Efficacy Of Intranasal Fentanyl Research Articles

434 The Safety and Efficacy of Intranasal Fentanyl and Midazolam for Pediatric Anxiolysis

434 The Safety and Efficacy of Intranasal Fentanyl and Midazolam for Pediatric Anxiolysis

What is the Evidence for Using Intranasal Medicine in the Prehospital Setting? A Systematic Review

Objectives Intranasal (IN) medications offer a safe non-invasive way to rapidly deliver drugs in situations where intravenous (IV) access and intramuscular (IM) administration is challenging or not feasible. In the prehospital setting, this can be an essential alternative in time critical situations including trauma management, seizures, and agitated patients. However, there is a paucity of evidence summarizing its efficacy in this environment. This systematic review aims to assess the current evidence supporting the use of IN medicine (midazolam, ketamine, fentanyl, morphine, glucagon, and naloxone) in the prehospital setting alone. Methods A systematic literature search (PROSPERO CRD42023440713) of PubMed, Web of Science, OVID Medline, “Cochrane Central Register of Controlled Trials,” Cochrane reviews and Embase was performed from inception to June 2023 to identify studies where IN medications were administered to patients in the prehospital setting. All randomized controlled trials, observational cohort studies, case series, and case reports were included. Papers not written in English, review articles, abstracts, and non-published data (including letters to the editor) were excluded. The methodological quality of the included studies was interpreted using the Cochrane risk of bias tool and rated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. No funding was received. Results From 4818 studies, 39 were included (seven for midazolam, five for ketamine, twelve for fentanyl, one for diamorphine, two for glucagon, and twelve for naloxone). A total of 24,097 patients were treated with IN medications across all the studies. There were five moderate quality, four low quality, and thirty very low quality studies. The potential efficacy of IN fentanyl and ketamine was demonstrated consistently throughout the studies with less clear evidence for midazolam, morphine, glucagon, and naloxone. This review was severely limited by the study quality, with most studies demonstrating “high concerns” for bias. Conclusions Prehospital IN medication administration has wide-ranging potential, particularly for administering analgesia. There are likely to be certain populations, for example, pediatrics, that will benefit the most, although conclusions are limited by the quality of evidence currently available. We encourage additional research in this area, particularly with robust prospective double-blind RCTs.

Intranasal Fentanyl for Acute Pain Management in Children, Adults and Elderly Patients in the Prehospital Emergency Service and in the Emergency Department: A Systematic Review.

This systematic review examined the efficacy and safety of intranasal fentanyl (INF) for acute pain treatment in children, adults, and the elderly in prehospital emergency services (PHES) and emergency departments (ED). ClinicalTrials.gov, LILACS, PubMed, SCOPUS, EMBASE, Google Scholar and Cochrane databases were consulted until 31 December 2022. A total of 23 studies were included: 18 in children (1 PHES, 17 ED), 5 in adults (1 PHES, 4 ED) and 1 in older people (1 PHES subgroup analysis). In children, INF was effective in both settings and as effective as the comparator drugs, with no differences in adverse events (AEs); one randomised controlled trial (RCT) showed that INF was more effective than the comparator drugs. In adults, one study demonstrated the efficacy of INF in the PHES setting, one study demonstrated the efficacy of INF in the ED setting, two RCTs showed INF to be less effective than the comparator drugs and one RCT showed INF to be as effective as the comparator, with no difference in AEs reported. In older people, one study showed effective pain relief and no AEs. In summary, INF appears to be effective and safe in children and adults in PHES and ED. More high-quality studies are needed, especially in PHES and older people.

