The association between physiologic dead-space fraction and mortality in subjects with ARDS enrolled in a prospective multi-center clinical trial

Richard H Kallet; Hanjing Zhuo; Kathleen D Liu; Carolyn S Calfee; Michael A Matthay; National Heart Lung and Blood Institute ARDS Network Investigators

doi:10.4187/respcare.02593

The association between physiologic dead-space fraction and mortality in subjects with ARDS enrolled in a prospective multi-center clinical trial

Respir Care. 2014 Nov;59(11):1611-8. doi: 10.4187/respcare.02593. Epub 2013 Dec 31.

Authors

Richard H Kallet¹, Hanjing Zhuo², Kathleen D Liu³, Carolyn S Calfee⁴, Michael A Matthay²; National Heart Lung and Blood Institute ARDS Network Investigators

Collaborators

National Heart Lung and Blood Institute ARDS Network Investigators:
J S Steingrub, M Tidswell, L DeSouza, C Kardos, L Kozikowski, K Kozikowski, R G Brower, H E Fessler, D N Hager, P A Mendez-Tellez, K Oakjones, D M Needham, J Sevransky, A Workneh, S Han, S Murray, C Shanholtz, G Netzer, P Rock, A Sampaio, J Titus, T Harrington, D Herr, B Lee, N Bolouri, G R Khorjekar, H P Wiedemann, R W Ashton, D A Culver, T Frederick, J J Komara, J A Guzman, A J Reddy, R Hejal, M Andrews, D Haney, A F Connors, S Lasalvia, J D Thornton, E L Warren, M Moss, A B Benson, E L Burnham, B J Clark, L Gray, C Higgins, B J Maloney, M Mealer, I Douglas, K Overdier, K Thompson, R Wolken, S S Carson, L Chang, J Lanier, R D Hite, P E Morris, A Howard, A Harvey, K Bender, P E Wright, C Carter-Cole, S Gross, J McLean, A Overton, J D Truwit, K Enfield, M Marshall, C G Irvin, T P Clemmer, L K Weaver, J Gleed, M Zenger, J Krueger, A H Morris, A Ahmed, A Austin, N C Dean, C K Grissom, E Hirshberg, N Kumar, R R Miller, L Napoli, J F Orme, S Pandita, G Schreiber, L Struck, F Thomas, G E Thomsen, C Lawton, F Leung, P Kim, T Fujii, J Baughman, B Kerwin, D Hanselman, J d'Hulst, K M Sundar, W Alward, T Hill, E J Campbell, K A Ludwig, D B Nielsen, M J Pearce, M A Matthay, C S Calfee, B M Daniel, M Eisner, O Garcia, E R Johnson, K Kordesch, K D Liu, H Zhou, M W Peterson, J Blaauw, T E Albertson, E Vlastelin, J V Diaz, E R Johnson, R H Kallet, R D Hubmayr, D R Brown, O Gajic, R Hinds, S R Holets, D J Kor, M Passe, B P deBoisblanc, P Lauto, C Romaine, G Meyaski, J P Hunt, A Marr, S Brierre, C LeBlanc, T Jagneaux, D E Taylor, S Jain, L Seoane, F Simeone, J Fearon, J Duchesne, D A Schoenfeld, M Aquino, D Dorer, M Guha, E Hammond, N Lavery, P Lazar, I Molina, R Morse, C F Oldmixon, B Rawal, N J Ringwood, A Shui, E Smoot, B T Thompson, A L Harabin, S Bredow, M A Waclawiw, G G Weinmann, R G Spragg, A S Slutsky, M M Levy, B P Markovitz, E Petkova, C Weijer, D F Willson, J I Sznajder, M Begg, E Israel, J Lewis, P E Parsons

Affiliations

¹ Respiratory Care Services, University of California San Francisco Department of Anesthesia at San Francisco General Hospital.
² Cardiovascular Research Institute, University of California, San Francisco.
³ Department of Nephrology, University of California, San Francisco.
⁴ Department of Pulmonary and Critical Care Medicine, University of California, San Francisco, San Francisco, California.

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.

Keywords: acute lung injury; acute respiratory distress syndrome; mechanical ventilation; physiologic dead-space fraction; single-breath test for carbon dioxide.

Publication types

Multicenter Study
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Female
Follow-Up Studies
Humans
Intensive Care Units
Male
Middle Aged
Positive-Pressure Respiration / methods*
Prospective Studies
Respiratory Distress Syndrome / mortality
Respiratory Distress Syndrome / physiopathology*
Respiratory Distress Syndrome / therapy
Survival Rate / trends
Tidal Volume / physiology*
United States / epidemiology

Abstract

Publication types

MeSH terms

Grants and funding