IMPORTANCE:Asthma is a common chronic disease with significant morbidity and mortality. OBJECTIVES:To assess the safety and efficacy of subcutaneous epinephrine in addition to the standard first-line treatment of acute asthma in children. DATA SOURCE AND STUDY SELECTION:The following databases were inspected from 1966 to 22 June 2025: MEDLINE, EMBASE, CINAHL and the Cochrane Central Register of Controlled Trials. Only randomised controlled trials were included. DATA EXTRACTION AND SYNTHESIS:One study out of 197 citations was included in this review. MAIN OUTCOMES:The outcome measures were morbidity, escalation of care, length of hospital stay, adverse events, mortality due to exacerbation and change in lung function. RESULTS:We included one study with a total number of participants (n)=43. Participants who received subcutaneous epinephrine showed no significant difference in the asthma clinical score postintervention (3.3 compared with 4.0, respectively), as well as in the hospitalisation rate (risk ratio (RR) 0.38, 95% CI 0.04 to 3.40, p=0.39, n=43) and the need for additional intravenous medications (RR 0.23, 95% CI 0.03 to 1.81, p=0.16, n=43), or predicted increase in peak expiratory flow (PEF) percentage at 2 hours (mean difference -1.00, 95% CI -8.21 to 6.21, p=0.79, n=31). CONCLUSION:This review demonstrated very low certainty of evidence based on a single paper indicating that subcutaneous epinephrine does not benefit children with acute asthma in terms of asthma clinical score, hospitalisation rate and the need for additional intravenous medications. No significant improvement in PEF percentage was observed after the intervention. PROSPERO REGISTRATION NUMBER:CRD42023405407.

BACKGROUND:The role of inhaled/nebulised ipratropium bromide (IB) in asthma is unclear. AIMS:To assess the efficacy and safety of inhaled/nebulised IB for asthma management in children. METHODS:We searched MEDLINE, EMBASE, CINAHL, the Cochrane Central Register of Controlled Trials and the Web of Science until July 2024. We included randomised controlled trials (RCTs) and followed international guidelines for reporting systematic reviews. Outcomes included morbidity, escalation of care, length of hospital stay, mortality, adverse events and lung function. RESULTS:We included 24 studies (total participants n=3238). The hospitalisation rate (risk ratio (RR) 0.84, 95% CI 0.70 to 1.00, I² 30%), hospital stay in hours (MD 1.75, 95% CI -0.87 to 4.36, I² 15%) and paediatric intensive care (PICU) admission (RR 0.91, 95% CI 0.35 to 2.32, I² 0%) were similar. The hospitalisation rate was lower in patients who received IB nebuliser (RR 0.76, 95% CI 0.64 to 0.90, I² 0%).The asthma severity score was significantly better in the IB group (MD -0.38, 95% CI -0.63 to -0.12, I2 59%). No serious adverse events were reported. CONCLUSION:This review found high-certainty evidence that the IB nebuliser leads to a lower hospitalisation rate. However, when inhaled/nebulised IBs were analysed together, the hospitalisation rate was similar, with moderate certainty evidence. IB improved asthma clinical scores, with low certainty evidence. No difference was reported in other prespecified outcomes.Considering the current evidence and safety profile, inhaled/nebulised IB needs to be considered as an additional treatment for acute asthma exacerbation. PROSPERO REGISTRATION NUMBER:CRD42023405023.

