clinical opinion was that this was possibly a psychogenic non-epileptic seizure. The other patient responded initially, but within an hour had another seizure requiring further rescue treatment. No significant adverse effects were reported. Our study shows that intranasal midazolam, when used appropriately, is an effective treatment in those who require rescue treatment. There are clear advantages in the use of midazolam over diazepam in the treatment of acute seizures. These include the favourable pharmacokinetic and pharmacodynamic properties of midazolam as well as the potential of a more acceptable and dignified administration route.

Intranasal/intravenous sedation for the dental care of adults with severe disabilities: a multicentre prospective audit

“…Familiarity with the IN administration of midazolam may now be increasing among carers because of its use as a rescue medication for prolonged epileptic seizures. 9 It is also in line with current guidelines on minimal physical intervention, 10 as clinical holding of the patient is only required for the briefest of moments to administer the aerosol spray. Indeed, with the use of a tissue wiping the nose to distract the patient immediately before the spray is administered, little or no holding may be required.…”

Intranasal Delivery of Two Benzodiazepines, Midazolam and Diazepam, by a Microemulsion System

“…Interestingly, t 1/2 values obtained in rats were much closer to our data than those obtained in humans, 55.4 min and 105.5 min for MDZ and DZP, respectively [27]. In light of the pharmacokinetic data obtained in our study, it can be concluded that: a) there is a species difference between rabbits (and rodents) and humans with regard to the elimination rate of benzodiazepines, but there is no apparent difference in the absorption process, resulting in a very short onset of time in both MDZ and DZP administrations; b) the longer time to reach peak plasma level (t max ) of DZP relative to MDZ may explain the clinical advantage in the use of midazolam over diazepam in the treatment of acute seizures [11]. The microemulsion system of this study provided a high drug concentration of 25 mg/g and (or even 50 mg/g) compared with the 5 mg/ml MDZ-HCl and DZP in plain solutions.…”

“…It is also socially embarrassing, and although difficult to administer during con-vulsions can be used only in children and in a few cases in adolescents; 3) it is highly lipophilic and therefore has a large volume of distribution. Repeated doses are sometime needed and its accumulation may lead to complications such as bradypnea and even respiratory arrest [10,11]. Diazepam is also available in tablets; however, the oral route is not accessible during seizures and cannot be used.…”

“…The interest in intranasal drug delivery arises from the unique advantages presented by the nasal cavity such as: 1) A large surface area available for drug deposition and absorption, 2) The nasal epithelium is thin and highly vascularized, 3) Absorbed substances are transported directly into the systemic circulation thereby avoiding the first pass metabolic effect, and 4) In some cases, drug can be absorbed directly into the CNS by passing the tight blood brain barrier [19]. Intranasal midazolam has already been explored during the last decade and a number of clinical works revealed the potential of its administration via the nasal route [9][10][11]17,[20][21][22][23]. Nevertheless, there are still issues waiting to be resolved.…”

Atomised intranasal midazolam spray as premedication in pediatric patients: comparison between two doses of 0.2 and 0.3 mg/kg

“…In smaller children the titration of doses as per weight is a problem. A significant amount of the fluid can be swallowed and absorbed from the gastrointestinal tract, which decreases the bioavailability and therefore reduces efficacy [10]. Furthermore, treatment failure may occur due to poor technique in delivering an adequate volume of midazolam liquid.…”