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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.
... This method also prevents delays in treatment when compared to oral administration. [2][3][4] Many studies in the literature show the effectiveness of IN drug application. Ketamine, fentanyl, oxytocin, and calcitonin are a few examples that have been studied as IN applications. ...
... Ketamine, fentanyl, oxytocin, and calcitonin are a few examples that have been studied as IN applications. 3,[5][6][7] Paracetamol (also known as acetaminophen in the USA), ibuprofen, and diclofenac are over-the-counter analgesic drugs commonly used all over the world. Paracetamol is one of the most popular analgesic drugs used around the world, and it is a popular choice for children under 12 years of age and pregnant or breastfeeding women. ...
... 5,33 A total of 1.5 μg/kg (50 μg/mL) of IN fentanyl has been demonstrated to be an analgesic equivalent to 0.1 mg/kg of IV morphine and begins to take effect in as little as 7 min due to its high potency and lipophilicity. 3 IN fentanyl has been demonstrated to be a secure and well-tolerated approach to analgesia. This method has proven effective in both pre -and postoperative pain management among pediatric patients, 5 as well as in the immediate management of acute pain. ...
Objective
Intranasal analgesic sprays represent a safe, efficacious method for pain relief, with a shorter working time compared to oral painkillers. This study aimed to develop nasal sprays using commonly available over-the-counter analgesics, providing an alternative treatment option that is more convenient and potentially more effective in managing pain, particularly in pediatric patients.
Methods
Three different nasal spray formulations with the contents of diclofenac sodium, ibuprofen, and paracetamol were created, and characterization studies were completed. The possible cytotoxic, genotoxic, and apoptotic effects of nasal sprays were studied on human normal skin fibroblastic cells (CCD-1079Sk) using WST cell viability test, alkaline single-cell gel electrophoresis analysis, and acridine orange/ethidium bromide staining, respectively.
Results
The formulations’ physical appearance and drug content were assessed, yielding nonsignificant results (p > 0.05). All formulations were determined at pH 5.5–6.2 so that the pH values of the prepared formulations were compatible with the pH value of the nasal mucosa. Selected nasal spray formulations were stable for 90 days, and the safe doses were chosen as 0.0625, 0.375, and 1.25 mg/mL for diclofenac, ibuprofen, and paracetamol, respectively, by not showing toxicity even at 24 h.
Conclusion
This study demonstrated that nasal sprays containing paracetamol, ibuprofen, and diclofenac sodium can be successfully formulated. These new formulations may provide alternative treatment and easier application for patients unable to swallow or refuse to take oral analgesics.
... 4,5 As a result, IN administration has gained wide acceptance as a route of drug delivery for pediatric patients, particularly in emergency and perioperative settings where pain management, procedural sedation, and preanesthetic anxiolytic therapy are essential aspects of care. [6][7][8][9][10][11] Intranasal administration of opioids has been widely utilized as the primary class of analgesics for children experiencing severe pain. 12 However, its efficacy may be constrained by genetic factors that result in reduced sensitivity to opioids and the potential occurrence of adverse effects. ...
... This makes it especially beneficial for individuals who have minor injuries and do not need access to an IV line for resuscitation. 8 The authors confirm that the article has been read and approved by all named authors and that there are no other persons who satisfied the criteria for authorship but are not listed. They further confirm that the order of authors listed in the article has been approved by all of them. ...
... As a result, the utilization of INF has become increasingly common in pediatric EDs. 7,8,23,24 In addition, recent findings indicate that ketamine, when administered at subdissociative doses, has successfully managed pain in pediatric and adult patients. 25,26 These findings suggest that IN ketamine can be an efficacious nonopioid alternative for pain management in pediatric emergency care. ...
Background: Intranasal fentanyl (INF) has gained popularity in pediatric
emergency departments (EDs) as an effective alternative to intravenous
morphine for treating acute moderate to severe pain. Intranasal fentanyl
eliminates the need for invasive access,making it advantageous for patients
with minor injuries. Our study aims to provide a comprehensive evaluation
of the available evidence regarding the effectiveness and safety of INF administration
in pediatric emergency wards, particularly compared with
other treatment options described in the literature.
Methods: A thorough search strategy identified randomized controlled
trials assessing INF in the pediatric emergencyward. Eligible studieswere independently
screened, and relevant data were extracted. The analysis used
pooled risk ratio (RR) for dichotomous outcomes and the standardized mean
difference (SMD) for continuous ones. Randomized controlled trials' quality
was assessed using the Cochrane Risk of Bias Assessment Tool 2.