Importance The role of intravenous aminophylline in acute asthma in childhood is unclear.Objectives To assess the safety and efficacy of intravenous aminophylline for asthma in children.Methods From 1966 to May 2024, we searched MEDLINE, Embase, CINAHL, Web of Science and the Cochrane Central Register of Controlled Trials. We included only randomised controlled trials testing standard treatment in combination with aminophylline and followed the international guidelines for conducting systematic reviews. The outcomes measured were morbidity, escalation of care, length of hospital stay, adverse events, mortality and lung functions. We used the random-effects model for data analysis and the fixed-effects model to evaluate heterogeneity.Results Nine studies (466 participants) fulfilled our a priori eligibility criteria. No significant difference was found in post-treatment asthma severity score (mean difference (MD)=0.13, 95% CI -0.79 to 1.06, I2=0 %), hospitalisation rate (risk ratio (RR)=0.66, 95% CI 0.27 to 1.59, I2=0%), paediatric intensive care unit admission (RR=0.73, 95% CI 0.51 to 1.05, I2=0%), intubation rate (RR=0.09, 95% CI 0.01 to 1.64, p=0.1) or length of hospital stay (MD=-3.62, 95% CI -13.05 to 5.82, I2=31%). Emesis (RR=3.52, 95% CI 2.04 to 6.06, I2=0%) and nausea (RR=4.92, 95% CI 2.41 to 10.06, I2=0%) occurred more in the aminophylline group. One study showed improved lung function in the aminophylline group, while others showed no difference.Conclusion This review showed limited evidence of the benefit of intravenous aminophylline in managing asthma in most preventilation severity parameters. However, lowering the intubation rate and improving lung function deserve more attention.PROSPERO registration number CRD42023405234.

BACKGROUND:The role of intravenous magnesium sulfate in asthma exacerbation is unclear. AIMS:To determine the efficacy and safety of intravenous magnesium sulfate in managing asthma exacerbation in children. METHODS:We searched MEDLINE, EMBASE, CINAHL, the Cochrane Central Register of Controlled Trials and the Web of Science up to May 2024. We included randomised controlled trials and followed the international guidelines for conducting systematic reviews. Outcomes included morbidity, escalation of care, length of hospital stay, lung functions, adverse events, and mortality. RESULTS:Nine studies (total participants=473) were included. Hospitalisation rate and the need for non-invasive ventilation were less among the intravenous magnesium sulfate group (mean difference (MD)=0.70, 95% CI 0.54 to 0.90, I2 7%, n=115) and (risk ratio (RR)=0.17, 95% CI 0.15 to 0.54, p=0.003, n=143), respectively. Asthma severity scores (MD=-0.18, 95% CI -1.35 to 0.98, I2 2%, n=115), length of hospital stay (MD=-78.86, 95% CI -200.37 to 42.66, I2 99%, n=284) and the need for invasive ventilation (RR=0.35, 95% CI 0.11 to 1.17, I2 0%, n=237) were similar. There was no difference in the Paediatric Intensive Care Unit (PICU) admission rate (p=0.43 n=61). Peak expiratory flow improved in the intravenous magnesium group (p<0.001, n=20). No serious adverse events were reported. CONCLUSION:We found low-certainty evidence that intravenous magnesium sulfate results in a lower hospitalisation rate and less need for non-invasive ventilation. Asthma scores, PICU admission, invasive ventilation and length of hospital stay were similar. While the evidence base is weak, the favourable safety profile suggests that intravenous magnesium sulfate can be considered a treatment for asthma exacerbations. PROSPERO REGISTRATION NUMBER:CRD42023405261.

