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Three Part Question

In [children requiring shoulder dislocation reduction], is [intranasal fentanyl superior to inhaled methoxyflurane] for [procedural pain control and safety]?

Clinical Scenario

A 13-year-old child presents to the Emergency Department with an anterior shoulder dislocation. You must decide between intranasal fentanyl or inhaled methoxyflurane (Penthrox) for procedural analgesia. Which option provides better pain relief and overall patient experience?

Search Strategy

A focused literature search was conducted primarily using PubMed, accessing MEDLINE-indexed and additional relevant biomedical literature from 1995 to 2025. The aim was to identify evidence on intranasal fentanyl (INF) and inhaled methoxyflurane (Penthrox; MF) for procedural analgesia in paediatric patients presenting to Emergency Departments with traumatic injuries such as fractures or dislocations.

Due to the absence of direct comparative studies between the two agents, two separate searches were performed:

Search 1:
("methoxyflurane" OR "Penthrox") AND (children OR paediatric OR pediatric) AND ("emergency department") AND (injury OR fracture OR dislocation)
5 studies identified; 2 relevant.

Search 2:
("intranasal fentanyl") AND (children OR paediatric OR pediatric) AND ("emergency department") AND (injury OR fracture OR dislocation)
22 studies identified; 5 relevant

Search Outcome

A total of 7 relevant papers were identified (2 on methoxyflurane and 5 on intranasal fentanyl).

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Babl 2007 Australia	14 children aged 6–13 years undergoing painful procedures in the ED	Prospective Observation	Pain scores, depth of sedation, adverse events, satisfaction, methoxyflurane consumption	MF provided effective analgesia, especially as a self-administered “bridging” analgesic for children with high baseline pain scores (≥6). No serious adverse events occurred; mild, brief side effects (agitation, euphoria, dizziness, cough) were noted. MF was less effective for procedural analgesia when initial pain was low, highlighting the need for patient coaching and anticipation. All patients tolerated MF well with no deep sedation reported.	Small sample size (n=14), limiting generalizability. Lack of a control or comparison group. Observational design without randomization. Subjective outcome measures (pain scores, satisfaction) without blinding.
Bisso 2024 Aug 30 France	77 children with displaced fractures	Before-and-after	Pain relief, time to care, safety	NF significantly reduced time to adequate analgesia (median 10 vs. 80 minutes) and overall ED care time (median 150 vs. 215 minutes) compared to oral morphine. INF provided greater pain reduction before and during fracture reduction and required fewer additional doses. Pain scores at arrival were similar, but INF maintained lower pain levels during the procedure, allowing extension of use to lower limb fractures. No serious adverse events reported, indicating good safety and tolerability.	Non-randomized before-and-after design No direct comparison to methoxyflurane. Single-center study, which may affect generalizability. Lack of blinding could affect outcome assessment
Borland 2008 Dec;20 Australia	617 Children in ED with moderate/severe pain	Narrative review	Analgesic effectiveness and feasibility	INF was associated with significantly shorter time to analgesia compared to morphine ( ~23–31 min vs ~53–56 min). Increased use of INF over time corresponded with decreased morphine use and reduced need for intravenous access for analgesia. INF was most commonly used for fractures, morphine for abdominal pain, reflecting differing clinical indications. INF dosing increased over the study period with continued effectiveness and safety.	Narrative review, not primary data. No randomization or control group, limiting causal inferences. Data limited to a single center and specific timeframes, which may affect generalizability. Outcomes focused mainly on time metrics, with limited direct pain score comparisons.
Saunders 2010 Nov;17 USA	81 children aged 3–18 with suspected fractures	Prospective interventional	Pain reduction, adverse events	Single dose of intranasal fentanyl (2 μg/kg) provided significant pain reduction within 10 minutes, sustained at 20 and 30 minutes. Pain scores dropped substantially on Wong-Baker Faces and Visual Analog Scales. High satisfaction scores from providers, parents, and patients. No adverse events reported, indicating good safety profile	Non blinded design with no control or comparison group limits ability to draw definitive conclusions on efficacy relative to other analgesics. Small sample size and single center limit generalizability. Short follow-up (30 minutes) does not capture longer-term analgesia.
Hoeffe 2017 May France	90 children aged 4–18 undergoing fracture/dislocation reduction	Prospective observational	Pain scores, sedation levels, satisfaction, safety	Combination of INF and nitrous oxide was safe and effective with high satisfaction	No control group, INF not evaluated independently
Finn 2010 Apr UK	Children with severe pain in PED	Observational	Pain control, safety	INF safe and effective alternative to diamorphine	Observational design without a randomized control group limits strength of conclusions. Details on sample size, pain scores, and adverse event rates not clearly reported in abstract.
Babl 2006 Aug; Australia	105 children (15 months–17 yrs), prehospital	Observational case series	Pain relief, safety	Methoxyflurane provided effective analgesia for pediatric patients with mainly extremity injuries in the prehospital ambulance setting, with mean pain scores decreasing significantly from 7.9 to 3.2 within 10 minutes. No serious adverse events were reported, although mild adverse events occurred in about 36% of patients. Deep sedation was observed transiently in about one-third of children under 5 years old.	Prehospital only. The study was an observational case series without a control group, limiting the ability to establish causality or compare with other analgesics. The sample size was relatively small (105 patients) Lack of long-term follow-up or randomized comparison limits broader generalizability

