Flow-Controlled Ventilation Attenuates Lung Injury in a Porcine Model of Acute Respiratory Distress Syndrome: A Preclinical Randomized Controlled Study

OBJECTIVES: Lung-protective ventilation for acute respiratory distress syndrome aims for providing sufficient oxygenation and carbon dioxide clearance, while limiting the harmful effects of mechanical ventilation. "Flow-controlled ventilation", providing a constant expiratory flow, has been suggested as a new lung-protective ventilation strategy. The aim of this study was to test whether flow-controlled ventilation attenuates lung injury in an animal model of acute respiratory distress syndrome. DESIGN: Preclinical, randomized controlled animal study. SETTING: Animal research facility. SUBJECTS: Nineteen German landrace hybrid pigs. INTERVENTION: Flow-controlled ventilation (intervention group) or volume-controlled ventilation (control group) with identical tidal volume (7 mL/kg) and positive end-expiratory pressure (9 cm H2O) after inducing acute respiratory distress syndrome with oleic acid. MEASUREMENTS AND MAIN RESULTS: PaO2 and PaCO2, minute volume, tracheal pressure, lung aeration measured via CT, alveolar wall thickness, cell infiltration, and surfactant protein A concentration in bronchoalveolar lavage fluid. Five pigs were excluded leaving n equals to 7 for each group. Compared with control, flow-controlled ventilation elevated PaO2 (154 +/- 21 vs 105 +/- 9 torr; 20.5 +/- 2.8 vs 14.0 +/- 1.2 kPa; p = 0.035) and achieved comparable PaCO2 (57 +/- 3 vs 54 +/- 1 torr; 7.6 +/- 0.4 vs 7.1 +/- 0.1 kPa; p = 0.37) with a lower minute volume (6.4 +/- 0.5 vs 8.7 +/- 0.4 L/min; p < 0.001). Inspiratory plateau pressure was comparable in both groups (31 +/- 2 vs 34 +/- 2 cm H2O; p = 0.16). Flow-controlled ventilation increased normally aerated (24% +/- 4% vs 10% +/- 2%; p = 0.004) and decreased nonaerated lung volume (23% +/- 6% vs 38% +/- 5%; p = 0.033) in the dependent lung region. Alveolar walls were thinner (5.5 +/- 0.1 vs 7.8 +/- 0.2 microm; p < 0.0001), cell infiltration was lower (20 +/- 2 vs 32 +/- 2 n/field; p < 0.0001), and normalized surfactant protein A concentration was higher with flow-controlled ventilation (1.1 +/- 0.04 vs 1.0 +/- 0.03; p = 0.039). CONCLUSIONS: Flow-controlled ventilation enhances lung aeration in the dependent lung region and consequently improves gas exchange and attenuates lung injury. Control of the expiratory flow may provide a novel option for lung-protective ventilation.