Background Procalcitonin is a rapid response biomarker specific for bacterial infection, which is not routinely used in the UK National Health Service. We aimed to assess whether using a procalcitonin-guided algorithm would safely reduce the duration of antibiotic therapy compared with usual care, in which C-reactive protein is the commonly used biomarker. Methods The BATCH trial was a pragmatic, multicentre, open-label, parallel, two-arm, individually randomised, controlled trial conducted in 15 hospitals in England and Wales. Children aged 72 h to 18 years who were admitted to hospital and were being treated with intravenous antibiotics for suspected or confirmed bacterial infection and who were expected to remain on intravenous antibiotics for more than 48 h were enrolled. Participants were randomly assigned (1:1) to receive either current clinical management alone (usual care group) or clinical management with the addition of a procalcitonin test guided algorithm (procalcitonin group). Participants were randomly assigned by minimisation, with site and age group (0-6 months, 6 months to 2 years, 2-5 years, and older than 5 years) as minimisation factors and a random element to reduce predictability. Participants were randomly assigned remotely using a secure 24 h web-based randomisation programme. The coprimary outcomes were duration of intravenous antibiotic use, assessed for superiority, and a composite safety measure, assessed for non-inferiority (non-inferiority margin 5%). The primary analysis sample for each coprimary endpoint included all randomly assigned participants with available outcome data. This trial is registered with the International Standard Randomised Controlled Trial Number registry, ISRCTN11369832. Findings Between June 11, 2018, and Oct 12, 2022, 15 282 children were screened for eligibility, 1949 of whom were randomly assigned to receive procalcitonin-guided antibiotic therapy (n=977) or usual care (n=972). The median intravenous antibiotic duration was 960 h (IQR 595-1555) in the procalcitonin group and 997 h (612-1538) in the usual care group (hazard ratio 096 [95% CI 087-105]). 78 (9%) of 917 participants in the procalcitonin group and 85 (9%) of 904 participants in the usual care group had at least one event covered by the composite safety outcome measure (estimated adjusted risk difference -081% [95% CI upper bound 111]). Interpretation In children with suspected or confirmed bacterial infection admitted to hospitals in England and Wales for intravenous antibiotic treatment of at least 48 h, the introduction of a procalcitonin-guided algorithm did not reduce duration of intravenous antibiotics treatment and is non-inferior to usual care for safety outcomes. Therefore, evidence does not support the use of procalcitonin-guided algorithms where robust effective paediatric antibiotic stewardship programmes are established.

Rationale While there are numerous published paediatric asthma scores, it is unknown how commonly scores are recommended in asthma guidelines across different geographical regions globally, and what their validation status is. Objectives (1) To describe which clinical guidelines recommend asthma scores across different geographical regions. (2) To describe the initial and subsequent validation of the commonly recommended asthma scores. Methods Observational study of asthma scores recommended in guidelines for the management of acute paediatric asthma from institutions across the Pediatric Emergency Medicine Network; global paediatric emergency medicine research network comprising all eight local and regional paediatric emergency medicine research networks. Main results 158 guidelines were identified. Overall, 83/158 (53%) guidelines recommend a bedside clinical score for assessment of asthma severity. While a single country-specific clinical score was recommended in all guidelines from Spain and Canada, 27/28 (96%) of the USA guidelines recommend a wide variety of scores, and scores are rarely recommended in guidelines from other research networks (PERUKI, Paediatric Emergency Research in the UK and Ireland and PREDICT, Paediatric Research in Emergency Departments International Collaborative in Australia and New Zealand) and other countries (Costa Rica, South Africa, Nigeria, Singapore, India). The Pediatric Respiratory Assessment Measure (PRAM) and the pulmonary score (PS) were the most frequently used scoring instruments. While the PRAM has undergone the most extensive validation, including construct validity, validation studies for the PS are limited. Inter-rater reliability, as well as the criterion, responsiveness and discriminative validity aspects represent the most common limitations in many of the scores. Conclusions There are marked geographical differences in both the recommendation for and the type of clinical asthma score in clinical practice guidelines. While many asthma scores are recommended, most have insufficient validation.

IMPORTANCE:The role of intravenous short-acting beta-2 agonist (SABA) in acute asthma in childhood is unclear. OBJECTIVES:To assess the safety and efficacy of intravenous SABA versus placebo for acute asthma. DATA SELECTION AND EXTRACTION:We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, the Web of Science and the Cumulative Index to Nursing and Allied Health Literature up to May 2024. We included only randomised controlled trials (RCTs) and followed the international guidelines for conducting systematic reviews. Outcomes measured were morbidity, escalation of care, length of hospital stay, adverse events, mortality and changes in lung functions. RESULTS:Four RCTs were included (total participants=183). Intravenous SABA group had better asthma severity scores (risk ratio (RR)=0.38, 95% CI 0.19 to 0.78, p=0.009), similar need for mechanical ventilation (RR=0.13, 95% CI 0.01 to 2.42, p=0.17), similar escalation of intravenous treatment (RR=1.51, 95% CI 0.60 to 3.82, p=0.38), shorter duration of hospital stay (hours) (mean difference (MD)=-18.68, 95% CI -36.76 to -0.61) and less duration of oxygen supplementation (days) (MD=-1.73, 95% CI -3.01 to -0.45, p=0.008). Adverse events were tachycardia, hypotension and hypokalaemia. One study reported a single participant with arrhythmia and a non-significant increase in troponin I among the intravenous SABA group. CONCLUSION:This review found low-to-moderate certainty evidence that intravenous SABA would improve acute asthma severity with infrequent adverse events reported. However, this evidence is limited due to the limited number of included studies. PROSPERO REGISTRATION NUMBER:CRD42023405119.