Comment(s)

Currently, no high-quality direct comparison studies exist between intranasal fentanyl and inhaled methoxyflurane for paediatric procedural analgesia during fracture or dislocation reduction. Intranasal fentanyl is well-established, with substantial evidence supporting its safety, rapid onset, and ease of use in paediatric emergency care. Methoxyflurane demonstrates potential as a self-administered inhaled analgesic and is widely used in Australia and Europe, with growing adoption elsewhere. However, its paediatric licensing and evidence base remain limited. From a practical standpoint, intranasal fentanyl can be administered rapidly without IV access, which is ideal in the paediatric emergency setting. Methoxyflurane is delivered via a hand-held inhaler that allows self-titration and provides analgesia along with mild sedation; however, it requires patient cooperation and has been associated with transient deep sedation in some young children, necessitating careful monitoring. Well-designed head-to-head trials are needed to clarify the comparative effectiveness, safety, and patient-centered outcomes of these two agents

Clinical Bottom Line

No head-to-head trials comparing intranasal fentanyl and methoxyflurane for procedural analgesia in paediatric orthopaedic reductions currently exist. Intranasal fentanyl is a rapid-acting, non-invasive, and widely accepted analgesic with a strong safety profile; it is widely used in paediatric emergency settings. Methoxyflurane shows promise as a self-administered inhaled analgesic, particularly for older, cooperative children. Although not licensed for paediatric use in the UK, it has an emerging evidence base internationally, especially in Australia and parts of Europe. Until further evidence and licensing data are available, intranasal fentanyl remains the first-line procedural analgesic in paediatric EDs. ((Conclusion)): Due to limited direct comparisons, it is not currently possible to determine which agent is superior in terms of safety, efficacy, and overall patient experience. Intranasal fentanyl remains the standard option in many UK EDs due to its ease of use, clinician familiarity, and robust evidence base. Methoxyflurane may become a valuable option pending licensing and further paediatric-specific data, especially for older, cooperative children who can effectively self-administer the inhaler. ((Disclaimer)): As methoxyflurane is not currently licensed for paediatric use in the UK, this BET does not advocate or endorse its use in this population. Rather, it raises the clinical question of whether methoxyflurane might offer a useful alternative to intranasal fentanyl if future evidence and licensing support its use for paediatric procedural analgesia.

References

1. Babl FE, Barnett P, Palmer G, Oakley E, Davidson A. A pilot study of inhaled methoxyflurane for procedural analgesia in children. Emerg Med J. 2007;24(9):658-63. A pilot study of inhaled methoxyflurane for procedural analgesia in children 2007 Feb
2. Raoul Bisso 1, Alexandra Tielli, Anne-Aurelie Lopes Intranasal Fentanyl Versus Morphine in Fracture Reduction in a Pediatric Trauma Center 2024 Aug 30
3. Meredith Louise Borland 1, Lisa-Jayne Clark, Amanda Esson Comparative review of the clinical use of intranasal fentanyl versus morphine in a paediatric emergency department 2008 Dec;20
4. Mary Saunders 1, Kathleen Adelgais, Douglas Nelson Use of intranasal fentanyl for the relief of pediatric orthopedic trauma pain 2010 Nov;17
5. J Hoeffe 1, E Doyon Trottier 2, B Bailey 2, D Shellshear 3, M Lagacé 2, C Sutter 3, G Grimard 4, R Cook 2, F E Babl 5 Intranasal fentanyl and inhaled nitrous oxide for fracture reduction: The FAN observational study 2017 May
6. Maria Finn 1, Dan Harris Intranasal fentanyl for analgesia in the paediatric emergency department 2010 Apr
7. Franz E Babl 1, Sarah R Jamison, Maureen Spicer, Stephen Bernard Inhaled methoxyflurane as a prehospital analgesic in children 2006 Aug;