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Background. The mechanisms underlying oxygenation improvement after prone positioning in COVID-19 ARDS have not been fully elucidated yet. We hypothesized that the oxygenation increase with prone positioning is secondary to the improvement of ventilation-perfusion matching. Methods. In a series of consecutive intubated COVID-19 ARDS patients receiving volume-controlled ventilation, we prospectively assessed the percent variation of ventilation-perfusion matching by electrical impedance tomography (EIT) before and 90 minutes after the first cycle of prone positioning (primary endpoint). We also assessed changes in the distribution and homogeneity of lung ventilation and perfusion, lung overdistention and collapse, respiratory system compliance, driving pressure, optimal positive end-expiratory pressure (PEEP), as assessed by EIT, and the ratio of partial pressure to fractional inspired oxygen (PaO2/FiO2) (secondary endpoints). Data are reported as medians [25th - 75th] or percentages. Results. We enrolled 30 consecutive patients, all analyzed without missing data. Compared to supine position, prone positioning overall improved ventilation-perfusion matching from 58 [43-69] % to 68 [56-75] % (p=0.042), with a median difference of 8.0% (95% Confidence Interval 0.1 to 16.0%) . Dorsal ventilation increased from 39 [31-43] % to 52 [44-62] % (p<0.001), while dorsal perfusion did not significantly vary. Prone positioning also reduced lung overdistension from 9 [4-11] % to 4 [2-6] % (p=0.025), while it did not significantly affect ventilation and perfusion homogeneity, lung collapse, static respiratory system compliance, driving pressure, and optimal PEEP. PaO2/FiO2 overall improved from 141 [104-182] mmHg to 235 [164-267] mmHg (p=0.019). However, 9 (30%) patients were non-responders, experiencing an increase in PaO2/FiO2 <20% with respect to baseline. Conclusions. In COVID-19 ARDS patients, prone positioning overall produced an early increase in ventilation-perfusion matching and dorsal ventilation. These effects were, however, heterogeneous among patients.

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