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INTRODUCTION: Starship Hospital Children's Emergency Department (CED) uses EMLA for topical anaesthesia during insertion of intravenous cannula (IVC). Amethocaine has recently been shown to offer more effective pain relief and work faster than EMLA, but may be more expensive. AIM: To determine cost implications of introducing topical amethocaine into CED practice. METHODS: Data were obtained from a randomised controlled trial, quality assurance project and an audit of topical anaesthetic use, with economic evaluation performed from the District Health Board perspective in 2007 NZ dollars and Euros. Proportion of children receiving topical anaesthetic cream during insertion of IVC was the primary benefit measure, and cost per child presenting to the department was the primary cost measure. A decision tree model was developed as a baseline, and sensitivity analysis was conducted. Multiple clinical scenarios were modelled, and incremental cost effectiveness ratios calculated compared to the baseline model. RESULTS: Scenarios modelled include providing no topical anaesthesia, using amethocaine exclusively or using a mixture of amethocaine and EMLA. All models are sensitive to the amount of cream applied at triage. The most cost effective model provided EMLA at triage to those most likely to need IVC; then amethocaine to other children later thought to require IVC. This model would cost NZ$1.05 per child, down from NZ$1.47. Proportion of children receiving cream during insertion of IVC would increase from 51% to 64%. The recommended model dominated the current situation. CONCLUSION: Use of amethocaine in a mixed model in the CED could reduce cost and increase the proportion of children receiving topical anaesthetic during insertion of IVC. Trial registration number Australian New Zealand Clinical Trials Register ACTRN12606000409572. [ABSTRACT FROM AUTHOR]

BACKGROUND: Topical anaesthetics reduce the pain of venous cannulation. The emergency department at the Starship Children's Hospital in Auckland uses EMLA (an eutectic mixture of 25 mg/g lidocaine and 25 mg/g prilocaine) for topical anaesthesia. Amethocaine has recently been shown to be a more effective topical anaesthetic. It is suggested that, because amethocaine does not vasoconstrict veins, it may increase the success of cannulation. AIM: The primary aim was to determine if amethocaine improves the success of cannulation compared with EMLA. The secondary aim was to determine if amethocaine is a more effective topical anaesthetic in a children's emergency department. METHODS: A parallel, randomised, double-blind controlled study was performed in children aged 3 months to 15 years who were offered topical anaesthesia for venous cannulation. Caregivers gave verbal consent at triage, followed by written consent. Children were randomised into amethocaine or EMLA groups. Those who went on to have an intravenous cannula were analysed on an intention-to-treat basis. The primary outcome was a successful first attempt at cannulation. A convenience cohort was also observed for distress using a visual analogue scale and the Faces, Legs, Activity, Cry and Consolability Score. RESULTS: From November 2006 to June 2007, 2837 children were enrolled and 809 were known to have had intravenous cannulation. 679 complete data and consent forms were returned. There was no significant difference between the first attempt success rates (75.8% amethocaine vs 73.9% EMLA) or between pain scores for the 65 observed cannulations. CONCLUSION: Amethocaine is not more successful than EMLA for first attempt intravenous cannulation in a children's emergency department. [ABSTRACT FROM AUTHOR]

