Intranasal Medications

CASE

A 7 year-old girl presents after falling off a jungle gym.  She has a visible deformity of the left humerus and wrist.  She won’t let the nurse get close enough for a blow-dart, let alone an IV, and your attending slaps the IO kit out of your hands as you desperately try to boost your procedure numbers.  She needs pain relief.  Now what?

BACKGROUND

Intranasal (IN) administration of medications enables rapid systemic delivery, avoids first-pass metabolism, and negates the pain associated with IV access.  Delivery is quick and can be accomplished with minimal training.[1]

The rate limiting factor for IN administration is the area of available nasal mucosa, i.e. your absorptive surface.  Typically, IN administration is limited to volumes less than 1 mL per nostril, perhaps less with the presence of intranasal blood or mucous, necessitating a higher concentration to achieve the desired effect.

The most effective method of IN administration is an atomizer (Figure 1).  Crushing medications or using a syringe as a dropper results in incomplete distribution across the nasal mucosa, imprecise delivery, and unpredictable bloods levels.  Atomizers achieve better delivery, less drug loss to the oropharynx, and greater clinical efficacy.[1]

Figure 1: LMA MAD NASAL atomizer attached to 3 mL syringe

IN administration carries a low risk of adverse effects and beyond the time saved via ease of IN administration, the cost is comparable to IV delivery, usually under $10.00 per dose.

INDICATIONS

There has been a push in recent years to develop IN formulations of marketed products, including drugs for migraine management, smoking cessation, and even hormone replacement therapy.[2]  The full breadth of indications for the current IN drug pipeline is beyond the scope of this post, in which we will focus on the indications for which IN medications are used in emergency or pre-hospital settings.

Pain.  Acute pain is a common problem in pediatric medicine, and multiple studies have proven IN administration of opioids to be as effective as the IV route without the need to establish access, and faster onset than IM delivery.  The ease of administration has also made it popular with first responders and practitioners in austere environments.  At Hasbro Children’s Hospital, we commonly use fentanyl.  Dose at 1.5 - 2.0 mcg/kg, allow 10-15 minutes for full effect, and consider co-administration of an oral medication or bridge to IV for longer-term analgesia.[1]

Anxiolysis.  There are numerous reasons children need to stay still during treatments, such as procedures, imaging, or dressing changes.  Midazolam is the most commonly used and well-studied IN anxiolytic, although other options include ketamine and dexmedotomidine.  Although IN midazolam is associated with a transient burning sensation (due to a preservative) in the nares during administration, studies have shown monotherapy provides satisfactory anxiolysis, with minimal risk of adverse events.  Dose at 0.3 - 0.5 mg/kg and allow 5-7 minutes for the medication to take effect.

Seizure.  Because the well-vascularized nasal mucosa is brain-adjacent, IN administration can quickly achieve therapeutic levels in CSF.  In cases without IV access, IN midazolam was found to have a more rapid onset of action than rectal diazepam for better seizure control, and decreased need for intubation and hospital admission.[1]

Overdose.  The opioid epidemic is a national emergency, and with the rise in deaths has come a push for first responders to use naloxone in cases of suspected overdose.  Kits come in 2 and 4 mg doses, and include an ampule of naloxone and an atomizer.

Figure 2: Naloxone IN kit

ADMINISTRATION TECHNIQUE

Approach from the side.  Even without needles, children will react to seeing a syringe with a lot of anxiety.  Approaching from the side will minimize this, allow you to get in a better position, and achieve better drug delivery.

Use both nostrils.  If you only use one nostril, you’re missing out on an entire half of the nasal mucosa!  Instead of spraying the entire volume into your favorite nares, spread the dose equally between right and left.

Direct the spray.  When you introduce the atomizer, point the tip laterally towards the tip of the ear.  This will afford you better coverage of the turbinates and mucosa.

Use the right concentration.  Using a higher concentration of medication allows you to use less volume, and since absorption is limited by volume when it comes to IN delivery, less drug will be lost.[3] 

SUMMARY 

IN administration of medications is a safe and effective way to manage a number of conditions in situations where other means of drug delivery are inefficient, ineffective, or not available.  As for the patient from our introductory case, she received 25 mcg of IN fentanyl with great improvement in her pain, got x-rays that confirmed a displaced fracture, and tolerated reduction of her wrist with procedural sedation.

Faculty Reviewer: Dr. Chris Merritt

references 

1. Wolfe TR, Braude DA. Intranasal Medication Delivery for Children: A Brief Review and Update. Pediatrics. 2010; 126: 532-537.

2. Fortuna A, Alves G, Serralheiro A, Sousa J, Falcao A. Intranasal delivery of systemic-acting drugs: small-molecules and biomacromolecules. Eur J Pharm Biopharm. 2014; 88(1): 8-27.

3. Using the MAD Nasal Intranasal Mucosal Atomization Device. Teleflex Medical Europe Ltd. Ireland. www.lmaco.com/products. Accessed August 24, 2017.