title: Timing of low tidal volume ventilation and intensive care unit mortality in acute respiratory distress syndrome. A prospective cohort study.
abstract: BACKGROUND
  Reducing tidal volume decreases mortality in acute respiratory distress syndrome (ARDS). However, the effect of the timing of low tidal volume ventilation is not well understood.
  
  
  OBJECTIVE
  To evaluate the association of intensive care unit (ICU) mortality with initial tidal volume and with tidal volume change over time.
  
  
  METHODS
  Multivariable, time-varying Cox regression analysis of a multisite, prospective study of 482 patients with ARDS with 11,558 twice-daily tidal volume assessments (evaluated in milliliter per kilogram of predicted body weight [PBW]) and daily assessment of other mortality predictors.
  
  
  RESULTS
  An increase of 1 ml/kg PBW in initial tidal volume was associated with a 23% increase in ICU mortality risk (adjusted hazard ratio, 1.23; 95% confidence interval [CI], 1.06-1.44; P = 0.008). Moreover, a 1 ml/kg PBW increase in subsequent tidal volumes compared with the initial tidal volume was associated with a 15% increase in mortality risk (adjusted hazard ratio, 1.15; 95% CI, 1.02-1.29; P = 0.019). Compared with a prototypical patient receiving 8 days with a tidal volume of 6 ml/kg PBW, the absolute increase in ICU mortality (95% CI) of receiving 10 and 8 ml/kg PBW, respectively, across all 8 days was 7.2% (3.0-13.0%) and 2.7% (1.2-4.6%). In scenarios with variation in tidal volume over the 8-day period, mortality was higher when a larger volume was used earlier.
  
  
  CONCLUSIONS
  Higher tidal volumes shortly after ARDS onset were associated with a greater risk of ICU mortality compared with subsequent tidal volumes. Timely recognition of ARDS and adherence to low tidal volume ventilation is important for reducing mortality. Clinical trial registered with www.clinicaltrials.gov (NCT 00300248).
authors.affiliation: 1 Outcomes After Critical Illness and Surgery Group.
authors.forename: Dale M
authors.initials: DM
authors.lastname: Needham
authors.forename: Ting
authors.initials: T
authors.lastname: Yang
authors.forename: Victor D
authors.initials: VD
authors.lastname: Dinglas
authors.forename: Pedro A
authors.initials: PA
authors.lastname: Mendez-Tellez
authors.forename: Carl
authors.initials: C
authors.lastname: Shanholtz
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Sevransky
authors.forename: Roy G
authors.initials: RG
authors.lastname: Brower
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Pronovost
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Colantuoni
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D017052:Hospital Mortality; D006801:Humans; D007362:Intensive Care Units / Q000706:statistics & numerical data; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012121:Respiration, Artificial / Q000379:methods / Q000401:mortality*; D012128:Respiratory Distress Syndrome / Q000175:diagnosis / Q000401:mortality* / Q000628:therapy; D012307:Risk Factors; D013990:Tidal Volume / Q000502:physiology*; D013997:Time Factors
keywords: acute lung injury; artificial respiration; prospective studies; tidal volume