Background and Objectives: Bell palsy is the third most frequent diagnosis in children with sudden-onset neurologic dysfunction. The cost-effectiveness of treating Bell palsy with prednisolone in children is unknown. We aimed to assess the cost-effectiveness of prednisolone in treating Bell palsy in children compared with placebo., Methods: This economic evaluation was a prospectively planned secondary analysis of a double-blinded, randomized, placebo-controlled superiority trial (Bell Palsy in Children [BellPIC]) conducted from 2015 to 2020. The time horizon was 6 months since randomization. Children aged 6 months to <18 years who presented within 72 hours of onset of clinician-diagnosed Bell palsy and who completed the trial were included (N = 180). Interventions were oral prednisolone or taste-matched placebo administered for 10 days. Incremental cost-effectiveness ratio comparing prednisolone with placebo was estimated. Costs were considered from a health care sector perspective and included Bell palsy-related medication cost, doctor visits, and medical tests. Effectiveness was measured using quality-adjusted life-years (QALYs) based on Child Health Utility 9D. Nonparametric bootstrapping was performed to capture uncertainties. Prespecified subgroup analysis by age 12 to <18 years vs <12 years was conducted., Results: The mean cost per patient was A$760 in the prednisolone group and A$693 in the placebo group over the 6-month period (difference A$66, 95% CI -A$47 to A$179). QALYs over 6 months were 0.45 in the prednisolone group and 0.44 in the placebo group (difference 0.01, 95% CI -0.01 to 0.03). The incremental cost to achieve 1 additional recovery was estimated to be A$1,577 using prednisolone compared with placebo, and cost per additional QALY gained was A$6,625 using prednisolone compared with placebo. Given a conventional willingness-to-pay threshold of A$50,000 per QALY gained (equivalent to US$35,000 or £28,000), prednisolone is very likely cost-effective (probability is 83%). Subgroup analysis suggests that this was primarily driven by the high probability of prednisolone being cost-effective in children aged 12 to <18 years (probability is 98%) and much less so for those <12 years (probability is 51%)., Discussion: This provides new evidence to stakeholders and policymakers when considering whether to make prednisolone available in treating Bell palsy in children aged 12 to <18 years., Trial Registration Information: Australian New Zealand Clinical Trials Registry ACTRN12615000563561., (© 2023 American Academy of Neurology.)

Background: Paediatric distal forearm fractures are a common ED presentation. They can be diagnosed with point-of-care ultrasound (POCUS) as an alternative to X-rays. Given that ED nurse practitioners (NPs) are relied on for the diagnosis of paediatric fractures, it is important to describe the diagnostic accuracy of NP-conducted POCUS versus X-ray., Methods: This prospective diagnostic study was conducted in a tertiary paediatric hospital in Queensland, Australia, between February 2018 and April 2019. Participants were children aged 4-16 years with a clinically non-angulated, suspected distal forearm fracture. Diagnosis from 6-view NP-administered POCUS of the distal radius and ulna was compared against the reference standard of 2-view X-ray. Each patient received both imaging modalities. Overall forearm diagnosis was classified as 'no', 'buckle' or 'other' fracture for both modalities. The primary outcome was diagnostic accuracy for 'any' fracture ('buckle' and 'other' fractures combined). Secondary outcomes included diagnostic accuracy for 'other' fractures versus 'buckle' and 'no' fractures combined, and pain, imaging duration and preference for modality., Results: Of 204 recruited patients, 129 had X-ray-diagnosed forearm fractures. The sensitivity and specificity for NP-administered POCUS were 94.6% (95% CI 89.2% to 97.3%) and 85.3% (95% CI 75.6% to 91.6%), respectively. 'Other' fractures (mostly cortical breach fractures), when compared with 'buckle'/ 'no' fractures, had sensitivity 81.0% (95% CI 69.1% to 89.1%) and specificity 95.9% (95% CI 91.3% to 98.1%). Pain and imaging duration were clinically similar between modalities. There was a preference for POCUS by patients, parents and NPs., Conclusions: NP-administered POCUS had clinically acceptable diagnostic accuracy for paediatric patients presenting with non-angulated distal forearm injuries. This included good sensitivity for diagnosis of 'any' fracture and good specificity for diagnosis of cortical breach fractures alone. Given the preference for POCUS, and the lack of difference in pain and duration between modalities, future research should consider functional outcomes comparing POCUS with X-ray in this population in a randomised controlled trial., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Bell's palsy or acute idiopathic lower motor neurone facial paralysis is characterized by sudden onset paralysis or weakness of the muscles to one side of the face controlled by the facial nerve. While there is high level evidence in adults demonstrating an improvement in the rate of complete recovery of facial nerve function when treated with steroids compared with placebo, similar high level studies on the use of steroids in Bell's palsy in children are not available. The aim of this study is to assess the utility of steroids in Bell's palsy in children in a randomised placebo-controlled trial., Methods/design: We are conducting a randomised, triple-blinded, placebo controlled trial of the use of prednisolone to improve recovery from Bell's palsy at 1 month. Study sites are 10 hospitals within the Australian and New Zealand PREDICT (Paediatric Research in Emergency Departments International Collaborative) research network. 540 participants will be enrolled. To be eligible patients need to be aged 6 months to < 18 years and present within 72 hours of onset of clinician diagnosed Bell's palsy to one of the participating hospital emergency departments. Patients will be excluded in case of current use of or contraindications to steroids or if there is an alternative diagnosis. Participants will receive either prednisolone 1 mg/kg/day to a maximum of 50 mg/day or taste matched placebo for 10 days. The primary outcome is complete recovery by House-Brackmann scale at 1 month. Secondary outcomes include assessment of recovery using the Sunnybrook scale, the emotional and functional wellbeing of the participants using the Pediatric Quality of Life Inventory and Child Health Utility 9D Scale, pain using Faces Pain Scale Revised or visual analogue scales, synkinesis using a synkinesis assessment questionnaire and health utilisation costs at 1, 3 and 6 months. Participants will be tracked to 12 months if not recovered earlier. Data analysis will be by intention to treat with primary outcome presented as differences in proportions and an odds ratio adjusted for site and age., Discussion: This large multicenter randomised trial will allow the definitive assessment of the efficacy of prednisolone compared with placebo in the treatment of Bell's palsy in children., Trial Registration: The study is registered with the Australian New Zealand Clinical Trials Registry ACTRN12615000563561 (1 June 2015).

