title: Severity of Hypoxemia and Effect of High-Frequency Oscillatory Ventilation in Acute Respiratory Distress Syndrome.
abstract: High-frequency oscillatory ventilation (HFOV) is theoretically beneficial for lung protection, but the results of clinical trials are inconsistent, with study-level meta-analyses suggesting no significant effect on mortality.
  
  
  
  The aim of this individual patient data meta-analysis was to identify acute respiratory distress syndrome (ARDS) patient subgroups with differential outcomes from HFOV.
  
  
  
  After a comprehensive search for trials, two reviewers independently identified randomized trials comparing HFOV with conventional ventilation for adults with ARDS. Prespecified effect modifiers were tested using multivariable hierarchical logistic regression models, adjusting for important prognostic factors and clustering effects.
  
  
  
  Data from 1,552 patients in four trials were analyzed, applying uniform definitions for study variables and outcomes. Patients had a mean baseline PaO2/FiO2of 114 ± 39 mm Hg; 40% had severe ARDS (PaO2/FiO2<100 mm Hg). Mortality at 30 days was 321 of 785 (40.9%) for HFOV patients versus 288 of 767 (37.6%) for control subjects (adjusted odds ratio, 1.17; 95% confidence interval, 0.94-1.46; P = 0.16). This treatment effect varied, however, depending on baseline severity of hypoxemia (P = 0.0003), with harm increasing with PaO2/FiO2among patients with mild-moderate ARDS, and the possibility of decreased mortality in patients with very severe ARDS. Compliance and body mass index did not modify the treatment effect. HFOV increased barotrauma risk compared with conventional ventilation (adjusted odds ratio, 1.75; 95% confidence interval, 1.04-2.96; P = 0.04).
  
  
  
  HFOV increases mortality for most patients with ARDS but may improve survival among patients with severe hypoxemia on conventional mechanical ventilation.
authors.affiliation: 1 Department of Medicine and.|2 Department of Clinical Epidemiology & Biostatistics, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Maureen O
authors.initials: MO
authors.lastname: Meade
authors.affiliation: 3 University of Oxford, Oxford, United Kingdom.
authors.forename: Duncan
authors.initials: D
authors.lastname: Young
authors.affiliation: 1 Department of Medicine and.|2 Department of Clinical Epidemiology & Biostatistics, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Steven
authors.initials: S
authors.lastname: Hanna
authors.affiliation: 1 Department of Medicine and.|2 Department of Clinical Epidemiology & Biostatistics, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: 4 Czech Technical University-Prague, Kladno, Czech Republic.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Bachman
authors.affiliation: 5 Wilhelmina Children's Hospital, Utrecht, the Netherlands.
authors.forename: Casper
authors.initials: C
authors.lastname: Bollen
authors.affiliation: 6 Interdepartmental Division of Critical Care Medicine.|8 Department of Medicine, and.|7 Keenan Centre for Biomedical Research, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Canada.
authors.forename: Arthur S
authors.initials: AS
authors.lastname: Slutsky
authors.affiliation: 3 University of Oxford, Oxford, United Kingdom.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Lamb
authors.affiliation: 6 Interdepartmental Division of Critical Care Medicine.|8 Department of Medicine, and.|9 Department of Critical Care Medicine, Sunnybrook Health Science Centre, Toronto, Canada.
authors.forename: Neill K J
authors.initials: NKJ
authors.lastname: Adhikari
authors.affiliation: 10 Athens Medical School, Evaggelismos General Hospital, Athens, Greece.
authors.forename: Spyros D
authors.initials: SD
authors.lastname: Mentzelopoulos
authors.affiliation: 1 Department of Medicine and.|2 Department of Clinical Epidemiology & Biostatistics, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Cook
authors.affiliation: 11 Trillium Health Partners, University of Toronto, Mississauga, Ontario, Canada.
authors.forename: Sachin
authors.initials: S
authors.lastname: Sud
authors.affiliation: 12 Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Roy G
authors.initials: RG
authors.lastname: Brower
authors.affiliation: 13 Harvard University, Boston, Massachusetts.
authors.forename: B Taylor
authors.initials: BT
authors.lastname: Thompson
authors.affiliation: 14 University Hospitals Bristol, National Health Service Foundation Trust, Bristol, United Kingdom.
authors.forename: Sanjoy
authors.initials: S
authors.lastname: Shah
authors.affiliation: 15 12th Man Technologies, Garden Grove, California; and.
authors.forename: Alex
authors.initials: A
authors.lastname: Stenzler
authors.affiliation: 1 Department of Medicine and.|2 Department of Clinical Epidemiology & Biostatistics, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Gordon
authors.initials: G
authors.lastname: Guyatt
authors.affiliation: 6 Interdepartmental Division of Critical Care Medicine.|8 Department of Medicine, and.|16 Institute for Health Policy, Management, and Evaluation, University of Toronto, Toronto, Canada.|17 Division of Respirology, Department of Medicine, University Health Network and Mount Sinai Hospital, Toronto General Research Institute, Toronto, Canada.
authors.forename: Niall D
authors.identifier: 0000-0002-6213-5264
authors.initials: ND
authors.lastname: Ferguson
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D006612:High-Frequency Ventilation / Q000379:methods*; D006801:Humans; D000860:Hypoxia / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D012121:Respiration, Artificial / Q000379:methods*; D012128:Respiratory Distress Syndrome / Q000628:therapy*; D016896:Treatment Outcome
keywords: acute respiratory distress syndrome; high-frequency oscillatory ventilation; mechanical ventilation