Intranasal fentanyl is an equivalent analgesic to oral morphine in paediatric burns patients for dressing changes: A randomised double blind crossover study

doi:10.1016/j.burns.2005.05.001

Burns

Volume 31, Issue 7, November 2005, Pages 831-837

https://doi.org/10.1016/j.burns.2005.05.001 Get rights and content

Abstract

Introduction:

The ideal analgesic agent for burns wound dressings in paediatric patients would be one that is easy to administer, well tolerated, and produces rapid onset of analgesia with a short duration of action and minimal side-effects to allow rapid resumption of activities and oral intake. We compared our current treatment of oral morphine to intranasal fentanyl in an attempt to find an agent closer to the ideal.

Methods:

A randomised double blind two-treatment crossover study comparing intranasal administration of fentanyl (INF) to orally administered morphine (OM). Children with burn injury aged up to 15 years and weighing 10–75 kg were included. Primary end-point was pain scores. Secondary end-points were time to resumption of age-appropriate activities, time to resumption of fluid intake, sedation and cooperation. Routine observations and vital signs were also recorded.

Results:

Twenty-four patients were studied with a median age of 4.5 years (interquartile range 1.8–9.0 years) and a median weight of 18.4 kg (interquartile range 12.9–33.2 kg). Mean pain difference scores (OM-INF) ranged from −0.500 (95% CI = −1.653 to 0.653) at baseline to −0.625 (05% CI = −1.863 to 0.613) for a retrospective rating of worst pain experienced during the dressing procedure. All measurements were within a pre-defined range of equivalent efficacy. The median time to resumption of fluid intake was 108 min (range 44–175 min) with OM and 140 min (range 60–210 min) with INF. These differences were not statistically significant. Fewer patients experienced mild side-effects with INF compared to OM (n = 5 versus n = 10). No patients experienced depressed respirations or oxygen saturations.

Summary:

Intranasal fentanyl was shown to be equivalent to oral morphine in the provision of analgesia for burn wound dressing changes in this cohort of paediatric patients. It was concluded that intranasal fentanyl is a suitable analgesic agent for use in paediatric burns dressing changes either by itself or in combination with oral morphine as a top up titratable agent.

Introduction

Following a burn injury many children require daily wound dressing as part of their management. Once any intravenous cannulas have been removed oral morphine is routinely used as an analgesic for these dressing changes. Wound dressing is often exquisitely painful during the procedure although there may be little, if any pain afterwards. Analgesic requirements are commonly underestimated in patients with burns particularly during these dressing procedures.

The ideal analgesic agent for wound dressings should be easy to administer, be well tolerated by the child, and produce rapid onset analgesia with a short duration of action and minimal side-effects to allow rapid resumption of activities and oral intake.

Analgesic agents currently used for wound dressings fall short of this ideal agent. Although adequate analgesia during the painful procedure can be achieved, prolonged sedation following the procedure limits the child's ability to eat sufficiently to make up their calorie deficiency and to resume their rehabilitation programme. The child may have many hours a day when they are unable to eat, drink or undertake activities.

Morphine orally has an unpredictable onset and effect in clinical practice. It has well known side-effects of nausea, vomiting and sedation. Oral ketamine can be combined with morphine to achieve adequate analgesia, however ketamine also has side-effects of nausea, vomiting and dysphoria, which may be distressing. A commercially available 50:50 mix of nitrous oxide and oxygen gases (Nitronox^® Airliquide Healthcare, Entonox^® BOC) may be used but is not tolerated by all patients and is unsuitable for young children, when using self-administering devices.

Fentanyl is an opiate that is rapidly absorbed across mucous membranes and has a short onset and duration of analgesia. Intranasal opiates have been used successfully in the emergency department for analgesia in fractures [1], [2], [3], [4] and also for post-operative pain relief [5], [6]. Oral transmucosal fentanyl citrate (OTFC) has been used in the emergency department [7] and burns unit [8] setting with good effect. Intranasal fentanyl (INF) has been evaluated in a burns unit with encouraging results as a patient controlled medication [9], [10] but no studies have explored its use in the paediatric population.

