Treating impending status epilepticus with intranasal midazolam

As a pediatric neurology pharmacist, my role is to ensure safe and accurate use of medications. For patients with seizures, this includes addition of a rescue medication for prevention of status epilepticus (SE). Despite the fact that intranasal midazolam is evidence-based, inexpensive, accessible, and well-tolerated, it’s an underutilized option in all clinical settings, including hospice and palliative care.

Benzodiazepines are the preferred first-line option for patients with impending or established SE.1 First-line options with strong supporting evidence include intramuscular midazolam and intravenous lorazepam or diazepam. Unfortunately, these options require parenteral administration, which is undesirable in the hospice setting, particularly when care is provided in the home. Notably, common hospice ‘go-to’ regimens like sublingual lorazepam and rectal diazepam suppositories are not supported by evidence.

Instead, intranasal midazolam should be considered the preferred non-parenteral option for SE treatment. It works rapidly (full effect in 5-10 minutes) and studies demonstrate comparable efficacy to existing SE treatment standards.2-4 Not only is it fast-acting and effective, but the intranasal route is also generally preferred by patients and families over the less desirable rectal route.

Intranasal midazolam is an appropriate option for both pediatric and adult patients since the dose is customized based on patient weight. At first glance, it may seem a bit intimidating to prepare and administer intranasal midazolam, however with education and practice it is easy. Here’s how you do it:

Supplies:

  • Vial of midazolam (must be 5mg/ml concentration)
  • Sterile Luer-lock syringe (1ml or 3ml, depending on the dose) with approximately 22G x 1in. needle
  • Mucosal atomizing device such as Teleflex® MAD Nasal™ 5
  • Sharps container

Dosing

  • Rescue medication is typically administered after 5 minutes of continuous seizure.
    • If patients have a history of frequent status epilepticus, the minimum interval may be lowered to 2-3 minutes.
  • Typical dosing is 0.2mg/kg/dose, with a maximum of 10mg per dose.
    • If patients have partial or non-response, the dose can be increased to 0.3mg/kg with a typical maximum of 10mg.

Preparation and Administration (See videos below for visual demonstration)

  1. Remove the cap from the midazolam vial and remove the syringe and needle from its packaging.
  2. Fill the syringe with the volume of air equivalent to the dose that will be administered.
  3. Inject the air into the vial, then draw the prescribed dose of midazolam out of the vial.
  4. Remove the needle from the syringe and put it into the sharps container, then attach the nasal atomizer to the syringe.
  5. Place the atomizer against the nostril, pointing the atomizing device and syringe slightly outward towards the ear to place the medication in the correct part of the nose.
  6. Administer part or all of the medication (see 6a below) into the nose by pressing the syringe plunger firmly and continuously.
    1. If the dose is less than 1ml, administer the full dose in one nostril. If the dose is greater than or equal to 1ml, divide the dose evenly between the two nostrils.
  7. For subsequent administrations, use a new needle and midazolam vial each time. The nasal atomizers are marketed as single use products, but they can be re-used a few times, provided they are not dirty or damaged.

Video demonstrations:

 

 

Written By:

Rachel Kinn, PharmD, BCPPS

Pediatric Pharmacist Consultant, OnePoint Patient Care

 

References:

  1. Glauser R, Shinnar S, et al. Evidence-Based Guideline: Treatment of Convulsive Status Epilepticus in Children and Adults: Report of the Guideline Committee of the American Epilepsy Society. Epilepsy Currents. 2016; 16 (1): 48-61. https://dx.doi.org/10.5698%2F1535-7597-16.1.48
  2. Bailey AM, Baum RB, et al. Review of Intranasally Administered Medications for Use in the Emergency Department. J Emerg Med. 2017; 53(1):38-48. https://doi.org/10.1016/j.jemermed.2017.01.020
  3. Chhabra R, Gupta R, Gupta L. Intranasal midazolam versus intravenous/rectal benzodiazepines for acute seizure control in children: A systematic review and meta-analysis. Epilepsy Behav. 2021; 125: 108390. https://doi.org/10.1016/j.yebeh.2021.108390
  4. Alshehri A, Abulaban, A, et al. Intravenous versus Nonintravenous Benzodiazepines for the Cessation of Seizures: A Systematic Review and Meta-analysis of Randomized Control Trials. Academic Emergency Medicine. 2017; 24 (7): 875-883. https://doi.org/10.1111/acem.13190
  5. https://www.teleflex.com/usa/en/product-areas/anesthesia/atomization/mad-nasal-device/