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Educational Objectives:

After evaluating this article, participants will be able to:
1. Incorporate nebulized fentanyl into clinical practice, improving patient care
2. Develop new strategies for the provision of procedural sedation in pediatric patients
3. Reduce the need for intravenous narcotic analgesics in pediatric pain management

Q. Is nebulized fentanyl as effective as intravenous fentanyl in children with acute pain?

A.There are several studies evaluating the use of nebulized fentanyl. In this study, 3 ug/kg of nebulized fentanyl was a great alternative to intravenous fentanyl. Patients less than 3 years of age did not do as well, most likely due to difficulties with cooperation.


Miner JR, Kletti C, Herold M, Hubbard D, Biros MH. Randomized clinical trial of nebulized fentanyl citrate versus i.v. fentanyl citrate in children presenting to the emergency department with acute pain. Acad Emerg Med. 2007 Oct;14(10):895-8.

Objectives: To compare the pain relief achieved with nebulized fentanyl citrate with intravenous (i.v.) fentanyl citrate in children presenting to the emergency department (ED) with painful conditions to determine if nebulized fentanyl is a feasible alternative to i.v. fentanyl for the treatment of acute pain in children.

Methodology: This was a randomized controlled trial in an urban county medical center ED with an annual census of 99,000 visits. ED patients, aged 6 months to 17 years, presenting with acute pain who were going to be treated with i.v. pain medications, were eligible for enrollment. After the parents had provided informed consent, and children older than 6 years had provided assent, patients were randomized (1:2) to receive either fentanyl citrate i.v. (1.5 microg/kg) or fentanyl citrate by breath-actuated nebulizer (3.0 microg/kg). Patients aged 6 years and older completed a 100-mm visual analog scale (VAS) describing their pain, and patients younger than 6 years had their pain assessed by the treating physician using the Children’s Hospital of Eastern Ontario Pain Scale. Additionally, treating physicians used a 100-mm VAS to describe their perception of the patients’ pain. These pain measurements were taken before treatment and every 10 minutes thereafter for 30 minutes. Baseline blood pressure, heart rate, and oxygen saturation were also measured before treatment and every 10 minutes for 30 minutes. After 30 minutes, physicians were asked whether or not they believed the medication provided adequate pain relief for the patient. Parents were asked to rate their satisfaction with the treatment using a five-point scale. Patients who received additional pain medications by any method before the 30-minute measurement period was completed were considered treatment failures. Data were compared using descriptive statistics and 95% confidence intervals; the rates of adequate pain relief between the groups were compared using Fisher exact tests.

Findings: Forty-one patients were enrolled in the study; 14 were randomized to i.v. fentanyl (ten actually received it), and 27 patients were randomized to nebulized fentanyl (31 actually received it). In the four patients who were randomized to i.v. fentanyl but received nebulized fentanyl, the parents requested the nebulized medication after being told their child had been randomized to i.v. fentanyl. Baseline pain VAS scores were 82.8 mm (SD +/-14.3, 69-100) in the i.v. group and 76.2 mm (SD +/-20.5, 34-100) in the nebulized group. There were five treatment failures: one who received i.v. fentanyl and four who received nebulized fentanyl. The four patients who were considered treatment failures in the nebulized fentanyl group were all younger than 3 years and had difficulty triggering the breath-actuated nebulizer. The mean decrease in pain for patients remaining in the study was 55.1 mm (95% CI = 40.3 to 70.0) for the i.v. group and 77.8 mm (95% CI = 67.4 to 88.4) for the nebulized group. The pain treatment was described as adequate by the treating physician in eight of 14 patients in the i.v. group and 20 of 27 patients in the nebulized group (p = 0.42). No adverse events were detected.

Conclusion: Nebulized fentanyl citrate 3 microg/kg through a breath-actuated nebulizer appears to be a feasible alternative to i.v. fentanyl citrate for a variety of painful conditions in patients older than 3 years


Q. Is nebulized fentanyl as effective as intravenous morphine?

A. In the following 2 articles, nebulized fentanyl in doses ranging from 1.7ug/kg to 4 ug/kg was found to be as effective as intravenous morphine for acute pain relief in children..

