Abstract
BACKGROUND: We tested the association between pulmonary dead-space fraction (ratio of dead space to tidal volume [VD/VT]) and mortality in subjects with ARDS (Berlin definition, PaO2/FIO2 ≤ 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. VD/VT 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 VD/VT compared with survivors (0.62 ± 0.11 vs 0.56 ± 0.11, respectively, P = .08). Differences in VD/VT 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 VD/VT [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 VD/VT, PaO2/FIO2, oxygenation index, vasopressor use, and the primary risk for ARDS. Using a Cox proportional hazard model, VD/VT 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 VD/VT (≥ 0.60) in early ARDS is associated with higher mortality. Measuring VD/VT may be useful in identifying ARDS patients at increased risk of death who are enrolled into a therapeutic trial.
- acute lung injury
- acute respiratory distress syndrome
- mechanical ventilation
- physiologic dead-space fraction
- single-breath test for carbon dioxide
Footnotes
- Correspondence: Richard H Kallet MSc RRT FAARC, Department of Anesthesia, University of California San Francisco at San Francisco General Hospital, NH:GA-2, 1001 Potrero Avenue, San Francisco, CA 94110.
This study was supported by National Heart, Lung and Blood Institute contracts NO1-HR-56165–56713, and by material support (the loan of monitors, disposables and training) from Philips Respironics. RH Kallet and MA Matthay have received similar past support from Philips Respironics for other clinical trials. The other authors have disclosed no conflicts of interest.
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