Intranasal Fentanyl Administration Research Articles

Efficacy and Safety of Intranasal Fentanyl in Pediatric Emergencies: A Systematic Review and Meta-analysis.

Intranasal fentanyl (INF) has gained popularity in pediatric emergency departments (EDs) as an effective alternative to intravenous morphine for treating acute moderate to severe pain. Intranasal fentanyl eliminates the need for invasive access, making it advantageous for patients with minor injuries. Our study aims to provide a comprehensive evaluation of the available evidence regarding the effectiveness and safety of INF administration in pediatric emergency wards, particularly compared with other treatment options described in the literature. A thorough search strategy identified randomized controlled trials assessing INF in the pediatric emergency ward. Eligible studies were independently screened, and relevant data were extracted. The analysis used pooled risk ratio (RR) for dichotomous outcomes and the standardized mean difference (SMD) for continuous ones. Randomized controlled trials' quality was assessed using the Cochrane Risk of Bias Assessment Tool 2. In our study, 8 randomized controlled trials involving 806 patients, INF demonstrated superior effectiveness in reducing pain compared with other comparators at the 15- to 20-minute mark (SMD, -0.23; 95% confidence interval, -0.37 to -0.08; P = 0.002). However, no significant differences were found at the 30- and 60-minute time points (SMDs, -0.16; 95% CI, -0.50, 0.19; P = 0.37; and -0.16; 95% CI, -0.50 to 0.19; P = 0.78) except when excluding one study to resolve heterogeneity at the 30-minute mark (RR, -0.02; 95% CI, -0.24 to 0.20; P = 0.87). Intranasal fentanyl also exhibited a better adverse outcome profile, with a lower risk of total adverse events and nausea/vomiting (RR, 0.66; 95% CI, 0.48-0.91; P = 0.01; and RR, 0.43; 95% CI, 0.30-0.63; P > 0.001) compared with other analgesics. However, no significant differences were observed for dizziness and hallucination (RR, 0.43; 95% CI, 0.30-0.63; P = 0.68; and RR, 0.43; 95% CI, 0.30-0.63; P = 0.35). Our study assessed the effectiveness of INF compared with other analgesics in pain reduction. Intranasal fentanyl demonstrated superior pain reduction at the 15- to 20-minute point but showed no significant differences at 30 and 60 minutes. Intranasal fentanyl also had a more favorable adverse event profile, with a lower risk of nausea and vomiting than other analgesics. However, no significant differences were observed in dizziness and hallucination between the groups.

Intranasal Fentanyl for Procedural Analgesia in Preterm Infants.

BackgroundDespite the availability of evidence-based analgesic strategies, neonatal pain management continues to be suboptimal. Intranasal (IN) fentanyl is an alternative pharmacotherapy for procedural pain in neonatal units. The objective was to evaluate the effectiveness and safety of IN fentanyl for procedural pain in preterm infants.MethodsA retrospective cohort study was conducted in infants who received IN fentanyl between May 2019 and December 2020 at an academic neonatal intensive care unit. Main outcome measures were pain responses, physiological parameters before and up to 60 min after IN fentanyl administration, and adverse events. Paired t-test and analysis of variance were used to compare pain scores and physiological parameters, respectively.ResultsThirteen infants received IN fentanyl on 22 occasions. Median (interquartile range [IQR]) gestational age and birthweight were 27 (25, 27.6) weeks and 850 (530, 1,030) grams, while median (IQR) post-menstrual age and weight were 30.9 (28.9, 32.9) weeks and 1,280 (945, 1,623) grams at the time of IN fentanyl administration. IN fentanyl was most used for lumbar puncture (55%) followed by insertion of epicutaneo-caval catheters (27%). There was a difference between the mean pre- and post-procedure Premature Infant Pain Profile scores of 1.3 (95% CI = 0.07, 2.5; p = 0.04). Physiological parameters did not differ before and up to 60 min post IN fentanyl administration (p > 0.05). Two adverse events (one apnea and one desaturation) were noted.ConclusionIn our limited experience, IN fentanyl appears to be an alternative pharmacotherapy for procedural pain management in the absence of intravenous access in preterm infants.

