Near-apneic ventilation decreases lung injury and fibroproliferation in an ARDS model with ECMO

Abstract

Rationale: There is wide variability in mechanical ventilation settings during ECMO in ARDS patients. Although lung rest is recommended to prevent further injury, there is no evidence to support it. Objectives: To determine whether near-apneic ventilation decreases lung injury in a pig model of ARDS supported with ECMO. Methods: Pigs (26-36kg; n=24) were anesthetized and connected to mechanical ventilation. In 18 animals lung injury was induced by a double-hit consisting in repeated saline lavages followed by 2 hours of injurious ventilation. Then, animals were connected to high-flow veno-venous ECMO, and randomized into 3 groups: Non-protective (PEEP 5 cmH2O, tidal volume 10 ml/kg, respiratory rate 20 bpm); Conventional-protective (PEEP 10 cmH2O, tidal volume 6 ml/kg, respiratory rate 20 bpm); Near-apneic (PEEP 10 cmH2O, driving pressure 10 cmH2O, respiratory rate 5 bpm). Six other pigs were used as Sham. All groups were maintained during the 24-hour study period. Measurements and Main Results: Minute ventilation and mechanical power were lower in the Near-apneic group, but no differences were observed in oxygenation or compliance. Lung histology revealed less injury in the Near-apneic group. Extensive immunohistochemical staining for myofibroblasts and pro-collagen III was observed in the

Non-protective group, with the Near-apneic group exhibiting the least alterations. Near- apneic group showed significantly less matrix-metalloproteinase-2 and -9 activity.

Histological lung injury and fibroproliferation scores were positively correlated with driving pressure and mechanical power.