The primary aim of this study was to determine whether INF is equivalent in analgesic effect to oral morphine (OM) in children with burns during daily dressing changes that are part of their routine care. Secondary aims were to determine whether INF improved patient cooperation, sedation and reduced post-dressing recovery time and side-effects compared to OM.

Section snippets

Setting and population

The study was conducted in the Burns Unit of the Princess Margaret Hospital for Children, Perth, WA. Inpatients with burns covering more than 10% of body surface area or in specialised areas and requiring daily dressing with oral opiate analgesia cover were invited to take part in the study. Additional inclusion criteria were weight from 10 to 75 kg inclusive, age up to and including 15 years and an expected minimum requirement of two consecutive days of dressings with oral opiate cover.

Results

Twenty-eight patients were recruited and randomised to one of the two treatment sequences. The study protocol was completed by 24 (17 male, 7 female) patients. Of the four patients who did not complete the study protocol, two withdrew before outcomes were recorded and no outcomes were recorded on a further two patients. These four patients (two from each treatment sequence) could not be included in an intention-to-treat analysis because no data were collected on any of the outcome measures. The

Discussion

This investigation into the use of intranasal fentanyl for burns dressing changes in children has shown that it provides equivalent analgesia to oral morphine. We were able to demonstrate equivalence in the two agents by comparing the analgesics in similar clinical settings by crossing the patients over from one active opiate to the other over the two consecutive days of the trial. Of interest was the trend in greater alertness and interaction in the group receiving intranasal fentanyl although

Conclusion

INF has been demonstrated to be as effective as OM in providing pain relief during burns dressing changes. The trend towards improved recovery profile with INF will need confirmation by further larger cohort studies to quantify any advantages. The search for the ideal agent for burns wound dressing remains elusive but INF can be included as an alternative agent in the paediatric population either to be used by itself or in combination with OM as a top up titratable analgesic.

Acknowledgment

This study was funded by the Burns Research Fund at PMH.