Background: Intravenous racemic ketamine is commonly administered for procedural sedation, although few pharmacokinetic studies have been conducted among children. Moreover, an optimal sampling schedule has not been derived to enable the conduct of pharmacokinetic studies that minimally inconvenience study participants., Methods: Concentration-time data were obtained from 57 children who received 1-1.5 mg·kg(-1) of racemic ketamine as an intravenous bolus. A population pharmacokinetic analysis was conducted using nonlinear mixed effects models, and the results were used as inputs to develop a D-optimal sampling schedule., Results: The pharmacokinetics of ketamine were described using a two-compartment model. The volume of distribution in the central and peripheral compartments were 20.5 l∙70 kg(-1) and 220 l∙70 kg(-1), respectively. The intercompartmental clearance and total body clearance were 87.3 and 87.9 l·h(-1) ∙70 kg(-1), respectively. Population parameter variability ranged from 34% to 98%. Initially, blood samples were drawn on 3-6 occasions spanning a range of 14-152 min after dosing. Using these data, we determined that four optimal sampling windows occur at 1-5, 5.5-7.5, 10-20, and 90-180 min after dosing. Monte Carlo simulations indicated that these sampling windows produced precise and unbiased ketamine pharmacokinetic parameter estimates., Conclusion: An optimal sampling schedule was developed that allowed assessment of the pharmacokinetic parameters of ketamine among children requiring short-term procedural sedation., (© 2014 John Wiley & Sons Ltd.)

Aims: The aim of this study was to describe ketamine pharmacokinetics when administered orally to children suffering from burn injury in >10% body surface area., Methods: Children (n = 20) were given ketamine 5 or 10 mg·kg(-1) orally 20 min prior to presentation for surgical procedures. Anesthesia during procedures was maintained with a volatile anesthetic agent. Additional intravenous ketamine was given as a bolus (0.5-1 mg·kg(-1)) to nine children during the procedure while a further nine children were given an infusion (0.1 mg·kg(-1)·h(-1)) continued for 4-19 h after the procedure. Blood was assayed for ketamine and norketamine on six occasions over the study duration of 8-24 h. Data were pooled with those from an earlier analysis (621 observations from 70 subjects). An additional time-concentration profile from an adult given oral ketamine was gleaned from the literature (17 observations). A population analysis was undertaken using nonlinear mixed-effects models., Results: The pooled analysis comprised 852 observations from 91 subjects. There were 20 children who presented for procedures related to burns management (age 3.5 sd 2.1 years, range 1-8 years; weight 14.7 sd 4.9 kg, range 7.9-25 kg), and these children contributed 214 ketamine and norketamine observations. A two-compartment (central, peripheral) linear disposition model fitted data better than a one-compartment model. Bioavailability of the oral formulation was 0.45 (90% CI 0.33, 0.58). Absorption half-time was 59 (90% CI 29.4, 109.2) min and had high between-subject variability (BSV 148%). Population parameter estimates, standardized to a 70-kg person, were central volume 21.1 (BSV 47.1%) l·70 kg(-1), peripheral volume of distribution 109 (27.5%) l·70 kg(-1), clearance 81.3 (46.1%) l·h(-1)·70 kg(-1), and inter-compartment clearance 259 (50.1%) l·h(-1)·70 kg(-1). Under the assumption that all ketamine was converted to norketamine, the volume of the metabolite was 151.9 (BSV 39.1%) l·70 kg(-1) with an elimination clearance of 64.4 (BSV 63.4%) l·h(-1) ·70 kg(-1) and a rate constant for intermediate compartments of 26.2 (BSV 52.1%) h(-1)·70 kg(-1)., Conclusions: The ketamine pharmacokinetics in children with minor burns are similar to those without burns. The peak ratio of norketamine/ketamine at 1 h is 2.8 after oral administration allowing an analgesic contribution from the metabolite at this time. There is low relative bioavailability (<0.5) and slow variable absorption. Dose simulation in a child (3.5 years, 15 kg) suggests a dose regimen of oral ketamine 10 mg·kg(-1) followed by intravenous ketamine 1 mg·kg(-1) i.v. with the advent of short-duration surgical dressing change at 45 min., (© 2011 Blackwell Publishing Ltd.)

