Prone position can reduce mortality in acute respiratory distress syndrome (ARDS), but several studies found variable effects on oxygenation and lung mechanics. It is unclear whether different positive end-expiratory pressure (PEEP) titration techniques modify the effect of prone position. We tested, in an animal model of ARDS, if the PEEP titration method may influence the effect of prone position on oxygenation and lung protection. In a crossover study in 10 piglets with a two-hit injury ARDS model, we set the "best PEEP" according to the ARDS Network low-PEEP table (BP_ARDS) or targeting the lowest transpulmonary driving pressure (BP_DPL). We measured gas exchange, lung mechanics, aeration, ventilation, and perfusion with computed tomography (CT) and electrical impedance tomography in each position with both PEEP titration techniques. The primary endpoint was the PaO₂/FiO₂ ratio. Secondary outcomes were lung mechanics, regional distribution of ventilation, regional distribution of perfusion, and homogeneity of strain derived by CT scan. The PaO₂/FiO₂ ratio increased in prone position when PEEP was set with BP_ARDS [difference 54 (19-106) mmHg, p = 0.04] but not with BP_DPL [difference 17 (-24 to 68) mmHg, p = 0.99]. The transpulmonary driving pressure significantly decreased during prone position with both BP_ARDS [difference -0.9 (-1.5 to -0.9) cmH₂O, p = 0.009] and BP_DPL [difference -0.55 (-1.6 to -0.4) cmH₂O, p = 0.04]. Pronation homogenized lung regional strain and ventilation and redistributed the ventilation/perfusion ratio along the sternal-to-vertebral gradient. The PEEP titration technique influences the oxygenation response to prone position. However, the lung-protective effects of prone position could be independent of the PEEP titration strategy.

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