Use of an Emergency Department-Based Intranasal Fentanyl Protocol for Vaso-Occlusive Episodes in Sickle Cell Disease: The Unanticipated Consequences

Background: Acute management of pain associated with vaso-occlusive episodes (VOE) in patients with sickle cell disease (SCD) is an on-going challenge in the emergency department (ED) setting. The 2014 National Heart, Lung, and Blood Institute (NHLBI) guidelines recommend rapid evaluation and treatment for moderate-severe VOE, including administration of 1stparenteral opioid within 30 minutes (min) of triage or 60 min from registration, pain reassessment, and repeat opioid delivery within 15-30 min. Despite these recommendations, significant delays in providing optimal pain management is common for patients with SCD. Intranasal fentanyl (INF), a powerful parenteral analgesia with rapid onset is commonly used for pain in the ED, a practice that has recently been extended to treatment of VOE in some institutions. We and others have demonstrated that INF use is effective in helping with sickle-related pain management and achieving better adherence to NHLBI guidelines. However, the utilization of INF may have led to an unanticipated delay in administering intravenous (IV) opioids for this patient population.Objective: To evaluate the utilization of INF in the ED and its effect on the timeliness of 1st IV opioid administration for treatment of VOE in children with SCD.Methods: We conducted a retrospective review of electronic medical records in a single Pediatric ED from January 2017 to June 2017. We evaluated patients with SCD ages ≥ 2 years presenting with moderate-severe VOE (pain scores ≥6 on a severity scale of 0-10) after introduction of a nurse-initiated INF order (1.5 mcg/kg/dose; max 100 mcg/dose X2, 5 min apart) that was added to the standard institutional protocol for VOE treatment. Outcomes included: Time of ED arrival to 1st parenteral opioid, time to first IV opioid, and disposition. We also compared time to 1st IV opioid administration in patients who received INF with historical data of SCD patients treated at this ED with only IV opioids before INF use was standard practice (Jan-Dec 2012, n=231).Results: 250 patients met inclusion criteria. Mean age was 12.5 years, 52% female, and 66% had HbSS, 22% HbSC, 6% HbSB0 and 6% other. Admission rate was 60%. 183 (73%) patients received INF and 204 (82%) received an IV opioid, 141 of whom received both INF and IV opioids, while 42 (17%) patients received INF only. Mean time±standard deviation to first INF dose was 28.5±21 min; mean time to IV opioid delivery was 77±47 min compared to 35±18 min prior to initiation of the INF protocol (historical data, n=231, p<0.0001; Figure 1). In the current cohort, there was no statistically significant difference in time to IV opioid delivery in patients who received IV opioid after INF vs. IV opioid alone. However, only 52 (36%) of patients who received IV opioid after INF received IV opioid within 60 min of ED arrival compared to 36 (57%) who received IV opioids without INF (p<0.01). Of the 42 patients who received INF without any IV opioids, 39 patients (93%) were discharged home, while 5 (13%) of these discharged patients returned to the ED within 72 hours for VOE, similar to the 72 hour return rate in 7/39 (18%) patients discharged from the ED after receiving INF followed by IV opioids.Conclusion: Use of INF in the ED for pediatric patients with SCD and VOE is an excellent strategy to shorten time to administration of 1st dose of parenteral opioid and therefore improve adherence to the NHLBI guidelines recommending rapid administration of parenteral opioids within 60 min of ED arrival. Of interest, INF alone appeared to provide sufficient pain control without IV opioids for disposition home in one out of 6 children with VOE, an observation not previously reported. Whether this reflects adequate pain control or insufficient management requires further investigation. However, our experience also illustrates the potential pitfall of an ED-based INF protocol with respect to delays in delivery of IV opioids after initial administration of INF compared to our historical data prior to the INF protocol implementation. Although the significance of this delay is unknown, quality improvement efforts are underway to address this unanticipated consequence. [Display omitted] DisclosuresMorris:MAST Therapeutics: Research Funding; Calithera Biosciences: Consultancy; Nestle: Consultancy; Lifetrients: Patents & Royalties: I am inventor of IP owned by USCF-Benioff Children's Hospital Oakland, licensed to Lifetrients, generating royalties; Pfizer: Consultancy.

