Dataset Information

Effect of Nebulized Magnesium vs Placebo Added to Albuterol on Hospitalization Among Children With Refractory Acute Asthma Treated in the Emergency Department: A Randomized Clinical Trial.

ABSTRACT:

Importance

While intravenous magnesium decreases hospitalizations in refractory pediatric acute asthma, it is variably used because of invasiveness and safety concerns. The benefit of nebulized magnesium to prevent hospitalization is unknown.

Objective

To evaluate the effectiveness of nebulized magnesium in children with acute asthma remaining in moderate or severe respiratory distress after initial therapy.

Design, setting, and participants

A randomized double-blind parallel-group clinical trial from September 26, 2011, to November 19, 2019, in 7 tertiary-care pediatric emergency departments in Canada. The participants were otherwise healthy children aged 2 to 17 years with moderate to severe asthma defined by a Pediatric Respiratory Assessment Measure (PRAM) score of 5 or greater (on a 12-point scale) after a 1-hour treatment with an oral corticosteroid and 3 inhaled albuterol and ipratropium treatments. Of 5846 screened patients, 4332 were excluded for criteria, 273 declined participation, 423 otherwise excluded, 818 randomized, and 816 analyzed.

Interventions

Participants were randomized to 3 nebulized albuterol treatments with either magnesium sulfate (n = 410) or 5.5% saline placebo (n = 408).

Main outcomes and measures

The primary outcome was hospitalization for asthma within 24 hours. Secondary outcomes included PRAM score; respiratory rate; oxygen saturation at 60, 120, 180, and 240 minutes; blood pressure at 20, 40, 60, 120, 180, and 240 minutes; and albuterol treatments within 240 minutes.

Results

Among 818 randomized patients (median age, 5 years; 63% males), 816 completed the trial (409 received magnesium; 407, placebo). A total of 178 of the 409 children who received magnesium (43.5%) were hospitalized vs 194 of the 407 who received placebo (47.7%) (difference, -4.2%; absolute risk difference 95% [exact] CI, -11% to 2.8%]; P = .26). There were no significant between-group differences in changes from baseline to 240 minutes in PRAM score (difference of changes, 0.14 points [95% CI, -0.23 to 0.50]; P = .46); respiratory rate (0.17 breaths/min [95% CI, -1.32 to 1.67]; P = .82); oxygen saturation (-0.04% [95% CI, -0.53% to 0.46%]; P = .88); systolic blood pressure (0.78 mm Hg [95% CI, -1.48 to 3.03]; P = .50); or mean number of additional albuterol treatments (magnesium: 1.49, placebo: 1.59; risk ratio, 0.94 [95% CI, 0.79 to 1.11]; P = .47). Nausea/vomiting or sore throat/nose occurred in 17 of the 409 children who received magnesium (4%) and 5 of the 407 who received placebo (1%).

Conclusions and relevance

Among children with refractory acute asthma in the emergency department, nebulized magnesium with albuterol, compared with placebo with albuterol, did not significantly decrease the hospitalization rate for asthma within 24 hours. The findings do not support use of nebulized magnesium with albuterol among children with refractory acute asthma.

Trial registration

ClinicalTrials.gov Identifier: NCT01429415.

SUBMITTER: Schuh S

PROVIDER: S-EPMC7686869 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ImportanceDespite guidelines recommending administration of intravenous (IV) magnesium sulfate for refractory pediatric asthma, the number of asthma-related hospitalizations has remained stable, and IV magnesium therapy is independently associated with hospitalization.ObjectiveTo examine the association between IV magnesium therapy administered in the emergency department (ED) and subsequent hospitalization among pediatric patients with refractory acute asthma after adjustment for patient-level variables.Design, setting, and participantsThis post hoc secondary analysis of a double-blind randomized clinical trial of children with acute asthma treated from September 26, 2011, to November 19, 2019, at 7 Canadian tertiary care pediatric EDs was conducted between September and November 2020. In the randomized clinical trial, 816 otherwise healthy children aged 2 to 17 years with Pediatric Respiratory Assessment Measure (PRAM) scores of 5 points or higher after initial therapy with systemic corticosteroids and inhaled albuterol with ipratropium bromide were randomly assigned to 3 nebulized treatments of albuterol plus either magnesium sulfate or 5.5% saline placebo.ExposuresIntravenous magnesium sulfate therapy (40-75 mg/kg).Main outcomes and measuresThe association between IV magnesium therapy in the ED and subsequent hospitalization for asthma was assessed using multivariable logistic regression analysis. Analyses were adjusted for year epoch at enrollment, receipt of IV magnesium, PRAM score after initial therapy and at ED disposition, age, sex, duration of respiratory distress, previous intensive care unit admission for asthma, hospitalizations for asthma within the past year, atopy, and receipt of oral corticosteroids within 48 hours before arrival in the ED, nebulized magnesium, and additional albuterol after inhaled magnesium or placebo, with site as a random effect.ResultsAmong the 816 participants, the median age was 5 years (interquartile range, 3-7 years), 517 (63.4%) were boys, and 364 (44.6%) were hospitalized. A total of 215 children (26.3%) received IV magnesium, and 190 (88.4%) of these children were hospitalized compared with 174 of 601 children (29.0%) who did not receive IV magnesium. Multivariable factors associated with hospitalization were IV magnesium receipt from 2011 to 2016 (odds ratio [OR], 22.67; 95% CI, 6.26-82.06; P < .001) and from 2017 to 2019 (OR, 4.19; 95% CI, 1.99-8.86; P < .001), use of additional albuterol (OR, 5.94; 95% CI, 3.52-10.01; P < .001), and increase in PRAM score at disposition (per 1-U increase: OR, 2.24; 95% CI, 1.89-2.65; P < .001). In children with a disposition PRAM score of 3 or lower, receipt of IV magnesium therapy was associated with hospitalization (OR, 8.52; 95% CI, 2.96-24.41; P < .001).Conclusions and relevanceAfter adjustment for patient-level characteristics, receipt of IV magnesium therapy after initial asthma treatment in the ED was associated with subsequent hospitalization. This association also existed among children with mild asthma at ED disposition. Evidence of a benefit of IV magnesium regarding hospitalization may clarify its use in the treatment of refractory pediatric asthma.Trial registrationClinicalTrials.gov: NCT01429415.

