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Objective: Asthma is the most common chronic disease of childhood. Although asthma admissions to the pediatric intensive care unit (PICU) are increasing, there are no evidence-based guidelines on preferred escalation of therapies for patients with status asthmaticus who fail to respond to inhaled bronchodilators and systemic corticosteroids. The purpose of this study was to assess outcomes of PICU patients receiving aminophylline versus terbutaline as second-tier therapies for status asthmaticus., Design: Retrospective cohort study using Pediatric Health Information System from 2016-2019., Setting: Fifty-three tertiary children's hospitals., Subjects: Children aged 2 to 18 years admitted to the PICU in children's hospitals contributing data to the Pediatric Health Information System with a primary diagnosis of status asthmaticus., Interventions: None., Measurements and Main Results: Of 11 133 pediatric patients treated for status asthmaticus in the PICU during the study period, 1144 received either terbutaline or aminophylline. There was no difference in intubation and mechanical ventilation between patients who received aminophylline and those who received terbutaline. However, in African American patients, those who received terbutaline had a significantly higher odds of intubation and mechanical ventilation compared to those who received aminophylline (OR, 12.41; 95%CI, 1.61,95)., Conclusions: The use of aminophylline is associated with lower odds of intubation and mechanical ventilation in African American patients with status asthmaticus as compared to terbutaline., (© 2020 Wiley Periodicals LLC.)

Objective: Magnesium sulfate (Mg) is one of several "second-tier" therapies for treating severe status asthmaticus. Pediatric reports primarily describe bolus use with limited data regarding prolonged infusions. We sought to describe the safety of prolonged Mg infusions during therapy of status asthmaticus in critically ill children., Design: Single center, retrospective study., Setting: Thirty-four-bed tertiary level medical/surgical/cardiac surgical pediatric intensive care unit., Patients: Pediatric patients 2 to 18 years of age admitted with status asthmaticus receiving Mg infusion for more than 24 hours., Interventions: None., Measurements and Main Findings: A total of 154 children received Mg infusions for a median of 53.4 hours (interquartile range = 36.6-74.8). The most common adverse event (AE) was hypotension (48.1%), almost exclusively diastolic (94%), and was mostly limited to 1 blood pressure measurement (78%). 2.9% of events required intervention (fluids, decrease Mg infusion). Other AEs included nausea/emesis (22.7%), transient weakness (14.9%), and flushing (6.5%). Five patients experienced serious AEs including hypotonia (n = 1), escalation to continuous or bilevel positive airway pressure (n = 3), and sedation (n = 1), all attributed to progression of underlying medical disease. No patient required endotracheal intubation. Supratherapeutic levels (>6 mg/dL) were uncommon (2%) and were not more likely to be associated with AEs. Most (81%) patients were therapeutic by the 2nd Mg level check., Conclusion: Prolonged Mg infusions were well tolerated in pediatric status asthmaticus patients. While diastolic hypotension was not uncommon, rarely were interventions deemed necessary. No serious AEs were attributed to Mg. Toxicity was uncommon suggesting that Mg levels could potentially be checked less frequently than historically reported., (© 2019 Wiley Periodicals, Inc.)

Aim: Magnesium is an adjunctive therapy used in patients with status asthmaticus who do not respond to conventional therapy. The optimal time from initiation of therapy, to determination of response and administration of magnesium has not yet been resolved. Our objective was to determine if magnesium administered in the non-intensive care setting can decrease duration of continuous albuterol and hospital length of stay., Methods: We performed a retrospective cohort analysis of children ages 2-18 years admitted to the pediatric unit on continuous albuterol between January 2014 and December 2015 in a tertiary care children's hospital. Cohorts were matched on respiratory assessment score (RAS) obtained at a similar duration of albuterol therapy and evaluated for the total duration of continuous albuterol, length of stay (LOS), and adverse events., Results: Thirty-three patients who received magnesium were matched to 33 patients with the same RAS at a similar duration of continuous albuterol therapy who did not receive magnesium. Those who received magnesium had longer duration on continuous albuterol (34 vs 18 h; P = 0.001; 95% confidence interval [CI] 4-20; effect size 0.41) and longer LOS (72 vs 49 h; P = 0.037; 95% confidence interval [CI] 1-33; effect size 0.26) than those who did not receive magnesium., Conclusion: Children requiring continuous albuterol for status asthmaticus can be administered magnesium sulfate outside the PICU with a low incidence of adverse events; however, among a RAS matched cohort, those who received magnesium did not experience shorter time on continuous albuterol, or hospital length of stay., (© 2018 Wiley Periodicals, Inc.)

