Time-dependent effects in consecutive cycles of prone positioning for acute respiratory failure: insights from the PROVENT-C19 Registry

Background: Prone positioning is recommended for patients with acute respiratory distress syndrome not only to improve oxygenation, but also to reduce lung stress, and lower mortality. The association between improved oxygenation during prone position and reduced mortality is still controversial. In previous studies, oxygenation improvement during the first prone positioning cycle was linked to lower intensive care unit (ICU) mortality, especially with prolonged duration. However, physiological data during subsequent cycles were lacking. This study aims to explore the association between ICU mortality and physiological responses to prone positioning-such as arterial oxygenation, dead space, and respiratory mechanics-and to assess how the cumulative time spent in prone or supine positions across all studied cycles influences outcomes. Methods: International registry including adult patients who underwent prone positioning for acute hypoxemic respiratory failure due to COVID-19. We measured the difference for arterial partial pressure of oxygen to inspired fraction of oxygen ratio (PaO2/FiO2) and ventilatory ratio between baseline supine position and at either the end of cycle of prone position (Delta-PP) or re-supination (Delta-PostPP), focusing on the cycles following the first one. Results: We included 1523 patients from 53 centers. Both Delta-PP and Delta-PostPP for PaO2/FiO2 were significantly higher in ICU survivors than in ICU non-survivors for all the analyzed prone positioning cycles (p ≤ 0.001 for all comparisons). Delta-PP and Delta-PostPP for ventilatory ratio were significantly lower in ICU survivors than in ICU non-survivors for all the analyzed prone positioning cycles (p < 0.05 for all comparisons). No difference in the overall time spent in prone position was found between ICU survivors and non-survivors [61 (38, 84) h vs 58 (32, 85) h, respectively, p = 0.175]. The cumulative length of prone position was associated with ICU mortality only for the second prone positioning cycle [OR (95% CI) 0.986 (0.978, 0.994)]. No significant association was observed between the time spent in supine position and ICU mortality for all the analyzed prone positioning cycles. Conclusions: ICU survivors consistently demonstrated better oxygenation and more stable ventilatory ratio across studied prone positioning cycles, whereas non-survivors showed worsening oxygenation when returning supine and increased ventilatory ratio. Additionally, extending the duration of prone position beyond the second cycle may not significantly impact mortality.