Therapeutic
Intranasal Drug DeliveryNasal seizure medication overview
Topic summary:
Prolonged seizures and status epilepticus are extremely anxiety provoking for observers and dangerous to the patients. While the "gold standard" treatment is an IV benzodiazepine as initial therapy, this is often not possible outside the confines of an inpatient setting and it requires highly skilled personnel to safely and effectively deliver. The traditional outpatient treatment is rectal diazepam - but this drug is only about 60% effective and for some reason is very expensive (U.S. charges can exceed $200/dose). More recently a large study suggests that intramuscular injections of benzodiazepines are as effective as IV therapy and should displace both rectal and IV drugs as initial treatment. However, this requires an injection (not ideal for a parent to administer to a child) and will likely also be very expensive to justify the costs of bringing the drug to market. Interestingly, some thoughtful clinicians have been working on another concept - nasal delivery of generic benzodiazepine. Based on a moderately extensive bit of literature, nasal midazolam or lorazepam appears to be as effective as IV benzodiazepines, faster to deliver, and safe in terms of not inducing respiratory depression. They are more effective than rectal medication in most of the studies done, they can be safely delivered by parents at home - eliminating the need to call and ambulance and freeing the family up to travel further distances from the hospital, and they do not require much training to be effective. Finally, intranasal benzodiazepines are quite inexpensive - probably under $15 per dose including the delivery device. These insights are slowly beginning to push the use of nasal midazolam and/or lorazepam into the mainstream and increasingly pediatric neurologists and parents with epileptic children are becoming interested in this concept. This overview section provides a quick look at the topic and provides dosing and protocols. Digging deeper behind this page is an extensive review the literature with supporting references. (Click here to skip the overview below and to go directly to the deeper discussion).
Key Concepts regarding delivery of any nasal medication to the systemic circulation and brain
Use the right dose!
- For seizure therapy, the dose of benzodiazepines via the nose is nearly the same as the IV dose - without causing much sedation. Use the literature to guide your dosing (see below).
- Respiratory depression is rarely a concern with nasally delivered generic concentrations of drugs - so use the right dose. Click here for a brief but more in depth discussion on this concept.
Minimize volume, maximize concentration of the drug
- Use the most concentrated (potent) available formulation
appropriate for the task
- eg: IN Midazolam should be done using 5 mg/ml concentration, not the 1 mg/ml concentration.
Large volumes are lost into the pharynx or out the nostril.
Maximize total absorptive surface area
- Use BOTH nostrils for volumes over 0.3 ml. This doubles the absorptive surface area and reduces runoff.
- ABOUT half per nostril is clinically adequate - do not worry about being exact.
Use a delivery system that maximizes mucosal surface area coverage and minimizes loss to the environment and runoff
- Droppers work in research using cooperative patients who hold still for many minutes. They tend to be less effective in clinical trials.
- Atomization (not nebulization over minutes) allows immediate delivery of all the drug directly to the mucosa in a broad area of coverage with little loss to the environment. This improves clinical effect and does not require a cooperative patient.
- Account for device dead space in your dosing calculations especially for children or small drug volumes.
Be thoughtful about anatomic issues and head positioning to enhance delivery
- If possible place head with Occiput/crown down (neck extended) - this delivers more drug higher onto the turbinate's to enhance absorption and nose-brain transport.
- Blood and mucous should be suctioned if possible to enhance mucosal coverage.
Key Concepts related to nasally delivered sedatives
Dosing: See below for doses supported by the literature. Failure to use the adequate dose will likely lead to failure to control seizures.
Respiratory depression: Generic midazolam delivered intranasally does not lead to respiratory depression. Click here for a brief but more in depth discussion on this concept.
Titration: Repeated doses (or half doses) can be given every 10-15 minutes for the benzodiazepines can lead to more titrated effect.
Dosing information and delivery protocol
- Midazolam - 0.2 mg/kg
- Lorazepam - 0.1 mg/kg to max of 4 mg
Protocol for intranasal midazolam, lorazepam to treat seizures
Commonly used generic intranasal medications - single page dosing summary (click here)
In Depth literature review, discussion, bibliography (Click here)