Drugs delivered by nasal atomizer can save lives and alter bedside management
Every emergency physician knows that time is of the essence in the emergency department. Minutes—even seconds—can make the difference between life and death for a patient in extremis, and that can reverberate across a shift, affecting the care for dozens downstream from a critical or resource-intensive patient.
Having a variety of tools and resources at your disposal can make a profound difference, and incorporating intranasal medications into the EP's armamentarium is an important component of practice flexibility, with a number of commonly used medications demonstrating significant utility.
Intranasal medications can bypass the digestive barrier and rapidly cross the blood-brain barrier, allowing effective and noninvasive intervention without the pain, procedural skill, or cost required of other parenteral routes. Useful for clinical conditions from seizures and pain management to moderate sedation and even cardiac arrest, medications delivered via a nasal atomizer can save lives and alter management at the bedside.
Naloxone remains the poster child of intranasal medication success. The opioid antidote is given daily in emergency departments across the country as well as by EMS personnel, law enforcement, and family and bystanders witnessing an opioid overdose. The rapid uptake of intranasal naloxone and its subsequent spread into the hands of potential ad hoc rescuers is a public health success.
At this writing, the Food and Drug Administration has made a preliminary determination that naloxone may be safely distributed over the counter. For most, delivery of 2-4 mg intranasal naloxone is enough to reverse fatal overdose, though introduction of a concentrated 8 mg version has swirled controversy around whether higher doses are necessary and whether they may be harmful. (Int J Drug Policy. 2022;99:103457; https://bit.ly/3Yum7Qs.)
Some experts, including the Centers for Disease Control and Prevention (Dec. 17, 2020; http://bit.ly/3l4xYak), have warned that the synthetic opioid era and the higher doses and concentrations of opioids that patients are using may require higher doses of naloxone, and critics have argued that higher doses may cause more cases of precipitated withdrawal, creating an obstacle to use and implementation, and have pointed toward a literature base justifying higher doses as short on real-world data.
Higher Naloxone Doses
Nonetheless, with concerns remaining about rising opioid virulence and inadequate reversal with traditional doses of naloxone, the FDA approved Kloxxado, an 8 mg nasal spray, in April 2021. Recalling the naloxone discussions of yesterday (“Who needs 4 mg when 2 mg will do?”), it seems likely that we'll see widespread uptake of higher naloxone doses, despite the anemic data. Anecdotally, today's opioid overdoses feel different from those I recall from residency. I encounter patients more frequently who “fail” prehospital naloxone administration, but I also see more patients with precipitated withdrawal from the same.
Opioids, naturally, are similarly effective when administered via the nasal route, and intranasal fentanyl has slowly found its way into analgesic algorithms, particularly prehospital and pediatric ones, across the country. IN fentanyl, with an onset of two to seven minutes and a duration of just under an hour, is a potent and particularly effective tool for patients in whom IV access is difficult or not otherwise indicated, such as a child with a long-bone fracture or the otherwise stable patient with vaso-occlusive crisis.
Multiple studies have shown the efficacy of IN fentanyl compared with other parenteral opioids, and it's certainly safe. An institution in Tennessee gave intranasal fentanyl at doses of 2-5 mcg/kg to more than 3000 pediatric patients without any need for naloxone reversal. (Pediatr Emerg Care. 2022;38:e447; https://bit.ly/3l8UezD.)
Another study reported the 13-year success of New Mexico EMT-B ski patrollers administering 50-100 mcg of IN fentanyl on the slopes. (Wilderness Environ Med. 2022;33:296; http://bit.ly/3yo2fE3.) The effective dose (generally 2 mcg/kg) for many adults may be too much volume to administer effectively (more than 1 mL per nostril is likely to lead to too much drug loss and ineffective dosing), but it's an attractive option for nurse-driven analgesic protocols and safe out-of-hospital opioid dosing.
Ketamine for Analgesia
Similarly, intranasal ketamine can be a tremendous analgesic and one I employ most frequently in patients with severe treatment-resistant back pain. Administered in doses of 0.5-1.0 mg/kg, again taking care to minimize any drug runoff with higher volumes, IN ketamine reduces pain in ED patients (World J Emerg Med. 2016;7:19) and has also been translated into the prehospital setting. (Ann Emerg Med. 2019;74:241; https://bit.ly/3hM37uG.)
