intranasal medications pediaticFiona is a 6 year old female who presents to your emergency department after falling onto her left hand while racing on the playground. X-ray of the left upper extremity reveals a distal radius fracture with minimal displacement and angulation. You plan to place her arm in a splint and arrange for close orthopedic follow-up. The only problem: Fiona is in a lot of pain, especially with any manipulation of her arm, and Dad is worried that she will not be able to tolerate having a splint placed. You consider reaching for an intranasal medication to help Fiona feel more comfortable and to place the splint in a quick, efficient manner.

You are going to put WHAT in my nose?

Delivery of medications intranasally offers an alternative to oral and intravenous drug administration in the emergency department. This method is used to rapidly provide anxiolysis, sedation, amnesia, and/or analgesia in the pediatric population and can play an important role in a safe and successful intervention [1]. Let’s review four common intranasal medications used in the ER: fentanyl, versed, ketamine, and dexmedetomidine.

When to be … picking the nose: [2]

Intranasal medications can be optimal in a variety of clinical scenarios, particularly in a fast-paced and busy environment. They expedite patient care logistically—by limiting the need for patient cooperation and IV access—and pharmacokinetically—by providing rapid onset of effects due to bypass of first-pass metabolism and direct delivery through the blood-brain barrier [1,3]. Common situations amenable to this method of administration include orthopedic traumas, laceration repairs, burns, MRI and CT scans, and seizure control.

Delivering medications via this route can also be helpful to ameliorate problematic situations:

  • Increased stress of child or family
  • Decreased PO intake of patient
  • Inexperienced providers
  • Limited resources [3,4,5]

The atomizer:

Mucosal atomization devices (MAD) are the preferred method of delivering medications intranasally as they require minimal patient cooperativity and allow for maximal bioavailability.

  • Decide on your medication of choice.
  • Attach a Luer syringe of your desired dose, plus an additional 0.1 mL to account for “dead space” in the atomizer.
  • Suction any mucous or secretions that are present in the nasal passage.
  • Use volume of < 1 mL per nostril (ideally 0.2 to 0.5 mL), dividing evenly per nostril.
  • Administer over a few seconds and at small doses.
  • Start a timer so that you know the optimal time to perform your intervention [1].

When should I NOT reach for intranasal medications?

  • Severe upper respiratory infection
  • Large volume medication requirement
  • Nasal trauma or septal defects
  • Conjunction with intranasal vasoconstrictors [1]

Medication choice:

Once you have determined that intranasal medication will be helpful in caring for your patient, how do you decide which medication to use? Factors to consider include the following:

  • Patient-specific information (age, weight, etc.)
  • Nature of planned intervention
  • Desired effect of medication
  • Availability

Fentanyl:

Fentanyl is a synthetic opioid that can provide rapid analgesia for patients with acute pain. It has been shown to be safe and efficacious in managing orthopedic trauma, burn wounds, post-operative pain, dental extractions, and incision and drainages [6]. It exhibits an adverse-effect profile of which most providers are already well-familiar, similar to oral and intravenous opioids. Intranasal fentanyl works! It has been shown to be equally as effective as intravenous morphine in pediatric patients presenting to the emergency room with long-bone fractures [5]. Intranasal fentanyl is also associated with faster time to administration (thus more rapid pain-control and shorter length of stay) and decreased need for repeat dosing. These findings are likely related to the lack of need for IV access and reduced discomfort in parents and providers in administering intranasal opioids relative to IV opioids [1].

  • Dose: 1 – 2 mcg/kg, maximum dose of 100 mcg  [2]
  • Expected onset: 10 – 15 minutes [6]
  • Adverse effects: nausea, vomiting, pruritus, respiratory depression  [2]

Midazolam:

Midazolam is a benzodiazepine with anxiolytic and amnestic properties. Although it also has sedative properties, its concentration (5 mg/mL) may limit the ability to achieve the dose needed for sedation in a heavier or older patient [2]. Think about using intranasal midazolam in minor procedures such as laceration repair or foreign body removal. Midazolam may cause nasal burning and mucosal irritation, so also consider pre-treatment with intranasal lidocaine (0.5 mL about 5 minutes before midazolam) [7].

  • Dose for anxiolysis and sedation: 0.2 – 0.3 mg/kg, maximum dose of 10 mg [8]
  • Expected onset: between 5 – 10 minutes [8]
  • Adverse effects: mucosal irritation

Intravenous access can often be difficult to obtain in an actively seizing patient, and intranasal medications can be easily administered. While the first-line agents are intravenous lorazepam or intravenous diazepam, the time taken to obtain access can cause significant delay in administration—thus seizure cessation. Intranasal midazolam has demonstrated efficacy similar to that of IV midazolam and rectal diazepam in achieving seizure resolution in pediatric status epilepticus [9].

