Well, that didn't work.. my story with intranasal fentanyl

One of my first calls as a paramedic was to our local ski hill for a 26-year-old guy who crashed into a tree while snowboarding. The ski patrol brought him down to the patrol room and we met them inside. The guy was literally screaming in pain and saying: "just put me out, man!" I could see his leg was obviously deformed below the knee.
Now, this dude was covered in gear, and starting an IV was going to take a little while. I looked at my partner and remembered we had just got this new gadget that connects to the end of a syringe and lets you inject medication into someone's nose. It was called a mucosal atomizer device (MAD). I pulled up 100 mcg (2 ml) and gave 1 ml per nare.
I told the guy that he would be feeling reeeeallll good anytime now.
we waited..
and waited..

Those few minutes following me giving intranasal fentanyl made me feel more and more like a clown. It didn't even seem to touch his pain. This was one of many occurrences where adults just did not seem to get better when you shot fentanyl up their nose.
Was I doing it wrong?
Well let's take a look at the nostril anatomy (everyone hates that word)

When you atomize a solution into the nose, the majority of it will land on the turbinates that reside within the respiratory region. These are bony structures covered in a mucosal lining and make up the largest amount of surface area for absorption within the ... nostril.

The medication that lands on the turbinates will still need to be able to go through the blood-brain barrier in order for any central nervous system therapy to be noted. However, there is a shortcut that bypasses the blood-brain barrier. Remember in EMT school when they warned you about sticking a nasal airway up someone's nose if they had head trauma? That concern was because of this secret little path called the "cribriform." Cranial nerve 1 penetrates the cribriform and allows one of the few direct contacts with the outside world to the brain. This is how your brain can interpret smells instantly. This also means that some of the atomized drugs can bypass the blood-brain barrier. Because of the small surface area, the majority of the drug will still need to be absorbed through the turbinates.


So back to my story:
I went down a rabbit hole after I noticed this trend of me telling adults they would feel some relief after IN fentanyl... and it not working. I began to realize that the majority of the evidence looking at intranasal administration was pediatric. I could not find any good studies showing the effectiveness of IN fentanyl in adults. I remember listening to a podcast called the "Pediatric Emergency Playbook" and they had a physician on discussing intranasal medication delivery. He made the comment that the dose needs to be DOUBLE or sometimes TRIPLE the IV dose. Then the light bulb clicked (clicked?)

Well it looks like maybe I was just not giving enough. I just need to double the IV dose and try again before completely writing off IN fentanyl. Buuuuutt.. With common practice being to not inject more than 1 ml up an adult nare at a time, I began to see why it was largely used in the pediatric population.

With most fentanyl coming in 50mcg/ml, giving twice that dose would require a few transactions with the ole' nose hole. Not to mention the 0.1 ml of dead space within the actual atomizer itself. This is why you actually draw up an extra 0.1 ml of whatever you are administering.

Now you are probably thinking, well I have personally seen adult patients wake up after IN Narcan. That's because they are typically giving double to triple the dose. Most intranasal naloxone devices are 4-8 mg per spray.
In addition to the dose, there are a few other things you want to avoid when administering a drug through the schnauze.
Don't have them sniff. The act of sniffing generates negative pressure generated by inspiration. You want the medication to stay in the nose and not go down the throat. In addition, you want to aim at the helix (top) of the ear.

I absolutely love intranasal fentanyl for kids, but I am likely going IM for immediate pain relief in adults when an IV isn't any feasible given time or environment. I am sure there are some who have seen success, Including these patients who got a placebo and felt better (Kress, 2009). Another possible option is intranasal pain dosed ketamine. The PAIN-K study (Andolfatoo, 2019) found that a reduction in pain when 0.75 mg/kg of ketamine was given intranasal (3x the IV dose).
This blog is meant to be food for thought and not for practice. As always, stay in-line with your local guidelines but keep asking questions!
References:
Andolfatto, G., Innes, K., Dick, W., Jenneson, S., Willman, E., Stenstrom, R., … Benoit, G. (2019). Prehospital Analgesia With Intranasal Ketamine (PAIN-K): A Randomized Double-Blind Trial in Adults. Annals of Emergency Medicine.doi:10.1016/j.annemergmed.2019.01.048
Kress HG, Oronska A, Kaczmarek Z, et al. Efficacy and tolerability of intranasal fentanyl spray 50 to 200 [mu] g for breakthrough pain in patients with cancer: a phase III, multinational, randomized, double-blind, placebo-controlled, crossover trial with a 10-month, open-label extension treatment period. Clin Ther. 2009;31:1177–1191. [PubMed] [Google Scholar]
Wu H, Hu K, Jiang X. From nose to brain: understanding transport capacity and transport rate of drugs. Expert Opin Drug Deliv. 2008 Oct;5(10):1159-68. doi: 10.1517/17425247.5.10.1159. PMID: 18817519.