Article

A Randomized Controlled Trial Comparing Intranasal Fentanyl to Intravenous Morphine for Managing Acute Pain in Children in the Emergency Department

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Abstract

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

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... Intranasal administration of fentanyl is accomplished using the intravenous formulation. Doses of 1.5 µg/kg/ dose (range of 1-2 µg/kg with 100 µg maximum) have been studied [73,74]. Initial doses of 1.5 µg/kg/dose allow for additional doses of 0.3-0.5 µg/kg/dose to be administered every 5 min, not to exceed 3 µg/kg total dose) until successful pain control is achieved [73,74]. ...
... Doses of 1.5 µg/kg/ dose (range of 1-2 µg/kg with 100 µg maximum) have been studied [73,74]. Initial doses of 1.5 µg/kg/dose allow for additional doses of 0.3-0.5 µg/kg/dose to be administered every 5 min, not to exceed 3 µg/kg total dose) until successful pain control is achieved [73,74]. ...
... 7.1-7.4 [62,[71][72][73][74][75], the various routes of administration and the accumulated evidence on the use of fentanyl favor its use over the other derivatives. Remifentanil, with its rapid metabolism by plasma esterases, makes it attractive for use in patients with reduced hepatic function and those requiring prolonged use. ...
Article
Pain management in the pediatric population is complex for many reasons. Mild pain is usually managed quite well with oral acetaminophen or ibuprofen. Situations involving more severe pain often require the use of an opioid, which may be administered by many different routes, depending on clinical necessity. Acute and chronic disease states, as well as the constantly changing maturational process, produce unique challenges at every level of pediatrics in dosing and management of all medications, especially with regard to high-risk opioids. Although there has been significant progress in the understanding of opioid pharmacokinetics and pharmacodynamics in neonates, infants, children, and adolescents, somewhat limited data exist from which necessary information, concerning the safe and effective use of these agents, may be drawn. The evidence here provided is intended to be helpful in directing the practitioner to patient-specific reasons for preferring one opioid over another. As our knowledge of opioids and their effects has grown, it has become clear that older medications like codeine and meperidine (pethidine) have very limited use in pediatrics. This review provides pharmacokinetic and pharmacodynamic evidence on the currently available opioids: morphine, fentanyl (and derivatives), codeine, meperidine, oxycodone, hydrocodone, hydromorphone, methadone, buprenorphine, butorphanol, nalbuphine, pentazocin, ketobemidone, tramadol, piritramide, naloxone and naltrexone. Morphine, being the most studied opioid analgesic, is the standard against which all others are compared. Pharmacokinetic parameters of morphine that have been found in neonates, i.e., higher volume of distribution, immature metabolic processes that develop at various rates, elimination that is variable based on age and weight, as well as treated and untreated disease processes, are an example of all opioids in the population discussed in this review. Outside the premature and neonatal population, the use of opioids in infants, children, and adolescents quickly begins to resemble the established values found in adults. As such, the concerns (risks) of these medications become comparable to those seen in adults.
... Tab. 3 aufgeführt [19]. Für einzelne Gaben von Sedativa und Analgetika besteht auch die Möglichkeit zur intranasalen Verabreichung mithilfe eines Zerstäubers ("mucosal atomization device" [MAD]; [7]). Publizierte Erfahrungen liegen vor allem für Midazolam, Fentanyl, Sufentanil, Ketaminund Dexmedetomidinvor [20]. ...
... Zur Diagnosestellung müssen 3 von 5 Kriterien erfüllt sein [7] ...
Article
Background Thermal injuries are among the most common accidental injuries in childhood and can cause significant permanent functional and esthetic impairments. Aim In this review article the current recommendations for the treatment of thermal injuries in children are summarized. The special requirements and challenges in preclinical and inpatient treatment of children with thermal injuries are highlighted. Material and method In the context of the current literature clinical experiences are outlined to introduce treatment recommendations for children with thermal injuries. Contemporary treatment principles and special aspects are presented and discussed. Results The treatment of thermal injuries in children poses special challenges as it requires a differentiated approach adapted to the anatomy and physiology of the child. Acute preclinical treatment of thermal injuries is demanding, as a high standard has to be met even though the experience in pediatric emergencies is often limited. In the specialized clinic or center for children with severe burns, the treatment has to be adjusted to the severity of the burn or scald. In particular, special aspects of pediatric intensive care and surgical treatment have to be in focus to achieve satisfactory long-term functional and cosmetic results and decrease restrictions to a minimum. Conclusion The treatment of (severely) burnt children requires close interdisciplinary cooperation, starting from preclinical care through inpatient treatment and follow-up to long-term care.
... When i.v. access is unobtainable, clinicians should consider intranasal fentanyl, nebulized fentanyl, or morphine, transmucosal (fentanyl lollypops) or transbuccal (rapidly dissolving fentanyl tablets) routes of analgesia for acute painful conditions (44)(45)(46). Oral opioid administration is effective for most patients in the ED. Although there is no appreciable difference in analgesia provided between different oral opioids (hydrocodone, oxycodone, morphine), immediate-release morphine sulfate tablets are associated with a lesser degree of euphoria, which may decrease their abuse potential compared with other oral opioids (47,48). ...
Article
Background: Pain is one of the most common reasons patients present to the emergency department (ED). Emergency physicians should be aware of the numerous opioid and nonopioid alternatives available for the treatment of pain. Objectives: To provide expert consensus guidelines for the safe and effective treatment of acute pain in the ED. Methods: Multiple independent literature searches using PubMed were performed regarding treatment of acute pain. A multidisciplinary panel of experts in Pharmacology and Emergency Medicine reviewed and discussed the literature to develop consensus guidelines. Recommendations: The guidelines provide resources for the safe use of opioids in the ED as well as pharmacological and nonpharmacological alternatives to opioid analgesia. Care should be tailored to the patient based on their specific acute painful condition and underlying risk factors and comorbidities. Conclusions: Analgesia in the ED should be provided in the most safe and judicious manner, with the goals of relieving acute pain while decreasing the risk of complications and opioid dependence.
... This review included eight randomized controlled trials [21,28,29,[32][33][34][35][36] assessing analgesics via different routes with different drugs. Four of these studies considered ibuprofen as an analgesic medication [21,28,29,32]. ...
Article
Full-text available
Musculoskeletal (MSK) injuries are one of the most frequent reason for pain-related evaluation in the emergency department (ED) in children. There is still no consensus as to what constitutes the best analgesic for MSK pain in children. However, ibuprofen is reported to be the most commonly prescribed analgesic and is considered the standard first-line treatment for MSK injury pain in children, even if it is argued that it provides inadequate relief for many patients. The purpose of this study was to review the most recent literature to assess the efficacy of ibuprofen for pain relief in MSK injuries in children evaluated in the ED. We performed a systematic review of randomized controlled trials on pharmacological interventions in children and adolescents under 19 years of age with MSK injuries according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The primary outcome was the risk ratio for successful reduction in pain scores. Six studies met the inclusion criteria and provided data on 1028 children. A meta-analysis was not performed since studies were not comparable due to the different analgesic treatment used. No significant difference in term of main pain score reduction between all the analgesics used in the included studies was noted. Patients who received oral opioids had side effects more frequently when compared to children who received ibuprofen. The combination of effect on pain relief and tolerability would suggest ibuprofen as the initial drug of choice in providing relief from mild-to-moderate MSK pain in children in the ED. The results obtained in this review and current research suggest that there’s no straightforward statistically significant evidence of the optimal analgesic agent to be used. However, ibuprofen may be preferable as the initial drug of choice in providing relief from MSK pain due to the favorable combination of effectiveness and safety profile. In fact, despite the non-significant pain reduction as compared to children who received opioids, there are less side effect associated to ibuprofen within studies. The wide range of primary outcomes measured in respect of pain scores and timing of recorded measures warrants a future standardization of study designs.
... A couple of nasal delivery systems used in probationary studies are currently available to convey therapeutics into the nasal cavities, i.e. nasal drops as unit dose or multi dose formulation, aqueous nasal sprays, a nasal gels, pressurized MDIs and dry powder inhalers. Drug delivery through nose is now being utilized in medicines for a headache [6], smoking cessation [7], acute pain relief [8], osteoporosis [9], nocturnal enuresis [10] and vitamin-B12 deficiency [11]. For instance, butorphanol tartrate was presented in a nasal spray (STADOL NS) as a contrasting option to the injectable form for the alleviation of pain and migraine headaches [1]. ...
Article
Full-text available
Background and Objective: Intranasal drug delivery, being non-invasive in nature has turned out to be a promising option for drug administration. It is particularly valuable for drugs having low oral bioavailability due to degradation in Gastrointestinal Tract (GIT). Nasal route provides a unique microenvironment due to absence of deactivating enzymes and abundant vascular tissues which bring about direct systemic display, along with these lines abstaining the first pass hepatic metabolism. Conclusion: The present article provides in-depth information about the physicochemical parameters associated with drug absorption in nasal mucosa and factors influencing it. The pathways and mechanisms associated with nasal drug uptake alongside current pharmaceutical applications are additionally summarized.
... Intranasal drug administration has been studied widely in postoperative patients, 9 in burn patients 10 cessfully. 11,12 IN route is becoming a common route of administration in the emergency department setting, but also in prehospital and outpatient settings; it can be useful in cases where is difficult to find a venous access, in patients who abuse IV drugs or restless psychiatric patients. Many drugs can be administrated by IN route: sedative-hypnotic as midazolam, lorazepam and ketamine; analgesics as fentanyl and antipsychotics as haloperidol. ...
Article
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The usual treatment of pain in acute renal colic is analgesic in intravenous (IV) route. We tried a rapid, non-painful, non-invasive route of administration using intranasal ketorolac plus fentanyl versus IV standard treatment with non steroidal anti-inflammatory drug plus opioid for the relief of pain in renal colic presenting patients to an Emergency Department (ED). We conducted a prospective nonblinded clinical trial. A sample of 82 adult patients with clinical diagnosis of acute renal colic was included to receive either intravenous ketorolac plus fentanyl or intranasal ketorolac plus fentanyl. Pain score was rated by using a 10 cm visual analogue scale at 0, 30 and 60 minutes after the treatment. Primary outcome was pain reduction. Secondary outcomes were adverse events and rescue treatment. Eighty-two patients were enrolled. The first forty-one patients received intranasal ketorolac plus fentanyl and the second forty-one received intravenous ketorolac plus fentanyl. There were not statistically significant differences in reduction of pain between the two groups at 30 and 60 minutes (P-value at 30=0,225; P-value at 60=0,312) although the trend was in favour of IV group. There were no significant differences between the groups with regard to secondary outcomes (adverse events and rescue treatment). Intranasal ketorolac and fentanyl are equivalent in analgesic effect to intravenous ketorolac and fentanyl treatment for ED patients with acute renal colic and the intranasal treatment can be considered a valid alternative to the standard intravenous treatment.