The Use of Intranasal Fentanyl for the Palliation of Incident Dyspnea in Advanced Congestive Heart Failure: A Pilot Study.

Dyspnea is distressing in palliative patients with end-stage heart failure and many are hospitalized to optimize this symptom. We hoped to conduct a pilot study to determine whether the administration of intranasal fentanyl would decrease activity-induced dyspnea in this patient population. Patients performed two 6-minute walk tests with and without the administration of 50 μg of intranasal fentanyl. Vital signs were recorded before and after each walk, as were participant reported dyspnea and adverse events scores. Twenty-four patients were screened, 13 were deemed eligible, and 6 completed the study. Dyspnea scores changed from a mean of 6.00 immediately after the walk without fentanyl to a mean of 3.83 after the walk with fentanyl ( P = .048). Mean respiratory rate decreased from 21.0 to 18.7 ( P = .034) breaths per minute and was considered a favorable outcome by the participants. Distance walked did not significantly increase with the fentanyl pretreatment (136.0-144.2 m; P = .283), although the participants reported feeling better while walking a similar distance. In this pilot study, the preadministration of intranasal fentanyl prior to activity in palliative, end-stage hospitalized heart failure patients, safely reduced tachypnea, and the feeling of shortness of breath. This approach may help palliate advanced heart failure patients by alleviating symptoms brought on by exertional activities.

Pediatric emergency department triage-based pain guideline utilizing intranasal fentanyl: Effect of implementation

BackgroundPain management guidelines in the emergency department (ED) may reduce time to analgesia administration (TTA). Intranasal fentanyl (INF) is a safe and effective alternative to intravenous opiates. The effect of an ED pain management guideline providing standing orders for nurse-initiated administration of intranasal fentanyl (INF) is not known. The objective of this study was to determine the impact of a pediatric ED triage-based pain protocol utilizing intranasal fentanyl (INF) on time to analgesia administration (TTA) and patient and parent satisfaction. MethodsThis was a prospective study of patients 3–17 years with an isolated orthopedic injury presenting to a pediatric ED before and after instituting a triage-based pain guideline allowing for administration of INF by triage nurses. Our primary outcome was median TTA and secondary outcomes included the proportion of patients who received INF for pain, had unnecessary IV placement, and patient and parent satisfaction. ResultsWe enrolled 132 patients; 72 pre-guideline, 60 post-guideline. Demographics were similar between groups. Median TTA was not different between groups (34.5 min vs. 33 min, p = .7). Utilization of INF increased from 41% pre-guideline to 60% post-guideline (p = .01) and unnecessary IV placement decreased from 24% to 0% (p = .002). Patients and parents preferred the IN route for analgesia administration. ConclusionA triage-based pain protocol utilizing INF did not reduce TTA, but did result in increased INF use, decreased unnecessary IV placement, and was preferred by patients and parents to IV medication. INF is a viable analgesia alternative for children with isolated extremity injuries.

Intranasal fentanyl for the prehospital management of acute pain in children.

Acute pain is the most common symptom in the emergency setting and its optimal management continues to challenge prehospital emergency care practitioners, particularly in the paediatric population. Difficulty in establishing vascular access and fear of opiate administration to small children are recognized reasons for oligoanalgesia. Intranasal fentanyl (INF) has been shown to be as safe and effective as intravenous morphine in the treatment of severe pain in children in the Emergency Department setting. This study aimed to describe the clinical efficacy and safety of INF when administered by advanced paramedics in the prehospital treatment of acute severe pain in children. A 1-year prospective cross-sectional study was carried out of children (>1 year, <16 years) who received INF as part of the prehospital treatment of acute pain by the statutory national emergency medical services in Ireland. Ninety-four children were included in the final analysis [median age 11 years (interquartile range 7-13)]; 53% were males and trauma was implicated in 86% of cases. A clinically effective reduction in the pain score was found in 78 children [83% (95% confidence interval: 74-89%)]. The median initial pain rating score was 10. Pain assessment at 10 min after INF administration indicated a median pain rating of 5 (interquartile range 2-7). No patient developed an adverse event as a result of INF. INF at a dose of 1.5 µg/kg appears to be a safe and effective analgesic in the prehospital management of acute severe pain in children and may be an attractive alternative to both oral and intravenous opiates.

