Evaluation of positive end-expiratory pressure using transpulmonary compliance and electrical impedance tomography in patients with acute hypoxemic respiratory failure

ABSTRACT Background: Simultaneous optimization of alveolar distension and collapse, estimated by electrical impedance tomography (EIT), is increasingly used to guide positive end-expiratory pressure (PEEP) titration in critically ill patients. This approach conventionally determines regional compliance changes from airway pressure (PAW), implicitly assuming that chest wall compliance (CCW) remains constant across the explored PEEP range, making respiratory system compliance (CAW) a reliable surrogate for transpulmonary compliance (CL). Whether this assumption holds, and whether using transpulmonary rather than respiratory system pressure meaningfully changes the PEEP selected by EIT-based titration, has not been formally tested yet. So far, this has been validated only in patients receiving partial ventilatory support. Aims: To investigate whether the use of transpulmonary pressure (PL), compared with respiratory system pressure (PAW), influenced the selection of optimal PEEP identified by EIT-based titration in patients with acute hypoxemic respiratory failure (AHRF) receiving fully ventilatory support, and to characterize the physiological factors associated with any divergence between the two practices. As secondary aims, the study compares overdistension, collapse, lung recruitability, and respiratory mechanics between the two techniques throughout the decremental PEEP trial. It examines whether recruitability or overdistension risk influence the optimal PEEP identified by each method; and assesses how chest wall compliance varies with PEEP. Methods: We performed a multicenter physiological analysis of 36 intubated patients with acute hypoxemic respiratory failure. During decremental PEEP trials conducted under concurrent EIT and esophageal pressure monitoring, overdistension and collapse were calculated using either the change in airway pressure (ΔPAW) or in transpulmonary pressure (ΔPL). For both approaches, optimal PEEP was determined in two ways: as the crossing point between the cumulative overdistension and collapse curves, and as the PEEP level minimizing the absolute difference between overdistension and collapse. Results: Median optimal PEEP was 12 cmH2O (8-14) with both methods. At the individual level, the PL-based method selected a slightly higher optimal PEEP than the PAW-based method, with a mean paired difference of 0.44 cmH2O; Bland-Altman analysis showed 95% limits of agreements of -2.94 to +2.05 cmH2O. The two techniques identified the same optimal PEEP in 23 patients (64%); PL selected a higher PEEP in 10 patients (28%) and a lower PEEP in 3 (8%). This divergence demonstrated that PL-based method assigned a higher PEEP specifically to patients with greater lung recruitability and more severe hypoxemia, without a corresponding increase in overdistension and end-inspiratory PL. At the PL-based optimal PEEP, alveolar collapse was lower than at the PAW-optimal PEEP. Despite considerable inter-individual variability, increasing PEEP was associated with a significant decrease in CCW across the cohort, and patients with more impaired baseline compliance often showed the opposite pattern. A sensitivity analysis restricted to a narrower PEEP range demonstrated improved agreement between the two techniques. Conclusions: PAW- and PL-based EIT methods for optimal PEEP titration were broadly concordant at the population level, supporting the clinical robustness of the conventional, PAW-based approach to EIT-guided PEEP selection in AHRF. However, in a clinically relevant subgroup of more hypoxemic and more recruitable patients, the PAW-based technique may underestimate the optimal PEEP, as a PEEP-dependent decrease in chest wall compliance can lead to overestimation of lung overdistension when PAW, rather than PL, is used in PEEP titration.