IMPORTANCE:Evidence regarding second-line treatment for severe asthma is limited. OBJECTIVES:To evaluate the safety and efficacy of intravenous aminophylline, intravenous short-acting beta agonist (SABA), intravenous magnesium sulphate, intravenous ketamine or subcutaneous adrenaline as a second-line treatment for severe asthma. METHODS:We included only randomised controlled trials (RCTs) and followed the international guidelines for conducting systematic reviews. We performed a comprehensive literature search up to May 2024. Outcomes included morbidity, escalation of care, length of hospital stay, adverse events, mortality and changes in lung functions. RESULTS:Nine RCTs were included (total participants=546). Compared with other treatments, intravenous aminophylline showed no significant difference in the duration of hospital stay in hours, except for critically ill ventilated patients who had a shorter stay (mean difference (MD)=-12.99, 95% CI -33.13 to 7.15). The need for additional intravenous medications (RR=2.17, 95% CI 0.48 to 9.71) and asthma severity scores postinterventions (MD=0.97, 95% CI -0.91 to 2.85) was similar. More nausea and emesis were observed in the intravenous aminophylline group. The intravenous SABA group showed no difference in hospital stay (MD=-10.12, 95% CI -45.74 to 25.49) or need for ventilation (RR=0.25, 95% CI 0.03 to 2.21). There were no frequent serious adverse events. The intravenous magnesium sulphate group had a lower hospitalisation rate (RR=1.52, 95% CI 1.26 to 1.84), reduced need for additional intravenous medication (RR=6.30, 95% CI 2.62 to 15.17) and a rapid improvement in asthma severity scores (p<0.05). CONCLUSION:There is low-to-very-low certainty evidence demonstrating the superiority of any intravenous second-line treatment options for acute asthma. PROSPERO REGISTRATION NUMBER:CRD42023405226.

Rationale There is significant practice variation in acute paediatric asthma, particularly severe exacerbations. It is unknown whether this is due to differences in clinical guidelines. Objectives To describe and compare the content and quality of clinical guidelines for the management of acute exacerbations of asthma in children between geographic regions. Methods Observational study of guidelines for the management of acute paediatric asthma from institutions across a global collaboration of six regional paediatric emergency research networks. Measurements and main results 158 guidelines were identified. Half provided recommendations for at least two age groups, and most guidelines provided treatment recommendations according to asthma severity. There were consistent recommendations for the use of inhaled short-acting beta-agonists and systemic corticosteroids. Inhaled anticholinergic therapy was recommended in most guidelines for severe and critical asthma, but there were inconsistent recommendations for its use in mild and moderate exacerbations. Other inhaled therapies such as helium-oxygen mixture (Heliox) and nebulised magnesium were inconsistently recommended for severe and critical illness. Parenteral bronchodilator therapy and epinephrine were mostly reserved for severe and critical asthma, with intravenous magnesium most recommended. There were regional differences in the use of other parenteral bronchodilators, particularly aminophylline. Guideline quality assessment identified high ratings for clarity of presentation, scope and purpose, but low ratings for stakeholder involvement, rigour of development, applicability and editorial independence. Conclusions Current guidelines for the management of acute paediatric asthma exacerbations have substantial deficits in important quality domains and provide limited and inconsistent guidance for severe exacerbations.

