Figure S1. In vitro and in vivo Pressure-Volume curves of the esophageal balloon. Within the intermediate linear section of the esophageal balloon PV curve, Pes is stable when the balloon is inflated in vitro (dotted line), whereas Pes linearly increases with the increase of the filling volume in vivo (open circles) due to esophageal elastance (Ees). When pressure generated by the esophageal wall is subtracted from Pes (Pes-Pew; closed circles), in vitro and in vivo curves closely parallel each other. Dotted line: in vitro PV curve obtained by progressive inflation of the balloon while the surrounding pressure was maintained at 10 cmH2O. Open circles: end-expiratory PV curve obtained in a patient under controlled mechanical ventilation with high positive end-expiratory pressure (15 cmH2O). Closed circles: end-expiratory PV curve obtained by subtraction of Pew from raw Pes values in the same patient. Figure S2. Average end-expiratory and end-inspiratory esophageal balloon pressure-volume curves in acute respiratory failure patients. Open circles: end-expiratory static Pes values (PesEE); open squares: end-inspiratory static Pes values (PesEI). Vertical lines refer to standard deviation of Pes. Horizontal lines refer to standard deviation of specific filling volumes detected on the esophageal balloon pressure-volume curves (VMIN, VBEST and VMAX). V0.5 was lower than VMIN, i.e. it was associated to balloon underfilling at end-expiration, in 42 cases (84 %); V0.5 was lower than VBEST, i.e. it was associated to suboptimal ΔPes in 47 cases (94 %). VMIN was lower than VBEST in 37 cases (74 %), being the VBEST - VMIN difference 2.0 ± 1.7 ml. Figure S3. End-expiratory static esophageal balloon pressure-volume curves at different PEEP levels. In panel A, raw Pes values are presented; in panel B, the pressure generated by the esophageal wall (Pew) is subtracted from Pes value. Circles: ZEEP; squares: PEEP 5 cmH2O; triangles: PEEP 15 cmH2O. Closed symbols refer to VBEST, i.e. the balloon filling volume corresponding to the largest respiratory ΔPes (not displayed in figure). In the same patient, at increasing level of PEEP, a progressively larger balloon filling volume is needed to optimize respiratory ΔPes. Optimal filling volume (VBEST) stimulates a variable esophageal pressure reaction, confounding Pes measurement. For example, by filling the esophageal balloon with 5 ml, corresponding to VBEST at PEEP 15 cmH2O, raw Pes values at the three PEEP levels are very similar (panel A). Once the pressure generated by the esophageal wall is subtracted from Pes values, the PEEP-induced increase of the pressure surrounding the esophagus becomes clearly detectable (Panel B). Figure S4. Pes measured with traditional low filling volume (V0.5) or with manufacturer’s recommended filling volume (V4.0) compared to calibrated Pes. Panel A. Compared to calibrated Pes, bias and precision (± 1.96 SD) of PesV0.5 were -4.1 ± 5.5 cmH2O. The Pes0.5 - PesCAL difference inversely correlated with the Pes0.5 - PesCAL mean value (R= -0.694, p<0.0001): the higher the Pes value, the higher the Pes underestimation due to balloon underfilling. Panel B. Compared to calibrated Pes, bias and precision (± 1.96 SD) of PesV4.0 were -2.9 ± 3.3 cmH2O. The Pes4.0 - PesCAL difference inversely correlated with the Pes4.0 - PesCAL mean value (R= -0.470, p<0.0001): the lower the Pes value, the higher the Pes overestimation due to the esophageal reaction to balloon inflation at 4 ml. (PDF 424 kb