title: Effects of interventions on survival in acute respiratory distress syndrome: an umbrella review of 159 published randomized trials and 29 meta-analyses.
abstract: OBJECTIVE
  Multiple interventions have been tested in acute respiratory distress syndrome (ARDS). We examined the entire agenda of published randomized controlled trials (RCTs) in ARDS that reported on mortality and of respective meta-analyses.
  
  
  METHODS
  We searched PubMed, the Cochrane Library, and Web of Knowledge until July 2013. We included RCTs in ARDS published in English. We excluded trials of newborns and children; and those on short-term interventions, ARDS prevention, or post-traumatic lung injury. We also reviewed all meta-analyses of RCTs in this field that addressed mortality. Treatment modalities were grouped in five categories: mechanical ventilation strategies and respiratory care, enteral or parenteral therapies, inhaled/intratracheal medications, nutritional support, and hemodynamic monitoring.
  
  
  RESULTS
  We identified 159 published RCTs of which 93 had overall mortality reported (n = 20,671 patients)--44 trials (14,426 patients) reported mortality as a primary outcome. A statistically significant survival benefit was observed in eight trials (seven interventions) and two trials reported an adverse effect on survival. Among RCTs with more than 50 deaths in at least one treatment arm (n = 21), two showed a statistically significant mortality benefit of the intervention (lower tidal volumes and prone positioning), one showed a statistically significant mortality benefit only in adjusted analyses (cisatracurium), and one (high-frequency oscillatory ventilation) showed a significant detrimental effect. Across 29 meta-analyses, the most consistent evidence was seen for low tidal volumes and prone positioning in severe ARDS.
  
  
  CONCLUSIONS
  There is limited supportive evidence that specific interventions can decrease mortality in ARDS. While low tidal volumes and prone positioning in severe ARDS seem effective, most sporadic findings of interventions suggesting reduced mortality are not corroborated consistently in large-scale evidence including meta-analyses.
authors.affiliation: Department of Pulmonary, Allergy, and Critical Care Medicine, Respiratory Institute, Cleveland, OH, USA.
authors.forename: Adriano R
authors.initials: AR
authors.lastname: Tonelli
authors.forename: Joe
authors.initials: J
authors.lastname: Zein
authors.forename: Jacob
authors.initials: J
authors.lastname: Adams
authors.forename: John P A
authors.initials: JP
authors.lastname: Ioannidis
mesh_terms: D006801:Humans; D015201:Meta-Analysis as Topic; D016032:Randomized Controlled Trials as Topic; D012128:Respiratory Distress Syndrome / Q000401:mortality* / Q000628:therapy*; D015996:Survival Rate