Safety and efficacy of intranasally administered medications in the emergency department and prehospital settings.

The safety and efficacy of medications that may be administered via the intranasal route in adult patients in the prehospital and emergency department (ED) settings are reviewed. When medications of appropriate molecular character and concentration are delivered intranasally, they are quickly transported across this capillary network and delivered to the systemic circulation, thereby avoiding the absorption-limiting effects of first-pass metabolism. Therapeutic drug concentrations are rapidly attained in the cerebrospinal fluid, making intranasal administration a very effective mode of delivery. To optimize the bioavailability of intranasally administered drugs, providers must minimize the barriers to absorption, minimize the volume by maximizing the concentration, maximize the absorptive surface of the nasal mucosa, and use a delivery system that maximizes drug dispersion and minimizes drug runoff. Medications can be instilled into the nasal cavity with syringes or droppers by applying a few drops at a time or via atomization. The intranasal route of administration may be advantageous for patients who require analgesia, sedation, anxiolysis, termination of seizures, hypoglycemia management, narcotic reversal, and benzodiazepine reversal in the ED or prehospital settings. Medications that have been studied in the adult population include fentanyl, sufentanil, hydromorphone, ketamine, midazolam, haloperidol, naloxone, flumazenil, and glucagon. The available data do indicate, however, that intranasal administration may be a safe, effective, and well tolerated route of administration. Based on the published literature, intranasal administration of fentanyl, sufentanil, ketamine, hydromorphone, midazolam, haloperidol, naloxone, glucagon, and, in limited cases, flumazenil may be a safe, effective, and well-tolerated alternative to intramuscular or intravenous administration in the prehospital and ED settings.

Does intranasal fentanyl provide efficient analgesia for renal colic in adults?

IntroductionIntranasal fentanyl provides rapid and powerful analgesia which is particularly interesting in patients without intravenous access. We propose to use it for analgesia in adults presenting renal colics.MethodsA prospective study was conducted from the 2nd January to February 2013 in our emergency department. Patients aged up to 18 years old who presented with renal colic were included in this audit. Patients were excluded if they had loss of consciousness, cognitive impairment, acute or chronic nasal problems. A formal written consent was obtained from patients. The research team was alerted by medical and nursing staff. A member of the research team would check with medical or nursing staff whether administration of Intra nasal (IN) fentanyl was required. It was administered at a pre-calculated dose of 1.5 mg/kg and 50 mg/ml concentration was used. Data was prospectively collected by one of the researchers at various intervals during the patient's presentation and recorded on a pre-formatted data sheet. Pain scores were collected at 5, 15, 30, 45 and 60 minutes following IN fentanyl using a visual analogue scale pain. Observations routinely collected for patients receiving IV opiates and any adverse events were also recorded.Results23 eligible patientswere enrolled; median age was 51,3years. 47,8% were women and the mean weight was 73 kg. Median dose of IN fentanyl was 106 μg. Two patients have required morphinic analgesia despite having received adapted dose of IN fentanyl. The initial pain scores before IN fentanyl were high with a median of 82,2 mm (59-100). Five minutes after IN fentanyl administration the median pain score dropped to 48mm(36-63) and achieved the lowest score of 8mm(0-22) at 30 min. Pain scores were significantly lower at 5 min (P < 0.001) and at all subsequent time points (P < 0.001). No side effects were recorded.ConclusionIntranasal fentanyl seems to be efficient for analgesia in adult patients with renal colic.

Intranasal fentanyl for the management of acute pain in children.