Project description:BackgroundIn prospective experimental studies in patients with asthma, it is difficult to determine whether responses to placebo differ from the natural course of physiological changes that occur without any intervention. We compared the effects of a bronchodilator, two placebo interventions, and no intervention on outcomes in patients with asthma.MethodsIn a double-blind, crossover pilot study, we randomly assigned 46 patients with asthma to active treatment with an albuterol inhaler, a placebo inhaler, sham acupuncture, or no intervention. Using a block design, we administered one each of these four interventions in random order during four sequential visits (3 to 7 days apart); this procedure was repeated in two more blocks of visits (for a total of 12 visits by each patient). At each visit, spirometry was performed repeatedly over a period of 2 hours. Maximum forced expiratory volume in 1 second (FEV(1)) was measured, and patients' self-reported improvement ratings were recorded.ResultsAmong the 39 patients who completed the study, albuterol resulted in a 20% increase in FEV(1), as compared with approximately 7% with each of the other three interventions (P<0.001). However, patients' reports of improvement after the intervention did not differ significantly for the albuterol inhaler (50% improvement), placebo inhaler (45%), or sham acupuncture (46%), but the subjective improvement with all three of these interventions was significantly greater than that with the no-intervention control (21%) (P<0.001).ConclusionsAlthough albuterol, but not the two placebo interventions, improved FEV(1) in these patients with asthma, albuterol provided no incremental benefit with respect to the self-reported outcomes. Placebo effects can be clinically meaningful and can rival the effects of active medication in patients with asthma. However, from a clinical-management and research-design perspective, patient self-reports can be unreliable. An assessment of untreated responses in asthma may be essential in evaluating patient-reported outcomes. (Funded by the National Center for Complementary and Alternative Medicine.).

Project description:BackgroundAcute asthma in children can be life-threatening and must be treated promptly in the emergency setting. Intravenous magnesium sulfate is recommended by various guidelines for cases of acute asthma that have not responded to first-line treatment with bronchodilators and steroids. The treatment has recently been shown to reduce the need for hospital admission for adults compared with placebo, but it is unclear whether it is equally effective for children.ObjectivesTo assess the safety and efficacy of intravenous magnesium sulfate (IV MgSO4) in children treated for acute asthma in the emergency department (ED).Search methodsWe identified studies by searching the Cochrane Airways Review Group Specialised Register up to 23 February 2016. We also searched ClinicalTrials.gov and reference lists of other reviews, and we contacted study authors to ask for additional information.Selection criteriaWe included randomised controlled trials of children treated in the ED for exacerbations of asthma if they compared any dose of IV MgSO4 with placebo.Data collection and analysisTwo review authors screened the results of the search and independently extracted data from studies meeting the inclusion criteria. We resolved disagreements through discussion and contacted study authors in cases of missing data and other uncertainties relating to the studies.We analysed dichotomous data as odds ratios and continuous data as mean differences, both using fixed-effect models. We assessed each study for risk of bias and rated the quality of evidence for each outcome with GRADE and presented the results in a 'Summary of findings' table. There was insufficient evidence to conduct the planned subgroup analyses.Main resultsFive studies (182 children) met the inclusion criteria, and four contributed data to at least one meta-analysis. The included studies were overall at low risk of bias, but our confidence in the evidence was generally low, mainly due to the small sample sizes. Treatment with IV MgSO4 reduced the odds of admission to hospital by 68% (odds ratio (OR) 0.32, 95% confidence interval (CI) 0.14 to 0.74; children = 115; studies = 3; I(2) = 63%). This result was based on data from just three studies including 115 children. Meta-analysis for the secondary outcomes was extremely limited by paucity of data. We performed meta-analysis for the outcome 'return to the emergency department within 48 hours', which showed a very imprecise effect estimate that was not statistically significant (OR 0.40, 95% CI 0.02 to 10.30; children = 85; studies = 2; I(2) = 0%). Side effects and adverse events were not consistently reported and meta-analysis was not possible, however few side effects or adverse events were reported.Authors' conclusionsIV MgSO4 may reduce the need for hospital admission in children presenting to the ED with moderate to severe exacerbations of asthma, but the evidence is extremely limited by the number and size of studies. Few side effects of the treatment were reported, but the data were extremely limited.