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Clinical and pharmacokinetics overview of intranasal administration of fentanyl
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Due to the presence of large surfaces and high blood supply, drug delivery through the nasal route of administration is the appropriate route to administrate drugs with rapid onsets of action. Bypassing first-pass metabolism can increase drug bioavailability. The physicochemical properties of fentanyl led to a need to develop formulations for delivery by multiple routes. Several approved inter-nasal fentanyl products in Europe and the USA have been used in prehospital and emergency departments to treat chronic cancer pain and used to treat severe acute abdominal and flank pain. Analgesia durations and onsets were not significantly different between intranasal and intravenous fentanyl in patients with cancer breakthrough pain and were well-tolerated in the long term. Intranasal Fentanyl (INF) at a 50 μg/ml concentration decreased renal colic pain to the lowest level in 30 min. Possible adverse effects specific to INF are epistaxis, nasal wall ulcer, rhinorrhea, throat irritation, dysgeusia, nausea, and vomiting. However, there is limited available literature about the serious adverse effects of INF in adults and children. Intranasal Fentanyl Spray (INFS) results in significantly higher plasma concentrations and has a lower T_max than oral transmucosal formulation, and the bioavailability of fentanyl in intranasal formulations is very high (89 %), particularly in pectin-containing formulations such as PecFent and Lazanda.
Evidence-based practical guideline for procedural pain management and sedation for burn pediatrics patients undergoing wound care procedures
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Almost all children with burns experience pain as a result of a complex pathophysiologic process that is usually untreated, and up to 38% of all pediatric burn victims develop anxiety disorders due to pain after hospital admission. Hence, it is important to manage pain and anxiety in the care of burn victim children. The goal of this review was to develop an evidence-based guideline for procedural pain management and sedation for burned children undergoing wound care procedures.
The review was reported according to Reporting Items for practice Guidelines in Healthcare (RIGHT) protocol. A search of literature was done from Cochrane review, PubMed, Google Scholar, Embase, web of science and Hinari database key words “pediatrics”, “children”, “burn”, “procedural wound care”, “wound dressing”, “non-pharmacological”, “analgesia”, “pain management” and “sedation” were used. Extraction and filtering of the results was determined based on the interventions, outcome, population, and methodological quality, and inclusion and exclusion criteria. Finally, 6 systematic review and meta-analysis, 1observational study, and 16 randomized control trial Studies were appraised for quality, and conclusion was made based on their level of evidence and grade of recommendation.
For effective management of procedural pain and accompanying anxiety during WCP in children, we recommend using non-pharmacological strategies as an adjunct with calculated dose of analgesics based on the children's analgesic requirements. We also recommend ketamine-dexmedetomidine as an effective first-line analgesic-sedation, and ketamine-propofol, propofol-remifentanil, propofol-fentanyl, and ketamine-midazolam as useful sedative-analgesic options.
Intranasal fentanyl for first-trimester uterine aspiration pain: A randomized controlled trial
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To evaluate whether administration of intranasal fentanyl reduces reported pain during first-trimester uterine aspiration.
We conducted a multicenter, randomized, double-blind, placebo-controlled trial of patients with pregnancies less than or equal to 14 weeks gestation seeking uterine aspiration for induced abortion, early pregnancy loss, or failed medication abortion. We randomized participants 1:1 to either intranasal fentanyl 100 mcg or intranasal placebo. All participants received ibuprofen and a standardized paracervical block. The primary outcome was pain indicated at the time of uterine aspiration on a 100 mm visual analog scale (VAS). We designed the study to detect a 15 mm difference in mean pain scores, which required 53 people in each arm for a total of 106 participants. Secondary outcomes included postprocedure pain and patient satisfaction with pain control.
From March 2017 through June 2018, we screened 355 people for eligibility and enrolled 107 participants. Those who received intranasal fentanyl reported similar uterine aspiration pain to participants who received placebo (58.4 ± 28.0 fentanyl vs 58.6 ± 24.5 placebo, p = 0.97). Participants who received intranasal fentanyl also reported similar postprocedure pain scores compared to participants who received placebo (19.1 ± 19.4 fentanyl vs 17.2 ± 19 placebo, p = 0.63), and were equally satisfied with procedure pain control (66.8 ± 31.2 fentanyl vs 63.3 ± 29.2 placebo, p = 0.57).
Intranasal fentanyl did not decrease reported pain with first-trimester uterine aspiration, nor did it decrease postprocedure pain compared to placebo. As an adjunct to ibuprofen and paracervical block, intranasal fentanyl did not improve patient satisfaction with pain control.
Intranasal fentanyl does not reduce reported pain with first-trimester uterine aspiration, however abortion-seeking patients are amenable to receiving intranasal medications for pain management.
Efficacy of opioids and non-opioid analgesics in the treatment of post procedure pain of burned patients: a narrative review
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Burns are a common trauma that cause acute severe pain in up to 80% of patients. The objective of this narrative review is to evaluate the efficacy of opioids, non-steroidal anti-inflammatory drugs, paracetamol, gabapentinoids, ketamine, and lidocaine in the treatment of acute pain in burn victims.
The databases explored were PubMed, Embase, ClinicalTrials, and OpenGrey. The included randomized, controlled clinical trials assessed the analgesic efficacy of these drugs on hospitalized patients, had no age limit, patients were in the acute phase of the burn injury and were compared to placebo or other analgesic drugs. Studies describing deep sedation, chronic opioid use, chronic pain, and patients taken to reconstructive surgeries were excluded. The Jadad scale was used to evaluate quality.
Six randomized controlled clinical trials (397 patients) that evaluated the analgesic efficacy of fentanyl (n = 2), nalbuphine (n = 1), ketamine (n = 1), gabapentin (n = 1), and lidocaine (n = 1) to treat post-procedural pain were included. Fentanyl, nalbuphine, and ketamine were effective, while lidocaine was associated with a slight increase in reported pain and gabapentin showed no significant differences. Two studies were of high quality, one was of medium high quality, and three were of low quality. No studies on the efficacy of NSAIDs or paracetamol were found.
Evidence of efficacy is very limited. Fentanyl, nalbuphine, and ketamine seem to be effective for controlling acute pain in burn patients, whereas gabapentin and lidocaine did not show any efficacy.
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2021, Journal of Emergency Medicine
Citation Excerpt :
This is likely due to the high vascularity and permeability of the nasal mucosa, as well as its large surface area (7). Studies have evaluated and validated the safety and efficacy of intranasal fentanyl and midazolam administration in the pediatric population, primarily in older children and adolescents (8,11–13,18–22). However, evidence examining their use in children 3 years of age and younger is limited (18–24).
Although the efficacy and safety profiles of both intranasal fentanyl and midazolam are well studied in pediatric patients, few studies examine their use in younger children.
To examine and report our experiences in a pediatric emergency department (ED) with intranasal fentanyl and midazolam in children aged 3 years and younger.
This retrospective study investigated intranasal fentanyl and midazolam administration, alone and in combination, in children 3 years and younger treated in a pediatric ED.
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Intranasal fentanyl and midazolam, alone and in combination, can provide analgesia and anxiolysis to children aged 3 years and younger in the ED setting. Further prospective studies are needed to better evaluate their safety and efficacy in this younger population.
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The development of acute outpatient clinics has enabled burns services to assess the majority of smaller paediatric burns the day after injury. This event can be distressing and it is therefore important to ensure that children are initially assessed in an optimal environment. The aim of this study is to understand how small acute paediatric burns are managed across the British Isles.
All paediatric burns services within the British Isles were contacted by telephone and information gained on how each unit manages new referrals of small acute paediatric burns in an outpatient setting.
This national survey has shown that 5% total body surface area (TBSA) is generally considered to be the upper limit for new paediatric referrals to be seen in the outpatient setting 5%. Furthermore, we advocate that Paracetamol and Ibuprofen be given 60 min prior to an allocated appointment time.

