title: The association between physiologic dead-space fraction and mortality in subjects with ARDS enrolled in a prospective multi-center clinical trial.
abstract: BACKGROUND
  We tested the association between pulmonary dead-space fraction (ratio of dead space to tidal volume [V(D)/V(T)]) and mortality in subjects with ARDS (Berlin definition, P(aO2)/F(IO2) ≤ 300 mm Hg; PEEP ≥ 5 cm H2O) enrolled into a clinical trial incorporating lung-protective ventilation.
  
  
  METHODS
  We conducted a prospective, multi-center study at medical-surgical ICUs in the United States. A total of 126 ALI subjects with acute lung injury were enrolled into a phase 3 randomized, placebo-controlled study of aerosolized albuterol. V(D)/V(T) and pulmonary mechanics were measured within 4 h of enrollment and repeated daily on study days 1 and 2 in subjects requiring arterial blood gases for clinical management.
  
  
  RESULTS
  At baseline, non-survivors had a trend toward higher V(D)/V(T) compared with survivors (0.62 ± 0.11 vs 0.56 ± 0.11, respectively, P = .08). Differences in V(D)/V(T) between non-survivors and survivors became significant on study days 1 (0.64 ± 0.12 vs 0.55 ± 0.11, respectively, P = .01) and 2 (0.67 ± 0.12 vs 0.56 ± 0.11, respectively, P = .004). Likewise, the association between VD/VT and mortality was significant on study day 1 (odds ratio per 0.10 change in V(D)/V(T) [95% CI]: 6.84 [1.62-28.84] P = .01; and study day 2: 4.90 [1.28-18.73] P = .02) after adjusting for V(D)/V(T), P(aO2)/F(IO2), oxygenation index, vasopressor use, and the primary risk for ARDS. Using a Cox proportional hazard model, V(D)/V(T) was associated with a trend toward higher mortality (HR = 4.37 [CI 0.99-19.32], P = .052) that became significant when the analysis was adjusted for daily oxygenation index (HR = 1.74 [95% CI 1.12-3.35] P = .04).
  
  
  CONCLUSIONS
  Markedly elevated V(D)/V(T) (≥ 0.60) in early ARDS is associated with higher mortality. Measuring V(D)/V(T) may be useful in identifying ARDS patients at increased risk of death who are enrolled into a therapeutic trial.
authors.affiliation: Respiratory Care Services, University of California San Francisco Department of Anesthesia at San Francisco General Hospital.
authors.forename: Richard H
authors.initials: RH
authors.lastname: Kallet
authors.affiliation: Cardiovascular Research Institute, University of California, San Francisco.
authors.forename: Hanjing
authors.initials: H
authors.lastname: Zhuo
authors.affiliation: Department of Nephrology, University of California, San Francisco.
authors.forename: Kathleen D
authors.initials: KD
authors.lastname: Liu
authors.affiliation: Department of Pulmonary and Critical Care Medicine, University of California, San Francisco, San Francisco, California.
authors.forename: Carolyn S
authors.initials: CS
authors.lastname: Calfee
authors.affiliation: Cardiovascular Research Institute, University of California, San Francisco.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Matthay
mesh_terms: D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D011175:Positive-Pressure Respiration / Q000379:methods*; D011446:Prospective Studies; D012128:Respiratory Distress Syndrome / Q000401:mortality / Q000503:physiopathology* / Q000628:therapy; D015996:Survival Rate / Q000639:trends; D013990:Tidal Volume / Q000502:physiology*; D014481:United States / Q000453:epidemiology
keywords: acute lung injury; acute respiratory distress syndrome; mechanical ventilation; physiologic dead-space fraction; single-breath test for carbon dioxide