Pain is the most common symptom in the emergency setting; however, timely management of acute pain in children continues to be suboptimal. Intranasal drug delivery has emerged as an alternative method of achieving quicker drug delivery without adding to the distress of a child by inserting an intravenous cannula. We identified and evaluated all randomized controlled trials (RCTs) and quasi-randomized trials to assess the effects of intranasal fentanyl (INF) versus alternative analgesic interventions in children with acute pain, with respect to reduction in pain score, occurrence of adverse events, patient tolerability, use of "rescue analgesia," patient/parental satisfaction and patient mortality. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2014, Issue 1); MEDLINE (Ovid SP, from 1995 to January 2014); EMBASE (Ovid SP, from 1995 to January 2014); the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (EBSCO Host, from 1995 to January 2014); the Latin American and Caribbean Health Science Information Database (LILACS) (BIREME, from 1995 to January 2014); Commonwealth Agricultural Bureaux (CAB) Abstracts (from 1995 to January 2014); the Institute for Scientific Information (ISI) Web of Science (from 1995 to January 2014); BIOSIS Previews (from 1995 to January 2014); the China National Knowledge Infrastructure (CNKI) (from 1995 to January 2014); International Standard Randomized Controlled Trial Number (ISRCTN) (from 1995 to January 2014); ClinicalTrials.gov (from 1995 to January 2014); and the International Clinical Trials Registry Platform (ICTRP) (to January 2014). We included RCTs comparing INF versus any other pharmacological/non-pharmacological intervention for the treatment of children in acute pain (aged < 18 years). Two independent review authors assessed each title and abstract for relevance. Full copies of all studies that met the inclusion criteria were retrieved for further assessment. Mean difference (MD), odds ratio (OR) and 95% confidence interval (CI) were used to measure effect sizes. Two review authors independently assessed and rated the methodological quality of each trial using the tool of The Cochrane Collaboration to assess risk of bias, as per Chapter 8 of the Cochrane Handbook for Systematic Reviews of Interventions. Three studies (313 participants) met the inclusion criteria. One study compared INF versus intramuscular morphine (IMM); another study compared INF versus intravenous morphine (IVM); and another study compared standard concentration INF (SINF) versus high concentration INF (HINF). All three studies reported a reduction in pain score following INF administration. INF produced a greater reduction in pain score at 10 minutes post administration when compared with IMM (INF group pain score: 1/5 vs IMM group pain score: 2/5; P value 0.014). No other statistically significant differences in pain scores were reported at any other time point. When INF was compared with IVM and HINF, no statistically significant differences in pain scores were noted between treatment arms, before analgesia or at 5, 10, 20 and 30 minutes post analgesia. Specifically, when INF was compared with IVM, both agents were seen to produce a statistically significant reduction in pain score up to 20 minutes post analgesia. No further reduction in pain score was noted after this time. When SINF was compared with HINF, a statistically and clinically significant reduction in pain scores over study time was observed (median decrease for both groups 40 mm, P value 0.000). No adverse events (e.g. opiate toxicity, death) were reported in any study following INF administration. One study described better patient tolerance to INF compared with IMM, which achieved statistical significance. The other studies described reports of a "bad taste" and vomiting with INF. Overall the risk of bias in all studies was considered low. INF may be an effective analgesic for the treatment of patients with acute moderate to severe pain, and its administration appears to cause minimal distress to children. However, this review of published studies does not allow any definitive conclusions regarding whether INF is superior, non-inferior or equivalent to intramuscular or intravenous morphine. Limitations of this review include the following: few eligible studies for inclusion (three); no study examined the use of INF in children younger than three years of age; no study included children with pain from a "medical" cause (e.g. abdominal pain seen in appendicitis); and all eligible studies were conducted in Australia. Consequently, the findings may not be generalizable to other healthcare settings, to children younger than three years of age and to those with pain from a "medical" cause.