Project description:Background Mechanically ventilated patients with coronavirus disease 2019 (COVID-19) have a mortality of 24-53%, in part due to distal mucopurulent secretions interfering with ventilation. Dornase alfa is recombinant human DNase 1 and digests DNA in mucoid sputum. Nebulized dornase alfa is FDA-approved for cystic fibrosis treatment. DNA from neutrophil extracellular traps (NETs) contributes to the viscosity of mucopurulent secretions. NETs are found in the serum of patients with severe COVID-19, and targeting NETs reduces mortality in animal models of acute respiratory distress syndrome (ARDS). Thus, dornase alfa may be beneficial to patients with severe COVID-19, acting as a mucolytic and targeting NETs. However, delivery of nebulized drugs can aerosolize SARS-CoV-2, which causes COVID-19, increasing the infection risk for staff. Here, we report a single center case series where dornase alfa was administered through an in-line nebulizer system to minimize risk of virus aerosolization. Methods Demographic, clinical data, and outcomes were collected from the electronic medical records of five mechanically ventilated patients with COVID-19, including three requiring veno-venous extracorporeal membrane oxygenation (VV-ECMO), treated with nebulized in-line endotracheal dornase alfa co-administered with albuterol (used to increase delivery to the alveoli), between March 31 and April 24, 2020. Data on tolerability and responses, including longitudinal values capturing respiratory function and inflammatory status, were analyzed. Results Following nebulized in-line administration of dornase alfa with albuterol, the fraction of inspired oxygen requirements was reduced for all five patients. All patients remain alive and two patients have been discharged from the intensive care unit. No drug associated toxicities were identified. Conclusions The results presented in this case series suggest that dornase alfa will be well-tolerated by critically ill patients with COVID-19. Clinical trials are required to formally test the dosing, safety, and efficacy of dornase alfa in COVID-19, and two have recently been registered ( NCT04359654 and NCT04355364 ). With this case series, we hope to contribute to the development of management approaches for critically ill patients with COVID-19.

Project description:ImportanceTonsillectomy is a common pediatric procedure for the treatment of sleep-disordered breathing and chronic tonsillitis. Up to half of children having this procedure experience a perioperative respiratory adverse event.ObjectiveTo determine whether inhaled albuterol sulfate (salbutamol sulfate) premedication decreases the risk of perioperative respiratory adverse events in children undergoing anesthesia for tonsillectomy.Design, setting, and participantsA randomized, triple-blind, placebo-controlled trial (the Reducing Anesthetic Complications in Children Undergoing Tonsillectomies [REACT] trial) was conducted at Perth Children's Hospital (formerly Princess Margaret Hospital for Children), the only tertiary pediatric hospital in Western Australia. Participants included 484 children aged 0 to 8 years who were undergoing anesthesia for tonsillectomy. The study was conducted between July 15, 2014, and May 18, 2017.InterventionsParticipants were randomized to receive either albuterol (2 actuations, 200 μg) or placebo before their surgery.Main outcomes and measuresOccurrence of perioperative respiratory adverse events (bronchospasm, laryngospasm, airway obstruction, desaturation, coughing, and stridor) until discharge from the postanesthesia care unit.ResultsOf 484 randomized children (median [range] age, 5.6 [1.6-8.9] years; 285 [58.9%] boys), 479 data sets were available for intention-to-treat analysis. Perioperative respiratory adverse events occurred in 67 of 241 children (27.8%) receiving albuterol and 114 of 238 children (47.9%) receiving placebo. After adjusting for age, type of airway device, and severity of obstructive sleep apnea in a binary logistic regression model, the likelihood of perioperative respiratory adverse events remained significantly higher in the placebo group compared with the albuterol group (odds ratio, 2.8; 95% CI, 1.9-4.2; P < .001). Significant differences were seen in children receiving placebo vs albuterol in laryngospasm (28 [11.8%] vs 12 [5.0%]; P = .009), coughing (79 [33.2%] vs 27 [11.2%]; P < .001), and oxygen desaturation (54 [22.7%] vs 36 [14.9%]; P = .03).Conclusions and relevanceAlbuterol premedication administered before tonsillectomy under general anesthesia in young children resulted in a clinically significant reduction in rates of perioperative respiratory adverse events compared with the rates in children who received placebo. Premedication with albuterol should be considered for children undergoing tonsillectomy.Trial registrationAustralian New Zealand Clinical Trials Registry identifier: ACTRN12614000739617.