Hypoxemia on life support for guiding acute respiratory distress syndrome therapy?
Editorial

Hypoxemia on life support for guiding acute respiratory distress syndrome therapy?

Elen Gusman1, Jeremy R. Beitler2

1Department of Medicine, 2Center for Acute Respiratory Failure, Columbia University College of Physicians and Surgeons and New York-Presbyterian Hospital, New York, NY, USA

Correspondence to: Jeremy R. Beitler, MD, MPH. Center for Acute Respiratory Failure, Columbia University College of Physicians and Surgeons, 622 West 168th Street, PH 8 East, Room 101, New York, NY 10032, USA. Email: jrb2266@cumc.columbia.edu.

Provenance and Peer Review: This article was commissioned by the editorial office, Journal of Thoracic Disease. The article did not undergo external peer review.

Comment on: van Meenen DM, Roozeman JP, Serpa Neto A, et al. Associations between changes in oxygenation, dead space and driving pressure induced by the first prone position session and mortality in patients with acute respiratory distress syndrome. J Thorac Dis 2019;11:5004-13.


Submitted Feb 16, 2020. Accepted for publication Mar 04, 2020.

doi: 10.21037/jtd.2020.03.72


Hypoxemia has been a defining feature of acute respiratory distress syndrome (ARDS) since its first description by Ashbaugh and colleagues in 1967 (1). In successive consensus definitions, severity of hypoxemia has been used as the principal variable for stratification of lung injury severity (2,3). Treatment strategies for ARDS often have been applied through this lens, with more severe hypoxemia used to guide initiation and termination of ARDS therapies in research and clinical practice (4).

Reliance on oxygenation as a primary guide for ARDS therapy warrants scrutiny. Conceptually, hypoxemia is a biomarker of lung injury but not clearly on the causal pathway to mortality: refractory hypoxemia occurs in a minority of deaths with ARDS in modern intensive care (5). By contrast, ventilation-induced lung injury (VILI) unequivocally is linked causally to ARDS mortality (6,7), making respiratory mechanics a logical focus for prognostication and guiding therapy.

Past experiences in clinical trials support this framing. Higher positive end-expiratory pressure (PEEP) often improves the ratio of partial pressure of arterial oxygen to fraction of inspired oxygen (PaO2/FiO2) (8,9), but trials comparing empirical higher versus lower PEEP have not revealed a survival benefit (10,11). In the ARDS Network tidal volume trial (6), survival improved with lower tidal volumes despite worsening of PaO2/FiO2 over the first several days. While prone positioning improved survival in the PROSEVA trial (12), a reanalysis of trial data found no correlation between improvement in gas exchange and survival among patients who underwent proning (13).

The work by van Meenen and colleagues, published recently in this journal (14), lends further caution against using gas exchange to gauge early response to ARDS therapy. In a substudy of 90 ARDS patients from the MARS Consortium cohort, PaO2/FiO2 improved in 90% of patients following the first session of prone positioning. However, proning-associated change in PaO2/FiO2 was not predictive of survival. Pulmonary dead space fraction and airway driving pressure decreased in 66% and 56% of patients, respectively, but only improved driving pressure was predictive of survival.

These findings are consistent with current understanding of the probable mechanism of survival benefit with prone positioning, protection against VILI. In patients with ARDS, proning appears to improve survival only when used concomitantly with low tidal volumes (15). In both healthy individuals and patients with ARDS, prone positioning redistributes mechanical forces to yield more homogeneous lung aeration (16), thereby attenuating stress concentration that otherwise may contribute to VILI (17). Based on geometric modeling of CT data, this more homogeneous redistribution likely occurs from conformational shape matching of the lungs to the chest cavity with proning, during which resultant forces act to oppose gravitational effects on the lungs (18,19).

Why would proning optimize human lung mechanics? Less heterogeneous regional lung strain in prone position may be an example of vestigial physiology. Most mammalian species are quadrupeds that ambulate in the prone position. Per evolutionary biology, an optimally designed respiratory mechanical system therefore should minimize lung stress and strain and maximize gas exchange efficiency when the body is prone (20). Likely for the same reason, pulmonary blood flow and ventilation-perfusion matching also are optimized in prone position (21).

The association of driving pressure change with survival, found by van Meenen and colleagues (14), is intriguing but should be interpreted cautiously. Driving pressure is a reasonable bedside marker of global overdistension lung injury risk (22), and a decrease in driving pressure may signify less VILI. However, proning acts primarily to homogenize regional mechanics with relatively little effect on global lung density. Thus, proning-associated decrease in driving pressure may not sufficiently identify all patients who experience less VILI with proning. Perhaps for this reason, the predictive value of driving pressure in their study was underwhelming. The authors appropriately advise against use of proning-associated change in driving pressure for prognostication.

The question of how to identify early a favorable response to prone positioning remains elusive. For ARDS patients with refractory hypoxemia, there is an obvious role for proning to improve oxygenation irrespective of VILI attenuation. For patients without refractory hypoxemia, for whom the benefit of proning is to attenuate VILI, there is no reliable short-term marker (23). Bedside visualization of regional mechanics, such as with lung electrical impedance tomography (24,25), could help gauge early lung-protective response with proning and warrants future investigation. Until more definitive data are available, the best approach would seem that employed by PROSEVA: prone for at least 16 hours per day until gas exchange improves sufficiently to permit weaning ventilator support to minimal settings while supine. Short-term oxygenation and dead space improvement without substantial ventilator weaning should not be used as markers of therapeutic efficacy (13,14).


Acknowledgments

Funding: None.


Footnote

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jtd.2020.03.72). JRB reports personal fees from Hamilton Medical, personal fees from Sedana Medical, outside the submitted work. EG has no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.


