The blog will offer a brief overview of some of the intranasal medications used in pediatric patients in the emergency department setting. Intravenous access may be a technically challenging and time consuming task in pediatric patients. Oral medication use may be limited by NPO status, poor taste, comparatively longer time to achieve desired medication effect, and/or poor patient compliance. Intranasal medication use offers the advantage of requiring minimal training and experience to achieve successful medication administration in comparison to obtaining intravenous access, particularly in young children. In general, the patients studied have been ASA Class I or II only.
The anterior portion of the nose is the main site of intranasal drug absorption because of its relatively large surface are and rich blood supply.1 Delivering half of the medication into each nostril maximizes the absorptive mucosal surface. The child is usually placed supine or seated with the head tilted back.2 Using a nasal mucosal atomizer device, a concentrated medication in a small volume (0.2-0.3 mL) is administered. Volumes in excess of 1 mL per nostril are not reliably absorbed as a result of mucosal surface saturation and runoff from the nasal cavity.3
Providing timely and adequate pain control is a standard of care in pediatric emergency medicine practice. Intranasal medication administration provides a route for rapid administration of analgesia. This route may be selected for patients who will not otherwise require intravenous access. Alternatively, a one-time nasal analgesic may be given while preparing for venous cannulation in those patients who will require IV placement. When placing IVs in children in a non-emergent situation, it is preferred to place topical lidocaine 4% (LMX) on the skin prior to cannulation. This topical mediation requires thirty minutes to achieve efficacy. Fentanyl, a synthetic opioid agonist, due to its lipophilicity is rapidly absorbed through the nasal mucosa.3 Intranasal fentanyl is suggested to be given in the does range of 1.5-2 µg/kg. The concentration of the drug is [50mcg/mL]. A max single dose of 100 mcg may be administered at a time, given the maximum recommendation volume per nostril is 1 mL. Consideration may be given for a repeat dose after 15 minutes.4 The maximum dose of 2 µg/kg intranasal fentanyl was similarly used in a study of children undergoing bilateral myringotomy and tympanostomy tube placement. The dose was given preoperatively. The authors noted the use of fentanyl did not increase intraoperative laryngospasm, postoperative emesis, oxygen requirements in the PACU, or the incidence of hypoventilation in their study.5
Children evaluated in the emergency department will also often require anxiolysis in addition to analgesia. Common procedures such as performing CT scans and laceration repairs require the child to be in a more cooperative and distractible state to achieve optimal results. Intranasal midazolam has been frequently studied in children. It is important to use the more concentrated form of intravenous midazolam [5mg/mL] in order to reduce the total volume to be atomized into the nostril.4 In the 2010 brief review and update article by Wolfe and Braude recommend a dose of 0.4-0.5 mg/kg of intranasal midazolam for anxiolysis based on the literature published at that time.4 For less anxious and/or less involved procedures, a lower starting dose of 0.2-0.3 mg/kg intranasal midazolam may be considered. It is always important to seek the input of family members who know the child’s previous response to painful or frightening experiences when making a treatment plan.
