The two main findings of the present study that systematically assessed the Pes-guided strategy in PP in ARDS patients were that: (1) PP had no impact on absolute Pes measurements, suggesting the accuracy of esophageal balloon manometry independent of the mass of the mediastinum if esophageal balloon was calibrated properly; (2) PP was effective to improve lung mechanics (immediate effect) and facilitate lung recruitment (slow effect) independent of PEEP levels.
Impact of PP on Pes measurements
The Pes-guided PEEP concept is primarily driven by Pes,ee. Contrary to our expectations, Pes,ee did not decrease in PP from SP at same PEEP. One explanation may be that in PP pericardial ligaments prevent compression of esophagus by the heart and mediastinum and, hence avoid any real compression onto the esophageal balloon. Another explanation may be that we compared SP30° to PP0°–15°. Pes,ee decreased by 2 cmH2O between SP0° and PP0° in ARDS patients , as in normal subjects experiencing spine surgery .
Since average Pes,ee did not change significantly between SP and PP, the PEEP level resulting from the Pes-guided strategy was the same in both positions and it was systematically 2 cmH2O above the amount of PEEP from the PEEP/FIO2 table. This small change can be due to the fact that PL,ee, set from PEEP/FIO2 table, was near our target.
Talmor et al.  reported an average 7 cmH2O rise of PEEP with an improvement in oxygenation and Est,rs , by using Pes-guided strategy in SP. Potential explanations for the discrepancy between Talmor’s  and the present study are: (1) our case mix included mostly primary ARDS; (2) we set a fixed PL,ee (3 ± 2 cmH2O) goal and did not use a PL,ee-FIO2-table; (3) the correct placement of the esophageal balloon was assessed by the Baydur maneuver, and minimal non-stress esophageal balloon volume was determined; (4) Pes,ee averaged 9 cmH2O in our study versus 17 cmH2O in Talmor et al’ study , for PEEP of 10 and 13 cmH2O, respectively.
Impact of PP on chest wall mechanics
Between SP and PP in our study, Est,cw did not change. This result differs from Mentzelopoulos et al. , who found an increase in Est,cw by about 5 cmH2O/L between SP60° and PP0°. This discrepancy may be explained by different angulations in SP, and higher VT and PEEP in their study, making the volume–pressure curve of the chest wall displaced upward. Indeed, between SP and PP, EELV increased from 1.0 to 1.5 L in Mentzelopoulos et al. study  and decreased from 1.4 to 1.1 L in our study. Since the abdominal content has a major influence on the position of the diaphragm, and hence lung volume, SP30° might pull it down while PP might push it upward, which could easily result in the average difference of 0.3 L in lung volume we observed. Pelosi et al. found that chest wall compliance significantly decreased in PP from SP . In two previous studies, we also found an increase in Est,cw in PP [25, 28] at 0° inclination in both positions, as Pelosi et al. . Therefore, the inclination in SP and PP should be taken into account for interpreting the effect of PP on Est,cw.
Early impact of prone position on lung mechanics
PP significantly improved lung mechanics in the present study independently of PEEP strategy. The decrease in Est,L in PP should indicate lung recruitment or overdistension reduction. Previous CT scan studies found that PP can promote lung recruitment and lessen overdistension . In the present study, EELV did not increase in PP. The effect of PP on EELV did vary across studies from no change  to increase . Recently, EELV was found increasing from 1.6 L ± 0.476 to 1.8 ± 0.7 L (P = 0.008) after 1 h in PP . In our study, moving the patients from SP30° to SP0° before proning may have significantly decreased EELV so that PP could not improve EELV immediately. Indeed, it took almost 14 h in PP for EELV to surpass its value in SP. The reduction in Est,L in PP could result from an imbalance between recruitment and derecruitment at the regional level with lung recruitment in the spinal parts of the lung being greater than the decrease in aerated lung volume in sternal parts . Our increase in spinal lung compliance in PP favors this hypothesis, even though whole EELV did not change.
DPL  should theoretically better reflect lung stress than DPrs . DPL decreased significantly in PP with no effect of PEEP strategy. Therefore, this finding may contribute to the better outcome of patients treated in PP.
PL,ei_elastance method may reflect lung stress in the sternal non-dependent parts of the lung in SP . Whether or not PL,ei_Elastance derived in PP still reflects non-dependent parts of the lung or explores the sternal lung region is unknown. We found a significant decrease in PL,ei_Elastance derived in PP irrespective of the PEEP strategy. The fact that the compliance of non-dependent lung as assessed with EIT increased in PP suggests that PL,ei_Elastance derived reflects lung stress in that lung region in PP. PL,ei was suggested to reflect lung stress in the spinal dependent parts of the lung in SP . Interestingly, PL,ei_Elastance derived remained greater than PL,ei in both SP and PP.
Taken together, these findings suggest that PP can prevent ventilator-induced lung injury regardless of PEEP strategy. Present results are important because they contribute to explain why survival was significantly improved in the Proseva trial  even though low levels of PEEP were used.
Slow effect of prone position on facilitation of lung recruitment
Over time in PP gas exchange and EELV improved. Increase in EELV may or may not include lung recruitment, defined as a decrease in non-aerated amount of lung tissue, i.e., as lung tissue that regains air. Poorly aerated lung regions that become well aerated can also contribute to higher EELV. The fact that increase in EELV was associated with better gas exchange argues in favor of the recruitment of functional lung tissue over time in PP. The improvement in sternal lung compliance over time in PP suggests a net gain of lung volume in dependent parts of the lung.
Impact of Pes-guided PEEP strategy on chest wall mechanics
With Pes-guided strategy, lung mechanics did not change but Est,cw increased between PEEP 10 and 12 cmH2O, on average, regardless of position or PP duration (Tables 1 and 2). This finding was uncommon in ARDS patients between 10 and 15 cmH2O PEEP [27, 33,34,35] and could be explained by a shift of chest wall volume–pressure curve toward its upper (higher PEEP) or lower (lower PEEP) less compliant parts. Since we did not find a significant increase in EELV with the Pes-guided strategy, we have no clear explanation for this finding. Higher Est,cw makes that Paw dissipates into the chest wall, which could protect the lung from excessive stress and strain.
First, in a patient receiving Pes-guided PEEP strategy, it is likely that PEEP in PP will be near that in SP.
Second, as EELV early went down from SP to PP, the PEEP should be increased at this step. On the other hand, if PP promotes lung recruitment over time, higher PEEP should be used after the resumption of proning, i.e., when turning the patient back to SP, to prevent derecruitment . However, whether EELV would decrease after turning patient back to SP at same PEEP was not assessed in the present study.
Third, continuous improvement in oxygenation and EELV over time in PP supports the use of prolonged proning sessions .
Limitations and strengths
Our study is limited by the lack of CT scan or other markers of ventilator-induced lung injury, the lack of EIT data in 11 patients and the not randomized design in the early application of PEEP strategy, which might have resulted in a carry-over effect since each patient was own control. Strengths include proper calibration of esophageal balloon, non-stress balloon volume implementation and detailed description of lung and chest wall mechanics in SP and PP with updated methodology.