... We controlled for intranasal fentanyl because a patient's time to first IV opioid may be delayed if their pain was adequately controlled using the intranasal route, which has shown equivalent efficacy to IV opioids in children with fractures. 16 Thus, we clinically did not consider administration of intranasal fentanyl a failure of the IV opioid process. Intranasal fentanyl was first used in this study population in 2009 and increased to 8% of patients by 2014 (data not shown). ...
Article
Full-text available
Objectives To determine the long-term sustainability and unintended consequences of a quality improvement project to improve the timeliness of intravenous (IV) opioid administration to patients with long-bone extremity fractures within a dynamic pediatric emergency department. Methods A retrospective study of patients with long-bone extremity fractures was conducted using electronic medical record data from 2007 to 2014. The primary outcome was the percentage of patients receiving timely IV opioids. Control charts and time series models were used to determine if changes in the clinical microenvironment were associated with shifts in the outcome measure. Unintended consequences included patients receiving potentially avoidable IVs and use of the quality improvement process for patients without long-bone extremity fractures. Results Improved timeliness of IV opioids was sustained. The type of physician who staffed the process and optimization of faculty staffing hours were associated with a 9.6% decrease and 11.8% increase in timely IV opioids, respectively. Implementation of the IV opioid process was not associated with increased placement of potentially avoidable IVs. Of patients receiving the IV opioid process, 22% did not have a long-bone extremity fracture, of whom 91% were diagnosed with a different painful injury. Conclusion Sustainability of IV opioid timeliness was robust, despite changes in the clinical microenvironment. Changes in physician staffing and responsibilities in a pediatric emergency department may be especially important to consider when planning future improvement initiatives. Our findings support the importance of higher reliability interventions, such as identification and utilization of existing patterns of behavior, as high yield for sustaining outcomes.
... 9 Its analgesic power is similar to intravenous morphine and its use is safe and effective in children with no reported adverse events. [10][11][12] The time to maximum plasma concentration is 5-16 min with a half life up to 65 min. 13 Adverse events like nausea and vertigo can occur during a PAS with N 2 O% and usually are self-resolving; however, vomiting may be a worrisome side effect because of the theoretical risk of aspiration during deep sedation during N 2 O 70% application. ...
Article
Objective Nitrous oxide 70% (N 2 O 70%) is an excellent medication for procedural analgosedation (PAS), yet the limit of its analgesic power remains uncertain; therefore, a combination with intranasal fentanyl (INF) was suggested. However, this combination seems to result in a higher rate of vomiting and deeper sedation. This study aimed at assessing the analgesic efficacy, sedation depth and rate of adverse events of PAS with N 2 O 70% with and without INF. Methods Patients aged 2–16 years who qualified for PAS with N 2 O 70% were randomly assigned to receive either INF or placebo prior to N 2 O inhalation in this randomised, double-blind study, which was performed in a tertiary children’s hospital ED between September 2015 and October 2017. Behaviour during the procedure was evaluated using the Face, Leg, Activity, Cry and Consolability (FLACC) scale and the Modified Behavioural Pain Scale (MBPS); analgesic efficacy was assessed with a self-reported pain scale. Sedation depth using the validated University of Michigan Sedation Scale and adverse events in the ED and during the following 12 hours were documented. Results A total of 402 patients were included; 3 did not tolerate N 2 O and therefore had to be excluded. Overall, 399 patients were analysed, of whom 201 (50.4%) received INF. No significant group differences with regard to FLACC scale score, self-reported pain, MBPS score and sedation depth were found. In addition, the two groups did not differ with regard to all types of adverse events. Conclusion Combining N 2 O 70% with INF resulted in no differences with regard to FLACC scale score, self-reported pain, MBPS score, patient and parental satisfaction rate, sedation depth, and adverse events. Trial registration number NCT02533908
... Many molecules have been evaluated, but they need to be at high concentrations (small volume vaporized) and liposoluble to be effective. Despite studies on fentanyl showing encouraging results and adequate IN-to-systemic pharmacokinetics [10][11][12], its use is still scarce in emergency practice. Sufentanil has the advantage of being a stronger opioid, well known by emergency physicians and intensivists, and available in high concentration, with known rapid peak action time (about 5 minutes) via an intravenous (IV) route [13]. ...
Article
Full-text available
Background: Intravenous morphine (IVM) is the most common strong analgesic used in trauma, but is associated with a clear time limitation related to the need to obtain an access route. The intranasal (IN) route provides easy administration with a fast peak action time due to high vascularization and the absence of first-pass metabolism. We aimed to determine whether IN sufentanil (INS) for patients presenting to an emergency department with acute severe traumatic pain results in a reduction in pain intensity non-inferior to IVM. Methods and findings: In a prospective, randomized, multicenter non-inferiority trial conducted in the emergency departments of 6 hospitals across France, patients were randomized 1:1 to INS titration (0.3 μg/kg and additional doses of 0.15 μg/kg at 10 minutes and 20 minutes if numerical pain rating scale [NRS] > 3) and intravenous placebo, or to IVM (0.1 mg/kg and additional doses of 0.05 mg/kg at 10 minutes and 20 minutes if NRS > 3) and IN placebo. Patients, clinical staff, and research staff were blinded to the treatment allocation. The primary endpoint was the total decrease on NRS at 30 minutes after first administration. The prespecified non-inferiority margin was -1.3 on the NRS. The primary outcome was analyzed per protocol. Adverse events were prospectively recorded during 4 hours. Among the 194 patients enrolled in the emergency department cohort between November 4, 2013, and April 10, 2016, 157 were randomized, and the protocol was correctly administered in 136 (69 IVM group, 67 INS group, per protocol population, 76% men, median age 40 [IQR 29 to 54] years). The mean difference between NRS at first administration and NRS at 30 minutes was -4.1 (97.5% CI -4.6 to -3.6) in the IVM group and -5.2 (97.5% CI -5.7 to -4.6) in the INS group. Non-inferiority was demonstrated (p < 0.001 with 1-sided mean-equivalence t test), as the lower 97.5% confidence interval of 0.29 (97.5% CI 0.29 to 1.93) was above the prespecified margin of -1.3. INS was superior to IVM (intention to treat analysis: p = 0.034), but without a clinically significant difference in mean NRS between groups. Six severe adverse events were observed in the INS group and 2 in the IVM group (number needed to harm: 17), including an apparent imbalance for hypoxemia (3 in the INS group versus 1 in the IVM group) and for bradypnea (2 in the INS group versus 0 in the IVM group). The main limitation of the study was that the choice of concomitant analgesics, when they were used, was left to the discretion of the physician in charge, and co-analgesia was more often used in the IVM group. Moreover, the size of the study did not allow us to conclude with certainty about the safety of INS in emergency settings. Conclusions: We confirm the non-inferiority of INS compared to IVM for pain reduction at 30 minutes after administration in patients with severe traumatic pain presenting to an emergency department. The IN route, with no need to obtain a venous route, may allow early and effective analgesia in emergency settings and in difficult situations. Confirmation of the safety profile of INS will require further larger studies. Trial registration: ClinicalTrials.gov NCT02095366. EudraCT 2013-001665-16.
... The patient feels comfortable and the drug can reach the central nervous system directly through the surface blood vessels of nasal mucosa. The system avoids the first-pass effect of the liver [8,9]. Dex can exert analgesic effect by activating locus coeruleus in the brainstem of the alpha 2 receptor in the nervous system, as well as acting on the alpha 2 receptor in the presynaptic membrane and neuron post-synaptic membrane of the spinal dorsal foot, which produces a sedative effect similar to natural sleep [10,11]. ...
... The intranasal (IN) route has been investigated as an alternative [9,10], Lazanda1 fentanyl nasal spray was approved by the FDA in July 2011 for the management of breakthrough pain in adult patients with cancer [11]. IN fentanyl administration might be preferred because IN delivery does not require establishment of IV access; thus, there are no inherent delays with drug-delivery preparation and administration, which would reduce time to analgesic relief compared with IV opioids [12]. ...
Article
Full-text available
Objective Intranasal fentanyl (INF) quickly and noninvasively relieves severe pain, whereas intravenous hydromorphone (IVH) reliably treats severe cancer pain but requires vascular access. The trial evaluated the efficacy of INF relative to IVH for treating cancer patients with severe pain in an emergency department (ED) setting. Methods We randomized 82 patients from a comprehensive cancer center ED to receive INF (n = 42) or IVH (n = 40). Eligible patients reported severe pain at randomization (≥7, scale: 0 “none” to 10 “worst pain”). We conducted non-inferiority comparisons (non-inferiority margin = 0.9) of pain change from treatment initiation (T0) to one hour later (T60). T0 pain ratings were unavailable; therefore, we estimated T0 pain by comparing 1) T60 ratings, assuming similar group T0 ratings; 2) pain change, estimating T0 pain = randomization ratings, and 3) pain change, with T0 pain = 10 (IVH group) or T0 pain = randomization rating (INF group). Results At T60, the upper 90% confidence limit (CL) of the mean log-transformed pain ratings for the INF group exceeded the mean IVH group rating by 0.16 points (>pain). Substituting randomization ratings for T0 pain, the lower 90% CL of mean pain change in the INF group extended 0.32 points below (<pain relief) mean change in the IVH group. Finally, assuming all subjects in the IVH group had maximum pain at T0 and that T0 pain for the INF group remained unchanged from randomization, the lower bound of the 90% CL for mean pain decrease in the INF group extended 1.37 points below (<pain relief) mean decrease in the IVH group. Time (minutes) from randomization until T0 was longer for the IVH (Median 23, IQR 12) versus INF (Median 15, IQR 11) group (P<0.001). Conclusions Two of three analyses supported non-inferiority of INF versus IVH, while one analysis was inconclusive. Compared to IVH, INF had the advantage of shorter time to administration. Trial registration ClinicalTrials.gov Identifier: NCT02459964
... Children with musculoskeletal injuries commonly experience moderate to severe pain, 13 without a close relationship with the presence of bone fractures. 14 In the ED setting, pain management significantly varies among institutions and emergency physicians. ...
... The intranasal route for medication delivery has been shown to provide effective, well-tolerated analgesia that can be delivered more quickly than that provided by parenteral administration. [5][6][7] Ketamine is a nonopioid N-methyl-Daspartate receptor antagonist that is an effective analgesic with no deleterious effects on cardiorespiratory function when used in low doses. 7,8 The bioavailability through the nasal route is approximately 45%. ...
