Intranasal Fentanyl for Pain Management in Children: A Systematic Review of the Literature

ARTICLE

Intranasal Fentanyl for Pain Management in Children: A Systematic Review of the Literature Shawna Mudd, DNP, PNP-BC

ABSTRACT Intranasally administered fentanyl (INF) has been studied as an alternate route of delivery for pain relief in children. The purpose of this systematic review is to evaluate the available research evidence on the use of INF in the pediatric population. A search was conducted of PubMed, ISI, Scopus, Popline, CINAHL, and Embase for research studies evaluating INF in this population (0-18 years of age). The studies were graded on the strength of the evidence and the results reviewed. All of the reviewed studies showed similar or improved pain scores when compared with other opioids and administration methods. No severe adverse outcomes were reported. Current evidence suggests that INF is a safe and effective method of pain management for children in a variety of clinical settings. J Pediatr Health Care. (2011) 25, 316-322.

KEY WORDS Intranasal, fentanyl, administration, pediatric, pain, analgesia

Providing effective acute pain management in children can be challenging. Current practices vary among health care providers. Inadequate and inconsistent pain

Shawna Mudd, Pediatric Nurse Practitioner, The Johns Hopkins University, Baltimore, MD. Conflicts of interest: None to report. Correspondence: Shawna Mudd, DNP, PNP-BC, 600 N Wolfe St, CMSC 144, Baltimore, MD 21287; e-mail: [email protected]. 0891-5245/$36.00 Copyright Q 2011 by the National Association of Pediatric Nurse Practitioners. Published by Elsevier Inc. All rights reserved. doi:10.1016/j.pedhc.2010.04.011

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control practices in pediatrics have been documented throughout the literature, despite the availability of effective alternatives (Friedland, Pancioli, & Duncan, 1997; MacLean, Obispo, & Young, 2007; Magaret, Clark, Warden, Magnusson, & Hedges, 2002; Rupp & Delaney, 2004). Inadequate pain control is commonly referred to as the ‘‘treatment gap,’’ when pain is experienced does not correlate with received pain management (Leykin, Pellis, & Ambrosio, 2007). Despite advancements in pediatric pain management, children receive only a fraction of the recommended and available treatment options available in the research literature (MacLaren & Kain, 2008). Methods of pain control options are affected by numerous variables, including adequate fasting time, availability of resources, patient age, parent/patient/staff preference, the patient’s overall health status, and providers’ level of knowledge about analgesia options. Similarly, decisions are made based on personal biases and beliefs. Many health care providers and laypersons believe that pain medication is harmful and that pain is an invariable part of hospital care (MacLean et al., 2007). Pain management in a busy clinical setting often is given secondary importance, hampered by the burdens of practice (Kavanagh et al., 2007). All these assumptions and beliefs can affect how pain is approached and can have a negative impact on the successful implementation of evidence-based pediatric pain practices (Dooks, 2001). While effective pain management is an important part of ethical practice, providing effective pain relief also can modify the physiologic response to injury. A patient’s response to injury can promote catabolism, increase sympathetic activity, and cause a degree of immunosuppression. Through effective analgesia, Journal of Pediatric Health Care

these pathophysiologic changes caused by injury can be modified (Australian and New Zealand College of Anaesthetists and Faculty of Pain Medicine, 2005). For severe, acute, and procedural pain in children, options for short-acting and effective pain relief are limited. Opioids administered intravenously and intramuscularly, while effective, both require Fentanyl is used painful placement of frequently because intravenous lines or injections. Orally adminit has a rapid onset istered opioids, while and short duration also effective, can of action, a lack of have a prolonged and unpredictable onset histamine release, and duration of action and fewer and can be affected by cardiovascular oral intake status (Finn et al., 2004). Children effects than do report venipuncture as other opioids. one of the worst types of pain they experience in the hospital (Cummings, Reid, Finley, McGrath, & Ritchie, 1996; Kennedy, Luhmann, & Zempsky, 2008), and it has been suggested that children may not report their pain as often if obtaining relief involves a painful injection (Food and Drug Administration, 2002). Creating pain to relieve pain (such as the pain associated with intramuscular injections) should happen on a limited basis in children. An ideal analgesic would have a short onset of action and minimal adverse effects, provide effective acute pain relief, and be painless to administer. Fentanyl is a potent and highly selective opioid agonist that works primarily at the mu receptor and is primarily metabolized in the liver. It alters the transmission of pain signals and diminishes the perception and emotional response to pain. Fentanyl is used frequently because it has a rapid onset and short duration of action, a lack of histamine release, and fewer cardiovascular effects than do other opioids. It is 80 to 100 times more potent than morphine in adults, although this potency decreases with younger age (Friedrichsdorf & Kang, 2007). When given intravenously, it has an onset of action of 2 to 3 minutes and a duration of action of 20 to 30 minutes, making it useful in children (Mace et al., 2004). Fentanyl has no inherent anxiolytic or amnestic properties, and sedation typically does not occur at low doses (1-2 mg/kg) (Krauss & Green, 2006). Its most serious side effect is respiratory depression, which is often dose related (Grape, Schug, Lauer, & Schug, 2010). The intranasal administration of medications has been practiced for many years (Goldman, 2006). The nose has a rich vascular supply, providing quick and rapid mucosal absorption into the blood stream (Goldman, 2006) and is particularly conducive to the www.jpedhc.org

