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Intranasal fentanyl or diamorphine versus intravenous morphine for analgesia in adults

Three Part Question

In [adults presenting to the Emergency Department in pain] is [intranasal fentanyl superior to intravenous morphine] at [reducing pain]?

Clinical Scenario

It is 7:45am and you are just winding down with a coffee before the end of a shift and the doors to the Emergency Department (ED) burst open. Lying on a stretcher is a young, obese lady who is screaming in agony. She has an obvious fracture dislocation of the ankle. Just when you thought things couldn't get any worse the paramedics inform you that she has no visible peripheral veins. While you evaluate your options of escape you ask yourself the question: "Would intranasal fentanyl be as efficacious as intravenous morphine in the reduction of pain from this broken ankle"?

Search Strategy

Medline 1950—March Week 2, 2010 via the Ovid interface.

EMBASE 1980—2010 Week 11 via the Ovid interface.

( OR exp Fentanyl/OR exp Heroin/OR AND (exp Administration, Intranasal/OR AND ( OR exp Morphine/OR exp Morphine Derivatives/) AND (exp Infusions, Intravenous/OR OR exp Injections, Intravenous/) AND ( OR exp Pain/OR exp Pain Measurement/OR exp Analgesia/OR analgesi$.mp.) limit to all adult (19 plus years).

Cochrane Library, accessed 22 March, 2010:

(fentanyl OR diamorphine) AND intranasal.

Search Outcome

Six papers were identified in Medline, 78 in EMBASE and 52 in the Cochrane Library. One paper was relevant to the three-part question.

Relevant Paper(s)

Author, date and country Patient group Study type (level of evidence) Outcomes Key results Study Weaknesses
Rickard et al,
258 patients requiring analgesia (for cardiac pain refractory to GTN with pain score >5/10 or non-cardiac pain with verbal rating score >2/10) in the prehospital setting Prospective, multicentred, open-labelled, RCT consisting of two treatment arms with patients receiving either intranasal fentanyl (180 mcg via an atomiser) or intravenous morphine (2.5–5 mg) at time 0, and further doses (60 mcg fentanyl or 2.5–5 mg morphine) at 5 min intervals if requiredVerbal rating scores (VRS) at baseline, before each dose of analgesia and at destination (T0, T1, T2 and Td) No significant difference in VRS at any time point (T0, T1, T2 or T3)Initial sample size estimates of 200 per arm not met (400 total) therefore strong potential for type 2 error. Open-labelled design may have resulted in operator bias. No comment why different inclusion VRS scores were required for chest pain (>5) as opposed to non-cardiac pain (>2).


Severe pain is common among patients presenting to the ED. The traditional ‘gold standard’ analgesic agent is intravenous morphine. Unfortunately, this is not without its complications. Failure to cannulate, pain and fear of cannulation, and the risk of infection are all important considerations. Intranasal administration of opiate analgesia has some potential advantages over intravenous morphine due to its ease of administration, rapid onset, shorter duration and the lack of histamine release. It has been demonstrated that intranasal fentanyl or diamorphine are effective alternatives to intravenous morphine among children in the ED and for relief of postoperative pain and anxiety in children undergoing ear, nose and throat (ENT) surgery. There remains a lack of robust evidence, however, in the ED setting. The one randomised controlled trial identified failed to achieve the target sample size, and may, therefore, have been underpowered to detect a small but clinically significant difference. Intranasal administration of opiates remains a promising alternative to the intravenous route in the ED, but more research is required in order to provide an evidence-based recommendation for its implementation.

Editor Comment

GTN, Glyceryl trinitrate; RCT, randomized controlled trial; VRS, verbal rating scores

Clinical Bottom Line

Intranasal opiates have the clear theoretical advantage of providing rapid analgesia to patients where cannulation is undesirable or impossible. However, there is limited available evidence to suggest that intranasal fentanyl may provide similar analgesia to intravenous morphine in the Emergency Department. Further evidence from larger trials is still required to eliminate the possibility of type 2 error.

Level of Evidence

Level 2 - Studies considered were neither 1 or 3.


  1. Rickard, C; O'Meara P; McGrail M et al. A randomized controlled trial of intranasal fentanyl vs intravenous morphine for analgesia in the prehospital setting. American Journal of Emergency Medicine 2007; 25: 911– 917.
  2. Braude D; Richard M. Appeal for fentanyl prehospital use. Prehospital Emergency Care 2004; 8; 441-2.
  3. Borland MI; Jacobs I; Geelhoed G. Intranasal fentanyl reduces acute pain in children in the Emergency Department: a safety and efficacy study. Emergency Medicine 2002; 14(3):275-80.
  4. Fazi LM; Cuy RM; Chiavacci RM; et al. Use of intranasal fentanyl in children undergoing myringotomy and tube placement during halothane and sevoflurane anesthesia Anesthesiology 2000; 93(6):1378-83.