Article
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Study objective: We compare intranasal ketamine with intranasal placebo in providing pain reduction at 30 minutes when added to usual paramedic care with nitrous oxide. Methods: This was a randomized double-blind study of out-of-hospital patients with acute pain who reported a verbal numeric rating scale (VNRS) pain score greater than or equal to 5. Exclusion criteria were younger than 18 years, known ketamine intolerance, nontraumatic chest pain, altered mental status, pregnancy, and nasal occlusion. Patients received usual paramedic care and were randomized to receive either intranasal ketamine or intranasal saline solution at 0.75 mg/kg. The primary outcome was the proportion of patients with VNRS score reduction greater than or equal to 2 at 30 minutes. Secondary outcomes were pain reduction at 15 minutes, patient-reported comfort, satisfaction scores, nitrous oxide consumption, and incidence of adverse events. Results: One hundred twenty subjects were enrolled. Seventy-six percent of intranasal ketamine patients versus 41% of placebo patients reported a greater than or equal to 2-point VNRS reduction at 30 minutes (difference 35%; 95% confidence interval 17% to 51%). Median VNRS reduction at 15 minutes was 2.0 and 1.0 and at 30 minutes was 3.0 and 1.0 for ketamine and placebo, respectively. Improved comfort at 15 and 30 minutes was reported for 75% versus 57% and 61% versus 46% of ketamine and placebo patients, respectively. Sixty-two percent of patients (95% confidence interval 49% to 73%) versus 20% (95% confidence interval 12% to 32%) reported adverse events with ketamine and placebo, respectively. Adverse events were minor, with no patients requiring physical or medical intervention. Conclusion: Added to nitrous oxide, intranasal ketamine provides clinically significant pain reduction and improved comfort compared with intranasal placebo, with more minor adverse events.
... It's short onset of action (30-60 s) and 45-minute duration of action make it a suitable molecule for IN administration. 15 Several studies have demonstrated the efficacy and good tolerance of intranasal fentanyl administration in children for acute pain in the ED, [16][17][18][19][20] and other trials have found IN sufentanil to be safe and effective in adults in the ED. [21][22][23][24][25][26] Previous small-scale randomized trials comparing IN sufentanil to IV morphine showed encouraging results, ranging from no difference between the two treatments 23,24 to non-inferior results. ...
Article
Introduction Pain is a frequent complaint in the emergency department and should be measured and treated according to the existing protocols. The intranasal route offers several advantages over the oral or intravenous routes. The aim of the study was to evaluate the efficacy and safety of intranasal sufentanil as the primary opioid for acute pain in the emergency department. Materials and methods This was a prospective open-label sequential study in patients who presented to the emergency department with severe non-visceral pain. The control group was treated according to the current standard of care including oral or intravenous opioids whereas the intervention group was treated according to a modified protocol, including intranasal sufentanil as the only opioid. Pain intensity was measured at different time points. The occurrence of side effects, the placement of intravenous lines and the need for additional analgesia were also recorded. Results Pain intensity in the two groups was not comparable at baseline (8.5; IQR 8–10 in the intervention group vs 7.9; IQR 7–9.4 in the control group; p = .026). However, the median reduction of the pain score was significantly larger in the intervention group compared to the control group after 15 minutes (2.5; IQR 1.2 – 4 vs 1.6; IQR 1–2.4; p = .005) and after 30 min (4; IQR 3–5.7 vs 3.1; IQR 2–4.4; p = .02). No significant difference in pain scores between the two groups was observed after 60 min from baseline. Conclusions Patients receiving intranasal sufentanil for severe pain achieved better pain relief at 15 min and 30 min compared to those receiving standard care. Vertigo, nausea, vomiting and diaphoresis were side effects more frequently observed in the sufentanil group. No differences in pain relief were observed after 30 and 60 min from baseline.
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Background: Respiratory distress is one of the most common and frightening symptoms of children with life-limiting conditions. Because treatment of the underlying cause is frequently impossible or insufficient, in many children, symptomatic treatment is warranted. The purpose of this study was to describe the circumstances of the use of intranasal fentanyl in an acute attack of respiratory distress (AARD) in children receiving palliative care, as well as to describe outcomes and adverse events after its use. Methods: Children and adolescents treated in a pediatric palliative unit or attended by a specialized home care team between 2010 and 2016 were included in this study. A retrospective chart review was conducted of those who were treated with intranasal fentanyl for an AARD. Results: During the study period 16 children (0.5-18.6 years) with various life-limiting conditions were treated with intranasal fentanyl for AARD. In total, 70 AARDs were analyzed. In 74% of all AARDs, a single dose of intranasal fentanyl was used. Frequent causes for an AARD were excessive secretions and acute respiratory infection. The median starting dose of intranasal fentanyl was 1.5 μg/kg body weight. Labored breathing (96%), tachypnea (79%) and related suffering (97%) improved after treatment. An adverse event occurred in one child. Conclusions: Intranasal fentanyl may be a safe and effective medication for the treatment of acute attacks of respiratory distress in children with life-limiting conditions. However, prospective studies with larger sample sizes and a control group are needed to validate these findings.
Chapter
Im alpinen Gelände werden Schmerzen oft nur unzureichend behandelt. Die Verwendung einer Schmerzskala und von Analgesieprotokollen ist sinnvoll. Training in der Schmerzerkennung und -behandlung sollte etabliert und die Wichtigkeit einer nichtpharmakologischen Therapie unterstrichen werden. Das perfekte Analgetikum gibt es nicht. Der Einsatz verschiedener Analgetika ist sinnvoll, jedoch sollte die Zahl der mitgeführten Analgetika auf ein Minimum reduziert werden. Analgetika, die über diverse Applikationswege verabreicht werden können und eine hohe therapeutische Breite haben, sollten bevorzugt werden. Eine multimodale Analgesie kann Vorteile bieten. Ein starkes Opioid ist für die Behandlung von moderaten und starken Schmerzen empfohlen. Ketamin hat den Vorteil einer hohen therapeutischen Breite, wobei eine Kombination mit Midazolam oder einem länger wirksamen Opioid sinnvoll ist. Regionalanästhesie kann besonders bei längeren Transporten eine Alternative zur systemischen Analgesie sein.
Article
The goal of our study was to determine if an intranasal (IN) dose of sufentanil delivered in the ED triage zone would improve the management of severely painful patients. We performed a randomized, double blind and placebo-controlled trial on adult patients suffering from an acute severe pain (≥ 6/10) consecutive to an isolated limb injury. We compared 2 analgesic strategies: the usual pain treatment with IV-only multimodal analgesics (IVMA) including IV opioids if needed (control group) and another strategy (active group) based on a single dose of IN sufentanil (0.4 μg/kg) given at triage and followed by IV multimodal analgesia. Our primary outcome was the proportion of patients reaching pain-relief (≤ 3/10) 30 min after IN injection at triage. Secondary outcomes were rates of adverse events, frequency of clinical interventions required by these events, and satisfaction of patients. A total of 144 adult participants completed the study, 72 in each group. Compared with usual IV-only pain management, the analgesic strategy initiated in triage zone with a dose of IN sufentanil increased the proportion of patients reaching pain relief in 30 min: 72.2% versus 51.4%, in our trial (p = 0.01 and number needed to treat of 5). There was no serious adverse event (AE) in both groups. Patients who received IN sufentanil experienced more frequently minor opiate side effects. Proportion of respiratory AEs was higher in the active group (12.5% of bradypnea < 10 cycles per minute versus 1.4%) but these events were of mild severity, as only 2 participants (one in each group) received temporary low dose oxygen therapy, and none required naloxone. Lengths of stay in the ED were similar in both groups, as well as satisfaction of patients (above 9/10) and pain scores at discharge (< 2/10). We found that a single dose of IN sufentanil delivered in the ED triage zone significantly increases the proportion of severely painful patients reaching painrelief in 30 min, compared to usual analgesia with IV-only multimodal analgesia.
Article
Background: The intranasal route is a minimally invasive method for rapidly delivering midazolam and fentanyl to provide short-term analgesia and sedation in infants. However, intranasal use of midazolam and fentanyl is not labeled for infants and safety data are sparse. The objective of this study is to evaluate the safety of intranasal midazolam and intranasal fentanyl in infants admitted to the Neonatal Intensive Care Unit (NICU). Methods: We retrospectively identified all infants receiving intranasal midazolam or fentanyl in the NICU from 2009 to 2015. We recorded indication for use and vital signs and determined the proportion of infants experiencing the following adverse events: death within 24 hours, hypotension, bradycardia, worsening respiratory status, and chest wall rigidity. Vital signs 4 hours before and after each dose were compared using the Wilcoxon signed-rank test. Results: We identified 17 infants (gestational ages 23- 41 weeks) receiving 25 intranasal doses. None of the infants died or developed hypotension, bradycardia, or chest wall rigidity. Intranasal delivery was most commonly used for sedation during magnetic resonance imaging studies. Other indications include analgesia or sedation for retinopathy of prematurity surgery, intubation, and peripherally inserted central catheter placement. One infant receiving intranasal midazolam experienced worsening respiratory status. Vital signs before and after dosing were not significantly different. Conclusions: Intranasal midazolam and fentanyl use in term and preterm infants appeared safe and well-tolerated in this small cohort of infants. Larger, prospective studies evaluating the safety and efficacy of intranasal midazolam and fentanyl use in infants are warranted.
Article
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Context: The aim of this review is to recognizing different methods of analgesia for emergency medicine physicians (EMPs) allows them to have various pain relief methods to reduce pain and to be able to use it according to the patient's condition and to improve the quality of their services. Evidence acquisition: In this review article, the search engines and scientific databases of Google Scholar, Science Direct, PubMed, Medline, Scopus, and Cochrane for emergency pain management methods were reviewed. Among the findings, high quality articles were eventually selected from 2000 to 2018, and after reviewing them, we have conducted a comprehensive comparison of the usual methods of pain control in the emergency department (ED). Results: For better understanding, the results are reported in to separate subheadings including "Parenteral agents" and "Regional blocks". Non-opioids analgesics such as nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen are commonly used in the treatment of acute pain. However, the relief of acute moderate to severe pain usually requires opioid agents. Considering the side effects of systemic drugs and the restrictions on the use of analgesics, especially opioids, regional blocks of pain as part of a multimodal analgesic strategy can be helpful. Conclusion: This study was designed to investigate and identify the disadvantages and advantages of using each drug to be able to make the right choices in different clinical situations for patients while paying attention to the limitations of the use of these analgesic drugs.
Article
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Aim: 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. Methods: 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. Results: All but one study showed that INF was efficacious for pain relief in this select pediatric population. Conclusion: 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.
Article
Background Intravenous ketorolac is commonly used for treating migraine headaches in children. However, the prerequisite placement of an intravenous line can be technically challenging, time-consuming, and associated with pain and distress. Intranasal ketorolac may be an effective alternative that is needle-free and easier to administer. We aimed to determine whether intranasal ketorolac is non-inferior to intravenous ketorolac for reducing pain in children with migraine headaches. Methods We conducted a randomized double-blind non-inferiority clinical trial. Children aged 8-17 years with migraine headaches, moderate to severe pain, and requiring parenteral analgesics received intranasal ketorolac (1 mg/kg) or intravenous ketorolac (0.5 mg/kg). Primary outcome was reduction in pain at 60 minutes after administration measured using the Faces Pain Scale-Revised (scored 0-10). Non-inferiority margin was 2/10. Secondary outcomes included time to onset of clinically meaningful decrease in pain; ancillary emergency department outcomes (e.g. receipt of rescue medications, headache relief, headache freedom, percentage improvement); 24-hour follow-up outcomes; functional disability; and adverse events. Results Fifty-nine children were enrolled. We analyzed 27 children who received intranasal ketorolac and 29 who received intravenous ketorolac. The difference in mean pain reduction at 60 minutes between groups was 0.2 (95% CI -0.9, 1.3), with the upper limit of the 95% CI being less than the non-inferiority margin. There were no statistical differences between groups for secondary outcomes. Conclusions Intranasal ketorolac was non-inferior to intravenous ketorolac for reducing migraine headache pain in the emergency department.
