Intravenous Magnesium: Prompt Use for Asthma in Children Treated in the Emergency Department (IMPACT-ED): Protocol for a Multicenter Pilot Randomized Controlled Trial.

BACKGROUND: Children managed for asthma in an emergency department (ED) may be less likely to be hospitalized if they receive intravenous magnesium sulfate (IVMg). Asthma guidelines recommend IVMg for severely sick children but note a lack of evidence to support this recommendation. All previous trials of IVMg in children with asthma have been too small to answer whether IVMg is effective and safe. A few major questions remain about IVMg. First, it has not been tested early in the course of ED treatment, when the impact on hospitalization would be greatest. Second, the clinical impact of hypotension, a known adverse effect of IVMg, has not been well characterized in previous research. Third, no trials have compared different IVMg doses or serial serum magnesium (total and ionized) concentrations to optimize dosing, so the most effective dose is unknown. A large, conclusive, randomized, placebo-controlled clinical trial of IVMg might be challenging due to the need to enroll and complete study procedures quickly, a lack of understanding of blood pressure changes after IVMg, and a lack of pharmacologic information to guide the optimal doses of IVMg to be tested. Therefore, a pilot study to inform the above gaps is warranted before conducting a definitive trial. OBJECTIVE: The objectives of this study are to (1) demonstrate the feasibility of enrolling children with severe acute asthma in the ED in a multicenter, randomized controlled trial of a placebo, low-dose IVMg, or high-dose IVMg; (2) demonstrate the feasibility of timely delivery of study medication, assessment of blood pressure, and evaluation of adverse events in a standardized protocol; and (3) externally validate a previously constructed pharmacokinetic model and develop a combined pharmacokinetic/pharmacodynamic model for IVMg using magnesium (total and ionized) serum concentrations and their correlation with measures of efficacy and safety. METHODS: This pilot trial tests procedures and gathers information to plan a definitive trial. The pilot trial will enroll as many as 90 children across 3 sites, randomize each child to 1 of 3 study arms, measure blood pressure frequently, and collect 3 blood samples from each participant with corresponding clinical asthma scores. RESULTS: The project was funded by the National Heart, Lung, and Blood Institute (1 R34HL152047-2) in March 2022. Enrollment began in September 2022, and 43 children have been enrolled as of April 2023. We will submit the results for publication in late 2023. CONCLUSIONS: The results of this study will guide the planning of a large, definitive, multicenter trial powered to evaluate if IVMg reduces hospitalization. Blood pressure measurements will inform a monitoring plan for the larger trial, and blood samples and asthma scores will be used to validate pharmacologic models to select the optimal dose of IVMg to be evaluated in the definitive trial. TRIAL REGISTRATION: ClinicalTrials.gov NCT05166811; https://clinicaltrials.gov/ct2/show/NCT05166811. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/48302.

Reducing Albuterol Use in Children With Bronchiolitis.

OBJECTIVES: In 2014, the American Academy of Pediatrics published bronchiolitis guidelines recommending against the use of bronchodilators. For the winter of 2015 to 2016, we aimed to reduce the proportion of emergency department patients with bronchiolitis receiving albuterol from 43% (previous winter rate) to <35% and from 18% (previous winter rate) to <10% in the inpatient setting. METHODS: A team identified key drivers of albuterol use and potential interventions. We implemented changes to our pathway and the associated order set recommending against routine albuterol use and designed education to accompany the pathway changes. We monitored albuterol use through weekly automated data extraction and reported results back to clinicians. We measured admission rate, length of stay, and revisit rate as balancing measures for the intervention. RESULTS: The study period included 3834 emergency department visits and 1119 inpatient hospitalizations. In the emergency department, albuterol use in children with bronchiolitis declined from 43% to 20% and was <3 SD control limits established in the previous year, meeting statistical thresholds for special cause variation. Inpatient albuterol use decreased from 18% to 11% of patients, also achieving special cause variation and approaching our goal. The changes in both departments were sustained through the entire bronchiolitis season, and admission rate, length of stay, and revisit rates remained unchanged. CONCLUSIONS: Using a multidisciplinary group that redesigned a clinical pathway and order sets for bronchiolitis, we substantially reduced albuterol use at a large children's hospital without impacting other outcome measures.

Factors associated with the use of procedural sedation during incision and drainage procedures at a children's hospital.

