Introduction: Despite advances in lung-protective ventilation strategies, acute respiratory distress syndrome (ARDS) mortality remains high. Emerging evidence suggests some patients may continue to experience mechanical lung injury despite current standard of care, highlighting the need to personalize tidal volume and positive end-expiratory pressure to reduce lung stress and strain. Methods: This two-hospital prospective cohort enrolled adult patients receiving invasive mechanical ventilation within four days of meeting ARDS criteria. Serial measurements of lung mechanics and plasma were collected at enrollment and every 12 ± 4 hours, up to 72 hours after enrollment or extubation, whichever came first. Two indices of overdistension were assessed: tidal volume per predicted body weight (Vt/PBW), and airway driving pressure (∆P). Two plasma biomarkers of lung injury—soluble receptor for advanced glycation (sRAGE) and surfactant protein-D (SPD)—were measured concomitantly with lung mechanics. Linear regression models evaluated the link between lung injury biomarkers and mechanics at enrollment. The relationship between lung injury biomarkers and respiratory mechanics within patients over time was analyzed using linear mixed models, adjusting for illness severity, Vt/PBW, and time. Cox models evaluated ∆P and VT with clinical outcomes. Biomarker levels were transformed on the log scale in all models. P< 0.05 defined statistical significance. Results: Seventy-two patients were enrolled (62.5% male), with a VT of mean 5.9 (SD ±1.4) mL/kg PBW and plateau pressure of 25 (±6) cm H2O at enrollment. In an unadjusted model, at baseline, higher airway driving pressure was significantly associated with higher log-sRAGE (ß 0.07, 95% CI 0.02 to 0.11; p<.01). After adjusting for APACHE II and VT/PBW, the association of ∆P with each of sRAGE (ß 0.07, 95% CI 0.02 to 0.11; p<.01) and SPD (ß 0.11, 95% CI 0.05 to 0.11; p<.01) remained statistically significant. ∆P remained independently associated with increased 28-day mortality after adjusting for VT/PBW and APACHE II score (HR: 1.09, 95% CI 1.00 to 1.18; p=04). Conclusions: Elevated driving pressure is independently associated with higher serum levels of alveolar epithelial injury markers and clinical outcomes in patients with ARDS.
Garcia et al. (Sun,) studied this question.