Implementation of a Physician Incentivized QI Strategy to Address Time to Parenteral Analgesia in Patients with Voe in the Pediatric Emergency Department

IntroductionVaso-occlusive episodes (VOE) are the most common cause of pediatric Emergency Department (ED) visits and hospitalizations in Sickle Cell Disease (SCD). The National Heart Lung and Blood Institute published an Expert Panel Report regarding the management of SCD and VOE. Their consensus statement recommends initiating analgesic therapy within 30 minutes of triage or within 60 minutes of registration in the Emergency Department. Previous studies have demonstrated that earlier maximum opioid has been associated with shorter length of hospitalization and improved time to ED disposition decision.Despite the overwhelming evidence for timely administration of parenteral analgesic, significant delays still exist in delivery of pain medication in the pediatric SCD population. Barriers to timely administration include rapid triage of SCD patients, provider ordering of pain medication, and peripheral intravenous access. Therefore, a standardized approach to pain management may improve ED management of SCD crises.In order to address timely administration of opiates to SCD patients with VOE episodes in our pediatric ED a SCD pain order set was developed. This order set implemented the use of intranasal (IN) fentanyl as a first line analgesic for SCD patients who presents to the ED with VOE. The purpose of this study was addressing barriers to decrease time to parenteral opioid administration in the pediatric ED.MethodsThis Quality Improvement (QI) measure was performed at a free-standing, urban pediatric ED. Patients were included if they had a diagnosis of SCD and presented with a pain score >5 and without fever.A PDSA cycle was utilized for designing and evaluating the proposed changes. This cycle consisted of three intervention phases: (1) electronic medical record (EMR) order set development in October 2019, (2) provider incentive for order set use in January 2020, and (3) nursing/patient & family education in April 2020. Baseline data was collected pre-intervention from April-September 2019.The outcomes measures were mean time to 1 st analgesic, mean time from triage to disposition, Hospital Length of Stay, and overall admission rates. Our balancing measure included 48 hour ED re-visits after discharge.ResultsThere were 67 ED visits from April-September 2019 (pre-intervention) and 104 ED visits in the post-intervention data from October-June 2020. There was no significant difference in age or initial pain score in the pre- and post- intervention groups. Improvements were seen in: mean time to first analgesic (58 to 26 minutes), time to disposition (271 to 213 minutes). Hospital length of stay was found to increase with the introduction of IN fentanyl: pre-intervention (120 hours), phase 1 (148 hours), phase 2 (152 hours), phase 3 (218 hours). However, the overall admission rate decreased (55% to 44%). The number of 48-hour ED re-visits remained stable.ConclusionBy using QI methods to address key barriers in the pediatric ED, we demonstrated that timely administration of parenteral analgesic can be achieved for SCD patients with VOE. Utilizing the EMR order set allowed for more stream-lined care, both by physicians and nursing staff, resulting in more rapid ordering of medication therefore decreasing time to ED disposition. Additional interventions such as provider incentivization to meet the goal of parenteral opioids within 30 minutes of patient arrival led to further improvement. One of the greatest barriers to our QI intervention was hesitancy both by patients and their caregivers regarding the efficacy of IN fentanyl in decreasing pain compared to IV opioid. Further education was needed both for families and medical staff regarding the efficacy of IN fentanyl as a first line analgesic.It is unclear why overall hospital length of stay was not shown to be decreased with these interventions but this can be offset by an overall decrease in hospital admissions seen with our interventions. This data may be limited by the SARS-CoV-2 pandemic and how psychosocial stressors can impact patients with chronic medical conditions. Length of stay is also confounded by other factors during the hospitalization and acquisition of other diagnoses such as acute chest. Future research is needed to determine if the demonstrated trend of admission rates and hospital length of stay can be replicated in other pediatric EDs and whether earlier opioid administration affects the outcome of VOEs beyond the ED. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Treatment of pain with intranasal fentanyl in pediatric patients in an acute care setting: a systematic review.

The primary objective of this review is to provide an updated, comprehensive overview on the efficacy of intranasal fentanyl (INF) for acute pain relief in the pediatric population. Utilizing the Preferred Reporting Instructions for Systematic Reviews and Meta-Analyses (PRISMA), we were able to screen articles based on key words to reach a final number of 10 studies. All but one study showed that INF was efficacious for pain relief in this select pediatric population. It is evident that INF is efficacious for analgesia, but other agents should also be considered in this patient population. As a result, further research is needed to investigate the clinically efficacy of INF in an acute care setting for pediatric patients.

Randomized Trial of Intranasal Fentanyl Versus Intravenous Morphine for Abscess Incision and Drainage.