Introduction A well-developed procedural sedation programme in the paediatric emergency department can minimise adverse events. We examined how adherence to current best evidence ensures safe delivery of paediatric sedation in a newly established tertiary paediatric hospital. Methods Our sedation service uses a robust provider training and privileging system, standardised policy and procedures and rigorous data collection all within an evidence-based clinical governance process. We examined sedation data from the first 3 years of operation. Results From July 2018 to May 2022, ketamine was used in 3388 of the 3405 sedations. The mean age of sedated children was 5.5 years (range 6 months to 17.8 years) and common indications were closed reduction of fractures and laceration repairs. A total of 148 (4.37%, 95% CI 3.68% to 5.06%) adverse events were documented, including 88 (2.59%, 95% CI 2.06% to 3.13%) cases of vomiting, 50 (1.48%, 95% CI 1.07% to 1.88%) cases related to airway and breathing with 40 (1.18%, 95% CI 0.82% to 1.54%) cases of oxygen desaturation, 6 (0.18%, 95% CI 0.04% to 0.32%) cases of laryngospasm, 4 (0.12%, 95% CI 0% to 0.23%) cases of apnoea. Conclusion This study presents a large single-centre dataset on the use of intravenous ketamine in paediatric procedural sedation. Adhering to international standards and benchmarks for provider skills and training, drug administration and monitoring facilities, with a strict clinical governance process, optimizes patient safety.

ObjectivesTo describe the incidence of and patterns of ‘escalated care’ (care in addition to standard treatment with systemic corticosteroids and inhaled bronchodilators) for children receiving prehospital treatment for asthma.DesignRetrospective observational study.SettingState-wide ambulance service data (Ambulance Victoria in Victoria, Australia, population 6.5 million)ParticipantsChildren aged 1–17 years and given a final diagnosis of asthma by the treating paramedics and/or treated with inhaled bronchodilators from 1 July 2019 to 30 June 2020.Primary and secondary outcome measuresWe classified ‘escalation of care’ as parenteral administration of epinephrine, or provision of respiratory support. We compared clinical, demographic and treatments administered between those receiving and not receiving escalation of care.ResultsParamedics attended 1572 children with acute exacerbations of asthma during the 1 year study period. Of these, 22 (1.4%) had escalated care, all receiving parenteral epinephrine. Patients with escalated care were more likely to be older, had previously required hospital admission for asthma and had severe respiratory distress at initial assessment.Of 1307 children with respiratory status data available, at arrival to hospital, the respiratory status of children had improved overall (normal/mild respiratory distress at initial assessment 847 (64.8%), normal/mild respiratory distress at hospital arrival 1142 (87.4%), p<0.0001).ConclusionsMost children with acute exacerbations of asthma did not receive escalated therapy during their pre-hospital treatment from ambulance paramedics. Most patients were treated with inhaled bronchodilators only and clinically improved by the time they arrived in hospital.

Background Acute exacerbations of asthma are common in children, however, treatment decisions for severe exacerbations are challenging due to a lack of robust evidence. In order to create more robust research, a core set of outcome measures needs to be developed. In developing these outcomes, it is important to understand the views of clinicians who care for these children in particular, views that relate to outcome measures and research priorities.Methods To determine the views of clinicians, a total of 26 semistructured interviews based on the theoretical domains framework were conducted. These included experienced clinicians from emergency, intensive care and inpatient paediatrics across 17 countries. The interviews were recorded, and later transcribed. All data analyses were conducted in Nvivo by using thematic analysis.Results The length of stay in hospital and patient-focused parameters, such as timing to return to school and normal activity, were the most frequently highlighted outcome measures, with clinicians identifying the need to achieve a consensus on key core outcome measure sets. Most research questions focused on understanding the best treatment options, including the role of novel therapies and respiratory support.Conclusion Our study provides an insight into what research questions and outcome measures clinicians view as important. In addition, information on how clinicians define asthma severity and measure treatment success will assist with methodological design in future trials. The current findings will be used in parallel with a further Paediatric Emergency Research Network study focusing on the child and family perspectives and will contribute to develop a core outcome set for future research.