Objective: To audit pain management practices and organization in paediatric ED across Australia and New Zealand., Methods: Retrospective audit of pain management practices in Paediatric Research in Emergency Departments International Collaborative ED in 20 cases each of migraine, abdominal pain and femoral shaft fracture. Review of organizational status of pain management at Paediatric Research in Emergency Departments International Collaborative sites., Results: Of 14 ED, 10 participated in the clinical audit. A total of 196 migraine, 197 abdominal pain and 177 femur fracture cases were reviewed. Less than half had degree of pain measured or had pain score documented on triage. Migraine received analgesia in 62% of cases (opioids in 11%). Abdominal pain received analgesia in 62% of cases (opioids in 14%). Fractured femurs received analgesia in 78% of cases (opioids 49%, femoral nerve blocks 40%). Median minutes to enteral medication were 100, 85 and 75, and for parenteral medication (mainly opiates) 103, 137 and 26, for migraine, abdominal pain and femur fracture, respectively. Thirteen hospitals participated in the organizational audit. Of all ED, 92% had pain management policies or guidelines, 92% taught pain management topics in education programmes and 62% used mandatory pain competencies. Only 15% had quality improvement programmes for pain reduction., Conclusion: We found a notable lack of pain assessment documentation and delays to analgesia. There is a need to improve pain assessment and management, although a majority of paediatric ED surveyed had important organizational and educational structures in place. Issues to explore include use of opioids in migraine and the underuse of femoral nerve blocks.

Aim: We aimed to produce a racemic ketamine manual infusion regimen capable of maintaining a steady-state blood concentration associated with anesthesia in children aged 1.5-12 years., Method: The literature was searched for a ketamine blood concentration associated with anesthesia in humans. Pharmacokinetic parameter estimates were taken from published studies of infusion data in children and used in a pharmacokinetic simulation program to predict likely ketamine blood concentrations during infusions. A variability of 10% was allowed about the chosen target concentration., Results: A target concentration of 3 mg.l(-1) was chosen for simulation modeling. This target is greater than that associated with anesthesia when supplemented by nitrous oxide or midazolam in adults. Arousal to light touch or voice appears to occur at a mean plasma concentration of 0.5 mg.l(-1) in both children and adults. A loading dose of 2 mg.kg(-1) followed by an infusion rate of 11 mg.kg(-1).h(-1) for the first 20 min, 7 mg.kg(-1).h(-1) from 20 to 40 min, 5 mg.kg(-1).h(-1) from 40 to 60 min and 4 mg.kg(-1).h(-1) from 1 to 2 h resulted in a steady-state target concentration of 3 mg.l(-1) in children 1.5-12 years. Arousal, either spontaneous or to speech, is anticipated 3 h 47 min after a 2 h infusion in an average 6-year-old child. The context sensitive half-time in children was shorter than in adults after 1.5 h, rising from 30 min at 1 h to 55 min at 5 h after an infusion of 3 mg.kg(-1).h(-1) in a 10 kg child., Conclusion: Children require higher infusion rates than adults to maintain steady-state concentrations of 3 mg.l(-1) and have shorter context sensitive half-times than adults after prolonged infusion. These differences can be attributed to age-related pharmacokinetics. We anticipate slow return to full consciousness after prolonged infusion, suggesting that a lower target concentration with supplementation from adjuvant short acting anesthetic drugs may be advantageous.