Article
Objectives: To compare the efficacy and adverse events of 2 pharmacological strategies: intranasal fentanyl and nitrous oxide (FN) inhaled against intravenous ketamine and midazolam (KM) as procedural sedation and analgesia (PSA) in painful orthopedic procedures in the pediatric emergency department (ED). Methods: This is an observational retrospective cohort study. Patients were included that submitted to PSA for carrying out a painful orthopedic procedure in the ED of a tertiary hospital over a period of 2 years. The main outcome variable was efficacy and adverse events of the PSA procedure. Results: Eighty-three patients were included. Fifty-two patients received FN and 31 KM. The PSA strategy was considered efficacious in 82.7% of the patients in the KM group and 80.6% in the FN cohort. No differences between both strategies were found (P = 0.815). Seventeen children showed early adverse events, 2 in the FN cohort and 15 in the KM group (relative risk of the KM strategy, 23.48; 95% confidence interval (CI), 3.24-169.99). The average of satisfaction obtained by the families was of 10 (CI, 10-10) in the KM cohort and of 9 (CI, 8-9.5) in the FN group (P = 0.152). The length of stay in the ED was longer in the KM cohort (P < 0.001). Hospital admission rate differences were not statistically different (9.6% vs 22.6%, P = 0.144) in the KM versus FN cohort. Conclusions: Both PSA strategies presented similar efficacy. The FN strategy was associated with a lower risk of adverse events and shorter ED length of stay than KM in this ED setting.
Article
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Background Clinically meaningful pain reduction with respect to severity and the adverse events of drugs used in prehospital pain management for children are areas that have not received sufficient attention. The present systematic review therefore aims to perform a comprehensive search of databases to examine the preferable drugs for prehospital pain relief in paediatric patients with acute pain, irrespective of aetiology. Methods The systematic review includes studies from 2000 and up to 2020 that focus on children’s prehospital pain management. The study protocol is registered in PROSPERO with registration no. CRD42019126699. Pharmacological pain management using any type of analgesic drug and in all routes of administration was included. The main outcomes were (1) measurable pain reduction (effectiveness) and (2) no occurrence of any serious adverse events. Searches were conducted in PubMed, Medline, Embase, CINAHL, Epistemonikos and Cochrane library. Finally, the risk of bias was assessed using the Joanna Briggs Institute (JBI) checklist and a textual narrative analysis was performed due to the heterogeneity of the results. Results The present systematic review on the effectiveness and safety of analgesic drugs in prehospital pain relief in children identified a total of eight articles. Most of the articles reviewed identified analgesic drugs such as fentanyl (intranasal/IV), morphine (IV), methoxyflurane (inhalational) and ketamine (IV/IM). The effects of fentanyl, morphine and methoxyflurane were examined and all of the included analgesic drugs were evaluated as effective. Adverse events of fentanyl, methoxyflurane and ketamine were also reported, although none of these were considered serious. Conclusion The systematic review revealed that fentanyl, morphine, methoxyflurane and combination drugs are effective analgesic drugs for children in prehospital settings. No serious adverse events were reported following the administration of fentanyl, methoxyflurane and ketamine. Intranasal fentanyl and inhalational methoxyflurane seem to be the preferred drugs for children in pre-hospital settings due to their ease of administration, similar effect and safety profile when compared to other analgesic drugs. However, the level of evidence (LOE) in the included studies was only three or four, and further studies are therefore necessary.
Article
Background 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. Objectives To examine and report our experiences in a pediatric emergency department (ED) with intranasal fentanyl and midazolam in children aged 3 years and younger. Methods This retrospective study investigated intranasal fentanyl and midazolam administration, alone and in combination, in children 3 years and younger treated in a pediatric ED. Results Of 6198 patients included, 1762 received intranasal fentanyl alone, 1115 received intranasal midazolam alone, and 3321 received combination therapy. The median (interquartile range [IQR]) patient age was 2.2 (1.5–3) years. Initial median (IQR) fentanyl dose was 2.7 (2, 3) µg/kg, with 13.3% receiving a repeat dose. Initial median (IQR) midazolam dose was 0.3 (0.2–0.3) mg/kg, with 3.3% receiving a second dose. Children receiving both fentanyl and midazolam had median (IQR) initial doses of 2.8 (2.1–3) µg/kg and 0.3 (0.2–0.3) mg/kg, respectively. Of these, 3.2% received repeat doses of both medications. Laceration repairs (33.8%) and incision and drainage (22.2%) accounted for the majority of indications. Only 2.9% (n = 178) received additional opioids. No serious adverse events requiring a reversal agent or respiratory support were reported. Conclusions 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.
Article
Objectives: To investigate whether growing human nasal epithelium as primary cultures alters aminopeptidase B (APB), aminopeptidase N (APN) and dipeptidyldipeptidase (DPPIV) metabolic characteristics, and mRNA gene transcript expression. Methods The formation of 7-amino-methyl coumarin from specific substrates for APN (L-alanine-4-methyl-coumaryl-7-amide, APB (L-arginine-4-methyl-coumaryl-7-amide) and DPPIV (glycyl-L-proline-4-methyl- coumaryl-7-amide) was used to estimate the KM, Vmax and the effect of aminopeptidases inhibitors on the enzymes. Polymerase chain reaction was used to investigate gene expression. Key findings: Results of this study showed that: (1) both the excised tissues and primary cultures of human nasal epithelium expressed APN, APB and DPPIV activity; (2) the KM of APB, APN and DPPIV was not significantly different in cell and tissue homogenates; (3) except for APN, the Vmax was not significantly different in the two metabolism models; (4) there was no statistically significant difference in the behaviours of APB, APN and DPPIV in response to inhibition by puromycin and bestatin in the two models; (5) the mRNA transcripts that encode APB, APN and DPPIV were expressed in both cell culture and tissue homogenate. Conclusions: Based on the results of this study, it may be concluded that nasal primary culture system is suitable for investigating peptide and protein metabolism and enzymatic stability in human nasal epithelium. Except for APN, the tissue culture conditions did not significantly alter the functional and molecular expression of the aminopeptidases.
Article
Objective: To examine the safety and effectiveness of intranasal midazolam and fentanyl used in combination for laceration repair in the pediatric emergency department. Methods: We performed a retrospective chart review of a random sample of 546 children less than 18 years of age who received both intranasal midazolam and fentanyl for laceration repair in the pediatric emergency department at a large, urban children's hospital. Records were reviewed from April 1, 2012 to June 31, 2015. The primary outcome measures were adverse events and failed laceration repair. Results: Of the 546 subjects analyzed, 5.1% had multiple lacerations. Facial lacerations were the most common site representing 70.3%, followed by lacerations to the hand (9.9%) and leg (7.0%). The median length of lacerations was 1.5 cm [1.0-2.5]. The median dose of fentanyl was 2.0 μg/kg [1.9-2.0] and midazolam was 0.2 mg/kg [0.19-0.20]. There were no serious adverse events reported. The rate of minor side effects was 0.7% (95% CI 0.2% to 1.9%); 0.5% (95% CI 0.1% to 1.6%) experienced anxiety and 0.2% (95% CI 0.0% to 1.0%) vomited. No patients developed hypotension or hypoxia. Of the 546 patients, 2.4% (95% CI 1.3% to 4.0%) experienced a treatment failure. 2.0% (95% CI 1.3% to 4.0%) required IV sedation and 0.4% (95% CI 0.0% to 1.3%) were repaired in the operating room. Conclusions: Our results suggest that the combination of INM and INF may be a safe and effective strategy for procedural sedation in young children undergoing simple laceration repair.
Article
Objectives: This study aimed to determine if the use of intranasal (IN) fentanyl in the pediatric emergency department of 2 to 5 μg/kg at doses greater than 100 μg is associated with adverse events in pediatric patients. Methods: We performed a retrospective chart review of patients receiving IN fentanyl at an urban, tertiary care emergency department in Memphis, TN, from January 1, 2011, to December 31, 2017. All adverse events documented through the hospital's voluntary safety reporting system involving IN fentanyl were reviewed to determine patient outcomes. Results: A total of 3205 patients received greater than 100 μg of IN fentanyl during the study period from 2011 to 2017. The average (SD) patient age was 13.7 (2.65) years, ranging from 5 to 18 years. The mean (SD) initial dose was 162 (30) μg ranging from 102 to 265 μg (2 doses were given greater than 200 μg in the study period). Initial average (SD) dose for weight was 2.62 (0.5) μg/kg. A total of 13 adverse events were documented, with only 3 occurring at doses greater than 100 μg. No patients required the reversal agent naloxone or invasive respiratory support. Conclusions: To our knowledge, this is the first study using doses greater than 100 μg of IN fentanyl in a pediatric population. Our results indicate that fentanyl can be safely administered at doses of greater than 100 μg without any clinically significant adverse outcomes observed for 7 years of use. It is our hope that this information will increase utilization of IN fentanyl for treatment of acute pain in emergency departments and in the prehospital setting.
Chapter
This chapter summarizes the state-of-the-art approach to several critical aspects of pediatric emergency care. While the field of pediatric emergency medicine is much broader, we have chosen some key topics which are essential for every physician providing care to children. The resuscitation section highlights the challenges and the particularities of pediatric airway management as well as the correct technique for effective cardiopulmonary resuscitation, defibrillation and vascular access. The sepsis section stresses that the key to a successful outcome is early recognition; it outlines the clinical spectrum of sepsis, the systemic inflammatory response and the pathophysiology of septic shock, with emphasis on early clinical signs, airway management, volume resuscitation, vasoactive support and antibiotic therapy. In the last decade, attention to pediatric pain management has resulted in increasing awareness of assessment tools and pharmacologic as well as non-pharmacologic strategies for pain control and anxiolysis. The pain section updates these important aspects of pediatric care and includes management of procedural sedation. Although the general principles of trauma care in children are similar to those of adults, the trauma section highlights the key differences, with respect to anatomy and physiology, and how these impact on early recognition of hemorrhagic shock, susceptibility to specific injuries, indications for imaging (no pan-CTs!) and the more prevalent non-surgical management. Healthcare providers must also know how to safely transport a child who requires additional resources or an escalation in level of care. The regionalization of pediatric intensive care units and trauma services has made it imperative for pediatricians to understand the general principles of transport medicine outlined in this chapter. The overview of pediatric inter-facility transport discusses choice of transport team and modality, emphasizes patient stabilization prior to transport and outlines required medications and supplies.
