Global versus regional effects of PEEP on recruitment and strain: insights from preclinical and clinical studies

In acute respiratory distress syndrome (ARDS), regional aeration is often gravity-dependent, with positive end-expiratory pressure (PEEP) recruiting the lung dorsally. Although recruitability can be assessed globally, our aim was to determine the impact of PEEP on regional recruitability and regional strain. To achieve a large representation of recruitability, we studied two preclinical porcine models of acute lung injury [(ALI) 19 symmetrical and 10 asymmetrical ALI], 20 patients with ARDS of mixed etiology (mixed ARDS), and 15 with COVID-19 ARDS. All study subjects underwent a single-breath derecruitment maneuver from high-to-low PEEP to quantify recruitability using the recruitment-to-inflation ratio (R/I). The regional effects of PEEP on strain were assessed using electrical impedance tomography (EIT). Symmetrical ALI animals had the highest R/I (1.39 [1.04-1.66]), followed by mixed ARDS (1.06 [0.70-1.23]), COVID-19 ARDS (0.66 [0.51-0.98]), and asymmetrical ALI (0.45 [0.22-0.85]). Dorsal regions had the highest recruitability (<i>P</i> = 0.001), and differences between dorsal and ventral regions were higher in recruitable subjects. Increasing PEEP decreased ventral dynamic strain (<i>P</i> < 0.01), with varying effects on dorsal dynamic strain. A paradoxical increase in dorsal dynamic strain associated with ventral hyperinflation could be observed across all groups, but more frequently in the less recruitable subjects. It was predicted by the EIT ventral-to-dorsal shift in ventilation normalized to the change in dorsal lung volume (<i>P</i> < 0.001). In animals and patients with varying recruitability, a higher global R/I is associated with a higher effect on the dorsal versus ventral R/I. PEEP can paradoxically increase dorsal strain due to ventral overdistention, and this is detectable by EIT.<b>NEW & NOTEWORTHY</b> Dorsal regions are more recruitable than ventral, decreasing their dynamic strain with PEEP, but relative PEEP effects vary across ARDS phenotypes with different global recruitability. The higher the global recruitability, the higher the effect on the dorsal part. This was demonstrated across two acute lung injury (ALI) animal models and two patient cohorts, mixed ARDS, and COVID-19 ARDS. PEEP can paradoxically increase dynamic dorsal strain despite recruitability if ventral overdistention occurs. EIT can detect this.