  • Dose for status epilepticus: 0.2 mg/kg, maximum dose of 10 mg

Ketamine:

Ketamine is a phencyclidine (PCP) derivative that antagonizes the N-methyl-D-aspartate receptor (NMDA-r) to provide sedative and analgesic effects [10]. It is routinely used intravenously for procedural sedation as an opioid and benzodiazepine sparing agent that also rarely causes respiratory depression. However, more recently ketamine has been studied via the intranasal route to achieve a lighter, sub-dissociative sedation. Generally, ketamine has been shown to be as effective as fentanyl when administered intranasally, although with greater rates of mild and well-tolerated side effects. Intranasal ketamine may be ideal management of patients who are opioid-tolerant or who are at higher risk of hypotension (e.g trauma patients) [10].

  • Dose: 1 – 1.5 mg/kg (although wide ranges have been cited), maximum dose of 100 mg – 200 mg [11]
  • Expected onset: 5 – 10 minutes  [12]
  • Adverse effects: nausea, dizziness, unpleasant taste

Dexmedetomidine:

Dexmedetomidine is an α2 agonist that produces sedation, also with less respiratory depression than opioids or benzodiazepines. It is said to mimic a state that is similar to sleep [13]. Intranasal dexmedetomidine is a relatively new agent that is currently not commonly used in the emergency room, given varying time of action and prolonged time to onset. Intranasal dexmedetomidine has primarily been cited in dental and anesthesia literature in studies with limited sample sizes. However, it has shown promise in that it has been shown to achieve equal or superior sedation for imaging studies than oral or intranasal midazolam [14]. Its use may be applicable in the ED setting to achieve sedation for patients in need of a CT or MRI scan, but there is less evidence to support its use as monotherapy for analgesia [15].  Risks of cardiovascular effects are also of significant concern, and more studies are needed to ensure a practical and safe use of intranasal dexmedetomidine.

  • Dose: 1 – 2 mcg/kg, maximum dose 200 mcg [16]
  • Expected onset: 45 – 60 minutes [16]
  • Adverse effects: bradycardia, hypotension, oxygen desaturation

 

DrugFentanylMidazolamKetamineDexmedetomidine
Primary useAnalgesiaAnxiolysis/sedation
Seizure
Amnesia
Analgesia
Anxiolysis/sedation
Amnesia
Anxiolysis/sedation
Analgesia
Dose1 –  2 mcg/kg0.2 –  0.3 mg/kg
*Seizure 0.2 mg/kg
0.5  –  1.5 mg/kg1 – 2 mcg/kg
Max dose (limited by volume)100 mcg10 mg100 mg (50 mg/mL)
200 mg (100 mg/mL) [2]
200 mcg [2]
Onset (minutes)10 – 1510 – 155 –1045 – 60
Duration (minutes)30 – 60306040 – 90 [15]

 

Multiple intranasal agents?

Pain and anxiety go hand in hand, especially in the pediatric population. Can you safely use multiple intranasal agents in combination to address both of these factors? One retrospective study evaluated 546 children who received intranasal fentanyl and intranasal midazolam for laceration repair at a large, urban pediatric emergency department. It reported no significant adverse events and low treatment failure suggesting that the combination may be a safe and effective strategy for sedation in young children [17].  Another retrospective study evaluated pediatric patients at urgent care clinics and found similar results. This use of these intranasal medications together in an outpatient setting highlights an important point—the consideration of these medications in combination as procedural sedation varies from institution to institution. Minimal sedation, a state in which a patient can respond verbally to commands with maintained cardiovascular and ventilatory function can be favorable to procedural sedation in that it requires less stringent monitoring and staffing resources. Both studies are are suggestive that the combination of intranasal fentanyl and intranasal midazolam, if used appropriately, may be safe under monitoring standards required for minimal sedation. Check your local institution’s guidelines when considering this option [18].

Take home points and our case:

  • Intranasal medications are safe and effective tools when performing interventions in the pediatric emergency department.
  • Consider these medications in patients with painful injuries or in anxiety-inducing scenarios.
    • Use small volumes to ensure adequate drug administration.
    • Check drug-specific details to determine which intranasal medication is appropriate for your patient.
  • Fiona’s fracture:
    • Administer 1 mcg/kg of intranasal fentanyl.
    • Check in on her pain level at 15 minutes.
    • Place the splint within the next 1 hour and send her home to follow-up!