Article
Purpose: Nasal packing is an option for bleeding control after endoscopic sinus surgery and septoplasty. Although new packing materials have been developed, patients still suffer from pain and require additional analgesics treatments. In this study, a prospective, randomized, and double-blind controlled trial was designed to evaluate the effect of fentanyl-soaked packing on pain after endoscopic sinus surgery and septoplasty. Methods: One hundred fifty-two patients who underwent nasal surgeries due to chronic rhinosinusitis or nasal septal deviation were enrolled in this study. At the end of operation, 50 mcg fentanyl-soaked biodegradable synthetic polyurethane foams packing Nasopore or Merocel were applied to a group of 79 patients, and saline-soaked ones were applied to another group of 73 patients. To evaluate the influence of fentanyl on postoperative nasal pain, patients' conditions were assessed via means of Numeric Rating Scale, patient satisfaction, and Ramsay Sedation Scale. In addition, symptoms of headache or sore throat and any signs of cardiopulmonary-relevant indicators were monitored. Results: The fentanyl group had significantly decreased Numeric Rating Scale and increased patient satisfaction in every operation type for the majority of postoperative time periods ( P < .05) with reduced postoperative headache and sore throat compared to the control group. The fentanyl group showed a higher score on Ramsay Sedation Scale than the control group ( P < .05 in group including endoscopic sinus surgery). There were no significant differences in cardiopulmonary-relevant indicators between the 2 groups ( P > .05). Conclusion: Fentanyl group showed significantly reduced postoperative pain without serious adverse effects. We suggest that topical fentanyl application to nasal packs can be a useful method to reduce pain during the early postoperative period after endoscopic sinus surgery and septoplasty.
Article
Purpose: This study aimed to compare analgesic efficacy of intranasal (IN) ketamine to IN fentanyl for moderate to severe pain in children in a pediatric emergency department. Methods: A prospective, randomized, double-blinded, noninferiority study evaluating children aged 3 to 17 years in a pediatric emergency department with acute moderate to severe pain was conducted. Patients received either 1 mg/kg of IN ketamine or 1.5 μg/kg of IN fentanyl and were evaluated after 10, 20, 30, and 60 minutes. The primary outcome was the degree of pain reduction after 20 minutes. Results: Twenty-two patients were enrolled (11 in each group). Underlying pain conditions represented were musculoskeletal injury (73%) and abdominal pain (27%). At 20 minutes after analgesia, there was no significant difference in pain scores between the fentanyl (median, 2; range, 0-8) and ketamine groups (median, 4; range, 0-7; P = 0.20). The ketamine group showed a significantly greater rate of adverse effects, 73% versus 9% (P = 0.002), and throughout the course of the study period, 7 patients in the ketamine group (64%) group showed some degree of sedation versus no one in the fentanyl group (P = 0.004). Conclusions: There was insufficient power to support the analgesic noninferiority of IN ketamine at a dose of 1 mg/kg compared with IN fentanyl at a dose of 1.5 μg/kg in children experiencing painful conditions at 20 minutes after administration. Intranasal ketamine was found to be inferior to IN fentanyl in relieving pain at 10 minutes and was found to have significantly greater rates of sedation and dizziness.
Article
Background: The recent addition of intranasal medication options for procedural sedation and analgesia has decreased the need for additional painful procedures such as intravenous lines for medication administration. Intranasal fentanyl (INF) has been used in the prehospital setting, as well as in the emergency department for several years, and is increasingly utilized in other locations such as the neonatal intensive care unit (NICU). A paucity of data exists in these smallest children, so we sought to explore trends in INF use in our NICU. Objective: The objective of the study was to describe INF use in the NICU from December 2014 to December 2017. Design/Methods: A retrospective cohort study was conducted of patients receiving INF in the NICU of a large free-standing quaternary inner-city children’s hospital from December 2014 to 2017. Demographic data were abstracted from the medical record including gestational age on administration, post-menstrual age, day of life on administration, sex, medication initial and total dose, reported indication, and documented adverse events. This study was approved by our local institutional review board. Results: A total of 54 patients received a total of 67 INF administrations: 32 women (59%), median day of life on administration = 57.1 (interquartile range [IQR] = 33.7-110.4), median weeks gestation = 26.0 (IQR = 24.1-36.1), post-menstrual age = 38.1 weeks (IQR = 33.1-45.4). Initial doses of medications were 1.49 µg/kg/dose INF (range = 0.5-2 µg/kg). Conclusions: Intranasal adjuncts are increasingly used in the NICU. Starting dose of INF is 1.5 µg/kg/dose, and typically, one dose is given.
Preprint
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Background For military physicians, practice in tactical and austere environments, particularly during deployments, requires optimized pain management. Several recent studies have shown a definite interest in the intranasal (IN) route for analgesia. Few published series show efficacy and variable times of action depending on the drug used (ketamine, sufentanil and fentanyl), with exceptional side effects. The aim of this study is to evaluate the medical practice of the French Military Health Service (FMHS) physicians. Methods We carried out a declarative and multicentric survey from January 15, 2020, to April 14, 2020. The surveyed population was the physicians of the FMHS, 727 working in medical units and 55 in emergency departments (EDs) in France and overseas. Results In all, 259 responses were collected, giving a 33% return rate; 77.6% of physicians reported being familiar with the IN route for analgesia. However, only 18.4% had already used it. Physicians trained in emergency medicine and assigned to highly operational units were more familiar with this route and used it more frequently. The most common drug used was ketamine (51%). Finally, 90% of respondents expressed an interest in training and use of intranasal analgesia. Conclusions If a majority of physicians from the FMHS are familiar with IN analgesia, only few use it in practice. Therefore, specific training is suitable to improve this knowledge and homogenize guidelines. Having been the subject of numerous studies in progress in civilian and military medicine, the IN route seems to be a promising solution for remote and austere environments.
Article
Objective: Sports-related injuries in young athletes are increasingly prevalent with an estimated 2.6 million children and adolescents sustaining a sports-related injury annually. Acute sports-related injuries and surgical correction of sports-related injuries cause physical pain and psychological burdens on pediatric athletes and their families. This article aims to evaluate current acute pain management options in pediatric athletes and acute pain management strategies for postoperative pain after sports-related injuries. This article will also elucidate which areas of pain management for pediatric athletes are lacking evidence and help direct future clinical trials. Data sources: We conducted a literature search through PubMed and the Cochrane Central Register of Controlled Trials to provide an extensive review of initial and postoperative pain management strategies for pediatric sports-related musculoskeletal injuries. Main results: The current knowledge of acute pain management for initial sports-related injuries, postoperative pain management for orthopedic surgeries, as well as complementary and alternative medical therapies in pediatric sports-related injuries is presented. Studies evaluating conservative management, enteral and nonenteral medications, regional anesthesia, and complementary medical therapies are included. Conclusions: Adequate pain management is important for sports injuries in children and adolescents for emotional as well as physical healing, but a balance must be achieved to provide acceptable pain relief while minimizing opioid use and side effects from analgesic medications. More studies are needed to evaluate the efficacy of nonopioid analgesic medications and complementary therapies in pediatric patients with acute sports-related injuries.
Chapter
Sickle cell disease (SCD) encompasses multiple inherited hemoglobin disorders that are identified on routine newborn screening, affecting an estimated 100,000 individuals in the United States. The bulk of the disease burden is found outside the United States with an estimated 300,000 babies born annually in sub-Saharan Africa, the Middle East, and Indian subcontinent affected by SCD. The use of preventive strategies including penicillin prophylaxis, childhood vaccinations against encapsulated organisms, stroke-risk screening using transcranial Doppler ultrasound, and hydroxyurea to raise hemoglobin F levels has resulted in increased survival to adulthood for children with access to these therapies. This chapter focuses on expanding knowledge of the pathophysiology of SCD, advances in prevention, and treatment and novel curative therapies.
Chapter
A clear understanding of the pharmacology of sedating agents is essential in order to provide effective and safe sedation. The type and goal of the planned procedure and the desired depth of sedation should guide the selection of medications and dosages. Sedation practitioners should be trained and prepared to administer additional medications if necessary and should be knowledgeable in the expected effects of individual drugs and any synergistic effects of drug combinations. Practitioners should always be ready to rescue a sedated patient; there are some reversing agents and pharmacological antagonists available. Lastly, there are limited published pediatric data on most of medications used to sedate children.
Article
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To study the efficacy of intranasal fentanyl as an adjunct for pain management during screening for retinopathy of prematurity (ROP) in preterm infants. In this single center, double blinded, randomized controlled trial, preterm neonates between 30 and 34 weeks postmenstrual age received either intranasal fentanyl (2 mcg/kg) or intranasal normal saline through a mucosal atomization device 5 min prior to the first ROP-screening examination. Both the groups received standard pain relief strategies (oral sucrose, 0.5% proparacaine eye drops and physical containment). The primary outcome was premature infant pain profile-revised (PIPP-R) score during the screening. A total of 111 infants were enrolled. PIPP-R score during the retinal examination was significantly lower in the fentanyl group (8.3 versus 11.5, mean difference: 3.2 (2.46–4.06), P < 0.001). There was no significant difference in the incidence of adverse effects. Intranasal fentanyl significantly reduced the pain associated with retinal examination without increasing the risk of respiratory depression. Large RCTs are required to verify the efficacy and safety of intranasal fentanyl for acute procedural pain in neonates. CTRI/2017/12/011016.
Chapter
Regulations encouraging pediatric investigation of new drugs are advancing the therapeutic pharmacopoeia, but for many commonly used medicines, the lack of well-conducted pharmacokinetic–pharmacodynamic (PKPD) studies is replaced by extrapolation from adult or nonhuman data. While neonates, infants, and children have different psychology, social structure, behavior, and disease spectrum from adults, they also share many similarities. Growth and developmental aspects account for major differences between neonates and infants and adults. Once out of infancy, body size alone can account for many of the pharmacokinetic differences between children and adults. Pharmacodynamic factors that may influence response in early life remain poorly defined. Most PK and PD differences occur in the first few years of postnatal life with major changes occurring during the neonatal period that are mature by the end of infancy (i.e., 2 years of age). Knowledge of pediatric PKPD, changes seen during growth, and maturation and drug adverse effect spectrum are essential for dosing sedatives in children.
Article
Objectives: Renal colic is one of the most common painful disorders in patients referred to the emergency department. The main purpose of this study was to compare the efficiency of two methods of intravenous (IVF) and intranasal (INF) fentanyl administration in pain management in patients with severe renal colic. Materials & methods: This was a single-blind randomized clinical trial performed on patients with severe renal colic. The severity of pain was ≥8 based on the Numerical Rating Scale (NRS). The efficacy of pain management was compared within and between the IVF (intramuscular Ketorolac + intravenous fentanyl) and INF (intramuscular Ketorolac + intranasal fentanyl) groups at different times points. Oral consent was obtained from all the patients. Results: Of 220 individuals, 96 (43.60%) were women and 124 (56.40%) were men. There were no significant differences between the two groups regarding the baseline pain severity, age, sex, history of urolithiasis and body mass index (BMI). The pain severity showed a significant reducing trend in both groups (p < 0.0001). There was also a significant difference comparing the mean pain severity between groups at different times (p < 0.0001). In each group, the severity of pain showed significant reduction compared with its prior measurement (P < 0.0001). Conclusion: Fentanyl is highly effective in controlling pain in patients with severe renal colic referring to the emergency department. Intranasal administration of fentanyl combination with ketorolac can be an appropriate, non-invasive, easy-to-use and fast alternative to the intravenous method to manage pain in these patients.
