Randomized pilot trial of ipratropium versus placebo in children with critical asthma.

OBJECTIVE: To test the effects of inhaled ipratropium on clinical outcomes of critical asthma in the first randomized trial of this adjunctive therapy in critically ill children. DESIGN: Pilot, placebo-controlled, double-blinded, and randomized-controlled trial PATIENTS: Thirty children (15 per group) with critical asthma receiving high-intensity albuterol per a standardized pathway utilizing objective assessments to wean patients to less frequent albuterol administration. INTERVENTIONS: Subjects were randomized to receive either nebulized ipratropium bromide (500 µg in 0.9% saline per dose) or an equivalent volume of nebulized 0.9% saline every 6 h until the patient was successfully weaned to albuterol doses every 2 h ("q2 albuterol"). MEASUREMENTS AND MAIN RESULTS: Demographics, initial clinical severity score, and asthma histories were similar between groups. There was no significant difference in the median duration of high-intensity albuterol between the treatment group (17.5 [10.3-22.1] h) and placebo group (14.6 [12.7-24.5] days; p = .56). Similarly, there was no significant difference in pediatric intensive care unit length of stay (22.6 [21.1-33.6] vs. 21.4 [16.1-35.8] h; p = .74) or hospital length of stay (48.0 [41.8-59.8] vs. 47.3 [37.2-63.1] h; p = .67). In multivariate linear regression adjusting for identified confounders, treatment with ipratropium was not significantly associated with any of the three outcomes. Side effects were rare and occurred with equally between both groups CONCLUSIONS: Adjunctive therapy with ipratropium was not associated with decreased duration of high-intensity albuterol or shortened length of stay when compared to placebo. A larger, multicenter trial is warranted to confirm that ipratropium does not improve clinical outcomes.

Characteristics and Outcomes of Children With Coronavirus Disease 2019 (COVID-19) Infection Admitted to US and Canadian Pediatric Intensive Care Units.

IMPORTANCE: The recent and ongoing coronavirus disease 2019 (COVID-19) pandemic has taken an unprecedented toll on adults critically ill with COVID-19 infection. While there is evidence that the burden of COVID-19 infection in hospitalized children is lesser than in their adult counterparts, to date, there are only limited reports describing COVID-19 in pediatric intensive care units (PICUs). OBJECTIVE: To provide an early description and characterization of COVID-19 infection in North American PICUs, focusing on mode of presentation, presence of comorbidities, severity of disease, therapeutic interventions, clinical trajectory, and early outcomes. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study included children positive for COVID-19 admitted to 46 North American PICUs between March 14 and April 3, 2020. with follow-up to April 10, 2020. MAIN OUTCOMES AND MEASURES: Prehospital characteristics, clinical trajectory, and hospital outcomes of children admitted to PICUs with confirmed COVID-19 infection. RESULTS: Of the 48 children with COVID-19 admitted to participating PICUs, 25 (52%) were male, and the median (range) age was 13 (4.2-16.6) years. Forty patients (83%) had significant preexisting comorbidities; 35 (73%) presented with respiratory symptoms and 18 (38%) required invasive ventilation. Eleven patients (23%) had failure of 2 or more organ systems. Extracorporeal membrane oxygenation was required for 1 patient (2%). Targeted therapies were used in 28 patients (61%), with hydroxychloroquine being the most commonly used agent either alone (11 patients) or in combination (10 patients). At the completion of the follow-up period, 2 patients (4%) had died and 15 (31%) were still hospitalized, with 3 still requiring ventilatory support and 1 receiving extracorporeal membrane oxygenation. The median (range) PICU and hospital lengths of stay for those who had been discharged were 5 (3-9) days and 7 (4-13) days, respectively. CONCLUSIONS AND RELEVANCE: This early report describes the burden of COVID-19 infection in North American PICUs and confirms that severe illness in children is significant but far less frequent than in adults. Prehospital comorbidities appear to be an important factor in children. These preliminary observations provide an important platform for larger and more extensive studies of children with COVID-19 infection.

Adjunctive Pharmacotherapies in Children With Asthma Exacerbations Requiring Continuous Albuterol Therapy: Findings From The Ohio Pediatric Asthma Repository.

OBJECTIVES: To identify associations between use of ipratropium and/or intravenous magnesium and outcomes of children hospitalized with acute asthma exacerbations and treated with continuous albuterol. METHODS: Secondary analysis of data from children prospectively enrolled in the multicenter Ohio Pediatric Asthma Repository restricted to only children who were treated with continuous albuterol in their initial inpatient location. Children were treated with adjunctive therapies per the clinical team. RESULTS: Among 242 children who received continuous albuterol, 94 (39%) received ipratropium only, 13 (5%) received magnesium alone, 42 (17%) received both, and 93 (38%) received neither. The median duration of continuous albuterol was 7.0 (interquartile range [IQR]: 2.8-12.0) hours. Ipratropium use was associated with a shorter duration of continuous albuterol (4.9 [IQR: 2.0-10.0] hours) compared with dual therapy (11.0 [IQR: 5.6-28.6] hours; P = .001), but magnesium use was not (7.5 [IQR: 2.5-16.0] hours; P = .542). In Cox proportional models (adjusted for hospital, demographics, treatment location, and respiratory failure), magnesium was associated with longer durations of continuous albuterol (hazard ratio, 0.54 [95% confidence interval: 0.37-0.77]; P < .001) and hospitalization (hazard ratio, 0.41 [95% confidence interval: 0.28-0.60]; P < .001), but ipratropium was not. CONCLUSIONS: Ipratropium and magnesium were both often used in children with severe asthma hospitalizations that required continuous albuterol therapy. Magnesium use was associated with unfavorable outcomes, possibly reflecting preferential treatment to patients with more severe cases and differing practices between centers. Given the high prevalence of asthma, wide variations in practice, and the potential to improve outcomes and costs, prospective trials of these adjunctive therapies are needed.