Liquid Ventilation Improves Pulmonary Function, Gas Exchange, and Lung Injury in a Model of Respiratory Failure

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Abstract
The authors evaluated gas exchange, pulmonary function, and lung histology during perfluorocarbon liquid ventilation (LV) when compared with gas ventilation (GV) in the setting of severe respiratory failure. The efficacy of LV in the setting of respiratory failure has been evaluated in premature animals with surfactant deficiency. However, very little work has been performed in evaluating the efficacy of LV in older animal models of the adult respiratory distress syndrome (ARDS). A stable model of lung injury was induced in 12 young sheep weighing 16.4 +/- 3.0 kg using right atrial injection of 0.07 mL/kg of oleic acid followed by saline pulmonary lavage and bijugular venovenous extracorporeal life support (ECLS). For the first 30 minutes on ECLS, all animals were ventilated with gas. Animals were then ventilated with either 15 mL/kg gas (GV, n = 6) or perflubron ([PFC], LV, n = 6) over the ensuing 2.5 hours. Subsequently, ECLS was discontinued in five of the GV animals and five of the LV animals, and GV or LV continued for 1 hour or until death. Physiologic shunt (Qps/Qt) was significantly reduced in the LV animals when compared with the GV animals (LV = 31 +/- 10%; GV = 93 +/- 4%; p < 0.001) after 3 hours of ECLS. At the same time point, pulmonary compliance (CT) was significantly increased in the LV group when compared with the GV group (LV = 1.04 +/- 0.19 mL/cm H2O/kg; GV = 0.41 +/- 0.02 mL/cm H2O/kg; p < 0.001). In addition, the ECLS flow rate required to maintain the PaO2 in the 50- to 80-mm Hg range was substantially and significantly lower in the LV group when compared with that of the GV group (LV = 14 +/- 5 mL/kg/min; GV = 87 +/- 15 mL/kg/min; p < 0.001). All of the GV animals died after discontinuation of ECLS, whereas all the LV animals demonstrated effective gas exchange without extracorporeal support for 1 hour (p < 0.01). Lung biopsy light microscopy demonstrated a marked reduction in alveolar hemorrhage, lung fluid accumulation, and inflammatory infiltration in the LV group when compared with the GV animals. In a model of severe respiratory failure, LV improves pulmonary gas exchange and compliance with an associated reduction in alveolar hemorrhage, edema, and inflammatory infiltrate.