Historia Natural De La Enfermedad

RESEARCH
Steroids and bronchodilators for acute bronchiolitis in the first two years of life: systematic review and meta-analysis
Lisa Hartling, assistant professor,1 Ricardo M Fernandes, PhD student,2 Liza Bialy, project coordinator,1 Andrea Milne, research assistant,1 David Johnson, professor,3 Amy Plint, associate professor,4 Terry P Klassen, professor,5 Ben Vandermeer, biostatistician1
1Alberta Research Centre for Health Evidence, Department of Pediatrics, University of Alberta, 11402 University Avenue, Edmonton, AB, Canada T6G 2J3 2 Gulbenkian Program for Advanced Medical Education; Child and Family Department, Hospital de Santa Maria; Clinical Pharmacology and Therapeutics, Institute of Molecular Medicine, Lisbon, Portugal 3 Department of Pediatrics and Department of Physiologyand Pharmacology, University of Calgary and Alberta Children’s Hospital, Calgary, AB, Canada 4 Department of Pediatrics and Department of Emergency Medicine, University of Ottawa, Ottawa, ON, Canada 5 Manitoba Institute of Child Health, Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, MB, Canada Correspondence to: L Hartling hartling@ualberta.ca

Cite this as: BMJ2011;342:d1714 doi:10.1136/bmj.d1714

ABSTRACT 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 outcomeswere 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) wereincluded. 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 biasshowed 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 anddexamethasone.

INTRODUCTION Bronchiolitis is the most common disease of the lower respiratory tract during the first year of life.1 Respiratory syncytial virus is the underlying cause of most bronchiolitis and this infection is associated with substantial morbidity in young children.2 3 Ongoing research in bronchiolitis reflects both the burden of disease in developed and developing countries and a lack...