absorption of lipid soluble drugs such as fentanyl (Shelley & Paech, 2008). The goal of this manuscript is to review the available research on intranasally administered fentanyl (INF) to help evaluate its role in safe and effective pain relief for children in a variety of clinical settings. EVIDENCE SEARCH Search Strategy and Study Selection An exhaustive literature search was conducted for available studies using various databases for all available years until February 2010. In PubMed, a medical subjects heading (MeSH) search was conducted using Administration, Intranasal (MeSH) AND Fentanyl (MeSH) OR 437-38-7. Included studies were the following: meta-analyses, randomized controlled trials, comparative studies, multicenter studies, newborn: birth to 1 month, infant: 1 to 23 months, preschool child: 2 to 5 years, child: 6 to 12 years, and adolescent: 13 to 18 years. A total of 23 studies were screened for retrieval from this search. ISI, Scopus, Popline, CINAHL, and Embase were searched using TITLE-ABS-KEY ((intranasal AND fentanyl) AND (rct OR random* OR multicenter OR review*) AND (infan* OR child* OR adolesc* OR teen* OR ‘‘young adult’’ OR ‘‘young adults’’)). A hand search of each of these databases also was conducted using the key words ‘‘intranasal’’ and ‘‘fentanyl’’ as well as a review of secondary references. Only English language studies involving children from birth to age 18 years were included. Methodological Quality A critical evaluation of the studies used was based on the strength and quality of the evidence using the Johns Hopkins Hospital/Johns Hopkins University Evidence rating scale (Figure). Studies were evaluated by a single reviewer. A grading of I/A would be considered the highest quality and strength. Four studies were graded I/A. RESULTS One hundred eighty-eight articles were identified through an electronic literature search. The research evidence for the use of INF in the pediatric population dates back to 1999, with the most recent studies available in February 2010. Excluded articles included those that were not research studies, studies not using INF, studies done in the adult population (no studies included both children and adults), and two animal studies. Redundant studies were removed. A total of 12 studies were reviewed and graded for the strength and quality of their evidence (Table). The age of the study participants in the included studies ranged from 6 months to eighteen years. Studies compared the effectiveness of pain control with INF to morphine administered intravenously, orally, and intramuscularly and to fentanyl administered September/October 2011

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FIGURE. Evidence rating scale. q The Johns Hopkins Hospital/The Johns Hopkins University.

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STRENGTH of the Evidence Experimental study/randomized controlled trial (RCT) or meta Level I analysis of RCT Quasi-experimental study Level II Level III Non-experimental study or qualitative study Level IV Level V

QUALITY of the Evidence Good Scientific

B

Opinion of nationally recognized experts based on scientific evidence or consensus panel Opinion of expert based on experiential evidence (includes case studies, literature review, organizational experience, clinical expertise, quality improvement, financial data)

QUALITY of the Evidence High Scientific

A

Summative reviews

Journal of Pediatric Health Care

Experiential

Consistent results with sufficient sample size, adequate control, and definitive conclusions; consistent recommendations based on extensive literature review that includes thoughtful reference to scientific evidence Well-defined, reproducible search strategies; consistent results with sufficient numbers of well defined studies; criteria-based evaluation of overall scientific strength and quality of included studies; definitive conclusions Expertise is clearly evident

