Programme Hospitalier Recherche Clinique, Institut Pasteur, Inserm, French Public Health Agency.

Background Although lung protection with low tidal volume and limited plateau pressure ( P plat ) improves survival in acute respiratory distress syndrome patients (ARDS), the best way to set positive end-expiratory pressure (PEEP) is still debated. Methods This study aimed to compare two strategies using individual PEEP based on a maximum P plat (28–30 cmH 2 O, the Express group) or on keeping end-expiratory transpulmonary pressure positive (0–5 cmH 2 O, P Lexpi group). We estimated alveolar recruitment (Vrec), end-expiratory lung volume and alveolar distension based on elastance-related end-inspiratory transpulmonary pressure ( P L,EL ). Results Nineteen patients with moderate to severe ARDS (PaO 2 /FiO 2 < 150 mmHg) were included with a baseline PEEP of 7.0 ± 1.8 cmH 2 O and a PaO 2 /FiO 2 of 91.2 ± 31.2 mmHg. PEEP and oxygenation increased significantly from baseline with both protocols; PEEP Express group was 14.2 ± 3.6 cmH 2 O versus 16.7 ± 5.9 cmH 2 O in P Lexpi group. No patient had the same PEEP with the two protocols. Vrec was higher with the latter protocol (299 [0 to 875] vs. 222 [47 to 483] ml, p = 0.049) and correlated with improved oxygenation ( R 2 = 0.45, p = 0.002). Two and seven patients in the Express and P L,expi groups, respectively, had P L,EL > 25 cmH 2 O. Conclusions There is a great heterogeneity of P Lexpi when P plat is used to titrate PEEP but with limited risk of over-distension. A PEEP titration for a moderate positive level of P Lexpi might slightly improve alveolar recruitment and oxygenation but increases the risk of over-distension in one-third of patients.