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A Randomized Controlled Trial Comparing Intranasal Fentanyl to Intravenous Morphine for Managing Acute Pain in Children in the Emergency Department
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.
... 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. ...
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.
... Moreover, its topic administration has been found to be effective in controlling postoperative pain in children after tonsillectomy [124][125][126]. More details about tramadol's efficacy were obtained by pooling the results of 20 randomized controlled trials involving 1170 patients who had received the drug for postoperative pain treatment [127]. In this meta-analysis, it was shown that children receiving tramadol needed less rescue analgesia in the postoperative care unit than those given a placebo (relative risk (RR), 0.40; 95% CI, 0.20-0.78). ...
Pain is a biopsychosocial experience characterized by sensory, physiological, cognitive, affective, and behavioral components. Both acute and chronic pain can have short and long-term negative effects. Unfortunately, pain treatment is often inadequate. Guidelines and recommendations for a rational approach to pediatric pain frequently differ, and this may be one of the most important reasons for the poor attention frequently paid to pain treatment in children. This narrative review discusses the present knowledge in this regard. A literature review conducted on papers produced over the last 8 years showed that although in recent years, compared to the past, much progress has been made in the treatment of pain in the context of the pediatric emergency room, there is still a lot to do. There is a need to create guidelines that outline standardized and easy-to-follow pathways for pain recognition and management, which are also flexible enough to take into account differences in different contexts both in terms of drug availability and education of staff as well as of the different complexities of patients. It is essential to guarantee an approach to pain that is as uniform as possible among the pediatric population that limits, as much as possible, the inequalities related to ethnicity and language barriers.
... Il Box 2 riporta in sintesi le modalità d'uso della dexmedetomidina per via IN. Farmaci intranasali nel bambino, cosa devono sapere i pediatri ha dimostrato che una dose di 1,5 μg/kg di fentanyl IN ha la stessa efficacia analgesica della somministrazione di 0,1 mg/kg di morfina per via endovenosa nei bambini con frattura 28 . La somministrazione IN del fentanyl è ideale per la facilità di utilizzo e la rapidità di azione. ...
The use of the intranasal route of administration to deliver drugs in children became more and more popular in the last decades. Seizure, severe acute pain, and severe hypoglycemia in diabetic patients, may be managed with intranasal drugs. The intranasal administration is minimally invasive, not painful, needleless, and easy to learn and use. The evidence shows that it is a safe and effective way to deliver lipophilic drugs, that are quickly absorbed. This article is a practical guide that provides indications, dosages, and some “tricks” for this way of administration.
... In addition, transmucosal administration typically causes less discomfort than intravenous sedation, making it a more favorable option for patients (42). The extensively vascularized nasal mucosa and the olfactory tissue in direct proximity to the central nervous system expedite swift transportation into the bloodstream and brain, with onsets of action comparable to that of intravenous therapy (43). Despite its simplicity, relative painlessness, and the need for less patient cooperation, intranasal administration has been linked with mucosal irritation (44). ...
Procedural sedation and analgesia are now considered standard care for managing pain and anxiety in pediatric dental patients undergoing diagnostic and therapeutic procedures outside of the operating room. Anxiolysis, which combines both pharmacologic and non-pharmacologic approaches, plays a significant role in procedural sedation. Non-pharmacologic interventions such as Behavior Management Technology can help reduce preprocedural agitation, ease the transition to sedation, reduce the required amount of medication for effective sedation, and decrease the occurrence of adverse events. As the introduction of novel sedative regimen and methods in pediatric dentistry, the potential role of mainstay sedatives administered by new routes, for new indications, and with new delivery techniques, should be considered. The purpose of this paper is to examine and discuss the current state of sedation techniques in pediatric dentistry.
... IN fentanyl provides effective analgesia without the need for intravenous access or iatrogenic pain from intramuscular injections. This makes it particularly useful for patients with minor injuries who do not require intravenous access for resuscitation [30,31]. Holdgate et al. found that the use of IN fentanyl significantly reduced the time from patient arrival to initial analgesia compared with intravenous morphine [32]. ...
