Prognostic value of disease severity and mechanical ventilation intensity in Acute Respiratory Distress Syndrome. Analysis of the LUNG SAFE cohort

Background We aimed to assess the prognostic performance of different indexes of oxygenation, respiratory mechanics and ventilation intensity in predicting 90-day mortality, and to estimate their independent associations, in a “real world” observational cohort of acute respiratory distress syndrome (ARDS) patients on ICU mortality. Methods This is a secondary analysis of the “Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure” (LUNG SAFE), an international prospective cohort study of patients with severe respiratory failure involving 459 Intensive Care Units (ICUs) from 50 countries. We evaluated prognostic performance of oxygenation (PaO 2 /FiO 2 ), respiratory mechanics (normalized elastance) and ventilation intensity (plateau pressure, driving pressure (DP); 4DP+RR and mechanical power (MP)) measured on day 1 of controlled mechanical ventilation in ARDS patients, with respect to ICU mortality within 90 days of admission. For each parameter, associations with mortality were assessed using logistic regression models, estimating effect sizes (odds ratios, OR with 95% confidence interval, CI), model discrimination (area under the ROC curve), calibration, and overall predictive accuracy. Results Among 2813 early ARDS patients, 516 (18.3%) met inclusion criteria: mean age 60 years (±16), 61% male. Normalized elastance, plateau, DP and 4DP+RR were significantly associated with mortality, with adjusted ORs ranging from 1.02 (95%CI 1.01–1.03) for 4DP+RR to 1.48 (95%CI 1.15–1.95) for normalized elastance. These parameters showed higher predictive accuracy for mortality compared to PaO 2 /FiO 2 and MP. MP showed a U-shaped relationship with mortality abut it was not significantly associated with it. Its predictive accuracy decreased after accounting for positive end-expiratory pressure (PEEP) and dynamic resistance, with PEEP also demonstrating a U-shaped association with mortality. Conclusions Normalized elastance, DP and 4DP+RR-measured at day1 of ARDS-were best predictors of ICU mortality, and outperformed oxygenation and MP. DP showed the best balance between predictive accuracy and clinical simplicity. These results reinforce the importance of focusing on DP and 4DP+RR as key metrics to guide lung-protective strategies and ARDS severity classification.