title: Oxygenation response to positive end-expiratory pressure predicts mortality in acute respiratory distress syndrome. A secondary analysis of the LOVS and ExPress trials.
abstract: BACKGROUND
  Previous trials of higher positive end-expiratory pressure (PEEP) for acute respiratory distress syndrome (ARDS) failed to demonstrate mortality benefit, possibly because of differences in lung recruitability among patients with ARDS.
  
  
  OBJECTIVE
  To determine whether the physiological response to increased PEEP is associated with mortality.
  
  
  METHODS
  In a secondary analysis of the Lung Open Ventilation Study (LOVS, n = 983), we examined the relationship between the initial response to changes in PEEP after randomization and mortality. We sought to corroborate our findings using data from a different trial of higher PEEP (ExPress, n = 749).
  
  
  RESULTS
  The oxygenation response (change in ratio of arterial partial pressure of oxygen to fraction of inspired oxygen: P/F) after the initial change in PEEP after randomization varied widely (median, 9.5 mm Hg; interquartile range, -16 to 47) and was only weakly related to baseline P/F or the magnitude of PEEP change. Among patients in whom PEEP was increased after randomization, an increase in P/F was associated with reduced mortality (multivariable logistic regression; adjusted odds ratio, 0.80 [95% confidence interval, 0.72-0.89] per 25-mm Hg increase in P/F), particularly in patients with severe disease (baseline P/F [less-than-or-equal-to] 150 mm Hg). Changes in compliance and dead space were not associated with mortality. These findings were confirmed by a similar analysis of data from the ExPress trial.
  
  
  CONCLUSIONS
  Patients with ARDS who respond to increased PEEP by improved oxygenation have a lower risk of death. The oxygenation response to PEEP might be used to predict whether patients will benefit from higher versus lower PEEP.
authors.affiliation: 1 Interdepartmental Division of Critical Care Medicine.
authors.forename: Ewan C
authors.initials: EC
authors.lastname: Goligher
authors.forename: Brian P
authors.initials: BP
authors.lastname: Kavanagh
authors.forename: Gordon D
authors.initials: GD
authors.lastname: Rubenfeld
authors.forename: Neill K J
authors.initials: NK
authors.lastname: Adhikari
authors.forename: Ruxandra
authors.initials: R
authors.lastname: Pinto
authors.forename: Eddy
authors.initials: E
authors.lastname: Fan
authors.forename: Laurent J
authors.initials: LJ
authors.lastname: Brochard
authors.forename: John T
authors.initials: JT
authors.lastname: Granton
authors.forename: Alain
authors.initials: A
authors.lastname: Mercat
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Marie Richard
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Chretien
authors.forename: Graham L
authors.initials: GL
authors.lastname: Jones
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Cook
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Stewart
authors.forename: Arthur S
authors.initials: AS
authors.lastname: Slutsky
authors.forename: Maureen O
authors.initials: MO
authors.lastname: Meade
authors.forename: Niall D
authors.initials: ND
authors.lastname: Ferguson
mesh_terms: D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D010101:Oxygen Consumption / Q000502:physiology*; D011175:Positive-Pressure Respiration / Q000379:methods / Q000401:mortality / Q000706:statistics & numerical data*; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D012128:Respiratory Distress Syndrome / Q000401:mortality / Q000628:therapy*; D012720:Severity of Illness Index; D013990:Tidal Volume / Q000502:physiology; D016896:Treatment Outcome; D055397:Ventilator-Induced Lung Injury / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*
keywords: positive end-expiratory pressure; respiratory distress syndrome, adult; ventilator-induced lung injury