Summative reviews

Experiential

C

Low quality Scientific or major flaws

Summative reviews

Experiential

Reasonably consistent results, sufficient sample size, some control, with fairly definitive conclusions; reasonably consistent recommendations based on fairly comprehensive literature review that includes some reference to scientific evidence Reasonably thorough and appropriate search; reasonably consistent results with sufficient numbers of well defined studies; evaluation of strengths and limitations of included studies; fairly definitive conclusions Expertise appears to be credible Little evidence with inconsistent results, insufficient sample size, conclusions cannot be drawn Undefined, poorly defined, or limited search strategies; insufficient evidence with inconsistent results; conclusions cannot be drawn Expertise is not discernable or is dubious

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TABLE. Evidence summary Author/year

Study design

Study size

Younge et al. 1999

Prospective, randomized, open-label 2-arm pilot study

N = 47

Galinkin et al. 2001

Prospective, placebo-controlled, double-blind; 2-phase

Phase I: N = 26 Phase II: N = 260

Finkel et al. 2001

Randomized controlled trial

N = 150

Borland et al. 2002

Pilot study

N = 45

Manjushree et al. 2002

Prospective, randomized, blinded study Randomized, double-blind, 2-treatment crossover study

N = 40

Prospective, randomized, double-blind, placebocontrolled clinical trial Retrospective review

N = 67

Voronov et al. 2008

Description

Evidence rating

Summary

Otherwise healthy children ages 3-10 y with clinical limb fractures; comparing IM morphine to INF Phase I: determination of serum fentanyl concentrations Phase II: Evaluation of emergence agitation postoperatively after INF administration Evaluation of emergence agitation postoperatively after INF administration in children ages 6 mo to 5 y Children ages 3 to 12 y presenting to triage at a pediatric tertiary care ED requiring immediate analgesia, INF administered IV fentanyl compared with INF postoperatively Compared pain scores in patients with burns receiving INF versus oral morphine in newborns to age 15 y Compared IV morphine to INF in children ages 7 to 15 y

II/B

INF comparable to IM morphine in effectiveness and better tolerated

I/A

Decreased postoperative agitation in patients receiving INF without increased vomiting, hypoxemia, or discharge times

I/A

Significantly reduced agitation scores in patients receiving INF compared with control Early and significant reductions in pain scores with INF

N = 617

Compared time to analgesia with INF and IV morphine; IV access requirements

III/A

Double-blind, prospective, randomized control trial

N = 200

I/A

Cole et al. 2009

Prospective, non-randomized, no control group

N = 46

Holdgate et al. 2010

Before and after observational study

N = 181

Crellin et al. 2010

Prospective, observational audit

N = 36

Compared a regional nerve block with bupivacaine to INF in children 6 mo to 6 y having myringotomy tube placement Determined effectiveness of INF in significantly reducing pain scores in children ages 1 to 3 y Compared time to opioid administration with INF compared with IV morphine in children aged 1 to 15 y Determined efficacy of INF in reducing pain in children ages 5-18 y with upper limb injuries at standard 50 mg/mL concentration

Borland et al. 2005

Borland et al. 2007

Borland et al. 2008

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IM, Intramuscular; INF, Intranasal fentanyl; IV, intravenous.

N = 28

III/B

II/B II/A

I/A

III/B

III/B

III/B

Adequate analgesia achieved via both IV fentanyl and INF INF equivalent to oral morphine in patients with burns INF effective at 1.7 mg/kg when compared with IV morphine at 0.1 mg/kg for children with fractures Significantly reduced time to analgesia with INF when compared with IV morphine No difference in pain scores between groups

INF was safe, effective, and well tolerated in children with moderate to severe pain Children with acute pain were treated faster with INF than with IV morphine 50 mg/mL concentration of INF has analgesic efficacy in children with upper limb injuries