The therapeutic window for ketamine while avoiding adverse effects such as nausea and vomiting can be narrow in my experience, and premedication with oral ondansetron and benzodiazepines is worth consideration. Interestingly, intranasal ketamine has seen some increased utilization for procedural sedation (PLoS One. 2017;12:e0173253; http://bit.ly/3yrgojN) (dosing varies widely in the literature, 5-10 mg/kg), but published studies supporting its use as monotherapy for sedation run short. Frankly, that was a surprising revelation for me, one ripe for investigation and development. Limited again by volume and concentration, growing clinical experience with ketamine makes it an attractive candidate for further study and potentially expanded use in pediatric procedural sedation.
Intranasal midazolam is perhaps the more commonly encountered intranasal sedative, and is effective at doses of 0.2-0.5 mg/kg. High-concentration midazolam is a must, and dosing may be ineffective if it's hastily sprayed into the flowing nose of a crying and screaming patient, making this medication and route most ideal for more minor procedures, such as IV placement for laceration repair. (Am J Emerg Med. 2019;37:85; https://bit.ly/3ypb5kL.) Importantly, IN midazolam is a safe and equally effective option in children with seizures compared with IV or rectal benzodiazepines. (Epilepsy Behav. 2021;125:108390.) Intranasal midazolam at 0.2 mg/kg can be used quickly and easily inside and outside (with the release of prescription intranasal benzodiazepines) a hospital setting for rapid acute seizure cessation.
In a what-was-old-is-new-again fashion, intranasal dexmedetomidine is an alpha-2 adrenergic receptor agonist gaining increasing clinical interest for ED sedation for sedation indications similar to IN midazolam. At doses of 2-3 mcg/kg (up to 200 mcg), dexmedetomidine offers similar anxiolysis (and procedural success) to IN midazolam (Acad Emerg Med. 2016;23:910; https://bit.ly/3Yzn75Q), and is a valuable option and powerful tool in the emergency department.
Dexmedetomidine's highly selective alpha-2 agonism produces gentle and effective sedation and anxiolysis without respiratory depression or significant cardiovascular effects. Administered intranasally, the median sedation onset is less than 20 minutes and recovery time within an hour, making DEX particularly useful for short procedures such as IV placement, foreign body removal, or laceration repair. (BMC Anesthesiol. 2020;20:61; http://bit.ly/3JrRbMg.)
Intranasal lidocaine has also gained recent popularity for its role in potentially causing sphenopalatine ganglion blockade in patients with severe headache in the emergency department (though likely unsuccessful, as I discussed: EMN. 2019;41:20; http://bit.ly/2oqWIvN). Intranasal lidocaine is an effective analgesic in its own right, though, leading to rapid relief even when traditional neuroleptic therapy fails or among craniofacial pain syndromes not amenable to typical ED headache treatments. (J Res Med Sci. 2014;19:331; https://bit.ly/315vVTa.)
To instill nasal lidocaine, load 2% lidocaine into a syringe fitted with an atomization device. Then instill 2 ml lidocaine into the bilateral nostrils and hold pressure for 30 seconds. Reassess the patient 10 minutes after the procedure.
Recent data have shown that glucagon, a potentially life-saving medication given in patients with severe hypoglycemia, can safely and effectively be given intranasally (Ann Pharmacother. 2020;54:780; https://bit.ly/3ZBV9rx), and the FDA approved a 3 mg nasal powder nearly four years ago. (July 24, 2019; http://bit.ly/3mGDfFt.) The nasal powder is easy to administer and can be quickly absorbed through the nasal mucosa, leading to rapid increases in blood glucose levels. It's an attractive option to broaden the scope of first responders and may see wider implementation in the years to come.
Intranasal medications have revolutionized the field of emergency medicine, providing an effective and noninvasive alternative to traditional parenteral routes. Incorporating intranasal medications into the emergency physician's toolkit has enabled faster and more efficient intervention in life-threatening situations, from hypoglycemic emergencies to opioid overdoses and beyond. Intranasal sedatives are also an attractive option for effective anxiolysis in minor pediatric procedures. Gaining proficiency in using intranasal medications can make a significant difference in patient outcomes and the overall delivery of care in the emergency department.
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Dr. Pescatoreis clinical faculty and an attending emergency physician at Einstein Healthcare Network in Philadelphia. Follow him on Twitter@Rick_Pescatore.
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