Biological Response to Time-Controlled Adaptive Ventilation Depends on Acute Respiratory Distress Syndrome Etiology

Objectives: To compare a time-controlled adaptive ventilation strategy, set in airway pressure release ventilation mode, versus a protective mechanical ventilation strategy in pulmonary and extrapulmonary acute respiratory distress syndrome with similar mechanical impairment. Design: Animal study. Setting: Laboratory investigation. Subjects: Forty-two Wistar rats. Interventions: Pulmonary acute respiratory distress syndrome and extrapulmonary acute respiratory distress syndrome were induced by instillation of Escherichia coli lipopolysaccharide intratracheally or intraperitoneally, respectively. After 24 hours, animals were randomly assigned to receive 1 hour of volume-controlled ventilation (n = 7/etiology) or time-controlled adaptive ventilation (n = 7/etiology) (tidal volume = 8mL/kg). Time-controlled adaptive ventilation consisted of the application of continuous positive airway pressure 2cm H2O higher than baseline respiratory system peak pressure for a time (T-high) of 0.75-0.85 seconds. The release pressure (P-low = 0cm H2O) was applied for a time (T-low) of 0.11-0.18 seconds. T-low was set to target an end-expiratory flow to peak expiratory flow ratio of 75%. Nonventilated animals (n = 7/etiology) were used for Diffuse Alveolar Damage and molecular biology markers analyses. Measurement and Main Results: Time-controlled adaptive ventilation increased mean respiratory system pressure regardless of acute respiratory distress syndrome etiology. The Diffuse Alveolar Damage score was lower in time-controlled adaptive ventilation compared with volume-controlled ventilation in pulmonary acute respiratory distress syndrome and lower in time-controlled adaptive ventilation than nonventilated in extrapulmonary acute respiratory distress syndrome. In pulmonary acute respiratory distress syndrome, volume-controlled ventilation, but not time-controlled adaptive ventilation, increased the expression of amphiregulin, vascular cell adhesion molecule-1, and metalloproteinase-9. Collagen density was higher, whereas expression of decorin was lower in time-controlled adaptive ventilation than nonventilated, independent of acute respiratory distress syndrome etiology. In pulmonary acute respiratory distress syndrome, but not in extrapulmonary acute respiratory distress syndrome, time-controlled adaptive ventilation increased syndecan expression. Conclusion: In pulmonary acute respiratory distress syndrome, time-controlled adaptive ventilation led to more pronounced beneficial effects on expression of biomarkers related to overdistension and extracellular matrix homeostasis.