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Burns

Abstract

Introduction:

Methods:

Results:

Summary:

Introduction

Section snippets

Setting and population

Results

Discussion

Conclusion

Acknowledgment

References (17)

Patient controlled intranasal analgesia for the management of postoperative pain: a pilot study

J Clin Anesth

Oral transmucosal fentanyl citrate for premedication of children undergoing laceration repair

Ann Emerg Med

A randomised crossover trial of patient controlled intranasal fentanyl and oral morphine for procedural wound care in adults patients with burns

Burns

A study of the bispectral index monitor during procedural sedation and analgesia in the emergency department

Ann Emerg Med

Determining the minimum clinically significant difference in visual analog pain score for children

Ann Emerg Med

Intranasal fentanyl reduces acute pain in children in the emergency department: A safety and efficacy study

Emerg Med

A prospective randomised pilot comparison of intranasal fentanyl and intramuscular morphine for analgesia in children presenting to the emergency department with clinical fractures

Emerg Med

Intranasal diamorphine for paediatric analgesia: assessment of safety and efficacy

J Accid Emerg Med

Cited by (101)

Clinical and pharmacokinetics overview of intranasal administration of fentanyl

Evidence-based practical guideline for procedural pain management and sedation for burn pediatrics patients undergoing wound care procedures

Intranasal fentanyl for first-trimester uterine aspiration pain: A randomized controlled trial

Efficacy of opioids and non-opioid analgesics in the treatment of post procedure pain of burned patients: a narrative review

Intranasal Fentanyl and Midazolam Use in Children 3 Years of Age and Younger in the Emergency Department

Pre-attendance analgesia advice for small acute paediatric burns in the British Isles: A National Survey