OBJECTIVE: The incidence of skin and soft tissue infections requiring incision and drainage has increased. Little evidence exists about the use of procedural sedation (PS) for these procedures in children. Our objective was to determine factors associated with the use of PS during incision and drainage procedures at a tertiary children's hospital. METHODS: This was a nested cohort study that combined a retrospective medical record review with prospectively collected data for children 2 months to 18 years old who had an incision and drainage procedure performed at a children's hospital over a 1-year period. Procedural sedation was defined as the use of pharmacologic agents to alter patient consciousness. Patient, lesion (eg, size and induration), provider (eg, years of experience), and emergency department (eg, patient volume and wait time) factors were analyzed. Emergency department physicians were divided into tertiles by frequency of sedation (high/medium/low) to assess provider practice variation. χ(2) Analysis and multivariable logistic regression were used to identify factors associated with PS use. RESULTS: Of the 215 enrolled patients, 95 (44.2%) received PS. Ninety (94.7%) of 95 sedated patients received ketamine as their primary sedation agent. On univariate analysis, emergency department volume, wait time, duration of illness, and provider experience were not associated with PS use. With multivariable regression, patient age, abscess size, and provider frequency of sedation were all independently associated with the decision to sedate. CONCLUSIONS: Patient age and abscess size are independent predictors of the use of PS for incision and drainage procedures. Provider practice patterns are also independently associated with PS use.

Pediatric integrated delivery system's experience with pandemic influenza A (H1N1).

OBJECTIVE: To describe 1 pediatric integrated delivery system's experience with the influenza A (H1N1) pandemic in 2009 to illustrate the benefits of coordination, scale, scope, and flexibility in handling large volumes of patients in many locations. METHODS: Through multidisciplinary planning across a large, multisite pediatric delivery system, an effective 3-tier plan was developed to handle anticipated increased volumes associated with the fall 2009 influenza pandemic in the Philadelphia region. RESULTS: Patient demand for services increased to record-setting levels, particularly for emergency department visits and phone calls. The 3-tier plan of response allowed for graded and appropriate response to volumes that more than doubled in many locations. Measured by wait times and leftwithout- being-seen rates, the system appeared to match capacity to demand effectively. Lessons learned in terms of successes and challenges are useful for future planning. CONCLUSIONS: The experience of 1 pediatric delivery system in handling increased volume due to pandemic influenza may hold lessons for other organizations and for policy makers seeking to improve the preparedness, quality, and value of healthcare. These experiences do not imply the need for vertical integration with ownership, but do support tight coordination, communication, integration, and alignment in any management structure.

Management of acute asthma.

Current management of acute asthma has been defined in clinical practice guidelines developed from systematic reviews and expert opinion. Initial treatment with inhaled high-dose beta-agonists and anticholinergics is recommended for severe exacerbations. Most patients treated in emergency departments should receive systemic corticosteroids. Adjunctive therapy for those not improving is less well-defined, but options include intravenous magnesium sulfate and heliox-driven nebulized beta-agonists. Poor adherence to preventive therapies and infrequent primary care follow-up are well documented among children and adolescents treated in emergency departments. These factors may contribute to disparities in outcomes for minority populations and are important considerations during acute care visits.

High-dose continuous nebulized levalbuterol for pediatric status asthmaticus: a randomized trial.

OBJECTIVE: To assess the use of high-dose continuous levalbuterol (LEV), the single active (R)-enantiomer of racemic albuterol (RAC), in the treatment of status asthmaticus. STUDY DESIGN: Children age 6 to 18 years with severe asthma exacerbation were enrolled in this randomized, double-blind trial if they failed initial emergency department (ED) therapy with RAC and systemic steroids. Subjects received equipotent doses of RAC (20 mg/hour) or LEV (10 mg/hour) within a standardized inpatient protocol. Blood samples for measurements of albuterol enantiomer, potassium, and glucose levels were obtained from the first 40 subjects. The median time until discontinuation of continuous therapy was compared using the rank-sum test, and other outcomes were compared using general linear mixed models. RESULTS: A total of 81 subjects (40 in the RAC group and 41 in the LEV group) were enrolled; the 2 groups were similar at baseline. Both groups tolerated continuous therapy with similar changes in heart rate and serum potassium and glucose levels but higher serum (S)-albuterol concentrations in the subjects treated with RAC. The median time for continuous therapy was similar in the RAC and LEV groups (18.3 hours vs 16.0 hours), as were the other clinical measures. CONCLUSIONS: Substituting high-dose continuous LEV for RAC did not reduce the time on continuous therapy and had similar adverse effects in children who had failed initial treatment with RAC.