title: Randomized, placebo-controlled clinical trial of an aerosolized β₂-agonist for treatment of acute lung injury.
abstract: BACKGROUND
  β₂-Adrenergic receptor agonists accelerate resolution of pulmonary edema in experimental and clinical studies.
  
  
  OBJECTIVE
  This clinical trial was designed to test the hypothesis that an aerosolized β₂-agonist, albuterol, would improve clinical outcomes in patients with acute lung injury (ALI).
  
  
  METHODS
  We conducted a multicenter, randomized, placebo-controlled clinical trial in which 282 patients with ALI receiving mechanical ventilation were randomized to receive aerosolized albuterol (5 mg) or saline placebo every 4 hours for up to 10 days. The primary outcome variable for the trial was ventilator-free days.
  
  
  RESULTS
  Ventilator-free days were not significantly different between the albuterol and placebo groups (means of 14.4 and 16.6 d, respectively; 95% confidence interval for the difference, -4.7 to 0.3 d; P = 0.087). Rates of death before hospital discharge were not significantly different between the albuterol and placebo groups (23.0 and 17.7%, respectively; 95%confidence interval for the difference,-4.0 to 14.7%;P = 0.30). In the subset of patients with shock before randomization, the number of ventilator-free days was lower with albuterol, although mortality was not different. Overall, heart rates were significantly higher in the albuterol group by approximately 4 beats/minute in the first 2 days after randomization, but rates of new atrial fibrillation (10% in both groups) and other cardiac dysrhythmias were not significantly different.
  
  
  CONCLUSIONS
  These results suggest that aerosolized albuterol does not improve clinical outcomes in patients with ALI. Routine use of β₂-agonist therapy in mechanically ventilated patients with ALI cannot be recommended. Clinical trial registered with www.clinicaltrials.gov (NCT 00434993).
authors.forename: Michael A
authors.initials: MA
authors.lastname: Matthay
authors.forename: Roy G
authors.initials: RG
authors.lastname: Brower
authors.forename: Shannon
authors.initials: S
authors.lastname: Carson
authors.forename: Ivor S
authors.initials: IS
authors.lastname: Douglas
authors.forename: Mark
authors.initials: M
authors.lastname: Eisner
authors.forename: Duncan
authors.initials: D
authors.lastname: Hite
authors.forename: Steven
authors.initials: S
authors.lastname: Holets
authors.forename: Richard H
authors.initials: RH
authors.lastname: Kallet
authors.forename: Kathleen D
authors.initials: KD
authors.lastname: Liu
authors.forename: Neil
authors.initials: N
authors.lastname: MacIntyre
authors.forename: Marc
authors.initials: M
authors.lastname: Moss
authors.forename: David
authors.initials: D
authors.lastname: Schoenfeld
authors.forename: Jay
authors.initials: J
authors.lastname: Steingrub
authors.forename: B Taylor
authors.initials: BT
authors.lastname: Thompson
mesh_terms: D055371:Acute Lung Injury / Q000097:blood / Q000401:mortality / Q000628:therapy*; D000280:Administration, Inhalation; D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000420:Albuterol / Q000008:administration & dosage* / Q000493:pharmacokinetics; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D012121:Respiration, Artificial; D012189:Retrospective Studies; D015996:Survival Rate / Q000639:trends; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D000420:Albuterol