Biological Impact of Transpulmonary Driving Pressure in Experimental Acute Respiratory Distress Syndrome

Background: Ventilator-induced lung injury has been attributed to the interaction of several factors: tidal volume (V-T), positive end-expiratory pressure (PEEP), transpulmonary driving pressure (difference between transpulmonary pressure at end-inspiration and end-expiration, P,L), and respiratory system plateau pressure (Pplat,rs). Methods: Forty-eight Wistar rats received Escherichia coli lipopolysaccharide intratracheally. After 24h, animals were randomized into combinations of V-T and PEEP, yielding three different P,L levels: P,L-LOW (V-T = 6ml/kg, PEEP = 3cm H2O); P,L-MEAN (V-T = 13ml/kg, PEEP = 3cm H2O or V-T = 6ml/kg, PEEP = 9.5cm H2O); and P,L-HIGH (V-T = 22ml/kg, PEEP = 3cm H2O or V-T = 6ml/kg, PEEP = 11cm H2O). In other groups, at low V-T, PEEP was adjusted to obtain a Pplat,rs similar to that achieved with P,L-MEAN and P,L-HIGH at high V-T. Results: At P,L-LOW, expressions of interleukin (IL)-6, receptor for advanced glycation end products (RAGE), and amphiregulin were reduced, despite morphometric evidence of alveolar collapse. At P,L-HIGH (V-T = 6ml/kg and PEEP = 11cm H2O), lungs were fully open and IL-6 and RAGE were reduced compared with P,L-MEAN (27.412.9 vs. 41.6 +/- 14.1 and 0.6 +/- 0.2 vs. 1.4 +/- 0.3, respectively), despite increased hyperinflation and amphiregulin expression. At P,L-MEAN (V-T = 6ml/kg and PEEP = 9.5cm H2O), when PEEP was not high enough to keep lungs open, IL-6, RAGE, and amphiregulin expression increased compared with P,L-LOW (41.6 +/- 14.1 vs. 9.0 +/- 9.8, 1.4 +/- 0.3 vs. 0.6 +/- 0.2, and 6.7 +/- 0.8 vs. 2.2 +/- 1.0, respectively). At Pplat,rs similar to that achieved with P,L-MEAN and P,L-HIGH, higher V-T and lower PEEP reduced IL-6 and RAGE expression. Conclusion: In the acute respiratory distress syndrome model used in this experiment, two strategies minimized ventilator-induced lung injury: (1) low V-T and PEEP, yielding low P,L and Pplat,rs; and (2) low V-T associated with a PEEP level sufficient to keep the lungs open.