Steroids and bronchodilators for acute bronchiolitis in the first two years of life: systematic review and meta-analysisBMJ 2011; 342 doi: https://doi.org/10.1136/bmj.d1714 (Published 06 April 2011) Cite this as: BMJ 2011;342:d1714
- Lisa Hartling, assistant professor1,
- Ricardo M Fernandes, PhD student2,
- Liza Bialy, project coordinator1,
- Andrea Milne, research assistant1,
- David Johnson, professor3,
- Amy Plint, associate professor4,
- Terry P Klassen, professor5,
- Ben Vandermeer, biostatistician1
- 1Alberta Research Centre for Health Evidence, Department of Pediatrics, University of Alberta, 11402 University Avenue, Edmonton, AB, Canada T6G 2J3
- 2Gulbenkian Program for Advanced Medical Education; Child and Family Department, Hospital de Santa Maria; Clinical Pharmacology and Therapeutics, Institute of Molecular Medicine, Lisbon, Portugal
- 3Department of Pediatrics and Department of Physiology and Pharmacology, University of Calgary and Alberta Children’s Hospital, Calgary, AB, Canada
- 4Department of Pediatrics and Department of Emergency Medicine, University of Ottawa, Ottawa, ON, Canada
- 5Manitoba Institute of Child Health, Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, MB, Canada
- Correspondence to: L Hartling
- Accepted 27 January 2011
Objective To evaluate and compare the efficacy and safety of bronchodilators and steroids, alone or combined, for the acute management of bronchiolitis in children aged less than 2 years.
Design Systematic review and meta-analysis.
Data sources Medline, Embase, Central, Scopus, PubMed, LILACS, IranMedEx, conference proceedings, and trial registers.
Inclusion criteria Randomised controlled trials of children aged 24 months or less with a first episode of bronchiolitis with wheezing comparing any bronchodilator or steroid, alone or combined, with placebo or another intervention (other bronchodilator, other steroid, standard care).
Review methods Two reviewers assessed studies for inclusion and risk of bias and extracted data. Primary outcomes were selected by clinicians a priori based on clinical relevance: rate of admission for outpatients (day 1 and up to day 7) and length of stay for inpatients. Direct meta-analyses were carried out using random effects models. A mixed treatment comparison using a Bayesian network model was used to compare all interventions simultaneously.
Results 48 trials (4897 patients, 13 comparisons) were included. Risk of bias was low in 17% (n=8), unclear in 52% (n=25), and high in 31% (n=15). Only adrenaline (epinephrine) reduced admissions on day 1 (compared with placebo: pooled risk ratio 0.67, 95% confidence interval 0.50 to 0.89; number needed to treat 15, 95% confidence interval 10 to 45 for a baseline risk of 20%; 920 patients). Unadjusted results from a single large trial with low risk of bias showed that combined dexamethasone and adrenaline reduced admissions on day 7 (risk ratio 0.65, 0.44 to 0.95; number needed to treat 11, 7 to 76 for a baseline risk of 26%; 400 patients). A mixed treatment comparison supported adrenaline alone or combined with steroids as the preferred treatments for outpatients (probability of being the best treatment based on admissions at day 1 were 45% and 39%, respectively). The incidence of reported harms did not differ. None of the interventions examined showed clear efficacy for length of stay among inpatients.
Conclusions Evidence shows the effectiveness and superiority of adrenaline for outcomes of most clinical relevance among outpatients with acute bronchiolitis, and evidence from a single precise trial for combined adrenaline and dexamethasone.
We thank the following for their contributions to this project: Annabritt Chisholm (article retrieval), Heather McPhee (data extraction), Nicola Hooton (protocol development, study selection), Özge Tunçalp (Turkish translation), Joy Lee (Korean translation), Paolo Valerio (Dutch translation), and João Franco (Spanish translation). This work is based on two systematic reviews produced for the Cochrane Collaboration on glucocorticoids and adrenaline (epinephrine) for bronchiolitis, respectively.
Contributors: LH, RF, DJ, AP, TK, BV conceived and designed the study. LH, RF, LB, and AM screened the literature search results and identified articles for retrieval, reviewed full papers for inclusion, and extracted data for meta-analysis. BV and RF analysed data and carried out multiple treatment comparisons. All authors interpreted the data, critically revised the draft, and gave final approval of the version to be published. LH is the guarantor for the study.
Funding: This research was supported by the Canadian Institutes of Health Research knowledge synthesis grant programme. The funding agency was not involved with the study design or collection, analysis, and interpretation of the data. RMF is supported by the Calouste Gulbenkian Foundation (Programme for Advanced Medical Education; www.gulbenkian.pt), and Fundação Ciência e Tecnologia.
Competing interests: All authors have completed the Unified Competing Interest form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare that (1) LH, DJ, AP, TPK, and BV have support from the Canadian Institutes for Health Research for the submitted work; (2) none of the authors has relationships with Canadian Institutes for Health Research that might have an interest in the submitted work in the previous 3 years; (3) none of their spouses, partners, or children has financial relationships that may be relevant to the submitted work; and (4) the authors have no non-financial interests that may be relevant to the submitted work.
Ethical approval: Not required.
Data sharing: No additional data available.
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