Book
Pain management in emergency setting. Rescue, Pain and its Treatment. Pain evaluation and the right medications for the correct medical response. Ways of drugs administration. Ethical considerations.
Chapter
Safe and effective management of procedure-related pain and anxiety in the emergency department (ED) has become expected. It facilitates controlled accomplishment of therapeutic and diagnostic procedures, reduces psychological trauma and its sequelae, reduces healthcare provider and parental distress, and improves parental acceptance of rendered care. Many advances in procedural sedation and analgesia (PSA) for nonelective procedures in non-fasted patients in the ED have occurred over the past 30 years as a result of intense interest in this concept and the development of general and pediatric emergency medicine specialties, for whom PSA is now considered core training. This chapter reviews some of the PSA techniques shown to safely and effectively decrease children’s pain and anxiety associated with procedures in the ED. Since pain and anxiety are frequently indistinguishable, the combination will often be referred to as distress.
Article
Objectives: The primary objective of this study was to evaluate the management of pain after traumatic injury in the pediatric emergency department (ED) as measured by time to analgesic administration and pain resolution, stratified by triage acuity level. Methods: This is a retrospective descriptive study evaluating the management of children who presented with pain after injury to an urban level 1 trauma center. Consecutive enrollment of 1000 patients identified by ICD-9 codes that included all injuries or external causes for injury (700-999 and all E codes) and who had pain identified by triage pain assessment was performed. For analysis, patients were grouped according to triage level. Results: Fifty-one percent (511/1000) of patients achieved pain resolution, and an additional 20% (200/1000) of patients had documented improvement in pain score during their ED visit. Triage acuity level 1 group received medications the fastest with a median time of 12 minutes (interquartile range, 10-53 minutes); 65.3% of patients (653/1000) received a pain medication during their ED visit; 54.3% of these patients received oral medications only. Average time to intravenous line placement was 2 hours 35 minutes (SD, 2 hours 55 minutes). Only 1.9% of patients received any medications prior to arrival. Conclusions: Higher-acuity patients received initial pain medications and had initial pain score decrease before lower-acuity patients. Given the retrospective nature of the study, we were unable to clearly identify barriers that contributed to delay in or lack of pain treatment in our patient population.
Chapter
Intranasal administration is an attractive option for the delivery of many therapeutic agents especially for the treatment of central nervous system (CNS). In contrast to drugs that require delivery by peripheral injection, which requires blood brain barrier permeability of the injected drug for CNS delivery and may cause anxiety and infection, the intranasal route allows drugs to bypass the BBB due to its highly specialized nasal anatomy and the olfactory pathway. Due to its non-invasive nature and easy procedure, intranasal drug delivery is particularly suited for use in children and may be performed by medical staff or family members. This article will review the use of intranasal medications with a focus on their utility in children. We will provide an overview of the nasal anatomy and its impact on drug delivery, the side effects of drugs specific to intranasal delivery, and a list of the medications which are currently administered intranasally. The most common drug classes for intranasal delivery in pediatrics include sedatives and analgesia, drugs for seizure control, opioid antagonists, and antimigraine medications. In summary, intranasal delivery is a versatile method for drug application with a wide range of clinical utility, and especially effective in the pediatric population.
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Study Objective Patients with sickle cell disease (SCD) have many emergency department visits because of painful vaso-occlusive episodes (VOE). Guidelines recommend treatment within 30 minutes of triage, but this is rarely achieved in clinical practice. Our goal was to develop an order set that is being implemented in the ED to facilitate and standardize emergency care for SCD patients in acute pain from VOEs presenting to the emergency department (ED) in New York City (NYC). Methods Using a RAND/University of California, Los Angeles modified Delphi panel, we convened a multidisciplinary panel and reviewed evidence on how to best manage SCD pain in the ED. Panelists collaboratively developed then rated 202 items that could be included in an ED order set. Results A consensus order set, a practical how-to guide for managing SCD pain in the ED, was developed based on items that received high median ratings. Conclusions The management of acute pain experienced during VOEs is critical to patients with SCD; ED order sets, such as this one, can help standardize pain management, including at triage, evaluation, discharge, and follow-up care. After implementation in NYC EDs, studies to examine changes in quality care metrics (eg, wait times, readmissions) are planned.
Article
Objectives: We aimed to describe the analgesic efficacy, duration of analgesia, and adverse event profile associated with intranasal hydromorphone in children with acute pain presenting to an emergency department. Methods: Prospective dose titration pilot study of otherwise healthy children 4 to 17-years-old with moderate to severe pain who required a parenteral opioid. All patients received an initial intranasal hydromorophone dose of 0.03 mg/kg. The need for additional analgesia was assessed at 15 and 30 min; an additional 0.015 mg/kg was given at each assessment, if required. Need for rescue analgesic, pain intensity and adverse events were assessed until 6 h after hydromorphone administration or until patients were discharged, underwent a procedure to treat their painful condition, or received a rescue analgesic. Results: We enrolled 35 children. Fifteen, 11, and 9 children required a total dose of 0.03, 0.045, and 0.06 mg/kg, respectively. Patients in each dose group experienced an absolute decrease in pain score of ≥3/10 and percent reduction >40% within 5-15 min of completing dose-titration administration of hydromorphone. Duration of analgesia (i.e. time until rescue analgesic administered) >1 h was observed in 85.7% of patients. Patients not requiring rescue analgesics had mild or no pain until discharged or their painful conditions were treated. Three (8.6%) patients required a rescue analgesic <1 h after hydromorphone administration. There were no major adverse events. Conclusions: Intranasal hydromorphone led to rapid, clinically significant and frequently sustained decreases in pain intensity in children. No major adverse events were observed in this preliminary sample. Clinical Trials Registration Number: NCT02437669.
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Introduction: Fentanyl is a lipid soluble, highly potent opioid. The lipid solubility of fentanyl makes it an ideal opioid to be administrated by inhalation. The current study compared ketamine infusion and nebulized fentanyl in bone fracture pain relief. Methods: In this double-blind, randomized clinical trial, patients aged 18 to 55 years who were admitted to the emergency department (ED) with limb fracture were recruited. A total of 127 patients were included in the study, 51.1% (65) of whom were male and 48.9% (62) of whom were female. The patients were divided equally into two groups: Group I received 100 cm3 IV infusion of normal saline and 4 μg/kg of 50 μg/ml nebulized fentanyl; Group II received 0.4 mg/kg ketamine in 10 min and 5 cm3 nebulized normal saline. Pain was assessed using a visual analog scale just before treatment and 5, 10, 15, 30, and 60 min post-treatment. Results: Before intervention, the pain scores of both groups showed no significant difference. However, log linear analysis in both groups showed a significantly decrement during the follow up (60 min) (p < 0.0001). Multiple comparison analysis showed that pain scores were significantly higher in the patients of Group I. Moreover, patients in Group I required additional treatment. Conclusion: Ketamine can be used as an alternative non-invasive treatment to successfully relieve pain in patients with limb fractures.
Article
Objectives: Intranasal fentanyl and midazolam use is increasing in the acute care setting for analgesia and anxiolysis, but there is a lack of literature demonstrating their use, alone or in combination, at pediatric urgent care centers. Methods: This retrospective study investigated intranasal fentanyl and midazolam use at an urgent care center located within Le Bonheur Children's Hospital and 2 affiliated off-site centers from September 22, 2011, to December 30, 2015. Data collected included patient demographics, initial fentanyl dose, initial midazolam dose, type of procedure, and serious adverse drug reactions. Results: Of the 490 patients who met the inclusion criteria, 143 patients received intranasal fentanyl alone, 92 received intranasal midazolam alone, and 255 received fentanyl in combination with midazolam. The overall patient population was 50% male with a median (range) age of 4.5 (0.2-17.9) years, and most patients were black at 57.1%. The median (range) initial intranasal fentanyl dose was 2.02 (0.99-4.22) μg/kg, and the median initial (range) intranasal midazolam dose was 0.19 (0.07-0.42) mg/kg. In cases where fentanyl and midazolam were administered in combination, the median (range) initial fentanyl dose was 2.23 (0.6-4.98) μg/kg and median (range) initial midazolam dose was 0.2 (0.03-0.45) mg/kg. There were no serious adverse drug reactions reported. Conclusions: Intranasal fentanyl and midazolam when administrated alone and in combination can provide analgesia and anxiolysis for minor procedures in pediatric patients treated in the urgent care setting.
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Introduction: The undertreatment of acute pain presents a significant challenge in the Emergency Department. This post hoc subgroup analysis of a previously reported randomized controlled UK study reports the efficacy and safety of low-dose methoxyflurane analgesia in treating adolescent patients with moderate-to-severe trauma pain. Patients and methods: Three hundred patients (96 in the adolescent subgroup) aged ≥12 years requiring analgesia for acute trauma pain (pain score of 4-7 on the Numerical Rating Scale) at triage were randomized 1:1 to methoxyflurane (up to 6 mL) or placebo (normal saline), both administered using a Penthrox® inhaler. The patient could request rescue medication (paracetamol/opioids) at any time. The primary endpoint was the change from baseline in visual analog scale (VAS) pain intensity. Results: Mean VAS pain score for the adolescent subgroup at baseline was ~ 61 mm. Adjusted mean change in VAS pain intensity from baseline to 5, 10, 15, and 20 minutes was -24.5, -28.1, -31.6, and -31.7 mm for methoxyflurane and -14.6, -18.8, -19.2, and -23.7 mm for placebo, with a statistically significant treatment effect in favor of methoxyflurane overall across all four time points (-9.9 mm; 95% CI: -17.4, -2.4 mm; P=0.0104). Median time to first pain relief was significantly shorter with methoxyflurane (1 minute) than placebo (3 minutes, P<0.0001). Pain relief was reported within 1-10 inhalations in 95.7% of methoxyflurane-treated patients and 64.6% of placebo-treated patients. Rescue medication was requested by two (4.3%) methoxyflurane-treated patients and three (6.3%) placebo-treated patients. Over 95% of patients, physicians, and nurses rated methoxyflurane treatment as "Excellent", "Very Good" or "Good" compared with between 64% and 68% for placebo. The incidence of adverse events was higher with methoxyflurane (51%) than placebo (42%), mostly comprising mild/transient dizziness and headache. Conclusion: This subgroup analysis shows that low-dose inhaled methoxyflurane is a rapid-acting and effective analgesic in adolescent patients presenting with moderate-to-severe trauma pain. Trial registration: Clinicaltrials.gov identifier: NCT01420159, EudraCT number: 2011-000338-12.
