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Three Part Question

In [children presenting to Accident & Emergency in acute pain] is [intranasal fentanyl a better analgesic than intravenous or intramuscular morphine] at [reducing pain]

Clinical Scenario

A child presents to the paediatric emergency department in acute pain but you cannot give him intranasal diamorphine due to both a departmental and nationwide shortage. You are able to give them either IM or IV morphine but wonder whether you can use intranasal fentanyl instead

Search Strategy

Medline 1950-September week 4 2011 using the OVID interface
(exp pediatrics OR pediatric.mp OR paediatric.mp OR child.mp OR exp child, preschool OR exp child OR exp adolescent OR adolescent.mp OR ped$.mp OR paed$.mp OR infant.mp OR exp infant) AND (fentanyl.mp OR exp fentanyl) AND (exp administration, intranasal OR intranasal.mp)

Search Outcome

51 papers found of which 47 failed to answer the three part question

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Borland, M et al 2007 Australia	67 children presenting with closed long-bone fractures. Randomised to intranasal fentanyl (INF) or intravenous morphine (IVM).	Double-blind, placebo RCT	Reduction in pain score	No statistically significant difference in pain scores at 5, 10, 20 or 30 minutes (p=0.333)	Difficulty in using VAS in younger children, however this is acknowledged in the study, and the use of a VAS has been validated in previous studies.
			Pooled VAS	significant reduction in VAS at 5 mins (p=0.000), 10 mins (p=0.012) and 20 mins (p=0.000)
			Routine observations	no significant change in observations
			Adverse events	INF: 3 children reported a bad taste in their mouth, and one vomited, but had been pre-analgesia. IVM: 1 child experienced flushing at the IV site
Younge P et al 1999 UK	47 children clinical fracture of the upper or lower limbs randomised to intranasal fentanyl (INF) or intramuscular morphine (IMM).	Open-label RCT	Pain score	Significant difference at 10 minutes with INF (p=0.014)	Small study, but authors acknowledge need for a sample size of 250 to detect a 5% difference in pain score with 90% power. Not blinded. Use of only a 5 point VAS making discrimination between points less reliable.
			Parents pain score	No significant difference at any time period
			Tolerance to administration	INF significantly better tolerated (p<0.001)
			Adverse effects	Insufficient subjects
Borland, M et al 2008 Australia	617 children on the controlled drug register were identified in a 3 month period for 3 subsequent years (2005, 2006 & 2007). The time to analgesia in these groups was then compared.	Retrospective case-note review	Time to analgesia	significantly lower time to analgesia for INF vs morphine in 2006 and 2007	Retrospective based on case-notes therefore limited by information supplied in notes
			Rate of IV access	decrease from 100% in 2005 to 41.8% in 2007
Bendall JC et al 2011 Australia	3,312 children aged 5-15 with moderate to severe pain (pain score 5 or more) who recieved either IV morphine, IN fentanyl or inhaled methoxyflurane. Logistic regression analysis of exisitng database.	Retrospective comparative study	Analgesic effect	87.5% morphine 89.5% fentanyl	Retrospective study. Pre-hospital study but this equates well to ED population.
			Odds ratio effectiveness fentanyl compared to morphine for successful analgesia	OR 1.22; (95% CI 0.74-2.01) therefore no significant difference

Comment(s)

This topic has been addressed previously, however a new study on the topic has since been published, and included in this Best Evidence Topic. The study from 2007 does demonstrate a significant reduction in pooled pain scores with intranasal fentanyl when compared to intravenous morphine, with no change in routine observations and a low rate of adverse effects. The 2008 study, also assessing intranasal fentanyl vs intravenous morphine, also demonstrates a significantly reduced time to analgesia with intranasal fentanyl, and in addition a significant reduction in IV access requirements. In conclusion, the above studies suggest that intranasal fentanyl is at least as effective as IV or IM morphine. Importantly, it is well tolerated and its use can reduce the need for IV access or painful IM injections in children. While difficulties securing stocks of diamorphine continue, fentanyl looks to be a reasonable, less expensive agent to be administered via the intranasal route.

Clinical Bottom Line

Intranasal fentanyl is a proven effective and safe alternative to IV or IM morphine for managing acute pain in children presenting to A&E.

References

1. Borland, M et al A Randomised Controlled Trial Comparing Intranasal Fentanyl to Intravenous Morphine for Managing Acute Pain in Children in the Emergency Department Annals of Emergency Medicine 2007;49:335-340
2. Younge P et al A Prospective Randomised Pilot Comparison of Intranasal Fentanyl & Intramuscular Morphine For Analgesia in Children Presenting to the Emergency Department with Clinical Fractures Emergency Medicine 1999;11:90-94
3. Borland, M et al Comparative review of the Clinical use of Intranasal Fentanyl Versus Morphine in a Paediatric Emergency Department Emergency Medicine Australasia 2008;20:515-520
4. Bendall, Jason C. Simpson, Paul M. Middleton, Paul M. Effectiveness of prehospital morphine, fentanyl, and methoxyflurane in pediatric patients. Prehospital Emergency Care. 15(2):158-65, 2011 Apr-Jun