This systematic review examined the efficacy and safety of intranasal fentanyl (INF) for acute pain treatment in children, adults, and the elderly in prehospital emergency services (PHES) and emergency departments (ED). ClinicalTrials.gov, LILACS, PubMed, SCOPUS, EMBASE, Google Scholar and Cochrane databases were consulted until 31 December 2022. A total of 23 studies were included: 18 in children (1 PHES, 17 ED), 5 in adults (1 PHES, 4 ED) and 1 in older people (1 PHES subgroup analysis). In children, INF was effective in both settings and as effective as the comparator drugs, with no differences in adverse events (AEs); one randomised controlled trial (RCT) showed that INF was more effective than the comparator drugs. In adults, one study demonstrated the efficacy of INF in the PHES setting, one study demonstrated the efficacy of INF in the ED setting, two RCTs showed INF to be less effective than the comparator drugs and one RCT showed INF to be as effective as the comparator, with no difference in AEs reported. In older people, one study showed effective pain relief and no AEs. In summary, INF appears to be effective and safe in children and adults in PHES and ED. More high-quality studies are needed, especially in PHES and older people.
... The standard IN dose of 1.5 µg/kg fentanyl has been shown to provide effective analgesia comparable to the analgesic potency of IV morphine (7,8). As a selective mu-receptor agonist, fentanyl is safer than other opioids with fewer cardiovascular effects due to a lack of histamine release (9). ...
Background
Nurse-directed pain protocols for intranasal fentanyl administration are not widely implemented in European (EU) pediatric emergency departments (PED). Barriers include perceived safety concerns for intranasal (IN) fentanyl. The aim of this study is to describe our experience with a nurse-directed triage IN fentanyl protocol with a focus on safety in a tertiary EU PED.
Methods
We conducted a retrospective analysis of patient records of children aged 0–16 years who received nurse-directed IN fentanyl between January 2019 and December 2021 at the PED of the University Children's Hospital of Bern, Switzerland. Extracted data points included demographics, presenting complaint, pain score, IN fentanyl dosage, concomitant pain medication use, and adverse events.
Results
A total of 314 patients were identified with ages ranging from 9 months to 15 years. The main indication for nurse-directed fentanyl administration was musculoskeletal pain due to trauma ( n = 284, 90%). Mild adverse events (vertigo) were reported in two patients (0.6%), without a correlation to concomitant pain medication or protocol violation. The only reported severe adverse event of syncope and hypoxia in a 14-year-old adolescent occurred in a setting where the institutional nurse-directed protocol was violated.
Conclusion
In accordance with previous studies outside of Europe, our data support the case that when appropriately used, nurse-directed IN fentanyl is a safe potent opioid analgesic for pediatric acute pain management. We strongly encourage the introduction of nurse-directed triage fentanyl protocols Europe-wide in order to provide effective and adequate acute pain management in children.
... 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. ...
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.
... 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]. ...
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.
... 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 (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]. ...
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
... 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]. ...
... 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]. ...
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 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%. ...
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.
Background
Children in acute pain often receive inadequate pain relief, partly from difficulties administering injectable analgesics. A rapid-acting, intranasal (IN) analgesic may be an alternative to other parenteral routes of administration. Our review compares the efficacy, safety, and acceptability of intranasal analgesia to intravenous (IV) and intramuscular (IM) administration; and to compare different intranasal agents.
Methods
We searched Cochrane Library, MEDLINE/PubMed, Embase, Web of Knowledge, Clinicaltrials.gov, Controlled-trials.com/mrcr, Clinicaltrialsregister.eu, Apps.who.int/trialsearch. We also screened reference lists of included trials and relevant systematic reviews. Studies in English from any year were included.
Two authors independently assessed all studies. We included randomised trials (RCTs) of children 0–16, with moderate to severe pain; comparing intranasal analgesia to intravenous or intramuscular analgesia, or to other intranasal agents. We excluded studies of procedural sedation or analgesia.
We extracted study characteristics and outcome data and assessed risk of bias with the ROB 2.0-tool. We conducted meta-analysis and narrative review, evaluating the certainty of evidence using GRADE.
Outcomes included pain reduction, adverse events, acceptability, rescue medication, ease of and time to administration.
