The association between cumulative dose of inhaled bronchodilators and mortality in patients with severe ARDS

Abstract

Background: The purpose of this study was to examine bronchodilator use in patients with severe acute respiratory distress syndrome (ARDS) to determine if such use affected mortality. We compared cohorts of patients receiving and not receiving bronchodilators to determine clinical differences between the groups. We then sought associations with clinical risk factors, including cumulative doses of bronchodilators, with in-hospital mortality.Methods: This study was a retrospective analysis of patients diagnosed with severe ARDS treated at a large health care system between December 1, 2012 and February 10, 2018. From 1195 patients selected from the electronic medical records (EMR) we identified 312 patients for study after the application of inclusion and exclusion criteria. We compared cohorts of patients receiving and not receiving inhaled bronchodilators. We then performed first a univariable, followed by a multivariable analysis of clinical risk factors including the cumulative dose of bronchodilators to study their relationship with in-hospital mortality. Results: Of the 312 patients with moderate or severe ARDS selected for this study, 260 received bronchodilators and 52 did not receive them. Most patients (n=230) received both albuterol and ipratropium. Patients receiving bronchodilators had longer intensive care unit length of stay (ICULOS; 18.6+/-14.9 days v 9.0+/-7.4 days, p=0.000) but similar mortality compared to patients not receiving bronchodilators (112/260 versus 26/52, p=0.364). Clinical risk factors significantly associated with in-hospital mortality in a univariable analysis included the mortality prediction model II score (MPM, p=0.000), age (p=0.000), the ratio of PaO2:FiO2 (PF, p=0.000), the cumulative amount of short acting bronchodilator (SABD, p=0.004), the maximum heart rate (HRmax, p=0.023), and the minimum serum potassium level (Kmin, p=0.000). In a multivariable analysis the MPM (p=0.000, OR=7.543), PF (p=0.002, OR=0.988), cumulative SABD dose (p=0.002, OR=0.996), HRmax (p=0.001, OR=1.021), and Kmin (p=0.000, OR=3.509) remained significantly associated with inpatient mortality. Conclusions: Inhaled bronchodilators are frequently used in patients with severe ARDS despite clinical evidence that beta-agonists do not improve clinical outcome. We have demonstrated an association between the cumulative dose of SABD and decreased in-hospital mortality in patients with severe ARDS. Further study is needed to confirm these observations.