β2 Agonist for the Treatment of Acute Lung Injury: A Systematic Review and Meta-analysis

BACKGROUND: The use of beta(2) agonist as an intervention for acute lung injury (ALI) and ARDS patients is controversial, so we performed a systematic review and meta-analysis of the published randomized controlled trials of using beta(2) agonists to improve outcomes (mortality and ventilator free days) among patients with ALI/ARDS. METHODS: A comprehensive search of 7 major databases (Ovid MEDLINE In-Process and other non-indexed citations, Ovid MEDLINE, Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials (CENTRAL), Ovid Cochrane Database of Systematic Reviews, Web of Science, and Scopus) for randomized controlled trials using beta(2) agonists for ALI from their origin to March 2013 was conducted. The effect size was measured by relative risk for dichotomous outcomes, and mean difference for continuous outcomes, with 95% CI. The statistical heterogeneity between the studies was assessed with the Cochran Q test and I-2 statistic. The heterogeneity of > 50% was considered significant for the analysis. The Cochrane risk of bias tool was used to ascertain the quality of the included studies. RESULTS: Out of 219 studies screened, 3 randomized controlled trials reported mortality and ventilator-free days, in 646 ALL! ARDS subjects. Of the 646 subjects, 334 (51.7%) received beta(2) agonist and 312 (48.3%) received placebo. There was no significant decrease in 28-day mortality or hospital mortality in the beta(2)-agonist group: relative risk 1.04, 95% CI 0.50-2.16, and relative risk 1.22, 95% CI 0.95-1.56, respectively. The ventilator-free days and organ-failure-free days were significantly lower for the ALI subjects who received beta(2) agonists: mean difference -2.19 days (95% CI -3.68 to -1.99 d) and mean difference -2.04 days (95% CI -3.74 to -0.35 d), respectively. CONCLUSIONS: In subjects with ALI/ARDS, beta(2) agonists were not only nonbeneficial in improving the survival, but were harmful and increased morbidity (reduced organ-failure-free days and ventilator-free days). The current evidence discourages the use of beta(2) agonist in ALI/ARDS patients. (International Prospective Register of Systematic Reviews, http://www.crd.york.ac.uk/prospero, 2012:CRD42012002616.)