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

Date

2019

Type:

Preprint

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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.

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Citation

Araos J, Alegria L, Garcia P, Cruces P, Soto D, Erranz B, Amthauer M, Salomon T, Medina T, Rodriguez F, Ayala P, Borzone GR, Meneses M, Damiani F, Retamal J, Cornejo R, Bugedo G, Bruhn A. Near-Apneic Ventilation Decreases Lung Injury and Fibroproliferation in an Acute Respiratory Distress Syndrome Model with Extracorporeal Membrane Oxygenation. Am J Respir Crit Care Med. 2019 Mar 1;199(5):603-612. doi: 10.1164/rccm.201805-0869OC.

Keywords

Acute Respiratory Distress Syndrome, Extracorporeal membrane oxygenation, Ventilator-induced lung injury, Mechanical ventilation, Myofibroblast

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