intravenously with routine interval pain scoring. Studies comparing intranasally administered fentanyl to both orally and intravenously administered morphine reported that INF was an effective alternative to the use of morphine in the management of pain in children who had limb fractures and burns, as demonstrated by no statistically significant difference in pain scores after administration (Borland, Bergesio, Pascoe, Turner, & Woodger, 2005; Borland, Jacobs, & Geelhoed, 2002; Borland, Jacobs, King, & O’Brien, 2007). Based on parental perceptions, tolerance of INF was found to be significantly better than tolerance of intramuscularly administered morphine (Younge, Nicol, Kendall, & Harrington, 1999). No studies reported any serious adverse effects after INF administration. One study showed an increased incidence in vomiting in children receiving INF when compared with placebo (3.9%-12%), but this increased incidence was not reported in the other studies (Finkel et al., 2001). INF has been shown to be effective for relieving pain and agitation in the postoperative period (Finkel et al., 2001; Galinkin et al., 2001; Manjushree, Lahiri, Ghosh, Laha, & Handa, 2002; Voronov et al., 2008). A significant decrease in postoperative agitation scores for patients undergoing myringotomy and tube placement was found (Finkel et al., 2001; Galinkin et al., 2001), along with a higher level of nursing satisfaction (Galinkin et al., 2001). Voronov and colleagues (2008) compared a regional nerve block of the auricular branch of the vagus to 2 mg/kg of INF for management of postoperative pain in children undergoing myringotomy and tube placement. The study showed no difference in pain scores between groups and no difference in the incidence of nausea and vomiting. In another study comparing intravenously administered fentanyl to INF after surgery, no significant difference in pain relief or time to pain relief was reported (Manjushree et al., 2002). Dosing of INF can be variable. The standard dose of intravenously administered fentanyl in children is 1 to 2 mg/kg (Robertson & Shilkofski, 2005). Finkel and colleagues (2001) reported no statistically significant difference in agitation scores between children who received 1mg/kg or 2 mg/kg doses of INF, Because of its ease but there was a statistiof administration, cally significant reduction in agitation scores INF can have an (also referred to as effect on the overall pain-related behavtime to analgesia. iors) in the children who received 2 mg/kg of INF when compared with placebo. Both studies found that fentanyl significantly decreased the incidence of postoperative agitation (i.e., crying and consolability) when administered at 2 mg/kg intranasally, 320

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without adversely affecting recovery times. Numerous other studies have demonstrated effective analgesia at the standard 1 to 2 mg/kg per dose when administered intranasally (Borland et al., 2002; Borland et al., 2005; Borland et al., 2007; Crellin, Ling, & Babl, 2010; Finkel et al., 2001; Galinkin et al., 2001; Holdgate, Cao, & Lo, 2010; Manjushree et al., 2002; Younge et al., 1999). Finkel and colleagues found that patients in the INF group required a statistically significant greater fentanyl dose than did those in the intravenous group, with the highest intranasal dose of 1.82 mg/kg per dose. This figure remains within the standard pediatric dose range for intravenous administration (1-2 mg/kg per dose). Because of its ease of administration, INF can have an effect on the overall time to analgesia. Studies have shown significant pain improvement in children 10 minutes after administration (Borland et al., 2002; Cole, Shepherd, & Young, 2009; Manjushree et al., 2002; Younge et al., 1999). This quick onset of action and ease of administration can have a significant impact on patient care, as evidenced by Borland, Clark, and Esson (2008), who found a significantly reduced time to analgesia in patients receiving INF versus intravenously administered morphine. Similarly, the use of INF was found to have a significant decrease in the number of children needing intravenous line placement for opioid administration (100% intravenous line placement compared with 41.8%) (Borland et al., 2008). Holdgate, Cao, and Lo (2010) found a significant decrease in the time to analgesia administration with INF compared with intravenously administered morphine (140 minutes versus 32 minutes) for children presenting to the emergency department in acute pain (Holdgate et al., 2010). In the United States, fentanyl is available in a standard 50 mg/mL intravenous formulation. The intranasal form is the intravenous formulation instilled into the nares. In some studies conducted outside the United States, more concentrated forms have been used, from 100 to 150 mg/mL (Borland et al.,, 2002; Borland et al., 2005; Borland et al., 2007). This dosage affects the total volume of medication to be administered. Crellin, Ling, and Babl (2010) found statistically significant reductions in pain scores in children with upper limb injuries when the 50 mg/mL concentration was used at a dose of 1.5 mg/kg (maximum dose of 50 mg). LIMITATIONS A limitation of the studies of INF is in the method of administration, which was done either via a mucosal atomization device or by dripping into the nostrils. Mucosal atomizer devices are suggested to increase the mucosal coverage and absorption of the medication by atomizing particles and decreasing the amount of medication lost due to swallowing. The method of delivery differed depending on the study. In studies by Journal of Pediatric Health Care

