title: The beta agonist lung injury trial prevention. A randomized controlled trial.
abstract: BACKGROUND
  Experimental studies suggest that pretreatment with β-agonists might prevent acute lung injury (ALI).
  
  
  OBJECTIVE
  To determine if in adult patients undergoing elective esophagectomy, perioperative treatment with inhaled β-agonists effects the development of early ALI.
  
  
  METHODS
  We conducted a randomized placebo-controlled trial in 12 UK centers (2008-2011). Adult patients undergoing elective esophagectomy were allocated to prerandomized, sequentially numbered treatment packs containing inhaled salmeterol (100 μg twice daily) or a matching placebo. Patients, clinicians, and researchers were masked to treatment allocation. The primary outcome was development of ALI within 72 hours of surgery. Secondary outcomes were ALI within 28 days, organ failure, adverse events, survival, and health-related quality of life. An exploratory substudy measured biomarkers of alveolar-capillary inflammation and injury.
  
  
  RESULTS
  A total of 179 patients were randomized to salmeterol and 183 to placebo. Baseline characteristics were similar. Treatment with salmeterol did not prevent early lung injury (32 [19.2%] of 168 vs. 27 [16.0%] of 170; odds ratio [OR], 1.25; 95% confidence interval [CI], 0.71-2.22). There was no difference in organ failure, survival, or health-related quality of life. Adverse events were less frequent in the salmeterol group (55 vs. 70; OR, 0.63; 95% CI, 0.39-0.99), predominantly because of a lower number of pneumonia (7 vs. 17; OR, 0.39; 95% CI, 0.16-0.96). Salmeterol reduced some biomarkers of alveolar inflammation and epithelial injury.
  
  
  CONCLUSIONS
  Perioperative treatment with inhaled salmeterol was well tolerated but did not prevent ALI. Clinical trial registered with International Standard Randomized Controlled Trial Register (ISRCTN47481946) and European Union database of randomized Controlled Trials (EudraCT 2007-004096-19).
authors.affiliation: 1 Heart of England NHS Foundation Trust, Bordesley Green East, Birmingham, United Kingdom.
authors.forename: Gavin D
authors.initials: GD
authors.lastname: Perkins
authors.forename: Simon
authors.initials: S
authors.lastname: Gates
authors.forename: Daniel
authors.initials: D
authors.lastname: Park
authors.forename: Fang
authors.initials: F
authors.lastname: Gao
authors.forename: Chris
authors.initials: C
authors.lastname: Knox
authors.forename: Ben
authors.initials: B
authors.lastname: Holloway
authors.forename: Daniel F
authors.initials: DF
authors.lastname: McAuley
authors.forename: James
authors.initials: J
authors.lastname: Ryan
authors.forename: Joseph
authors.initials: J
authors.lastname: Marzouk
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Cooke
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Lamb
authors.forename: David R
authors.initials: DR
authors.lastname: Thickett
mesh_terms: D055371:Acute Lung Injury / Q000209:etiology / Q000517:prevention & control*; D000280:Administration, Inhalation; D058666:Adrenergic beta-2 Receptor Agonists / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000420:Albuterol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004334:Drug Administration Schedule; D017558:Elective Surgical Procedures; D016629:Esophagectomy; D005260:Female; D006801:Humans; D057194:Intention to Treat Analysis; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D019990:Perioperative Care / Q000379:methods*; D011183:Postoperative Complications / Q000517:prevention & control*; D000068299:Salmeterol Xinafoate; D016896:Treatment Outcome
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D000068299:Salmeterol Xinafoate; D000420:Albuterol