Response to exogenous surfactant is different during open lung and conventional ventilation

Objective: Previous studies have shown that the efficacy of exogenous surfactant is dose-dependent during conventional positive pressure ventilation (PPV_CON). The present study aimed to determine whether this dose-dependent relationship is also present during open lung (OLC) ventilation. We also explored the effect of exogenous surfactant on the ventilation pressures applied during ventilation. Design: Animal study. Setting: University-affiliated research laboratory. Subjects: Seventy-two newborn piglets. Interventions: After repeated whole lung lavage, animals were randomly allocated to two surfactant groups receiving either 100 mg/kg surfactant (S100) or 25 mg/kg surfactant (S25) or to a control group receiving a bolus of air. Within each group, animals were randomly assigned to either PPV_CON, open lung PPV (PPV_OLC), or open lung high-frequency oscillatory ventilation (HFOV_OLC) and ventilated for 5 hrs. Measurements and Main Results: The ventilation pressures decreased in a dose-dependent way, showing the largest reduction in the S100 group. In both OLC groups, oxygenation, lung mechanics, and polymorphonuclear neutrophils analyzed in bronchoalveolar lavage were Independent of the surfactant dose. In the PPV _CON group, however, there was a clear dose-dependency, resulting in a deterioration of oxygenation and lung mechanics and an increase in polymorphonuclear neutrophils as the surfactant dose decreased. Although comparable between the three ventilation groups, bronchoalveolar lavage interleukin-8 concentrations significantly increased in all ventilation groups as the surfactant dose increased. Alveolar protein influx and conversion of large to small aggregate surfactant were higher during PPV_CON compared with both OLC groups. There were no differences in the surfactant treatment response between PPV_OLC and HFOV_OLC. Conclusion: Exogenous surfactant enables a reduction in ventilation pressures. Compared with PPV_CON, the efficacy of surfactant treatment is less dose-dependent during open lung ventilation. Surfactant conversion during open lung ventilation is reduced compared with PPV_CON. Exogenous surfactant seems to up-regulate bronchoalveolar lavage interleukin-8 concentrations, independent of the ventilation strategy.