Borland and colleagues (2002, 2005, 2007), Cole and colleagues (2009), and Holdgate and associates (2010), INF was administered via a mucosal atomization device. Galinkin and colleagues (2001), Finkel and colleagues (2001), and Manjushree and associates (2002) administered INF by dripping it into the nares. Another limitation was in the quality of the studies and the use of a single reviewer to grade them. Four of the studies were level I/A. The remaining studies were level II/A (one study), II/B (two studies), III/A (one study), and III/B (four studies). No systematic reviews or meta-analyses were available. Several of the studies had small sample sizes. The highest level studies (I/A) involved pain in children who had burns, long bone fractures, and postoperative emergence agitation and pain. Safety studies have not been conducted to look at long-term effects on the nasal mucosa. Another limitation of the use of INF is its short duration of action, making it less suitable than other options for prolonged analgesia. DISCUSSION The evidence surrounding inadequate pain practices in children is substantial. INF has been shown to be equivalent or superior to morphine that is administered orally, intravenously, and intramuscularly and equivalent to intravenously administered fentanyl in providing pain control in children for many INF has been painful procedures shown to be and conditions; in addition, it decreases the equivalent or time to analgesia adsuperior to ministration and the morphine that is time to pain relief. INF has been incorporated administered orally, into the protocols of intravenously, and a number of hospitals intramuscularly and for pain management (Starship Children’s equivalent to Health, 2007; Sunshine intravenously Hospital, 2008). It has administered a strong safety profile, is easily available in fentanyl in the hospital setting, providing pain and does not require control in children additional pharmacy compounding in its for many painful commercially available procedures and form. This strong eviconditions.. dence, along with the significant ease of administration and no requirement for intravenous line placement or injection for administration, make it a potentially superior option and/or adjunct treatment for acute and procedural pain control in children. When compared with current practices, it has the www.jpedhc.org

potential to improve patient and family satisfaction and could have further implications related to improved cost-effectiveness and quality of care. REFERENCES Australian and New Zealand College of Anaesthetists and Faculty of Pain Medicine. (2005). Acute pain management: Scientific evidence (Australian Government-National Health and Medical Research Council No. 2). Retrieved from http://www.nhmrc. gov.au/publications/synopses/_files/cp104.pdf Borland, M. L., Bergesio, R., Pascoe, E. M., Turner, S., & Woodger, S. (2005). Intranasal fentanyl is an equivalent analgesic to oral morphine in paediatric burns patients for dressing changes: A randomised double blind crossover study. Burns, 31(7), 831-837. Borland, M. L., Clark, L. J., & Esson, A. (2008). Comparative review of the clinical use of intranasal fentanyl versus morphine in a paediatric emergency department. Emergency Medicine Australasia, 20(6), 515-520. Borland, M. L., Jacobs, I., & Geelhoed, G. (2002). Intranasal fentanyl reduces acute pain in children in the emergency department: A safety and efficacy study. Emergency Medicine, 14(3), 275-280. Borland, M., Jacobs, I., King, B., & O’Brien, D. (2007). A randomized controlled trial comparing intranasal fentanyl ot intravenous morphing for managing acute pain in children in the emergency department. Annals of Emergency Medicine, 49(3), 335-340. Cole, J., Shepherd, M., & Young, P. (2009). Intranasal fentanyl in 1-3-year olds: A prospective study of the effectiveness of intranasal fentanyl as acute analgesia. Pediatric Emergency Medicine, 21(5), 395-400. Crellin, D., Ling, R. X., & Babl, F. E. (2010). Does the standard intravenous solution of fentanyl (50mcg/mL) administered intranasally have analgesic efficacy. Pediatric Emergency Medicine, 22(1), 62-67. Cummings, E. A., Reid, G. J., Finley, G. A., McGrath, P. J., & Ritchie, J. A. (1996). Prevalence and source of pain in pediatric inpatients. Pain, 68(1), 25-31. Dooks, P. (2001). Diffusion of pain management research into nursing practice. Pain Management Research, 24(2), 99-103. Finkel, J. C., Hannallah, R. S., Patel, K. M., Kim, M. S., Hummer, K. A., Choi, S. S., . Zalzal, G. (2001). The effect of intranasal fentanyl on the emergence characteristics after sevoflurane anesthesia in children undergoing surgery for bilateral myringotomy tube placement. Pediatric Anesthesia, 92(5), 116. Finn, J., Wright, J., Fong, J., Mackenzie, E., Wood, F., Leslie, G., & Gelavis, A. (2004). A randomized crossover trial of patient controlled intranasal fentanyl and oral morphine for procedural wound care in adult patients with burns. Burns, 30(3), 262-268. Food and Drug Administration. (2002). Anesthetic and life support drugs advisory committee. Retrieved from http://www.fda. gov/ohrms/dockets/ac/02/minutes/3820m1.htm Friedland, L. R., Pancioli, A. M., & Duncan, K. M. (1997). Pediatric emergency department analgesic practice. Pediatric Emergency Care, 13(2), 103-106. Friedrichsdorf, S. J., & Kang, T. I. (2007). The management of pain in children with life-limiting illnesses. Pediatric Clinics of North America, 54, 645-672. Galinkin, J. L., Fazi, L. M., Cuy, R. M., Chiavacci, R. M., Kurth, C. D., Shah, U. K., . Watcha, M. F. (2001). Use of intranasal fentanyl in children undergoing myringotomy and tube placement during halothane and sevoflurane anesthesia. Anesthesiology, 93(6), 1378-1383. Goldman, R. D. (2006). Intranasal drug delivery for children with acute illness. Current Drug Therapy, 1(1), 127-130. Grape, S., Schug, S. A., Lauer, S., & Schug, B. S. (2010). Formulations of fentanyl for the management of pain. Drugs, 70(1), 57-72.