Safety of Intranasal Fentanyl in the Out-of-Hospital Setting: A Prospective Observational Study

Initial out-of-hospital analgesia is sometimes hampered by difficulties in achieving intravenous access or lack of skills in administering intravenous opioids. We study the safety profile and apparent analgesic effect of intranasal fentanyl in the out-of-hospital setting. In this prospective observational study, we administered intranasal fentanyl in the out-of-hospital setting toadults and children older than 8 years with severe pain resulting from orthopedic conditions, abdominal pain, or acute coronary syndrome refractory to nitroglycerin spray. Patients received 1 to 3 doses of either 50 or 100 μg, andthe ambulance crew recorded adverse effects and numeric rating scale (0 to 10) pain scores before and after treatment. Our 903 evaluable patients received a mean cumulative fentanyl dose of 114 μg (range 50 to 300 μg). There were no serious adverse effects and no use of naloxone. Thirty-six patients (4%) experienced mild adverse effects: mild hypotension, nausea, vomiting, vertigo, abdominal pain, rash, or decrease of Glasgow Coma Scale score to 14. The median reduction in pain score was 3 (interquartile range 2 to 5) after fentanyl administration. The out-of-hospital administration of intranasal fentanyl in doses of 50 to 100 μg is safe and appears effective.

Fentanyl nasal spray for the treatment of cancer pain

Introduction: Breakthrough pain, a transitory flare of pain in patients with otherwise controlled chronic pain, has been well characterized in cancer patients but despite medical awareness, sometimes remains underdiagnosed and therefore undertreated.Areas covered: Oral transmucosal fentanyl citrate (OTFC) and fentanyl buccal tablets are the first medications developed specifically for the treatment of breakthrough pain in opioid-tolerant patients. Since oral administration of fentanyl is not an option for many cancer patients, the development of intranasal fentanyl spray (INFS) emerged as a more effective method of administration. Intranasal administration of fentanyl has several advantages over the oral/gastrointestinal route and clinical trials have shown that it is superior to OTFC while being well tolerated and more acceptable by the majority of patients.Expert opinion: The aim of this review is to summarize the pharmacological characteristics and data obtained from clinical studies of INFS in the past few years, and present Fentanyl Pectin Nasal Spray (PecFent), which uses an innovative delivery system and is now approved in the EU. Finally, we discuss the impact that it may have in the future management of breakthrough pain in cancer patients, because an accurate diagnosis followed by the best treatment is crucial for effective pain alleviation.

Use of Intranasal Fentanyl for the Relief of Pediatric Orthopedic Trauma Pain

The objective was to evaluate the use of a single 2 μg/kg dose of intranasal fentanyl as analgesia for painful orthopedic injuries in children presenting to a pediatric emergency department (ED). This was a prospective, nonblinded interventional trial, in a convenience sample of patients 3 to 18 years of age seen in a tertiary care pediatric ED. All had clinically suspected fractures and were treated between July and November 2006. Eligible patients had moderate to severe pain based on initial pain scores using the Wong Baker Faces Scale (WBS) for patients aged 3-8 years or the Visual Analog Scale (VAS) for patients aged 9-18 years. All enrolled patients received fentanyl via intranasal atomization. Pain scores were obtained at baseline and at 10, 20, and 30 minutes after intranasal fentanyl administration. Satisfaction scores were obtained using a 100-mm VAS. Vital signs and adverse events were recorded. Eighty-one patients were enrolled, 28 in the VAS group and 53 in the WBS group. The mean patient age was 8 years. Fracture locations included forearm, 38 (47%); supracondylar, 16 (20%); clavicle, 7 (9%); tibia/fibula, 5 (6%); and other, 15 (18%). In the WBS group, the median pain scores decreased from five faces (interquartile range [IQR] = 4-6) at baseline to three faces (IQR = 2-5) at 10 minutes, two faces (IQR = 1-4) at 20 minutes, and two faces (IQR = 1-3) at 30 minutes. The mean pain score in the VAS group at baseline was 70 mm (95% confidence interval [CI] = 63 to 77 mm). In this group, the pain scores decreased by a mean of 21 mm (95% CI = 14 to 28 mm) at 10 minutes, 25 mm (95% CI = 15 to 34 mm) at 20 minutes, and 27 mm (95% CI = 16 to 37 mm) at 30 minutes. Mean satisfaction scores were 79 mm for providers, 74 mm for parents, and 62 mm for patients. No adverse events were recorded. Intranasal fentanyl at a dose of 2 μg/kg provides effective analgesia for pediatric ED patients with painful orthopedic trauma within 10 minutes of administration.

