β₂Agonist for the Treatment of Acute Lung Injury: A Systematic Review and Meta-analysis

Abstract

BACKGROUND: The use of ␤ 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 ␤ 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 ␤ 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 ALI/ ARDS subjects. Of the 646 subjects, 334 (51.7%) received ␤ 2 agonist and 312 (48.3%) received placebo. There was no significant decrease in 28-day mortality or hospital mortality in the ␤ 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 ␤ 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, ␤ 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 ␤ 2 agonist in ALI/ARDS patients. (International Prospective Register of Systematic Reviews, http://www.crd.york.ac.uk/prospero, 2012:CRD42012002616.)

Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016

“…Pooled analysis suggests β-agonists may reduce survival to hospital discharge in ARDS patients (RR 1.22; 95% CI 0.95-1.56) while significantly decreasing the number of ventilator-free days (MD, −2.19; 95% CI −3.68 to −0.71) [412]. β-Agonist use also led to more arrhythmias (RR 1.97; 95% CI 0.70-5.54) and more tachycardia (RR 3.95; 95% CI 1.41-11.06).…”

Scandinavian clinical practice guideline on fluid and drug therapy in adults with acute respiratory distress syndrome

“…Our recommendation is based on a recent systematic review of three randomized trials with either inhaled 32 or intravenous administration 33,34 of beta2 agonists. 35 The results show either no effect (inhaled) or increased (intravenous route) risk of death (aggregate risk ratio, 1.14; 95% CI, 0.91-1.42) and a significant increase in the risk of cardiac arrhythmias (risk ratio, 1.8; 95% CI, 1.24-2.62) and time on mechanical ventilation (both routes of administration; mean difference, 2.2 days; 95% CI, 0.71-3.68). The quality of evidence was downgraded due to imprecision and inconsistency.…”

Albuterol in the treatment of acute respiratory distress syndrome: A meta-analysis of randomized controlled trials

“…While conducting this study, we discovered a latest meta-analysis on the same question, [20] in which the conclusion is similar to us, but some important issues should be addressed. First, in that paper, the number of subjects was miscalculated in one of the cited RCTs (the number of subjects in the β 2 agonists/placebo group should be 19 and 21), resulting in conspicuous differentiation.…”

“…[14,15] However, there is no consensus on albuterol treatment for ARDS patients. [16][17][18][19] One meta-analysis [20] addressing similar research question has been published, but its methods compromised the reliability of the results. Therefore, a meta-analysis of RCTs was done to evaluate again the effect of albuterol on patients with ARDS.…”