References

  1. Ashbaugh DG, Bigelow DB, Petty TL, et al. Acute respiratory distress in adults. Lancet 1967;2:319-23. [Crossref] [PubMed]
  2. Bernard GR, Artigas A, Brigham KL, et al. The American-European Consensus Conference on ARDS. Definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med 1994;149:818-24. [Crossref] [PubMed]
  3. Ranieri VM, Rubenfeld GD, Thompson BT, et al. Acute respiratory distress syndrome: the Berlin Definition. JAMA 2012;307:2526-33. [PubMed]
  4. Prescott HC, Calfee CS, Thompson BT, et al. Toward smarter lumping and smarter splitting: rethinking strategies for sepsis and acute respiratory distress syndrome clinical trial design. Am J Respir Crit Care Med 2016;194:147-55. [Crossref] [PubMed]
  5. Thille AW, Esteban A, Fernández-Segoviano P, et al. Comparison of the Berlin definition for acute respiratory distress syndrome with autopsy. Am J Respir Crit Care Med 2013;187:761-7. [Crossref] [PubMed]
  6. Amato MB, Barbas CS, Medeiros DM, et al. Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome. N Engl J Med 1998;338:347-54. [Crossref] [PubMed]
  7. Brower RG, Matthay MA, Morris A, et al. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med 2000;342:1301-8. [Crossref] [PubMed]
  8. Villar J, Pérez-Méndez L, Kacmarek RM. Current definitions of acute lung injury and the acute respiratory distress syndrome do not reflect their true severity and outcome. Intensive Care Med 1999;25:930-5. [Crossref] [PubMed]
  9. Villar J, Pérez-Méndez L, Blanco J, et al. A universal definition of ARDS: the PaO2/FiO2 ratio under a standard ventilatory setting--a prospective, multicenter validation study. Intensive Care Med 2013;39:583-92. [Crossref] [PubMed]
  10. Brower RG, Lanken PN, MacIntyre N, et al. Higher versus lower positive end-expiratory pressures in patients with the acute respiratory distress syndrome. N Engl J Med 2004;351:327-36. [Crossref] [PubMed]
  11. Meade MO, Cook DJ, Guyatt GH, et al. Ventilation strategy using low tidal volumes, recruitment maneuvers, and high positive end-expiratory pressure for acute lung injury and acute respiratory distress syndrome: a randomized controlled trial. JAMA 2008;299:637-45. [Crossref] [PubMed]
  12. Guérin C, Reignier J, Richard JC, et al. Prone positioning in severe acute respiratory distress syndrome. N Engl J Med 2013;368:2159-68. [Crossref] [PubMed]
  13. Albert RK, Keniston A, Baboi L, et al. Prone position–induced improvement in gas exchange does not predict improved survival in the acute respiratory distress syndrome. Am J Respir Crit Care Med 2014;189:494-6. [Crossref] [PubMed]
  14. van Meenen DM, Roozeman JP, Serpa Neto A, et al. Associations between changes in oxygenation, dead space and driving pressure induced by the first prone position session and mortality in patients with acute respiratory distress syndrome. J Thorac Dis 2019;11:5004-13. [Crossref] [PubMed]
  15. Beitler JR, Shaefi S, Montesi SB, et al. Prone positioning reduces mortality from acute respiratory distress syndrome in the low tidal volume era: a meta-analysis. Intensive Care Med 2014;40:332-41. [Crossref] [PubMed]
  16. Gattinoni L, Pelosi P, Vitale G, et al. Body position changes redistribute lung computed-tomographic density in patients with acute respiratory failure. Anesthesiology 1991;74:15-23. [Crossref] [PubMed]
  17. Cressoni M, Cadringher P, Chiurazzi C, et al. Lung inhomogeneity in patients with acute respiratory distress syndrome. Am J Respir Crit Care Med 2014;189:149-58. [PubMed]
  18. Gattinoni L, Taccone P, Carlesso E, et al. Prone position in acute respiratory distress syndrome. Rationale, indications, and limits. Am J Respir Crit Care Med 2013;188:1286-93. [Crossref] [PubMed]
  19. Scholten EL, Beitler JR, Prisk GK, et al. Treatment of ARDS with prone positioning. Chest 2017;151:215-24. [Crossref] [PubMed]
  20. Hopkins SR, Henderson AC, Levin DL, et al. Vertical gradients in regional lung density and perfusion in the supine human lung: the Slinky effect. J Appl Physiol (1985) 2007;103:240-8. [PubMed]
  21. Henderson AC, Sá RC, Theilmann RJ, et al. The gravitational distribution of ventilation-perfusion ratio is more uniform in prone than supine posture in the normal human lung. J Appl Physiol (1985) 2013;115:313-24. [PubMed]
  22. Amato MB, Meade MO, Slutsky AS, et al. Driving pressure and survival in acute respiratory distress syndrome. N Engl J Med 2015;372:747-55. [Crossref] [PubMed]
  23. Beitler JR. Bedside respiratory physiology to detect risk of lung injury in acute respiratory distress syndrome. Curr Opin Crit Care 2019;25:3-11. [Crossref] [PubMed]
  24. Costa EL, Borges JB, Melo A, et al. Bedside estimation of recruitable alveolar collapse and hyperdistension by electrical impedance tomography. Intensive Care Med 2009;35:1132-7. [Crossref] [PubMed]
  25. Leonhardt S, Lachmann B. Electrical impedance tomography: the holy grail of ventilation and perfusion monitoring? Intensive Care Med 2012;38:1917-29. [Crossref] [PubMed]
Cite this article as: Gusman E, Beitler JR. Hypoxemia on life support for guiding acute respiratory distress syndrome therapy? J Thorac Dis 2020;12(6):3010-3012. doi: 10.21037/jtd.2020.03.72