Results: In our study, 8 randomized controlled trials involving 806 patients,
INF demonstrated superior effectiveness in reducing pain compared with
other comparators at the 15- to 20-minutemark (SMD, −0.23; 95% confidence
interval, −0.37 to −0.08; P = 0.002). However, no significant differences
were found at the 30- and 60-minute time points (SMDs, −0.16; 95% CI,
−0.50, 0.19; P = 0.37; and −0.16; 95% CI, −0.50 to 0.19; P = 0.78) except
when excluding one study to resolve heterogeneity at the 30-minute mark
(RR, −0.02; 95% CI, −0.24 to 0.20; P = 0.87). Intranasal fentanyl also exhibited
a better adverse outcome profile, with a lower risk of total adverse
events and nausea/vomiting (RR, 0.66; 95% CI, 0.48–0.91; P = 0.01; and
RR, 0.43; 95% CI, 0.30–0.63; P > 0.001) compared with other analgesics.
However, no significant differences were observed for dizziness and hallucination
(RR, 0.43; 95% CI, 0.30–0.63; P = 0.68; and RR, 0.43; 95% CI,
0.30–0.63; P = 0.35).
... Despite their efficacy, OPs are associated with adverse effects such as respiratory depression, nausea, vomiting and the risk of addiction. 5,6 Furthermore, obtaining intravenous (IV) access to administer parenteral OPs can be challenging, time-consuming and distressing for children. 7,8 Rescue analgesics are often required to manage breakthrough pain or insufficient response to initial analgesic regimens, further complicating pain management strategies. ...
Background
Ketamine (KT) is known to have analgesic and sedative effects. Intranasal (IN)/inhalational KT has been used in different trials involving paediatric patients for analgesic and anxiolytic function. The present meta-analysis was conducted to establish the role of IN/inhalational KT compared to that of inhalational opioids (OPs).
Summary
A systematic literature search was performed through the Cochrane Library, Pub Med and ClinicalTrials.gov databases from inception to February 2024 using the following keywords: inhalational OR IN OR nebulised’ and ‘ketamine’ and ‘analgesia’. Randomised clinical trials published in English that analysed the efficacy and safety of inhalational KT either alone or as an adjunct to the standard of care (SoC) compared to OP in paediatric patients undergoing various procedures were included in the analysis. The important outcomes included patients who were pain responders, required rescue analgesics, achieved mild-moderate sedation and experienced any adverse events (AEs), dizziness, nausea/vomiting or unpleasant taste. A trial sequential analysis (TSA) was also performed. The analysis included seven studies with 489 paediatric patients. In the KT group, a smaller number of patients were pain responders and required rescue analgesics (RR = 0.94; 95% CI = 0.78–1.13; P = .52 and RR = 0.80; 95% CI = 0.44–1.43; P = .45, respectively). Similarly, more patients in the KT group achieved mild-moderate sedation and experienced any AEs (RR = 1.44; 95% CI = 0.95–2.18; P = .09; and RR = 1.99; 95% CI = 1.47–2.69; P < .00001, respectively). A greater number of patients experienced dizziness (RR = 5.47; 95% CI = 3.12–9.58; P < .00001) and an unpleasant taste (RR = 2.91; 95% CI = 1.51–5.61; P = .001) in the KT group. In the meta-analysis, the required information size (RIS) could not be obtained.
Key Message
KT had efficacy outcomes comparable to those of OP, but KT had very high adverse effects. OP seems to have better tolerability than KT. However, as the number of patients was less than the RIS, it was not possible to draw any conclusions.
... Intranasal fentanyl provided similar analgesia to intravenous morphine in children with bone fractures. 9 Moreover, it was successfully employed for other causes of acute pain [10][11][12] and to control procedural pain. 13 14 Recently published trials showed a similar efficacy of intranasal ketamine compared with intranasal fentanyl. ...
Background
Despite evidence showing that the intranasal and sublingual routes are safe and effective in providing analgesia, no data are available about their day-to-day use in the emergency department (ED). The aim of this study was to assess the frequency of the use of the intranasal and sublingual routes, and the clinical characteristics of the patients receiving analgesia through these routes.
