Potentially modifiable ventilatory factors contributing to outcome in patients with pulmonary and extrapulmonary ARDS — An individual patient data analysis

BACKGROUND: Previous studies have identified potentially modifiable factors associated with mortality from acute respiratory stress syndrome (ARDS), however these studies did not differentiate between underlying causes of ARDS. As the etiology of ARDS may influence patient outcomes, we aimed to identify potentially modifiable factors associated with 60-day mortality from pulmonary and extrapulmonary ARDS. METHODS: Secondary pooled analysis of six observational studies studies on mechanical ventilation in patients with pulmonary and extrapulmonary ARDS. The primary endpoint was mortality at day 60 after inclusion. Exploratory outcomes included length of stay in hospital and ICU, duration of ventilation and ventilator-free days at day 28. RESULTS: Out of 7934 patients with pulmonary or extrapulmonary ARDS, 3402 (43%) did not survive. Potentially modifiable factors associated with 60-day mortality included high driving pressure (ΔP) and high respiratory rate (RR). There was an interaction between etiology of ARDS and ΔP on 60-day mortality, with ΔP showing a stronger association in pulmonary ARDS compared with extrapulmonary ARDS (p < 0.001). In a sensitivity analysis excluding COVID-19 patients, RR was no longer associated with 60-day mortality, whereas ΔP remained associated. Tidal volume was not associated with 60-day mortality in either pulmonary or extrapulmonary ARDS. No interaction was found between ARDS etiology and RR or tidal volume on 60-day mortality. CONCLUSION: High ΔP and high RR were associated with 60-day mortality in patients with pulmonary and extrapulmonary ARDS receiving mechanical ventilation, with ΔP showing a stronger association in pulmonary ARDS compared with extrapulmonary ARDS. REGISTRATION: The pooled database was registered at ClinicalTrials.gov (identifier NCT05650957).