Background: The aim of this study was to describe ketamine pharmacodynamics (PD) in children. Adult ketamine concentrations during recovery are reported as 0.74 mg.l(-1) (sd 0.24 mg.l(-1)) with an EC(50) for anesthesia of 2 mg.l(-1) (sd 0.5 mg.l(-1)), but pediatric data are few., Methods: Children presenting for painful procedures in an Emergency Department were given ketamine 1-1.5 mg.kg(-1) i.v. Blood was assayed for ketamine on three to six occasions (median 3) over the subsequent 14-152 min (median 28.5). Procedures were videotaped. Level of sedation (0-5; unresponsive - spontaneously awake without stimulus) and a test of memory were recorded. PD was investigated using a variable slope E(max) model (sedation) or logistic regression (arousal time, memory) with nonlinear mixed effects models., Results: In total 60 children were enrolled. Pharmacokinetic data were collected in 54 of these children and there were 43 children available for PD study. The mean age was 8.15 years (sd 3.5 years) and weight was 34.9 kg (sd 15.8 kg). The half-time describing equilibration between the effect compartment and central compartment was 11 s (95% CI 0.07-20 s). The EC(50) for arousal was 0.52 (90% CI 0.22-1.17) mg.l(-1). The E(max) model with a baseline (E(0)) of five (spontaneously awake without stimulus) yielded a fractional E(max) 0.939 [coefficient of variability (CV) 24%], an EC(50) 0.56 (CV 136%) mg.l(-1) and a Hill coefficient 3.71. The EC(50) for recall memory was 0.44 (90% CI 0.09-1.70) mg.l(-1). The EC(50) for remembering was 0.38 (90% CI 0.12-1.75) mg.l(-1)., Conclusions: Concentrations associated with arousal in children are analogous to adults. The ability to recall and remember occurs at similar concentrations to those associated with arousal. A concentration of 1 mg.l(-1) was associated with a sedation level of three or less (arouses to consciousness with moderate tactile or loud verbal stimulus) in 95% of children while 1.5 mg.l(-1) was associated with a sedation level of two or less (rouses slowly to consciousness with sustained painful stimulus) in 95% of children. These concentrations can be attained for 3-4 min after 1 mg.kg(-1) and 1.5 mg.kg(-1) ketamine IV bolus, respectively. The mean arousal time can be anticipated at approximately 10 min (1 mg.kg(-1)) and 15 min (1.5 mg.kg(-1)).

Background: Voiding cystourethrograms are distressing for children and parents. Nonpharmacological methods reduce distress. Pharmacological interventions for VCUG focus on sedation as well as analgesia, anxiolysis, and amnesia. Sedation has cost, time, and safety issues. Which agents and route should we use? Are we sure that sedation does not influence the ability to diagnose vesicoureteric reflux?, Methods: Literature search of Medline, EMBASE, and the Cochrane Database. Review of comparative studies found., Results: Seven comparative studies including two randomised controlled trials were reviewed. Midazolam given orally (0.5-0.6 mg/kg) or intranasally (0.2 mg/kg) is effective with no apparent effect on voiding dynamics. Insufficient evidence to recommend other sedating agents was found. Deeper sedating agents may interfere with voiding dynamics., Conclusion: Midazolam reduces the VCUG distress, causes amnesia, and does not appear to interfere with voiding dynamics. Midazolam combined with simple analgesia is an effective method to reduce distress to children undergoing VCUG.