Abscess incision and drainage (I&D) are painful and distressing procedures in children. Intranasal (IN) fentanyl is an effective analgesic for reducing symptomatic pain associated with fractures and burns but has not been studied for reducing procedural pain during abscess I&D. Our objective was to compare the analgesic efficacy of IN fentanyl with intravenous (IV) morphine for abscess I&D in children. We performed a randomized noninferiority trial in children aged 4 to 18 years undergoing abscess I&D in a pediatric emergency department. Patients received IN fentanyl (2 μg/kg; maximum, 100 μg) or IV morphine (0.1 mg/kg; maximum, 8 mg). The primary outcome, determined independently by blinded assessors, was the Observational Scale of Behavioral Distress-Revised (OSBD-R). The prestated margin of noninferiority (Δ) was 1.80. Secondary outcomes included self-reported pain, treatment failure, and patient and parental satisfaction. We enrolled 20 children (median age, 15.4 years), 10 in each group. The difference between total OSBD-R scores was -13.45 (95% confidence interval, -24.24 to -2.67), favoring IN fentanyl.There was less self-reported pain in patients who received IN fentanyl immediately after the procedure. Four patients (40%) receiving IV morphine had treatment failures and required moderate sedation or had the procedure terminated. More patients who received IN fentanyl were satisfied with the analgesic administered compared with those who received IV morphine. In a small sample of children aged 4 to 18 years undergoing abscess I&D, IN fentanyl was noninferior, and potentially superior, to IV morphine for reducing procedural pain and distress.

The Fan Study: Intranasal Fentanyl and Inhaled Nitrous Oxide for Fracture Reduction

Abstract BACKGROUND: Recently, intranasal (IN) fentanyl and inhaled nitrous oxide/oxygen (N2O) mixture have been increasingly used for procedural sedation and analgesia (PSA) alone or in combination. There is a lack of data on the efficacy of these combined agents. OBJECTIVES: To evaluate the efficacy of IN fentanyl and N2O as PSA for the reduction of mildly-to-moderately displaced fractures and dislocations. DESIGN/METHODS: We performed a prospective, observational cohort study between September 2014 and October 2015. Patients were recruited at CHU Sainte Justine (Montréal, Canada) and Royal Children Hospital (Melbourne, Australia). Patients between the age of 4 and 18 years were eligible if PSA consisted of IN fentanyl and N2O for the reduction of mildly-to-moderately displaced fractures or dislocations. Patients received at least IN fentanyl 1.5 mcg/kg (100 mcg max) and at least a 50/50% mixture of N2O with oxygen. Primary outcome was the efficacy of PSA measured by the patient assigned Facial Pain Scale-Revised (FPS-R). The Face, Legs, Activity, Cry, Consolability (FLACC) scale was also recorded. Depth of sedation was evalu-ated using the University of Michigan Sedation Scale (UMSS). Adverse events were recorded following the criteria of the Consensus Panel on Sedation Research of PERC/PECARN. Additional data concerning satisfaction or discomfort were evaluated via questionnaires, and follow-up telephone calls were made to elicit information on adverse events after discharge. RESULTS: A total of 91 patients aged 9.7±3.0 years were enrolled. There was no difference between the median FPS-R score during the procedure compared to before: Median 2 and 2 (median difference 0 [95% CI 0, 0]), respectively. The FLACC score was higher during the procedure than before: Median 4 and 0 (median difference 2 [95% CI 1, 3]). UMSS was 1 (95% CI 1, 2) during the procedure. 42 (46%) patients had adverse events, all mild: vertigo (20%), nausea (16%)]or vomiting (12%). A total of 85/88 (97%) parents and 82/85 (96%) ED physicians would want the same sedation in another procedure. CONCLUSION: PSA with IN fentanyl and N2O seems effective in our cohort study, as evaluated by patient assigned FPS-R. Patients were minimally sedated. Adverse events were frequent but mild. Overall, parents and medical staff would want the same agents used in another procedure. Thus, PSA with IN fentanyl and N2O appears to be an attractive option for reduction of mildly displaced fractures or dislocations.