Background: The ideal dosing of albuterol via metered-dose inhalers for acute childhood asthma is not well established. We hypothesized that greater doses of albuterol would result in less time in the hospital and lower admission rates., Methods: This was a randomized controlled double-blind multicenter study, conducted in emergency rooms (ER). We included patients with 2-17 years old with moderate to severe acute asthma (Pediatric Respiratory Assessment Measure, PRAM, score ≥5). Dosages administered during the first hour included: 6 (up to 25 kg) or 12 puffs (>25 kg) in the control group and 9 (up to 15 kg), 12 (>15-20 kg), 15 (>20-25 kg), or 18 puffs (>25 kg) in the study group. Several efficacy (changes in PRAM score, pulse oximetry, and FEV 1 , length of stay, and admission rates) and safety (albuterol plasma levels, heart rate, serum potassium, glucose and bicarbonate levels, EKG, and tremor rates) outcome measures were assessed., Results: We included 119 patients with similar baseline conditions, and no significant differences were observed between groups in the length of stay (P = 0.48) or admission rate (P = 0.55). No significant differences were observed in FEV 1 , PRAM score, and pulse oximetry changes after 1 hr and at discharge or admission. No significant differences were observed in safety outcomes between groups., Conclusions: Higher albuterol dosage regimens did not result in lower admission rate or shorter length of stay in the ER, but showed similar safety profile for children with moderate to severe acute asthma. Pediatr Pulmonol. 2016;51:1122-1130. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Objectives: While aerosolized administration of beta(2)-adrenergic receptor (beta(2)-AR) agonists is the mainstay of treatment for pediatric asthma exacerbations, the efficacy of intravenous (IV) delivery is controversial. Failure to demonstrate improved outcomes with IV beta(2)-AR agonists may be due to phenotypic differences within this patient population. Our hypothesis is that children who respond more slowly to IV beta(2)-AR agonist therapy comprise a distinct phenotype., Methods: Retrospective chart review of all children admitted to the ICU for status asthmaticus who were treated with IV terbutaline between December 2002 and September 2006., Results: Seventy-eight children were treated with IV terbutaline according to guidelines that adjusted the dose by clinical asthma score. After examining the histogram of duration of terbutaline infusions, a 48-hr cutoff was chosen to define responsiveness. Thirty-eight (49%) children were slow-responders by this definition. There were no significant differences in baseline asthma severity or severity on admission between the slow-responders and responders. Slow-responders required significantly higher total doses of IV terbutaline, higher maximum administration rates, and had longer ICU and hospital length of stay., Conclusion: There were significant differences in outcomes between the responders and slow-responders without differences in acute or chronic illness severity. Other factors may have lead to slower response to IV beta(2)-agonist therapy.

Chronic therapy with inhaled corticosteroids (ICS) suppresses airway inflammation and increases airway responsiveness to beta(2)-adrenergic receptor agonists. We hypothesized that the chronic use of ICS would be associated with shorter duration of hospitalization in severely ill children with status asthmaticus. An 8-year retrospective chart review was conducted of all children admitted to the ICU with status asthmaticus. During the study period, 241 children were admitted, and 44% reported the use of chronic ICS. ICS use was associated with increased baseline asthma severity, previous hospitalization for asthma, and public insurance status. However, ICS use had no effect on hospital or ICU length of stay, type, and duration of treatments received, or the rate of recovery determined by a standard severity of illness scoring system. In the subsets of patients including children with persistent asthma and those who received intravenous terbutaline, there was also no improvement in outcomes with the use of chronic ICS showing that the chronic use of ICS did not improve response to beta(2)-adrenergic receptor agonists in severely ill children with status asthmaticus. Although useful as a preventive therapy, the chronic use of ICS does not appear to affect the course of severe acute asthma exacerbations in pediatric patients once hospitalized.

This review assesses the evidence regarding the use of long-acting beta(2)-agonists in the management of pediatric asthma. Thirty double-blind, randomized, controlled trials on the effects of formoterol and salmeterol on lung function in asthmatic children were identified. Single doses of inhaled salmeterol or formoterol cause prolonged bronchodilatation (>12 h) and extended bronchoprotection against exercise-induced bronchoconstriction in children, some children achieving full protection for more than 12 h. Heterogeneity in bronchoprotection has been observed, and individual dose-titration may be attempted. The onset of action of formoterol is comparable to salbutamol, while salmeterol has a slower onset of action. Partial tolerance develops when long-acting beta(2)-agonists are used as regular treatment, including cross-tolerance to short-acting beta(2)-agonists. Regular treatment with salmeterol in children with or without corticosteroids provides statistically significant bronchodilatation, but the degree of improvement in lung function or bronchoprotection against exercise and nonspecific irritants is small with regular use. There is no evidence of anti-inflammatory effects from inhaled long-acting beta(2)-agonists, which is reflected by unchanged or increased bronchial hyperreactivity and no reduction of exacerbation rates. The evidence does not support a recommendation for long-acting beta(2)-agonists as monotherapy, nor does it support their general use as regular add-on therapy. In conclusion, long-acting beta(2)-agonists provide effective bronchodilatation and bronchoprotection when used as intermittent, single-dose treatment of asthma in children, but not when used as regular treatment. Future studies should examine the positioning of long-acting beta(2)-agonists as an "as needed" rescue medication instead of short-acting beta(2)-agonists for pediatric asthma management., (Copyright 2000 Wiley-Liss, Inc.)

The paper reports on a 13-year-old girl with chronic asthma who presented in acute respiratory failure following an exacerbation of her disease. Nitric oxide was added to the ventilator circuit at 7 ppm and then 15 ppm after the patient failed to respond to bronchodilators and steroids. This was followed by rapid improvement in respiratory mechanics and blood gases with no adverse effects. Nitric oxide appears to have a direct relaxing effect on the bronchial smooth muscle., (Copyright 1999 Wiley-Liss, Inc.)

The effects of chest physical therapy in acute severe asthma in children have been studied in 38 children aged 6 to 13 years in a randomized placebo controlled trial. The study began between 6 and 24 hours after admission to hospital; 19 children received chest physical therapy (PT) and 19 children received placebo visits. Each child had 4 treatments over 2 days which were preceded by nebulized salbutamol. Lung volumes and flow rates were measured in a body plethysmograph before salbutamol and before and after either PT or placebo on the first and fourth treatments. Throughout the study standard asthma drug therapy was given. In both groups characteristics such as sex, race, age, height, weight, severity, and baseline lung function were similar. Taking into account the baseline, lung function at the end of the study was similar in both groups. Three 12 year old children in the PT group showed improvements in flows above those seen in any children in the placebo group. We conclude that chest PT, when combined with asthma drug therapy, does not improve lung function in most children in this age group with acute severe asthma.