Methods
A multicentre study was performed in the EDs participating in the Pain in Paediatric Emergency Room research group. It included a survey and a retrospective data collection in which the medical records of all patients who received analgesia from 1 April 2022 to 31 May 2022 were collected.
Results
48 centres (91%) answered the survey. The intranasal and sublingual routes were used in 25 centres (52%). 13 centres (27%) used both routes, 9 centres (19%) used only the sublingual and 3 centres (6%) used only the intranasal route.
12 centres (48%) participated in the retrospective study. Data about 3409 patients, median age 9 years (IQR 5–12), were collected. Among them, 337 patients (9.6%) received sublingual analgesia, and 87 patients (2.5%) received intranasal analgesia. The intranasal route was employed for injuries in 79 (90.8%) cases, and fentanyl was the drug delivered in 85 (97.7%) cases. The sublingual route was used mainly for injuries (57.3%), but also for abdominal pain (15.4%), musculoskeletal pain (14.5%) and headache (10.7%). Paracetamol, ketorolac and tramadol were administered through this route.
Conclusions
The use of the intranasal and sublingual routes for analgesia in the paediatric ED is still limited.
... 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. ...
Background
Prehospital management of pain in children could be considered substandard, with not all children in pain receiving adequate and timely analgesia. With intravenous access being difficult to obtain and many children displaying a fear of needles, the common barrier highlighted is the route of easily administered analgesia.
Aims
To explore the use of intranasal analgesia for the management of children in pain in the prehospital environment.
Methods
A search was completed using One Search and EBSCOhost research interface of the CINAHL Plus database. This scoping review identified literature on the chosen topic of interest, which was then refined to six studies exploring three key themes: efficacy, safety and feasibility.
Results
621 children were included across the six studies, receiving either morphine, diamorphine, ketamine or fentanyl. Similar efficacy was seen between morphine and fentanyl, as well as fentanyl and ketamine. Adverse events were more prevalent in the ketamine groups; however, these were considered minor, and no serious adverse events were recorded. Sedation levels were not thought to be significant and could be considered advantageous in this patient group.
Conclusion
Intranasal drug administration provides an efficacious route that is non-invasive and safe to administer in challenging environments. A sub-dissociative dose of ketamine is as efficacious as fentanyl, while offering a non-opioid alternative.
Objectives:
Children make up 5-10% of emergency medical services (EMS) transports and are at risk for under-recognition and under-treatment of pain. Prior studies have identified enablers to pediatric analgesia including EMS pediatric analgesia education, agency leadership support, the availability of assistive guides and having positive relationships with online medical control. Prior barriers identified were intravenous (IV) line insertion pain, caregiver concerns, difficulty assessing pain, pain medication safety concerns, unfamiliarity with pediatrics, unwanted attention from authority figures and perceived superiority of hospital care. This study's objective was to evaluate enablers and barriers to prehospital analgesia for children presenting with traumatic pain after the introduction of intranasal (IN) fentanyl into EMS protocols.
Methods:
Focus groups with EMS clinicians were used to elicit perspectives on pediatric analgesia. EMS clinicians discussed transports of children in pain, decision-making regarding analgesic administration, available resources to treat pain including EMS protocols, patient and family reactions, and ways to improve pediatric oligoanalgesia. Themes were explored until thematic saturation was reached using a deductive approach with open-ended yet structured questions.
Results:
Enablers for pediatric analgesia included longer transports, desire to stabilize the patient, vital signs or injuries suggestive of severe pain, and clinician comfort with and availability of IN pain medication. Barriers to analgesia included concerns that the child was not stable enough for pain medication, avoiding masking symptoms prior to hospital arrival, lack of pediatric experience, lack of access to opiates in some ambulances, poor suspension in ambulances causing difficulty with IV access, patient refusal for an IV, caregivers' discomfort with opiates and caregivers' lack of knowledge of available prehospital medications. Focus group themes identified were that there was a lack of experience with pediatric patients, medical control was a helpful resource and training that approximated real-world situations was important.
Conclusions:
New enablers for pediatric analgesia identified were longer transports and EMS clinician comfort with IN pain medications. While many barriers to pediatric analgesia persist, new barriers identified were poor suspension in ambulances causing difficulty with IV access and caregivers' lack of knowledge of available prehospital medications. Additional EMS pediatric training and experience may improve pediatric oligoanalgesia.
