Static and Dynamic Transpulmonary Driving Pressures Affect Lung and Diaphragm Injury during Pressure-controlled versus Pressure-support Ventilation in Experimental Mild Lung Injury in Rats
Eliete F. Pinto, M.Sc.; Raquel S. Santos, Ph.D.; Mariana A. Antunes, Ph.D.; Ligia A. Maia, Ph.D.; Gisele A. Padilha, Ph.D.; et alJoana de A. Machado, M.S.; Anna C. F. Carvalho, M.S.; Marcos V. S. Fernandes, M.S.; Vera L. Capelozzi, M.D., Ph.D.; Marcelo Gama de Abreu, M.D., Ph.D.; Paolo Pelosi, M.D., F.E.R.S.; Patricia R. M. Rocco, M.D., Ph.D.; Pedro L. Silva, Ph.D.
 Author Notes
From the Laboratory of Pulmonary Investigation, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil (E.F.P., R.S.S., M.A.A., L.A.M., G.A.P., J.D.A.M., A.C.F.C., M.V.S.F., P.R.M.R., P.L.S.); Department of Pathology, School of Medicine, University of São Paulo, São Paulo, Brazil (V.L.C.); Pulmonary Engineering Group, Department of Anesthesiology and Intensive Care Therapy, University Hospital Carl Gustav Carus, Dresden University of Technology, Dresden, Germany (M.G.D.A.); Department of Integrated Surgical and Diagnostic Sciences, University of Genoa, Genoa, Italy (P.P.); and Institute of Admission and Care of a Scientific Nature, San Martino Policlinico Hospital, Genoa, Italy (P.P.).
Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are available in both the HTML and PDF versions of this article. Links to the digital files are provided in the HTML text of this article on the Journal’s Web site (www.anesthesiology.org).
The protocol and results of this study have been presented in part at the American Thoracic Society scientific meeting on May 23, 2018 in San Diego, California, and were previously published as an abstract (American Journal of Respiratory and Critical Care Medicine 2018; 197:A7523).
Submitted for publication September 26, 2018. Accepted for publication October 17, 2019.
Correspondence: Address correspondence to Dr. Silva: Laboratory of Pulmonary Investigation, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Centro de Ciências da Saúde, Avenida Carlos Chagas Filho, 373, Bloco G-014, Ilha do Fundão, Rio de Janeiro, RJ 21941-902, Brazil. pedro.leme@gmail.com. Information on purchasing reprints may be found at www.anesthesiology.org or on the masthead page at the beginning of this issue. Anesthesiology’s articles are made freely accessible to all readers, for personal use only, 6 months from the cover date of the issue.
Anesthesiology Newly Published on November 21, 2019. doi:https://doi.org/10.1097/ALN.0000000000003060


What We Already Know about This Topic:

Both pressure-support and pressure-controlled ventilation may be used in patients with acute respiratory distress syndrome

The importance of static and dynamic transpulmonary driving pressure during mechanical ventilation is not well understood

What This Article Tells Us That Is New:

In a rat model of mild lung injury caused by intratracheal endotoxin administration, animals received both pressure-support and pressure-controlled ventilation, and effects on driving pressures were measured, along with lung inflammation and diaphragm inflammation

Pressure-support versus pressure-controlled ventilation was associated with higher dynamic (but not static) transpulmonary driving pressure, while markers of lung and diaphragm inflammation did not differ between ventilation modes

Background: Pressure-support ventilation may worsen lung damage due to increased dynamic transpulmonary driving pressure. The authors hypothesized that, at the same tidal volume (VT) and dynamic transpulmonary driving pressure, pressure-support and pressure-controlled ventilation would yield comparable lung damage in mild lung injury.

Methods: Male Wistar rats received endotoxin intratracheally and, after 24 h, were ventilated in pressure-support mode. Rats were then randomized to 2 h of pressure-controlled ventilation with VT, dynamic transpulmonary driving pressure, dynamic transpulmonary driving pressure, and inspiratory time similar to those of pressure-support ventilation. The primary outcome was the difference in dynamic transpulmonary driving pressure between pressure-support and pressure-controlled ventilation at similar VT; secondary outcomes were lung and diaphragm damage.

Results: At VT = 6 ml/kg, dynamic transpulmonary driving pressure was higher in pressure-support than pressure-controlled ventilation (12.0 ± 2.2 vs. 8.0 ± 1.8 cm H2O), whereas static transpulmonary driving pressure did not differ (6.7 ± 0.6 vs. 7.0 ± 0.3 cm H2O). Diffuse alveolar damage score and gene expression of markers associated with lung inflammation (interleukin-6), alveolar-stretch (amphiregulin), epithelial cell damage (club cell protein 16), and fibrogenesis (metalloproteinase-9 and type III procollagen), as well as diaphragm inflammation (tumor necrosis factor-α) and proteolysis (muscle RING-finger-1) were comparable between groups. At similar dynamic transpulmonary driving pressure, as well as dynamic transpulmonary driving pressure and inspiratory time, pressure-controlled ventilation increased VT, static transpulmonary driving pressure, diffuse alveolar damage score, and gene expression of markers of lung inflammation, alveolar stretch, fibrogenesis, diaphragm inflammation, and proteolysis compared to pressure-support ventilation.

Conclusions: In the mild lung injury model use herein, at the same VT, pressure-support compared to pressure-controlled ventilation did not affect biologic markers. However, pressure-support ventilation was associated with a major difference between static and dynamic transpulmonary driving pressure; when the same dynamic transpulmonary driving pressure and inspiratory time were used for pressure-controlled ventilation, greater lung and diaphragm injury occurred compared to pressure-support ventilation.