Results
We included 12 RCTs with a total of 1163 children aged 3 to 20, most below 10 years old, with a variety of conditions. Our review shows that:
- There may be little or no difference in pain relief (single dose IN vs IV fentanyl MD 4 mm, 95% CI -8 to 16 at 30 min by 100 mm VAS; multiple doses IN vs IV fentanyl MD 0, 95%CI -0.35 to 0.35 at 15 min by Hannallah score; single dose IN vs IV ketorolac MD 0.8, 95% CI -0.4 to 1.9 by Faces Pain Scale-Revised), adverse events (single dose IN vs IV fentanyl RR 3.09, 95% CI 0.34 to 28.28; multiple doses IN vs IV fentanyl RR 1.50, 95%CI 0.29 to 7.81); single dose IN vs IV ketorolac RR 0.716, 95% CI 0.23 to 2.26), or acceptability (single dose IN vs IV ketorolac RR 0.83, 95% CI 0.66 to 1.04) between intranasal and intravenous analgesia (low certainty evidence).
- Intranasal diamorphine or fentanyl probably give similar pain relief to intramuscular morphine (narrative review), and are probably more acceptable (RR 1.60, 95% CI 1.42 to 1.81) and tolerated better (RR 0.061, 95% CI 0.03 to 0.13 for uncooperative/negative reaction) (moderate certainty); adverse events may be similar (narrative review) (low certainty).
- Intranasal ketamine gives similar pain relief to intranasal fentanyl (SMD 0.05, 95% CI -0.20 to 0.29 at 30 min), while having a higher risk of light sedation (RR 1.74, 95% CI 1.30 to 2.35) and mild side effects (RR 2.16, 95% CI 1.72 to 2.71) (high certainty). Need for rescue analgesia is probably similar (RR 0.85, 95% CI 0.62 to 1.17) (moderate certainty), and acceptability may be similar (RR 1.15, 95% CI 0.89 to 1.48) (low certainty).
Conclusions
Our review suggests that intranasal analgesics are probably a good alternative to intramuscular analgesics in children with acute moderate to severe pain; and may be an alternative to intravenous administration. Intranasal ketamine gives similar pain relief to fentanyl, but causes more sedation, which should inform the choice of intranasal agent.
Background:
Few studies have evaluated the rapid pain improvement provided by medications for children presenting to an emergency department (ED) with headaches.
Objective:
Our aim was to evaluate pain reduction provided by intranasal fentanyl (INF) compared with placebo in addition to ibuprofen.
Methods:
A single-center, double-blinded, randomized, placebo-controlled clinical trial was conducted in a tertiary care pediatric ED. All children aged 8-17 years presenting with a moderate to severe headache were eligible. Study participants were randomly allocated to receive INF 1.5 µg/kg (maximum dose of 100 µg) or similar placebo solution. Co-administration of oral ibuprofen 10 mg/kg (maximum dose of 600 mg) was also provided. The primary outcome was the mean pain rating reduction at 15 min.
Results:
Among the 62 participants, the median age was 14 years (interquartile range [IQR] 12-16 years in both groups) and the median initial visual analog scale (VAS) score was 64 (IQR 55-72 in the intervention group; IQR 50-81 in the control group). There was no difference in the mean pain score reduction at 15 min between the two groups (mean difference 2 mm; 95% CI -7 to 11 mm). Mean VAS score reductions were also similar at 30 and 60 min. Adverse events were more frequent in the INF group (risk ratio 2.8; 95% CI 1.29 to 6.22), but all events were minor and transient. No significant differences were found in other outcomes.
Conclusions:
This study did not find a benefit from INF for providing additional pain relief in children presenting to ED with headaches.
Children with sickle cell disease commonly experience vaso-occlusive pain episodes due to sickling of erythrocytes, which often requires care in the emergency department. Our objective was to assess the use and impact of intranasal fentanyl for the treatment of children with SCD-VOE on discharge from the emergency department in a multicenter study. We conducted a cross-sectional study at 20 academic pediatric emergency departments in the United States and Canada. We used logistic regression to test bivariable and multivariable associations between the outcome of discharge from the emergency department and candidate variables theoretically associated with discharge. There study included 400 patients; 215 (54%) were female. The median age was 14.6 (interquartile range 9.8, 17.6) years. Nineteen percent (n=75) received intranasal fentanyl in the emergency department. Children who received intranasal fentanyl had nearly nine-fold greater adjusted odds of discharge from the emergency department compared to those who did not (adjusted odds ratio 8.99, 95% CI 2.81-30.56, P<0.001). The rapid onset of action and ease of delivery without IV access offered by intranasal fentanyl make it a feasible initial parenteral analgesic in the treatment of children with sickle cell disease presenting with vaso-occlusive pain episodes in the acute-care setting. Further study is needed to determine potential causality of the association between intranasal fentanyl and discharge from the emergency department observed in this multicenter study. This article is protected by copyright. All rights reserved.