 

References:

    1. Corrigan M, Wilson SS, Hampton J. Safety and efficacy of intranasally administered medications in the emergency department and prehospital settings. Am J Health Syst Pharm. 2015;72(18):1544-1554. PMID: 26346210
    2. Rech MA, Barbas B, Chaney W, Greenhalgh E, Turck C. When to Pick the Nose: Out-of-Hospital and Emergency Department Intranasal Administration of Medications. Ann Emerg Med. 2017;70(2):203-211. PMID: 28366351
    3. Adelgais KM, Brent A, Wathen J, et al. Intranasal Fentanyl and Quality of Pediatric Acute Care. J Emerg Med. 2017;53(5):607-615.e2. PMID: 28967529
    4. Wolfe TR, Braude DA. Intranasal medication delivery for children: a brief review and update. Pediatrics. 2010;126(3):532-537. PMID: 20696726
    5. Borland M, Jacobs I, King B, O’Brien D. A randomized controlled trial comparing intranasal fentanyl to intravenous morphine for managing acute pain in children in the emergency department. Ann Emerg Med. 2007;49(3):335-340. PMID: 17067720
    6. Fentanyl. Lexi-Drugs. Lexicomp. Wolters Kluwer Health, Inc. Riverwoods, IL. Available at:  http://online.lexi.com. Accessed August 25, 2020.
    7. Smith D, Cheek H, Denson B, Pruitt CM. Lidocaine Pretreatment Reduces the Discomfort of Intranasal Midazolam Administration: A Randomized, Double-blind, Placebo-controlled Trial. Acad Emerg Med. 2017;24(2):161-167. PMID: 27739142
    8. Midazolam. Lexi-Drugs. Lexicomp. Wolters Kluwer Health, Inc. Riverwoods, IL. Available at:  http://online.lexi.com. Accessed August 26, 2020.
    9. McTague A, Martland T, Appleton R. Drug management for acute tonic-clonic convulsions including convulsive status epilepticus in children. Cochrane Database Syst Rev. 2018;1(1):CD001905. Published 2018 Jan 10. PMID: 29320603
    10. Guthrie AM, Baum RA, Carter C, et al. Use of Intranasal Ketamine in Pediatric Patients in the Emergency Department [published online ahead of print, 2019 Jul 8]. Pediatr Emerg Care. 2019;10. PMID: 31290798
    11. Frey TM, Florin TA, Caruso M, Zhang N, Zhang Y, Mittiga MR. Effect of Intranasal Ketamine vs Fentanyl on Pain Reduction for Extremity Injuries in Children: The PRIME Randomized Clinical Trial. JAMA Pediatr. 2019;173(2):140-146. PMID: 30592476
    12. Ketamine. Lexi-Drugs. Lexicomp. Wolters Kluwer Health, Inc. Riverwoods, IL. Available at:  http://online.lexi.com. Accessed August 25, 2020.
    13. Weerink MAS, Struys MMRF, Hannivoort LN, Barends CRM, Absalom AR, Colin P. Clinical Pharmacokinetics and Pharmacodynamics of Dexmedetomidine. Clin Pharmacokinet. 2017;56(8):893-913. PMID: 28105598
    14. Ghai B, Jain K, Saxena AK, Bhatia N, Sodhi KS. Comparison of oral midazolam with intranasal dexmedetomidine premedication for children undergoing CT imaging: a randomized, double-blind, and controlled study. Paediatr Anaesth. 2017;27(1):37-44. PMID: 27734549
    15. Poonai N, Spohn J, Vandermeer B, et al. Intranasal Dexmedetomidine for Procedural Distress in Children: A Systematic Review. Pediatrics. 2020;145(1):e20191623. PMID: 31862730
    16. Dexmedetomidine. Lexi-Drugs. Lexicomp. Wolters Kluwer Health, Inc. Riverwoods, IL. Available at:  http://online.lexi.com. Accessed August 29, 2020.
    17. Ryan PM, Kienstra AJ, Cosgrove P, Vezzetti R, Wilkinson M. Safety and effectiveness of intranasal midazolam and fentanyl used in combination in the pediatric emergency department. Am J Emerg Med. 2019;37(2):237-240. PMID: 30146398
    18. Williams JM, Schuman S, Regen R, et al. Intranasal Fentanyl and Midazolam for Procedural Analgesia and Anxiolysis in Pediatric Urgent Care Centers [published online ahead of print, 2019 Feb 15]. Pediatr Emerg Care. 2019;10. PMID: 30789872
Alia Church, MD

Alia Church, MD

Emergency Medicine Resident
University of California San Francisco
Alia Church, MD

Latest posts by Alia Church, MD (see all)

Sonny Tat, MD MPH

Sonny Tat, MD MPH

Assistant Professor
Pediatric Emergency Medicine
University of California, San Francisco
Zlatan Coralic, PharmD

Zlatan Coralic, PharmD

Assistant Clinical Professor
Emergency Department Clinical Pharmacist
University of California, San Francisco (UCSF)
Zlatan Coralic, PharmD

@ZEDPharm

Emergency Medicine Clinical Pharmacist. Views expressed here are my own. #FOAMed