Pharmacokinetics, analgesic effect, and tolerability of a single preprocedural dose of intranasal fentanyl in patients undergoing drain removal after breast reduction or augmentation surgery: A prospective, randomized, double-blind, placebo-controlled study

Background: Although acetaminophen is used to reduce pain after breast reduction or augmentation surgery, pain during the removal of the surgical drains is typically not specifically treated. Intranasally administered fentanyl may be suitable for pain control during removal of drains. The reported therapeutic window of fentanyl is between 0.2 and 1.2 ng/mL. Objective: The aim of this study was to evaluate the analgesic effect, tolerability, and pharmacokinetics of a single preprocedural dose of intranasal fentanyl administered before removal of surgical drains in patients who had undergone breast reduction or augmentation surgery. Methods: This was a randomized, double-blind, prospective study in healthy women (American Society of Anesthesiologists physical status I or II) between the ages of 18 and 65 years who were scheduled to undergo removal of surgical drains 1 to 4 days after breast reduction or augmentation surgery. A single dose of fentanyl nasal spray 0.05 mg/0.1 mL or placebo (preserved normal saline) 0.1 mL was administered 10 minutes before removal of drains. Because drain removal is generally carried out without specific analgesia, no rescue medication was provided. Pain intensity was measured on a visual analog scale (VAS) from 0 = no pain at all to 100 = worst pain possible. Pain intensity was evaluated immediately before administration of study medication (t = 0), at the time of drain removal (t = 10), and at 15, 20, 25, 40, and 70 minutes after administration of study medication. Safety measures included oxygen saturation, respiratory rate, heart rate, and blood pressure. Local and systemic adverse events were elicited by direct questioning throughout the study. Blood samples for pharmacokinetic analysis were collected at baseline and at 5, 10, 15, 30, 60, and 120 minutes after administration of study medication. The population pharmacokinetic parameters of fentanyl were calculated according to a 1-compartment open model with an iterative 2-stage Bayesian fitting procedure. Results: Thirty-six women were randomized to treatment, and 33 completed the study. Their mean (SD) age was 39.2 (13.0) years, and their mean weight was 68.9 (10.7) kg. Mean VAS scores at baseline were 14.8 (17.8) for the fentanyl group and 6.0 (9.7) for the placebo group ( P = NS); at the time of drain removal, the corresponding VAS scores were 31.0 (20.6) and 33.8 (25.7) ( P = NS). Analysis of a random-effects model with mean VAS scores as a function of time as the dependent variable indicated a significant difference in mean VAS scores between the fentanyl and placebo groups ( P = 0.006). The overall incidence of adverse events was 39.4% (13/33). Among the 17 patients in the fentanyl group, 8 reported ≥1 adverse event; among the 16 patients in the placebo group, 9 reported ≥1 adverse event. A mean estimated C max of 0.184 (0.069) ng/mL was reached at 13.76 (3.56) minutes after administration of intranasal fentanyl. The mean measured C max was 0.22 (0.088) ng/mL. Conclusions: In these women who had undergone breast reduction or augmentation surgery, a single preprocedural dose of intranasal fentanyl was significantly more effective than placebo in reducing pain intensity over the hour after removal of surgical drains. However, there was no significant difference in pain intensity between fentanyl at the time of drain removal and placebo. Intranasal fentanyl was generally well tolerated. At the dose used (0.05 mg), plasma fentanyl concentrations were below the reported therapeutic window.

Does the standard intravenous solution of fentanyl (50 µg/mL) administered intranasally have analgesic efficacy?