In recent years our understanding of molecular mechanisms of drug action and interindividual variability in drug response has grown enormously. Meanwhile, the practice of anesthesiology has expanded to the preoperative environment and numerous locations outside the OR. Anesthetic Pharmacology: Basic Principles and Clinical Practice, 2nd edition, is an outstanding therapeutic resource in anesthesia and critical care: Section 1 introduces the principles of drug action, Section 2 presents the molecular, cellular and integrated physiology of the target organ/functional system and Section 3 reviews the pharmacology and toxicology of anesthetic drugs. The new Section 4, Therapeutics of Clinical Practice, provides integrated and comparative pharmacology and the practical application of drugs in daily clinical practice. Edited by three highly acclaimed academic anesthetic pharmacologists, with contributions from an international team of experts, and illustrated in full colour, this is a sophisticated, user-friendly resource for all practitioners providing care in the perioperative period.
Introduction
Intranasal fentanyl offers a means for safe and effective pain management in austere environments. Prehospital analgesia traditionally involves intravenous or intramuscular medication. However, for wilderness rescuers, these methods are often impractical.
Methods
We conducted a retrospective review of health records to evaluate the safety and efficacy of intranasal fentanyl administered by EMT-Basic certified ski patrollers. Our primary aim was to measure the reduction in initial pain scores to subsequent measurements at 5, 10, and 15 min using the pain numeric rating scale (0–10). Clinically significant reduction in severe pain has been established as ≥1.8 points. We used paired t-tests and multilevel modeling to measure statistical significance and potential interactions and reviewed patient charts for adverse events, including respiratory depression or the use of naloxone.
Results
We compiled the results from the winter seasons for 2007 through 2012 and 2016 through 2020. A total of 247 patients were included. The initial pain score was 8.6±1.5 (mean±SD). The decrease in pain scores from 0 to 5, 10, and 15 min, respectively, was –1.8, –2.4, and –2.9 (P<0.0001), which demonstrated a clinically and statistically significant decrease in pain scores. There were no adverse events.
Conclusions
Traditional standard of care analgesics are invasive, elongate scene times, and increase the risk of environmental exposure and provider needlestick. Intranasal fentanyl offers a safe, noninvasive, and rapid analgesia that is well-suited for austere winter environments, such as those encountered at ski resorts. This study demonstrates the safety and efficacy of the administration of intranasal fentanyl by EMT-Basic certified providers.
Objectives:
Painful infectious mouth conditions such as herpangina, hand-foot-and-mouth disease, and herpetic gingivostomatitis can cause pain, dehydration, and hospitalization in young children. Treatment for these conditions is generally supportive and directed toward pain relief from ulcerative lesions, thus facilitating oral intake, and preventing dehydration. Attempts at oral therapy at home and in the emergency department are often refused and immediately spit back out. This study evaluated the efficacy of intranasal fentanyl (INF) compared with a commonly used oral (PO) acetaminophen/hydrocodone formulation for the treatment of children with painful infectious mouth conditions.
Methods:
This study was a prospective, nonblinded, randomized controlled noninferiority trial conducted in an academic tertiary care pediatric emergency department. The study enrolled children between the ages of 6 months and 18 years with painful infectious mouth lesions and poor oral intake. Patients were randomized to receive either INF (1.5 μg/kg, intervention) or PO acetaminophen/hydrocodone (0.15 mg/kg, control) based on the dose of hydrocodone. The primary outcome was volume of fluid intake per body weight (in milliliters per kilogram) 60 minutes after analgesic administration. Secondary outcomes included pain scores using a validated visual assessment scale (VAS; 1, no pain; 10, worst pain), hydration score (VAS; 1, well hydrated; 4, very dehydrated), admission rate and overall satisfaction score (VAS; 1, worst; 7, best). A priori power analysis indicated that 34 patients would achieve an 81% power with an α value of 0.05.