Article
Objective : To evaluate whether administration of intranasal fentanyl reduces reported pain during first-trimester uterine aspiration. Study Design : 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 post-procedure pain and patient satisfaction with pain control. Results : 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 receiving placebo (58.4±28.0 fentanyl vs 58.6±24.5 placebo, p=0.97). Participants receiving intranasal fentanyl also reported similar post-procedure pain scores compared to participants receiving 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). Conclusion : Intranasal fentanyl did not decrease reported pain with first-trimester uterine aspiration, nor did it decrease post-procedure pain compared to placebo. As an adjunct to ibuprofen and paracervical block, intranasal fentanyl did not improve patient satisfaction with pain control.
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To compare the effectiveness of nasal diamorphine spray with intramuscular morphine for analgesia in children and teenagers with acute pain due to a clinical fracture, and to describe the safety profile of the spray. Multicentre randomised controlled trial. Emergency departments in eight UK hospitals. Patients aged between 3 and 16 years presenting with a clinical fracture of an upper or lower limb. Patients' reported pain using the Wong Baker face pain scale, ratings of reaction to treatment of the patients and acceptability of treatment by staff and parents, and adverse events. 404 eligible patients completed the trial (204 patients given nasal diamorphine spray and 200 given intramuscular morphine). Onset of pain relief was faster in the spray group than in the intramuscular group, with lower pain scores in the spray group at 5, 10, and 20 minutes after treatment but no difference between the groups after 30 minutes. 80% of patients given the spray showed no obvious discomfort compared with 9% given intramuscular morphine (difference 71%, 95% confidence interval 65% to 78%). Treatment administration was judged acceptable by staff and parents, respectively, for 98% (199 of 203) and 97% (186 of 192) of patients in the spray group compared with 32% (64 of 199) and 72% (142 of 197) in the intramuscular group. No serious adverse events occurred in the spray group, and the frequencies of all adverse events were similar in both groups (spray 24.1% v intramuscular morphine 18.5%; difference 5.6%, -2.3% to 13.6%). Nasal diamorphine spray should be the preferred method of pain relief in children and teenagers presenting to emergency departments in acute pain with clinical fractures. The diamorphine spray should be used in place of intramuscular morphine.
Article
New drug choices and combinations have revolutionized the way sedation and analgesia are delivered in the emergency medicine setting. Current pharmacotherapy results in relief of anxiety, maximizes potential for amnesia, and eliminates or minimizes pain while guarding patients' safety. Major and minor interventions that were once painful and unpleasant are now virtually pain free, and often the child has no recollection of the event.
Article
OBJECTIVE: To compare the effectiveness of nasal diamorphine spray with intramuscular morphine for analgesia in children and teenagers with acute pain due to a clinical fracture, and to describe the safety profile of the spray. DESIGN: Multicentre randomised controlled trial. SETTING: Emergency departments in eight UK hospitals. PARTICIPANTS: Patients aged between 3 and 16 years presenting with a clinical fracture of an upper or lower limb. MAIN OUTCOME MEASURES: Patients' reported pain using the Wong Baker face pain scale, ratings of reaction to treatment of the patients and acceptability of treatment by staff and parents, and adverse events. RESULTS: 404 eligible patients completed the trial (204 patients given nasal diamorphine spray and 200 given intramuscular morphine). Onset of pain relief was faster in the spray group than in the intramuscular group, with lower pain scores in the spray group at 5, 10, and 20 minutes after treatment but no difference between the groups after 30 minutes. 80% of patients given the spray showed no obvious discomfort compared with 9% given intramuscular morphine (difference 71%, 95% confidence interval 65% to 78%). Treatment administration was judged acceptable by staff and parents, respectively, for 98% (199 of 203) and 97% (186 of 192) of patients in the spray group compared with 32% (64 of 199) and 72% (142 of 197) in the intramuscular group. No serious adverse events occurred in the spray group, and the frequencies of all adverse events were similar in both groups (spray 24.1% v intramuscular morphine 18.5%; difference 5.6%, -2.3% to 13.6%). CONCLUSION: Nasal diamorphine spray should be the preferred method of pain relief in children and teenagers presenting to emergency departments in acute pain with clinical fractures. The diamorphine spray should be used in place of intramuscular morphine.
Article
Objective: To evaluate the tolerability and efficacy of intranasal fentanyl analgesia for children. Methods: A prospective, open-label, two-arm pilot study was conducted. Children, aged 3 to 10 years, with clinical limb fractures were randomized to receive 1 μg/kg intranasal fentanyl via nasal spray or 0.2 mg/kg intramuscular morphine. Tolerance to administration, pain scores, rescue analgesia, adverse events and physiological data were recorded at intervals over 30 min. Results: Forty-seven children were recruited to the study. Tolerance to administration was better for intranasal fentanyl compared with intramuscular morphine (median scores 1 vs 2; P < 0.001). Pain scores over the trial period were similar in both groups. One child receiving intranasal fentanyl required rescue analgesia. No significant adverse effects were noted. Conclusions: Intranasal fentanyl provides effective paediatric analgesia comparable to intramuscular morphine and is better tolerated. A larger study is needed to determine dose range and confirm safety.
Article
Objective: To investigate the pharmacokinetics of intranasal fentanyl in adult post-operative female patients. Method: Patients received both intravenous and intranasal fentanyl (approximately 50 pg) in a randomised cross-over study. Results: Pharmacokinetic data sets from 19 patients showed intranasal fentanyl produced plasma levels within the therapeutic range within two minutes, with median bioavailability values of 55% (pH 6 formulation) and 71% (pH 8 formulation). Mean peak serum concentrations were 0.33 ng/mL (pH 6) and 0.37 ng/mL (pH 8) respectively, compared with 2.33 ng/mL after intravenous fentanyl. Conclusion: We conclude that the absorption of intranasal fentanyl is rapid, the bioavailability more than half that of intravenous administration and that the formulations studied are suitable for more extensive clinical evaluation.
Article
Painful therapeutic procedures are often necessary during emergency care of children who have already painful and frightening injuries and illnesses. These procedures are distressful for children, their parents, and their health care providers. Furthermore, inadequately relieved, procedure-related pain produces physiologic and psychological reactions that have acute and long-term consequences, 25,132,153,159,163,172 but children continue to receive less pain medication than do adults with similar significant injuries and illnesses, 15,55 and simple, readily available techniques to reduce pain and anxiety during relatively minor but frightening procedures are often not used. 84,119 A 1998 survey suggests that as many as 40% of children with angulated forearm fractures may receive no sedation-analgesia for fracture reductions in general emergency departments in the United States, 87 and a 1993 study found that 95% of lumbar punctures in a pediatric emergency department were performed without local anesthesia. 119 Advantages of safe and effective management of pain and anxiety in the emergency department include facilitation of controlled accomplishment of evaluations and procedures 31,83,153 ; reduction of psychological trauma and its sequelae 31,95,153,163 ; reduction of stress for the health care provider and parents 40 ; improvement of parental acceptance of rendered care; and, possibly, improvement of accurate evaluation of causes of pain. 112 Why, then, are effective anxiolysis, analgesia, and sedation not commonplace in the emergency department? Explanations are complex and include lack of consensus about optimal safe and effective methods, 25,132,153 medications, 25,34,74,87,153 and patient monitoring 35 ; lack of physician familiarity with psychological and local anesthetic techniques and dosing; fear of adverse effects of potent medications, including concern about addiction 87,115,139,164 ; insufficient time and resources to safely carry out sedations 87 ; minimization of children's pain or misinterpretation as anxiety; and belief that children have only short-term memory of pain. 105,159 Over the past decade, increased recognition of the importance and means for provision of safe and effective management of distress during elective painful procedures in fasted children with cancer and other chronic illnesses has occurred. * *Reference 25,31,40,54,56,60,80,100,105,133,134,155,159 and 163 . Which of these and other advances can safely provide relief during nonelective procedures in nonfasted patients in the emergency department has been the subject of increasing interest. Family and third-party payer desire for definitive management of acute injuries during initial emergency department visits also seems to be increasing. This article reviews some of the methods shown to safely and effectively decrease children's pain and anxiety associated with procedures in the emergency department (Table 1). Because pain and anxiety are frequently indistinguishable, the combination is often referred to as distress.
Article
Objective: To evaluate the tolerability and efficacy of intranasal fentanyl analgesia for children. Methods: A prospective, open-label, two-arm pilot study was conducted. Children, aged 3 to 10 years, with clinical limb fractures were randomized to receive 1 μg/kg intranasal fentanyl via nasal spray or 0.2 mg/kg intramuscular morphine. Tolerance to administration, pain scores, rescue analgesia, adverse events and physiological data were recorded at intervals over 30 min. Results: Forty-seven children were recruited to the study. Tolerance to administration was better for intranasal fentanyl compared with intramuscular morphine (median scores 1 vs 2; P < 0.001). Pain scores over the trial period were similar in both groups. One child receiving intranasal fentanyl required rescue analgesia. No significant adverse effects were noted. Conclusions: Intranasal fentanyl provides effective paediatric analgesia comparable to intramuscular morphine and is better tolerated. A larger study is needed to determine dose range and confirm safety.
Article
A randomized, double-blind study was undertaken to investigate the suitability of intranasally administered fentanyl for postoperative pain management under routine conditions in an unselected population. For postoperative pain relief, patients received either 0.027 mg fentanyl intranasally and sodium chloride 0.9% intravenously (intranasal group, n = 53) or sodium chloride 0.9% intranasally and 0.027 mg fentanyl intravenously (intravenous group, n = 59). These doses were repeated every 5 min until the patients were free of pain or refused further analgesia. Pain severity was evaluated before beginning opioid titration and 5, 10, 15, 20, 30, 40, 50, 60, 70 and 80 min thereafter. Adequate pain relief was achieved in 52 of 53 patients in the intranasal and in all patients in the intravenous group. Pain intensities evaluated on a 101-point numerical rating scale as well as on a verbal rating scale decreased significantly in both study groups within 5 min. At the 15 min measurement point, numerical rating scale pain intensity and at the 10 and 20 min point, verbal rating scale pain intensity was significantly lower in the intravenous group. The incidence of side effects was low in both groups and no patient complained of intranasal pain. Intranasally administered fentanyl would appear to be suitable for the management of postoperative pain.