Intranasal (IN) fentanyl provides rapid and powerful non-parenteral analgesia in the ED. A concentrated solution of fentanyl (300 microg/mL) has been used in prior trials, yet many ED use the standard solution at a concentration of 50 microg/mL, which is widely available and of low cost. We set out to determine if this lower concentration of fentanyl is also efficacious. Prospective audit in children aged 5-18 years presenting with upper limb injuries. Patients received IN fentanyl (50 microg/mL) at 1.5 microg/kg. Patient assessed pain scores were collected 5, 10, 20, 30 and 60 min following IN fentanyl administration using a visual analogue scale or Bieri Faces-Revised scale. Parental scores were used if patients were unable to provide a score. Of the 59 eligible patients, 36 were enrolled; median age was 6.8 years (range 5-15 years), and 89% (32/36) ultimately required fracture reduction. Median first dose of IN fentanyl was 1.4 microg/kg. Median pain scores dropped from 7 (interquartile range 5-10) pre-fentanyl to 5 (interquartile range 4-8) at 5 min and 2 (interquartile range 1-4) at 30 and 60 min. A total of 21 (58%) children did not require further analgesia in the ED. There were no adverse events. Standard i.v. concentration IN fentanyl (50 microg/mL) appears to have analgesic efficacy in children with upper limb injuries.

Intranasal fentanyl in 1–3‐year‐olds: A prospective study of the effectiveness of intranasal fentanyl as acute analgesia

The primary objective of the present study was to determine the effectiveness of intranasal fentanyl analgesia in children aged 1-3 years with acute moderate to severe pain presenting to the ED. We also aimed to gather information on the safety and acceptability of intranasal fentanyl in this age group. Two paediatric ED enrolled children aged 1-3 years, with acute moderate or severe pain. Intranasal fentanyl was administered (1.5 microg/kg) via a mucosal atomiser device using a 50 microg/mL solution of fentanyl. Physiological parameters (heart rate, respiratory rate, oxygen saturations and level of consciousness) were measured at regular intervals. Objective pain assessment was completed using the Faces, Legs, Arms, Cry, Consolability (FLACC) score. Forty-six children presenting with acute moderate to severe pain were included. The median FLACC score before intranasal fentanyl administration was 8 (interquartile range [IQR] 5-10), decreasing to 2 (IQR 0-4) 10 min post fentanyl (P < 0.0001) and 0 (IQR 0-2) 30 min post fentanyl (P < 0.0001). A clinically significant decrease in FLACC scores was seen in 93% of children 10 min post fentanyl administration and 98% of children 30 min post fentanyl. Intranasal fentanyl delivery using a mucosal atomiser was well tolerated by all children. There were no adverse drug reactions or adverse events detected. Intranasal fentanyl is an effective, safe and well-tolerated mode of analgesia for children aged 1-3 years with moderate to severe pain.

Early pharmacokinetics of nasal fentanyl: is there a significant arterio-venous difference?

We have investigated the arterio-venous difference in the pharmacokinetics of 50 microg fentanyl during the first hour following nasal administration and documented its tolerability in opioid-naïve middle-aged to elderly patients. Twelve male patients (range in age 47-84 years) scheduled for transurethral resection of the prostate gland received a 100-microl dose of 50 microg fentanyl base as a fentanyl citrate formulation in one nostril. Simultaneous arterial and venous blood samples for analyses of fentanyl were drawn at baseline and at 1, 3, 5, 7, 9, 13, 15, 20, 25, 35, 45 and 60 min after drug administration. Vital signs, sedation and symptoms of local irritation were recorded. The arterial C(max) (maximum serum concentration) of 0.83 ng/ml was nearly twofold higher than the venous C(max) of 0.47 ng/ml, and the arterial T(max) (time to maximum serum concentration) of 7.0 min was about 5 min shorter than the venous T(max) of 11.6 min. The arterial AUC(0-60) (area under the curve from 0 to 60 min after administration) of 21 min*ng/ml was approximately 30% larger than the venous AUC(0-60) of 15 min*ng/ml (all p values < or = 0.005). Venous T(max) and C(max) did not predict the corresponding arterial values. No significant adverse events were observed. A significant arterio-venous difference was present after intranasal administration of fentanyl. The short arterial T(max) complies with its rapid onset of action. The use of venous concentrations for the prediction of onset time of analgesia should be discouraged. A 50-microg dose of nasal fentanyl was well tolerated by opioid-naïve middle-aged to elderly male patients.

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

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.