Another use for intranasal midazolam in the care of children in the emergency setting is for seizure cessation. Obtaining IV access in child who is seizing may be very challenging. Historically, rectal diazepam has been the mainstay of treatment for those patients without IV access. Bhattacharyya et al demonstrated in patients 3 months to 12 years of age, intranasal midazolam 0.2 mg/kg was more effective than per rectum diazepam 0.3 mg/kg. Those patients receiving rectal diazepam had a higher rate of respiratory depression and hypoxia and 10 and 30 minutes post drug administration.6 Because of the preferred safety profile and lower cost, home use of intranasal midazolam has become mainstream. The emergency room provider should be aware and familiar with this practice. A 2010 study demonstrated a shorter median time to seizure cessation from medication administration in the group of children treated with intranasal midazolam 0.2 mg/kg compared to rectal diazepam. The mean age for the patient treated was 5.6 years. In this study rectal diazepam cost $211 per dose whereas intranasal midazolam cost $12 per dose. Ease of administration was higher with the intranasal dosing group.7 Similarly prehospital providers are using intranasal midazolam 0.2 mg/kg up to a maximum dose of 10 mg. Holsti et al studies patients 8 months to 16 years of age including more than 50 EMS agencies the efficacy of intranasal midazolam versus rectal diazepam. Their studied revealed the patients in the rectal diazepam group were significantly more likely to require EMS bag-mask ventilation, require emergency department (ED) intubation, need hospital admission, require oxygen at emergency room disposition, require anticonvulsants on the ED, and need pediatric intensive care unit admission.8
While the preceding paragraphs review well established pediatric emergency care practices, the ease of use of intranasal medications has stimulated new research protocols. Neveille et al published in 2016 the results of a double-blind randomized controlled trial of intranasal dexmedetomidine versus intranasal midazolam as anxiolysis prior to pediatric laceration repair in the emergency department.9 Patients received either 0.4 mg/kg midazolam or 2 µg/kg dexmedetomidine both given intranasally. The concentrations of the medications were [5 mg/mL] for midazolam and [100 µg/mL] for dexmedetomidine. Anxiety scores were measured at baseline, at time of positioning for procedure, at time of wound washout, and at the time of first suture placement. There results demonstrated the two medications performed similarly, except they found superiority of dexmedetomidine over midazolam in terms of anxiety level at positioning for procedure. They note the study dose used of 0.4 mg/kg of midazolam is higher than what many of their providers at their center routinely use. Similarly, a lower dose of 0.3 mg/kg is typically in our center.
In conclusion, the safety and ease of use of intranasal medications support the wide spread adoption of the method of medication administration in pediatric patients. Lack of intravenous access no longer needs to be a barrier for prompt treatment of analgesia, anxiety, and seizures.
Kathryn Martin DO, MS, FAAP
1. Grassin-Delyle S, Buenestado A et al. Intranasal drug delivery: an efficient and non-invasive route for systemic administration Focus on opioids. Pharmcol Ther. 2012; 134:336- 379.
2. Filho EM, Robinson F et al. Intranasal Dexmedetomidine for Sedation for Pediatric Computed Tomography Imaging. The Journal of Pediatrics. 2015;166:1313-1315.
3. Christrup LL, Foster D et al. Pharmacokinetics, Efficacy, and Tolerability of Fentanyl Following Intranasal Versus Intravenous Administration in Adults Undergoing Third-Molar Extraction: A Randomized, Double-Blind, Double-Dummy, Two-Way Crossover Study. Clinical Therapeutics. 2008;30:469-481.
4. Wolfe TR, Braude DA. Intranasal Medication Delivery for Children: A Brief Review and Update. Pediatrics 2010;126:532-537.
5. Galinkin JL, Fazi Lm et al. Use of Intranasal Fentanyl in Children Undergoing Myringotomy and Tube Placement during Halothane and Sevoflurane. Anesthesia. Anesthesiology 2000;93:1378-1383.
6. Bhattacharyya M, Kalra V et al. Intranasal Midazolam vs. Recta; Diazepam in Acute Childhood Seizures. Pediatric Neurology. 2006;34:355-359.
7. Dudley N, Schunk J et al. Intranasal Midazolam vs. Rectal Diazepam for the Home Treatment of Acute Seizures in Pediatric Patients with Epilepsy. Archives Pediatric Adolescent Medicine. 2010;164:747-753.
8. Holsti M, Sill B et al. Prehospital Intranasal Midazolam for the Treatment of Pediatric Seizures. Pediatric Emergency Care. 2007;23:148-153.
9. Neville DN, Hayes KR et al. Double-blind Randomized Controlled Trial of Intranasal Dexmedetomidine Versus Intranasal Midazolam as Anxiolysis Prior to Pediatric Laceration Repair in the Emergency Department. Academic Emergency Medicine. 2016;23:910-917.