Article
To determine the amount of change in pain severity, as measured by a visual analog scale, that constitutes a minimum clinically significant difference. Patients 18 years of age or older who presented with acute pain resulting from trauma were enrolled in this prospective, descriptive study. The setting was an urban county hospital emergency department with a Level 1 trauma center. In the course of a brief interview, patients were asked to indicate their current pain severity with a single mark through a standard 100-mm visual analog scale. At intervals of 20 minutes for the next 2 hours, patients were asked to repeat this measurement and, in addition, to contrast their present pain severity with that at the time of the previous measurement. They were to indicate whether they had "much less," "a little less," "about the same," "a little more," or "much more" pain. All contrasts were made without reference to prior visual analog scale measurements. A maximum of six measurements of pain change were recorded per patient. Measurements ended when the patient left the ED or when the patient reported a pain score of zero. The minimum clinically significant change in visual analog scale pain score was defined as the mean difference between current and preceding visual analog scale scores when the subject noted a little less or a little more pain. Forty-eight subjects were enrolled, and 248 pain contrasts were recorded. Of these contrasts, 41 were rated as a little less and 39 as a little more pain. The mean difference between current and preceding visual analog scale scores in these 80 contrasts was 13 mm (95% confidence interval, 10 to 17 mm). The minimum clinically significant change in patient pain severity measured with a 100-mm visual analog scale was 13 mm. Studies of pain experience that report less than a 13-mm change in pain severity, although statistically significant, may have no clinical importance.
Article
[Ho K, Spence J, Murphy MF: Review of pain-measurement tools. Ann Emerg Med April 1996;27:427-432.]
Article
To review recent acute pain management care issues in a pediatric emergency department (ED) in order to identify opportunities for a performance improvement program. Descriptive, retrospective chart review. Urban pediatric hospital ED. Between January 1 and December 31, 1994 consecutive patients identified by ED chart review with the following three acute painful conditions were included; sickle cell vasoocclusive crisis (VOC) not complicated by fever or neurologic symptoms, isolated lower extremity long bone fractures < 12 hours old that did not require a reduction, and second degree burns < 12 hours old. Data collection concluded when between 50 and 55 episodes of each painful condition were identified. ED analgesic administration, initial analgesic dose, initial time elapsed to analgesic administration, notation of pain relief, and home analgesic instruction. Recommended analgesic starting doses were chosen from the 1992 Agency for Health Care Policy and Research Clinical Practice Guidelines. None. ED analgesic use for VOC was 100%, for fracture was 31%, and for burn was 26%. A recommended starting analgesic dose was given to 78% with VOC, 69% with fracture, and 79% with burn. Mean time to initial analgesic for VOC was 52 minutes, for fracture was 86 minutes, and for burn was 29 minutes. In those given analgesics, notation of pain relief for fracture was 19% and for burn was 29%, this improved for VOC where it was 88%. Home analgesic instruction for VOC was 100%, for fracture was 74%, and for burn was 27%. These data from 1994 document suboptimal analgesic use and home analgesic instruction for children in our ED with burns and fractures. Other opportunities in our ED for acute pain management improvement include optimizing initial analgesic doses, shortening the time elapsed to initial analgesic administration, and documenting the response to pain management.
Article
Painful and frightening injuries and illnesses are frequent reasons for children to seek care in an emergency department. Painful therapeutic procedures are often a necessary part of emergency care and are very distressful for the children, their parents, and healthcare providers. Inadequately relieved pain and distress have acute and long-term consequences, yet methods for pain and anxiety reduction during frightening minor and major procedures are often not used because of lack of detailed knowledge of techniques and fear of adverse effects. This article reviews psychologic and pharmacologic means of safe and effective reduction of anxiety and pain during emergency department procedures.
Article
The challenge for emergency medicine physicians in the new millennium is to use these drugs and drug combinations to make ED visits pain-free and safe experiences. With dedication to research, a willingness to take the time to explore new options, and expansion of pharmacologic and nonpharmacologic interventions, physicians can make this lofty dream a reality.
Article
We sought to determine the minimum clinically significant difference in visual analog scale (VAS) pain score for children. We performed a prospective, single-group, repeated-measures study of children between 8 and 15 years presenting to an urban pediatric emergency department with acute pain. On presentation to the ED, patients marked the level of their pain on a 100-mm nonhatched VAS scale. At 20-minute intervals thereafter, they were asked to give a verbal categoric rating of their pain as "heaps better," "a bit better," "much the same," "a bit worse," or "heaps worse" and to mark the level of pain on a VAS scale of the same type as used previously. A maximum of 3 comparisons was recorded for each child. The minimum clinically significant difference in VAS pain score was defined as the mean difference between current and preceding scores when the subject reported "a bit worse" or "a bit better" pain. Seventy-three children were enrolled in the study, yielding 103 evaluable comparisons in which pain was rated as "a bit better" or "a bit worse." The minimum clinically significant difference in VAS score was 10 mm (95% confidence interval 7 to 12 mm). This study found the minimum clinically significant difference in VAS pain score for children aged 8 to 15 years (on a 100-mm VAS scale) to be 10 mm (95% confidence interval 7 to 12 mm). In studies of populations, differences of less than this amount, even if statistically significant, are unlikely to be of clinical significance.
Article
Background: Many children are restless, disoriented, and inconsolable immediately after bilateral myringotomy and tympanosotomy tube placement (BMT). Rapid emergence from sevoflurane anesthesia and postoperative pain may increase emergence agitation. The authors first determined serum fentanyl concentrations in a two-phase study of intranasal fentanyl. The second phase was a prospective, placebo-controlled, double-blind study to determine the efficacy of intranasal fentanyl in reducing emergence agitation after sevoflurane or halothane anesthesia. Methods: In phase 1, 26 children with American Society of Anesthesiologists (ASA) physical status I or II who were scheduled for BMT received intranasal fentanyl, 2 microg/kg, during a standardized anesthetic. Serum fentanyl concentrations in blood samples drawn at emergence and at postanesthesia care unit (PACU) discharge were determined by radioimmunoassay. In phase 2, 265 children with ASA physical status I or II were randomized to receive sevoflurane or halothane anesthesia along with either intranasal fentanyl (2 microg/kg) or saline. Postoperative agitation, Children's Hospital of Eastern Ontario Pain Scale (CHEOPS) scores, and satisfaction of PACU nurses and parents with the anesthetic technique were evaluated. Results: In phase 1, the mean fentanyl concentrations at 10 +/- 4 min (mean +/- SD) and 34 +/- 9 min after administering intranasal fentanyl were 0.80 +/- 0.28 and 0.64 +/- 0.25 ng/ml, respectively. In phase 2, the incidence of severe agitation, highest CHEOPS scores, and heart rate in the PACU were decreased with intranasal fentanyl. There were no differences between sevoflurane and halothane in these measures and in times to hospital discharge. The incidence of postoperative vomiting, hypoxemia, and slow respiratory rates were not increased with fentanyl. Conclusions: Serum fentanyl concentrations after intranasal administration exceed the minimum effective steady state concentration for analgesia in adults. The use of intranasal fentanyl during halothane or sevoflurane anesthesia for BMT is associated with diminished postoperative agitation without an increase in vomiting, hypoxemia, or discharge times.
Article
To evaluate intranasally administered fentanyl for postoperative analgesia in pediatric patients. Thirty-two children aged four to eight years, ASA physical status I and II were included in this prospective randomized controlled study. In the postoperative care unit, patients were allocated to receive fentanyl, using a double-blind study design, either intranasally (Group I) or intravenously (Group II) in small titrated doses until they became pain free or side effects appeared which prohibited continuation of the drug. Satisfactory analgesia was achieved in both groups, though the required drug dosage was higher in the intranasal group (1.43 +/- 0.39 microg.kg(-1)). Onset of analgesia tended to be slower via the intranasal route compared to the iv route (13 +/- 4.5 vs 8.3 +/- 3.08 min; P=not significant). Side effects observed in this series were within an acceptable range and similar for both modalities. The intranasal route provides a good alternative for administration of fentanyl in pediatric surgical patients.
Article
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.
Article
Twenty-four gynaecological patients receiving postoperative patient-controlled analgesia were enrolled in an open cross-over pilot study evaluating two new formulations of nasal fentanyl spray. The primary outcome was the bioavailability of nasal fentanyl in comparison with intravenous fentanyl. This manuscript describes the clinical outcomes of quality of postoperative analgesia and patient acceptability. There were 21 complete data sets for both sequences of the cross-over design. In randomised order, patients received approximately 50 microg of fentanyl in a single dose by intranasal and intravenous administration, but separated by at least 2 h. Analgesia was of rapid onset (within 5 min) and similar quality. There was no significant difference in side-effects. Four patients experienced mild nasal stinging and although 10 (42%) preferred intravenous administration, seven (29%) preferred intranasal and six (25%) had no preference. We conclude that these formulations of fentanyl, delivered as nasal spray, have potential clinical utility.
Article
This study sought to compare the analgesic efficacy and safety of patient controlled intra-nasal (PCIN) fentanyl with oral morphine for procedural wound care in burns patients. A randomised double-blind placebo controlled, two period, two-treatment crossover trial was conducted within the Burns Unit of a major teaching hospital in Perth, Western Australia. Patients requiring identical wound care procedures on two consecutive mornings (and not prescribed intravenous analgesia) were randomised to receive either PCIN fentanyl with oral placebo or oral morphine with intranasal placebo on 1 day, followed by the alternate active drug on the following day. Twenty-six patients (22 males), aged between 18 and 69 years (35.5 +/- 12.4 years), with total body surface burns (TBSA) range 1-25% (6.9 +/- 4.5), indicated their level of pain on a 10 point (0-10) numeric scale at various time periods before, during and after the procedure. A mean total dose of 1.48 +/- 0.57 microg/kg of PCIN fentanyl and 0.35 +/- 0.12 mg/kg of oral morphine was administered. No statistically significant difference was found between the pain scores recorded for patients during the procedure with PCIN fentanyl compared to that with oral morphine (mean difference = -0.75, 95% CI = -1.97 to 0.47, P = 0.22). Two patients experienced hypotension during the procedure--both had received active oral morphine. No patients experienced respiratory depression or a significant drop in oxygen saturation. There were four episodes (in three patients) where 'rescue analgesia' for severe pain was required--two episodes involving oral morphine and two involving PCIN fentanyl. It was concluded that PCIN fentanyl is similar in efficacy and safety to oral morphine for relief of procedural wound care pain in burns patients.
Article
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. 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. 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 12.9-33.2kg). 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. 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.
Article
To test the agreement between the visual analogue scale (VAS) and a verbal numeric rating scale (VNRS) in measuring acute pain, and measure the minimum clinically significant change in VNRS. Patients scored their pain by the VAS and the VNRS, then re-scored their pain every 30 min for up to 2 h. Patients also recorded whether their pain had improved or worsened. Agreement between scores was evaluated, and where patients scored their pain as 'a bit worse' or 'a bit better' the mean change in VNRS was calculated. A total of 309 paired observations were obtained from 79 patients. The VAS and VNRS were highly correlated (r = 0.95, 95% CI 0.94-0.96). The VNRS was significantly higher than the VAS for the paired observations, with 95% of the differences between VAS and VNRS lying between -2.3 and 1.3 cm. The minimum clinically significant difference in VNRS was 1.4 cm (95% CI 1.2-1.6). The VNRS performs as well as the VAS in assessing changes in pain. However, although the VAS and VNRS are well correlated, patients systematically score their pain higher on the VNRS, with an unacceptably wide distribution of the differences.