Hypothermic total liquid ventilation after experimental aspiration-associated acute respiratory distress syndrome

Jérôme Rambaud, Fanny Lidouren, Michaël Sage, Matthias Kohlhauer, Mathieu Nadeau, Étienne Fortin-Pellerin, Philippe Micheau, Luca Zilberstein, Nicolas Mongardon, Jean-Damien Ricard, Megumi Terada, Patrick Bruneval, Alain Berdeaux, Bijan Ghaleh, Hervé Walti, Renaud Tissier

Ultrafast cooling by total liquid ventilation (TLV) provides potent cardio- and neuroprotection after experimental cardiac arrest. However, this was evaluated in animals with no initial lung injury, whereas out-of-hospital cardiac arrest is frequently associated with early-onset pneumonia, which may lead to acute respiratory distress syndrome (ARDS). Here, our objective was to determine whether hypothermic TLV could be safe or even beneficial in an aspiration-associated ARDS animal model. ARDS was induced in anesthetized rabbits through a two-hits model including the intra-tracheal administration of a pH = 1 solution mimicking gastric content and subsequent gaseous non-protective ventilation during 90 min (tidal volume [Vt] = 10 ml/kg with positive end-expiration pressure [PEEP] = 0 cmH2O). After this initial period, animals either received lung protective gas ventilation (LPV; Vt = 8 ml/kg and PEEP = 5 cmH2O) under normothermic conditions, or hypothermic TLV (TLV; Vt = 8 ml/kg and end-expiratory volume = 15 ml/kg). Both strategies were applied for 120 min with a continuous monitoring of respiratory and cardiovascular parameters. Animals were then euthanized for pulmonary histological analyses. Eight rabbits were included in each group. Before randomization, all animals elicited ARDS with arterial oxygen partial pressure over inhaled oxygen fraction ratios (PaO2/FiO2) below 100 mmHg, as well as decreased lung compliance. After randomization, body temperature rapidly decreased in TLV versus LPV group (32.6 ± 0.6 vs. 38.2 ± 0.4 °C after 15 min). Static lung compliance and gas exchanges were not significantly different in the TLV versus LPV group (PaO2/FiO2 = 62 ± 4 vs. 52 ± 8 mmHg at the end of the procedure, respectively). Mean arterial pressure and arterial bicarbonates levels were significantly higher in TLV versus LPV. Histological analysis also showed significantly lower inflammation in TLV versus LPV group (median histological score = 3 vs. 4.5/5, respectively; p = 0.03). Hypothermic TLV can be safely induced in rabbits during aspiration-associated ARDS. It modified neither gas exchanges nor respiratory mechanics but reduced lung inflammation and hemodynamic failure in comparison with LPV. Since hypothermic TLV was previously shown to provide neuro- and cardio protective effects after cardiac arrest, these findings suggest a possible use of TLV in the settings of cardiac arrest-associated ARDS.