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Holdgate, A., Cao, A., & Lo, K. M. (2010, January). The implementation of intranasal fentanyl for children in a mixed adult and pediatric emergency department reduces time to analgesia administration. Society for Academic Emergency Medicine, 17, 1-4. Kavanagh, T., Watt-Watson, J., & Stevens, B. (2007). An examination of the factors enabling the successful implementation of evidence-based acute pain practices into pediatric nursing. Children’s Health Care, 36(3), 303-321. Kennedy, R. M., Luhmann, J., & Zempsky, W. T. (2008). Clinical implications of unmanaged needle-insertion pain and distress in children. Pediatrics, 122, S130-S133. 10.1542/peds. 2008-1055e. Krauss, B., & Green, S. M. (2006). Procedural sedation and analgesia in children. Lancet, 367(9512), 766-780. Leykin, Y., Pellis, T., & Ambrosio, C. (2007). Highlights in postoperative pain treatment. Expert Review of Neurotherapeutics, 7(5), 533-545. Mace, S. E., Barata, I. A., Cravero, J. P., Dalsey, W. C., Godwin, S. A., Kennedy, R. M., . Wears, R. L. (2004). Clinical policy: Evidence-based approach to pharmacologic agents used in pediatric sedation and analgesia in the emergency department. Annals of Emergency Medicine, 44(4), 342-377. MacLaren, J., & Kain, Z. N. (2008). Research to practice in pediatric pain: What are we missing? Pediatrics, 122, 443-444. MacLean, S., Obispo, J., & Young, K. (2007). The gap between pediatric emergency department procedural pain management treatments available and actual practice. Pediatric Emergency Care, 23(2), 87-93.

Magaret, N. D., Clark, T. A., Warden, C. R., Magnusson, A. R., & Hedges, J. R. (2002). Patient satisfaction in the emergency department—a survey of pediatric patients and their parents. Academic Emergency Medicine, 9(12), 1379-1388. Manjushree, R., Lahiri, A., Ghosh, B. R., Laha, A., & Handa, K. (2002). Intranasal fentanyl provides adequate postoperative analgesia in pediatric patients. Canadian Journal of Anesthesia, 49(2), 190-193. Robertson, J., & Shilkofski, N. (2005). The Harriet Lane handbook (17th ed.). Philadelphia, PA: Mosby. Rupp, T., & Delaney, K. A. (2004). Inadequate analgesia in emergency medicine. Annals of Emergency Medicine, 43(4), 494-503. Shelley, K., & Paech, M. J. (2008). The clinical application of intranasal opioids. Current Drug Delivery, 5(1), 55-58. Starship Children’s Health. (2007). Starship Children’s Health clinical guideline. Retrieved from http://www.starship.org.nz/ Clinical%20Guideline%20PDFs/Intranasal%20Fentanyl.pdf Sunshine Hospital. (2008). Intranasal fentanyl. Retrieved from http:// www.ozemedicine.com/blog/wp-content/uploads/2008/08/ sunshine-intranasal-fentanyl-policy.pdf Voronov, P., Tobin, M. J., Billings, K., Cote, C. J., Ayer, A., & Suresh, S. (2008). Postoperative pain relief in infants undergoing myringotomy and tube placement: Comparison of a novel regional anesthetic block to intranasal fentanyl—a pilot analysis. Pediatric Anesthesia, 18(12), 1196-1201. Younge, P. A., Nicol, M. F., Kendall, J. M., & Harrington, A. P. (1999). A prospective randomized pilot comparison of intranasal fentanyl and intramuscular morphine for analgesia in children presenting to the emergency department with clinical fractures. Emergency Medicine, 11, 90-94.

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