Nasal packing following nasal procedures are commonly used to reduce post operative bleeding and pain. Removal of nasal pack may be associated with mucosal injury which may cause delayed recovery. Various aspects of post-operative pain management have been studied. Opioids such as fentanyl, morphine and nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat postoperative pain. Fentanyl used topically results in a longer duration of action with a lower dosage and fewer adverse effects than IV therapy. To compare the efficacy of Fentanyl-soaked Nasal Packing on post operative pain in patients undergoing Nasal surgeries versus normal saline pack. A randomized control trial conducted among patients undergoing Nasal Surgery in the age group between 20 to 50 years at a tertiary care centre, Puducherry, India. Patients were randomly divided into two groups with 34 participants in each. Group A received Postoperative Nasal pack with 50mcg of Fentanyl and group B received Postoperative Nasal pack with Normal saline. Data were analysed using SPSS 21. The mean RSS score was 2.03 ± 0.83 and 1.38 ± 0.49 in group A and B respectively. The RSS score was significantly higher among group A than B. At all hours, mean Verbal pain intensity scale and numeric pain rating scale were significantly lower among Group A than B. At 1, 6,12 and 36 hours, Wong-Baker pain rating scale was significantly lower among Group A than B. There was no significant difference in hemodynamic parameters between the groups. The fentanyl group experienced much less postoperative pain without experiencing any significant adverse effects. We propose that applying topical fentanyl to nasal packs may be a feasible strategy to alleviate discomfort during the initial phases of recovery following nasal surgery.
Chronic pain is a complex condition that significantly impacts patients' quality of life and presents a substantial burden on healthcare systems. This paper reviews innovative approaches to chronic pain management, addressing existing pharmacological options and integrating therapies. In the context of emerging pharmacological treatments, including biologics and novel analgesics, targeted pain pathways are evaluated for their potential to provide more effective and reliable pain relief. Additionally, advancements in neuromodulation techniques, such as sleep-inducer rope provocation and Transcutaneous Electrical Nerve Stimulation (TENS), are explored for their role in modulating pain signals and reducing reliance on opioids. The integration of behavioral health sciences through mobile technology and wearable devices is examined for their ability to enhance patient self-management and facilitate real-time pain monitoring. Furthermore, this paper discusses the importance of combining various branches of care models that integrate medical, psychological, and physical therapy approaches to address the multifactorial nature of chronic pain. Case studies and objective challenges are reviewed to highlight the effectiveness and obstacles of these innovative approaches. By adopting a holistic and patient-centered perspective, this paper aims to provide a comprehensive understanding of future directions in chronic pain management, emphasizing the need for ongoing research and collaboration with healthcare professionals to improve patient outcomes and quality of life.
OBJECTIVES
The use of intranasal (IN) analgesics and sedatives has been studied among pediatrics patients in the emergency department and outpatient settings. However, less is known about their usage in inpatient settings. This study aims to evaluate the indications and safety profile for IN fentanyl and midazolam usage in pediatric patients admitted to a large tertiary care children’s hospital.
METHODS
This study is a retrospective chart review of admitted patients receiving IN fentanyl and/or midazolam over a 6-year period. Indications for medication use, medication dosages, patient characteristics, and any serious adverse drug reactions were recorded. Reported serious adverse outcomes include use of reversal agents as well as any documented respiratory depression, hypotension, or need for escalation of care.
RESULTS
Of 156 patients included, 119 (76%) received IN midazolam alone, 20 (13%) patients received IN fentanyl alone, and 17 (11%) patients received both medications. The most common applications for IN medication administration were nasogastric tube placements (n = 62), peripheral intravenous line insertions (n = 30), peripherally-inserted central catheter placements (n = 23), and lumbar punctures (n = 16). No serious adverse events were reported.
CONCLUSIONS
This study suggests that IN fentanyl and midazolam were administered to pediatric inpatients undergoing routine procedures without serious adverse drug reactions being reported. Although these findings are encouraging, more prospective studies are needed before wider implementation of IN fentanyl and midazolam administration in pediatric inpatients.
Objectives:
Intranasal (IN) medications offer a safe non-invasive way to rapidly deliver drugs in situations where intravenous (IV) access and intramuscular (IM) administration is challenging or not feasible. In the prehospital setting, this can be an essential alternative in time critical situations including trauma management, seizures, and agitated patients. However, there is a paucity of evidence summarizing its efficacy in this environment. This systematic review aims to assess the current evidence supporting the use of IN medicine (midazolam, ketamine, fentanyl, morphine, glucagon, and naloxone) in the prehospital setting alone.