Citation #1

Furyk JS, Grabowski WJ, Black LH. Nebulized fentanyl versus intravenous morphine in children with suspected limb fractures in the emergency department: a randomized controlled trial. Emerg Med Australas. 2009 Jun;21(3):203-9.  

Objective: To compare the efficacy of nebulized fentanyl (NF) with i.v. morphine (IVM) in paediatric patients presenting to the ED with clinically suspected limb fractures.

Methodology: A convenience sample of patients aged 4-13 years, presenting with clinically suspected limb fractures, were randomized to receive either NF at 4 microg/kg or IVM at 0.1 mg/kg. Pain scores were assessed at 0, 15 and 30 min using the Wong and Baker faces pain scale (0-10). Vital signs and adverse effects were also recorded.

Findings: Of the 77 patients enrolled in the study, data were available for analysis on 73 patients. Of those, 36 received NF and 37 received IVM. The two groups were similar in terms of demographics and initial pain scores. Mean pain score at 15 min was decreased by 3.06 (NF) and by 1.97 (IVM) (difference 1.09; 95% CI 2.32 to -0.32). At 30 min the decreases were 3.6 (NF) and 3.0 (IVM), respectively (difference 0.6; 95% CI 1.89 to -0.65). Decreases in pain scores for both NF and IVM were statistically significant (P < 0.0001), but the difference in the effect of NF and IVM did not reach statistical significance. There was no significant change in any vital signs or serious adverse events in either group.

Conclusion: NF in a dose of 4 microg/kg given via a standard nebulizer provided clinically significant improvements in pain scores, comparable to IVM. NF should be considered as a treatment option for use in children presenting in acute pain

Citation #2

Borland M, Jacobs I, King B, O’Brien D.A randomized controlled trial comparing intranasal fentanyl to intravenous morphine for managing acute pain in children in the emergency department. Ann Emerg Med. 2007 Mar;49(3):335-40. Epub 2006 Oct 25



click on image to enlarge


Objective: To compare the efficacy of intranasal fentanyl versus intravenous morphine in a pediatric population presenting to an emergency department (ED) with acute long-bone fractures.

Methodology: We conducted a prospective, randomized, double-blind, placebo-controlled, clinical trial in a tertiary pediatric ED between September 2001 and January 2005. A convenience sample of children aged 7 to 15 years with clinically deformed closed long-bone fractures was included to receive either active intravenous morphine (10 mg/mL) and intranasal placebo or active intranasal concentrated fentanyl (150 microg/mL) and intravenous placebo. Exclusion criteria were narcotic analgesia within 4 hours of arrival, significant head injury, allergy to opiates, nasal blockage, or inability to perform pain scoring. Pain scores were rated by using a 100-mm visual analog scale at 0, 5, 10, 20, and 30 minutes. Routine clinical observations and adverse events were recorded.

Findings: Sixty-seven children were enrolled (mean age 10.9 years [SD 2.4]). Fractures were radius or ulna 53 (79.1%), humerus 9 (13.4%), tibia or fibula 4 (6.0%), and femur 1 (1.5%). Thirty-four children received intravenous (i.v.) morphine and 33 received intranasal fentanyl. Statistically significant differences in visual analog scale scores were not observed between the 2 treatment arms either preanalgesia or at 5, 10, 20, or 30 minutes postanalgesia (P=.333). At 10 minutes, the difference in mean visual analog scale between the morphine and fentanyl groups was -5 mm (95% confidence interval -16 to 7 mm). Reductions in combined pain scores occurred at 5 minutes (20 mm; P=.000), 10 minutes (4 mm; P=.012), and 20 minutes (8 mm; P=.000) postanalgesia. The mean total INF dose was 1.7 microg/kg, and the mean total i.v. morphine dose was 0.11 mg/kg. There were no serious adverse events.

Conclusion: Intranasal fentanyl delivered as 150 microg/mL at a dose of 1.7 microg/kg was shown to be an effective analgesic in children aged 7 to 15 years presenting to an ED with an acute fracture when compared to intravenous morphine at 0.1 mg/kg

Nebulized fentanyl is an impressive alternative to intravenous medication in children. It would be nice to see trials researching the combination of midazolam and nebulized fentanyl to see if this combination provides an even better possibility for procedural sedation. This would be useful in children who have difficult intravenous access or who require simple, quick procedures.


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