title: Effect of intravenous β-2 agonist treatment on clinical outcomes in acute respiratory distress syndrome (BALTI-2): a multicentre, randomised controlled trial.
abstract: BACKGROUND
  In a previous randomised controlled phase 2 trial, intravenous infusion of salbutamol for up to 7 days in patients with acute respiratory distress syndrome (ARDS) reduced extravascular lung water and plateau airway pressure. We assessed the effects of this intervention on mortality in patients with ARDS.
  
  
  METHODS
  We did a multicentre, placebo-controlled, parallel-group, randomised trial at 46 UK intensive-care units between December, 2006, and March, 2010. Intubated and mechanically ventilated patients (aged ≥16 years) within 72 h of ARDS onset were randomly assigned to receive either salbutamol (15 μg/kg ideal bodyweight per h) or placebo for up to 7 days. Randomisation was done by a central telephone or web-based randomisation service with minmisation by centre, pressure of arterial oxygen to fractional inspired oxygen concentration (PaO(2)/F(I)O(2)) ratio, and age. All participants, caregivers, and investigators were masked to group allocation. The primary outcome was death within 28 days of randomisation. Analysis was by intention-to-treat. This trial is registered, ISRCTN38366450 and EudraCT number 2006-002647-86.
  
  
  RESULTS
  We randomly assigned 162 patients to the salbutamol group and 164 to the placebo group. One patient in each group withdrew consent. Recruitment was stopped after the second interim analysis because of safety concerns. Salbutamol increased 28-day mortality (55 [34%] of 161 patients died in the salbutamol group vs 38 (23%) of 163 in the placebo group; risk ratio [RR] 1·47, 95% CI 1·03-2·08).
  
  
  CONCLUSIONS
  Treatment with intravenous salbutamol early in the course of ARDS was poorly tolerated. Treatment is unlikely to be beneficial, and could worsen outcomes. Routine use of β-2 agonist treatment in ventilated patients with this disorder cannot be recommended.
  
  
  BACKGROUND
  UK Medical Research Council, UK Department of Health, UK Intensive Care Foundation.
authors.affiliation: Warwick Clinical Trials Unit, University of Warwick, Coventry, UK. f.gaosmith@bham.ac.uk
authors.forename: Fang
authors.initials: F
authors.lastname: Gao Smith
authors.forename: Gavin D
authors.initials: GD
authors.lastname: Perkins
authors.forename: Simon
authors.initials: S
authors.lastname: Gates
authors.forename: Duncan
authors.initials: D
authors.lastname: Young
authors.forename: Daniel F
authors.initials: DF
authors.lastname: McAuley
authors.forename: William
authors.initials: W
authors.lastname: Tunnicliffe
authors.forename: Zahid
authors.initials: Z
authors.lastname: Khan
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Lamb
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage* / Q000009:adverse effects; D000368:Aged; D000369:Aged, 80 and over; D000420:Albuterol / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D006801:Humans; D007262:Infusions, Intravenous; D008875:Middle Aged; D012128:Respiratory Distress Syndrome / Q000188:drug therapy*
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D000420:Albuterol