Methods:
A systematic literature search (PROSPERO CRD42023440713) of PubMed, Web of Science, OVID Medline, "Cochrane Central Register of Controlled Trials," Cochrane reviews and Embase was performed from inception to June 2023 to identify studies where IN medications were administered to patients in the prehospital setting. All randomized controlled trials, observational cohort studies, case series, and case reports were included. Papers not written in English, review articles, abstracts, and non-published data (including letters to the editor) were excluded. The methodological quality of the included studies was interpreted using the Cochrane risk of bias tool and rated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. No funding was received.
Results:
From 4818 studies, 39 were included (seven for midazolam, five for ketamine, twelve for fentanyl, one for diamorphine, two for glucagon, and twelve for naloxone). A total of 24,097 patients were treated with IN medications across all the studies. There were five moderate quality, four low quality, and thirty very low quality studies. The potential efficacy of IN fentanyl and ketamine was demonstrated consistently throughout the studies with less clear evidence for midazolam, morphine, glucagon, and naloxone. This review was severely limited by the study quality, with most studies demonstrating "high concerns" for bias.
Conclusions:
Prehospital IN medication administration has wide-ranging potential, particularly for administering analgesia. There are likely to be certain populations, for example, pediatrics, that will benefit the most, although conclusions are limited by the quality of evidence currently available. We encourage additional research in this area, particularly with robust prospective double-blind RCTs.
The Wilderness Medical Society (WMS) convened an expert panel to develop evidence-based guidelines for the management of pain in austere environments. Recommendations are graded based on the quality of supporting evidence as defined by criteria put forth by the American College of Chest Physicians. This is an update of the 2014 version of the “WMS Practice Guidelines for the Treatment of Acute Pain in Remote Environments” published in Wilderness & Environmental Medicine 2014; 25:41–49.
Acute pain is a common presenting symptom in children in the emergency setting and can be classified as mild, moderate or severe. Asssessment of pain is the first step to development of effective pain management strategies. Measures of pain include physiologic, observational/behavioural and self report which is considered the gold standard and can be used in children as young as 4 years of age. There are multiple validated tools for pain assessment that are both age and developmentally appropriate. Management interventions are most effective when they are multi-modal and incorporate physical, psychological and pharmacological techniques. Common pharmacological agents for mild pain include acetaminophen and/or ibuprofen with the addition of oral or intranasal opioids for moderate pain and intravenous opioids for severe pain. Procedures in the emergency department are often anxiety provoking and can be managed with a variety of techniques including use of procedural sedation. Indications for procedural sedation include non-invasive procedures requiring the child to be motionless as well as procedures with high level of anxiety and low to high level of pain. When procedural sedation is utilized, it is imperative to ensure that appropriate sedation guidelines and policies are implemented to minimize potential adverse effects.
Due to the presence of large surfaces and high blood supply, drug delivery through the nasal route of administration is the appropriate route to administrate drugs with rapid onsets of action. Bypassing first-pass metabolism can increase drug bioavailability. The physicochemical properties of fentanyl led to a need to develop formulations for delivery by multiple routes. Several approved inter-nasal fentanyl products in Europe and the USA have been used in prehospital and emergency departments to treat chronic cancer pain and used to treat severe acute abdominal and flank pain. Analgesia durations and onsets were not significantly different between intranasal and intravenous fentanyl in patients with cancer breakthrough pain and were well-tolerated in the long term. Intranasal Fentanyl (INF) at a 50 μg/ml concentration decreased renal colic pain to the lowest level in 30 min. Possible adverse effects specific to INF are epistaxis, nasal wall ulcer, rhinorrhea, throat irritation, dysgeusia, nausea, and vomiting. However, there is limited available literature about the serious adverse effects of INF in adults and children. Intranasal Fentanyl Spray (INFS) results in significantly higher plasma concentrations and has a lower Tmax than oral transmucosal formulation, and the bioavailability of fentanyl in intranasal formulations is very high (89 %), particularly in pectin-containing formulations such as PecFent and Lazanda.
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 (SCD) commonly experience vaso‐occlusive pain episodes (VOE) 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. The 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 < .001). The rapid onset of action and ease of delivery without intravenous access offered by intranasal fentanyl make it a feasible initial parenteral analgesic in the treatment of children with SCD presenting with VOE 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.
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 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.