Results:
Of the 34 patients enrolled, 17 were randomized to INF and 17 to PO. The demographics between both groups were similar in age, weight, sex, and race. There were no significant differences in parental perception of pain (P = 0.69) or hydration status (P = 0.78). Oral fluid intake at 60 minutes was 20 mL/kg for INF versus 18 mL/kg for PO (P = 0.53). Pain scores at 15 and 30 minutes were 1.7 versus 2.9 (P = 0.09) and 0.6 versus 1.6 (P = 0.59). Parental perceptions of pain and hydration status at 60 minutes were 2.2 versus 2.4 (P = 0.77) and 1.7 versus 1.5 (P = 0.37). Overall parental satisfaction was 6.4 for INF versus 6.5 for PO (P = 0.71), and admission rate was 0 vs 12% (P = 0.49). There were no adverse events such as respiratory, cardiac, or central nervous system depression in either group.
Conclusions:
Intranasal fentanyl seems to be a safe and effective alternative to acetaminophen with hydrocodone in reducing pain and improving hydration status in children with painful infectious mouth lesions and poor oral intake.
OBJECTIVE
Combining intranasal fentanyl (IN FENT) with inhaled nitrous oxide (N2O) seems to have good properties for pediatric procedural sedation and analgesia (PSA). This study aims to assess the side effect rate of the combined use of IN FENT and N2O.
METHODS
We performed a retrospective, single-center study. Patients treated in either the pediatric emergency department (PED) or the pediatric surgery outpatient clinic (PSOC) were included, if they received PSA with IN FENT and nitrous oxide with 50% oxygen (N2O 50%).
RESULTS
Three hundred seventy-five patients were included over a period of 4 years. Median age was 9.4 years (range, 3.1 to 15.9) and 39% of patients were female. Overall side effect rate was 30% (114 patients). Most frequent was dizziness (n = 63, 17%; 95% CI, 13–21), followed by nausea (n = 23, 6%; 95% CI, 4–9) and emesis (n = 14, 4%; 95% CI, 2–6), with 35 patients having either nausea and/or emesis (9%; 95% CI, 7–13). No serious side effects were recorded (0%; 95% CI, 0–0.1). Of 298 patients with information regarding satisfaction, 280 patients would like the same sedation for a similar procedure in the future (94%; 95% CI, 90–96). We found no relation between previously described risk factors and emesis and/or nausea.
CONCLUSIONS
N2O 50% combined with IN FENT can be recommended as an effective and safe treatment in the PED and the PSOC. While the side effect rate, primarily dizziness, nausea and emesis was substantial, antiemetic prophylaxis is not indicated owing to the overall low incidence of nausea and emesis.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Objectives:
Pain control remains suboptimal in pediatric emergency departments (EDs). Only 60% of pediatric patients requiring pain medications receive them in the ED, with an average time of administration being 90 minutes after arrival. Although pain protocols (PP) have been proposed and evaluated in children with long-bone fractures, data on PP utility for general pediatric patients with acute pain are limited. Our objective is to introduce a nursing-initiated PP with medication algorithms for use in triage, measure the improvement in management of severe pain on arrival to the ED and determine the effect on parental satisfaction.
Methods:
Prospective prestudy and poststudy conducted from June to October 2017. Patients aged 3 to 17 years presenting to a large tertiary pediatric ED with acute pain were eligible. Preprotocol demographics, clinical data, and pain interventions were obtained over a 6-week period. A convenience sample of parents completed a satisfaction survey rating their experience with ED pain management during this time. In the 4-week intervention phase, the PP was introduced to our ED nurses. Postintervention data were collected in the same fashion as the preintervention phase. Analysis was done using independent sample t test and χ models.
Results:
There were 1590 patients evaluated: preprotocol (n = 816), postprotocol (n = 774). Approximately 10% more patients with severe pain received pain medication in the post-PP sample compared with pre-PP (85.6% and 75.9% respectively). Parental satisfaction was higher in patients who received analgesic medications within 90 minutes of arrival to the ED (P = 0.007).
Conclusions:
The introduction of a PP in the ED setting improved the treatment of pain. There was a significant increase in patients with severe pain receiving analgesic medications. Additionally, parents were more satisfied if their children received pain medication in a more timely fashion. Pediatric EDs should consider introducing PPs to improve appropriate and timely administration of pain medication in triage.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Objective: To investigate the pharmacokinetics of intranasal fentanyl in adult post‐operative female patients.
Method: Patients received both intravenous and intranasal fentanyl (approximately 50 µg) 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.
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.
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.
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.
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.
[Ho K, Spence J, Murphy MF: Review of pain-measurement tools. Ann Emerg Med April 1996;27:427-432.]
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.