P030: The FAN study: intranasal fentanyl and inhaled nitrous oxide for fracture reduction

Introduction: Recently, intranasal (IN) fentanyl and inhaled nitrous oxide/oxygen (N2O) mixture have been increasingly used for procedural sedation and analgesia (PSA) alone or in combination. There is a lack of data on the efficacy of these combined agents. Methods: The objective was to evaluate the efficacy of IN fentanyl and N2O as PSA for the reduction of mildly-to-moderately displaced fractures and dislocations. We performed a prospective, observational cohort study between September 2014 and October 2015. Patients were recruited at CHU Sainte Justine (Montréal) and Royal Children Hospital (Melbourne, Australia). Patients aged 4 to 18 years were eligible if PSA consisted of IN fentanyl and N2O for the reduction of mildly-to-moderately displaced fractures or dislocations. Patients received at least IN fentanyl 1.5 mcg/kg (100 mcg max) and at least a 50/50% mixture of N2O with oxygen. Primary outcome was the efficacy of PSA measured by the patient assigned Facial Pain Scale-Revised (FPS-R). The Face, Legs, Activity, Cry, Consolability (FLACC) scale was also recorded. Depth of sedation was evaluated using University of Michigan Sedation Scale (UMSS). Adverse events were recorded following criteria of the Consensus Panel on Sedation Research of PERC/PECARN. Additional data concerning satisfaction or discomfort were evaluated via questionnaires, and follow-up telephone calls were made to elicit information on adverse events after discharge. Results: A total of 91 patients aged 9.7 ± 3.0 years were enrolled. There was no difference between the median FPS-R score during the procedure compared to before: Median 2 and 2 (median difference 0 [95% CI 0, 0]), respectively. The FLACC score was higher during the procedure than before: Median 4 and 0 (median difference 2 [95% CI 1, 3]). UMSS was 1 (95% CI 1, 2) during the procedure. 42 (46%) patients had adverse events, all mild: vertigo (20%), nausea (16%)]or vomiting (12%). A total of 85/88 (97%) parents and 82/85 (96%) ED physicians would want the same sedation in another procedure. Conclusion: PSA with IN fentanyl and N2O seems effective in our study, as evaluated by patient assigned FPS-R. Patients were minimally sedated. Adverse events were frequent but mild. Overall, parents and medical staff would want the same agents used in another procedure. Thus, PSA with IN fentanyl and N2O appears to be an attractive option for reduction of mildly displaced fractures or dislocations.

Long-term efficacy and tolerability of intranasal fentanyl in the treatment of breakthrough cancer pain.

The aim of the present study was to assess the long-term tolerability and efficacy of intranasal fentanyl (INFS) in opioid-tolerant patients with breakthrough cancer pain (BTP). A 6 months, observational, prospective, cohort study design was employed to follow advanced cancer patients with BTP receiving INFS under routine clinical practice. Eligible adult cancer patients suffering from BTP had been prescribed INFS at effective doses. Data were collected at T0 and at month intervals for six months. The principal outcomes were the evaluation of possible serious adverse effects with prolonged use of INFS, the efficacy of BTP treatment with INFS, the quality of sleep, the rate of INFS discontinuation, and reasons for that. Seventy-five patients were surveyed. Thirty-four patients (45.3 %) had a follow-up at 3 months, and twelve patients (16 %) were followed up at 6 months. The mean opioid doses, expressed as oral morphine equivalents, ranged 111-180 mg/day, while the mean INFS doses were 87-119 μg. Adverse effects were reported in a minority of patients and were considered to be associated with opioid therapy used for background pain. The quality of sleep significantly improved during the first 3-4 months. Finally, efficacy based on a general impression regarding the efficacy of INFS was good-excellent in most patients and statistically improved in time up to the third month. The long-term use of INFS in advanced cancer patients is effective and safe. No serious adverse effects were found up to six months of assessment. The level of quality of sleep and patients' satisfaction was relatively good, considering the advanced stage of disease.

