Total liquid ventilation in a porcine model of severe acute respiratory distress syndrome using a new generation of liquid ventilator

Total liquid ventilation (TLV) has been experimentally proposed as an alternative treatment for the management of Acute Respiratory Distress Syndrome (ARDS). Recent technological advances have led to the evaluation of a TLV prototype in patients resuscitated after cardiac arrest. Here, our goal was to determine whether a derived version of this prototype, so-called LV4B (liquid ventilation for breathing), could be used for normothermic TLV in a swine model of severe ARDS. Swine were anesthetized and instrumented for respiratory and hemodynamic evaluation. ARDS was induced by one or two administrations of oleic acid (0.1 mg/kg), until reaching a PaO2/FiO2 ratio < 100 mmHg. After ARDS induction, animals were allocated to undergo 60 min of either gas ventilation continuation (Control group) or TLV using a prototype that continuously controls respiratory rate (RR), liquid tidal volume (LqVt) and end-expiratory liquid volume (EELqV, respectively). Perfluorooctyl bromide was used as breathable liquid. After ARDS induction and group allocation, 2/5 animals (40%) survived in the Control groups versus 5/5 in the TLV group (100%). In the Control group, premature deaths were related to sustained hypoxemia (PaO2 < 50 mmHg) with hemodynamic failure. Surviving animals presented a trend toward better oxygenation in TLV versus Control, without achieving statistical significance due to the low number of survivors in the Control group. PaCO2, blood pH, lactate levels, or pulmonary and systemic hemodynamics were not different between groups in survivors. In the TLV group, the average LqVt, EELqV, and respiratory rate (RR) were 12.6 ± 0.4 mL/kg, 22.9 ± 2.9 mL/kg, and 5.3 ± 0.5 breath/min (mean ± SEM) at the end of the procedure, respectively. In all animals, pulmonary debris were washed out from the lung and collected by the TLV device throughout the procedure. After necropsy, histopathological examination demonstrated a significantly lower extent of inflammatory and congestion lesions in TLV versus Control. TLV with a liquid ventilator controlling EELqV, RR and LqVt is feasible and safe in large animals in a severe model of ARDS. This opens promising perspectives and warrants further investigation, including prolonged treatment durations and long-term follow-up.