Background: Norketamine, a metabolite of ketamine, is an analgesic with a potency one-third that of ketamine. The aim of this study was to describe norketamine pharmacokinetics in children in order to predict time-concentration profiles for this metabolite after racemic ketamine single dose and infusion administration. The possible analgesic potential resulting from norketamine concentration may then be predicted using simulation., Methods: Ketamine and norketamine data were available from two sources: (i) children presenting for procedural sedation in an emergency department given ketamine 1-1.5 mg.kg(-1) IV as a bolus dose; and (ii) a literature search of those studies describing ketamine and norketamine time-concentration profiles after either IV or IM single-dose ketamine in adults and children. A population pharmacokinetic analysis was undertaken using nonlinear mixed effects models (NONMEM). A two-compartment (central, peripheral) linear disposition model was used to fit the parent drug. An additional metabolite compartment was linked to the central compartment by series of intermediate compartments to account for norketamine delayed formation. Norketamine volume of distribution was fixed equivalent to central volume. Simulation was used to predict norketamine time-concentration profiles in children given either ketamine as an i.v. bolus 2 mg.kg(-1) or as an analgesic infusion 0.2 mg.kg(-1).h(-1) for 24 h., Results: The analysis comprised 621 observations from 70 subjects. There were 57 children (age 8.3, sd: 3.5 years, range: 1.5-14; weight 32.5, sd: 15.6 kg, range: 10.8-74.8) and 13 adults. Population parameter estimates for the parent drug, standardized to a 70 kg person using allometric models were central volume (V1) 22 (BSV 89.6%) l.70 kg(-1), peripheral volume of distribution (V2) 129 (30.9%) l.70 kg(-1), clearance other than that metabolized to norketamine (CLother) 47.8 (37.7%) l.h(-1).70 kg(-1) and intercompartment clearance (Q) 216 (54.5%) l.h(-1).70 kg(-1). The norketamine formation clearance (CL2M) was 12.4 (127%) l.h(-1).70 kg(-1), elimination clearance (CLM) was 13.5 (145%) l.h(-1).70 kg(-1), and the rate constant for intermediate compartments was 26.5 (59.1%) h(-1)., Conclusions: Ketamine has a longer elimination half-life (2.1 h) than norketamine (1.13 h). Simulation suggested that norketamine contributes to analgesia for 4 h after 2 mg.kg(-1) i.v. bolus, provided the assumption that a norketamine concentration above 0.1 mg.l(-1) contributes analgesia is true. Similarly, the norketamine metabolite may contribute to analgesia for 1.5 h after low-dose infusion (0.2 mg.kg(-1).h(-1)) cessation.

Objective: Voiding cystourethrography (VCU) is a distressing procedure for children. Conscious sedation using oral midazolam may reduce this distress, but its use may also alter the ability of the VCU to show vesicoureteric reflux (VUR). The objectives of our study were to assess the effectiveness of conscious sedation using oral midazolam when administered routinely in children undergoing VCU and to ensure that conscious sedation using oral midazolam does not alter the ability of VCU to show VUR., Subjects and Methods: Our study was a randomized double-blind controlled trial performed at a university teaching hospital; our study group consisted of children over the age of 1 year who been referred for their first VCU examination from July 2001 to July 2003. Participants were randomized to receive a placebo or midazolam syrup (0.5 mg/kg) before the examination. The primary outcome measures were the Groningen Distress Rating Scale (GDRS) and grading of VUR, as defined by the international grading system established by the International Reflux Study Group., Results: There were no serious adverse events. One hundred thirty-nine children were randomized in the study, and 117 underwent complete assessment. Eight who underwent VCU after the study day were included in a "complete case" intention-to-treat analysis. In the placebo group, 34 children (61%) experienced serious distress or severe distress (GDRS score, 3 or 4). In the midazolam group, 16 children (26%) experienced the same degree of distress. There was a significant difference between the GDRS scores (nonlinear mixed-model analysis, p < 0.001) of the two study groups. The number needed to treat to reduce serious or severe distress in one child was 2.9 (95% CI, 1.9-5.5). VUR was identified in 16% of all children. There was no difference in VUR grading between the groups (nonlinear mixed-model analysis, p = 0.31)., Conclusion: Routine use of oral midazolam (0.5 mg/kg) for conscious sedation of children undergoing VCU reduces distress and does not alter the ability of VCU to show VUR well enough to allow diagnosis.