Postoperative Analgesic and Behavioral Effects of Intranasal Fentanyl, Intravenous Morphine, and Intramuscular Morphine in Pediatric Patients Undergoing Bilateral Myringotomy and Placement of Ventilating Tubes

Bilateral myringotomy and placement of ventilating tubes (BMT) is one of the most common pediatric surgical procedures in the United States. Many children who undergo BMT develop behavioral changes in the postanesthesia care unit (PACU) and require rescue pain medication. The incidence of these changes is lower in children receiving intraoperative opioids by the nasal, IM, or IV route compared with placebo. However, there are no data to indicate which route of administration is better. Our study was designed to compare the immediate postoperative analgesic and behavioral effects of 3 frequently used intraoperative techniques of postoperative pain control for patients undergoing BMT under general anesthesia. One hundred seventy-one ASA physical status I and II children scheduled for BMT were randomized into 1 of 3 groups: group 1-nasal fentanyl 2 μg/kg with IV and IM saline placebo; group 2-IV morphine 0.1 mg/kg with nasal and IM placebo; or group 3-IM morphine 0.1 mg/kg with nasal and IV placebo. All subjects received a standardized general anesthetic with sevoflurane, N(2)O, and O(2) and similar postoperative care. The primary end point of the study was the pain scores measured by the Faces, Legs, Activity, Cry, and Consolability (FLACC) scale in the PACU. There were no significant differences in peak FLACC pain among the 3 groups (mean [95% CI] 2.0 [1.2-2.8] for intranasal fentanyl, 2.7 [1.7-3.6] for IV morphine, and 2.9 [2.1-3.7] for IM morphine, respectively). There were no differences in the scores on the Pediatric Anesthesia Emergence Delirium (PAED) scale, incidence of postoperative emergence delirium (PAED score ≥ 12), emesis, perioperative hypoxemia, or need for airway intervention, and postoperative rescue analgesia. There were also no differences in the duration of PACU stay or parental satisfaction among the groups. In this double-blind, double-dummy study, there was no difference in the efficacy of intranasal fentanyl, IM and IV morphine in controlling postoperative pain and emergence delirium in children undergoing BMT placement. The IM route is the simplest and avoids the potential for delays to establish vascular access for IV therapy and the risks of laryngospasm if intranasal drugs pass through the posterior nasopharynx and irritate the vocal cords.

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

Provision of rapid, painless and effective analgesia to children remains problematic in the prehospital and emergency setting. Intranasal fentanyl has the potential to eliminate many of the problems of narcotic administration in children. The aim of this study, conducted in a tertiary paediatric emergency department was to evaluate the safety and efficacy of intranasal fentanyl in children. Children in acute pain aged between three and 12 years inclusive were enrolled on presentation to the emergency department. Routine observations and pain scoring by the child and caregiver was undertaken prior to the child receiving fentanyl (20 micrograms for 3-7 year olds and 40 micrograms for 8-12 year olds) and at intervals of 5 min for 30 min Additional fentanyl at the dose of 20 micrograms was given 5 minutely as required. Caregivers and older children used a visual analogue scale (VAS) and the younger children used the Wong-Baker faces scale (WBS). Forty five children were enrolled with a mean age of 8.0 years. The median dose of fentanyl administered was 1.5 micrograms/kg. Mean pain score in 32 children using the VAS was 62.3 mm (95% confidence interval 53.2-69.4 mm) at presentation and reduced at 10 min to 44.6 mm (95% confidence interval 36.2-53.1 mm). In 16 children using WBS the initial mean reading was 4.0 (95% confidence interval 3.3-4.7) and reduced to 2.2 (95% confidence interval 1.3-3.1) at 10 min. Caregiver pain scores showed a mean preintervention pain score of 64.9 mm (95% confidence interval 57.7-72.2 mm) with a significant reduction at 10 min to 41.7 mm (95% confidence interval 34.7-48.6 mm). There was no significant alteration in pulse rate, respiratory rate, and blood pressure or oxygen saturations. There were no negative side-effects. Early and significant reduction in pain (compared to baseline assessments) was achieved in children using intranasal fentanyl by 10 min and sustained throughout the 30 min of observations. This raises the possibility of using intranasal fentanyl in children in the prehospital setting as well as a role for this form of analgesia as triage nurse-initiated administration in the emergency department.