Response to ventilator adjustments for predicting acute respiratory distress syndrome mortality: Driving pressure versus oxygenation

Rationale: Clinicians commonly use short-term physiologic markers to assess the benefit of ventilator adjustments. Improved arterial oxygen tension/pressure (Pa_O2)/fraction of inspired oxygen (FI_O2) after ventilator adjustment in acute respiratory distress syndrome is associated with lower mortality. However, as driving pressure (ΔP) reflects lung stress and strain, changes in ΔP may more accurately reflect benefits or harms of ventilator adjustments compared with changes in oxygenation. Objectives: We aimed to compare the association between mortality and the changes in Pa_O2/FI_O2 and ΔP following protocolized ventilator changes. Methods: We assessed associations between mortality and changes in Pa_O2/FI_O2 (ΔPa_O2/FI_O2) and ΔP (ΔΔP) after postrandomization positive end-expiratory pressure (PEEP) and tidal volume adjustment in reanalyses of the ALVEOLI (Assessment of Low Tidal Volume and Elevated End-Expiratory Volume to Obviate Lung Injury) and ExPress (Expiratory Pressure) trials. We included subjects with available pre- and postintervention Pa_O2/FI_O2 and ΔP (372 in ALVEOLI and 596 in ExPress). In each separate trial cohort, we performed multivariable Cox regression testing the association between ΔPa_O2/FI_O2 and ΔΔP with mortality. Results: In ALVEOLI, when analyzed as separate variables, DPa_O2/ FI_O2 was associated with mortality only in subjects in whom PEEP increased, whereas ΔΔP was associated with mortality irrespective of direction of PEEP change. When modeled together, improved ΔPa_O2/ FI_O2 was not associated with mortality, whereas ΔΔP remained associated with mortality (adjusted hazard ratio [aHR], 1.50 per 5 cm H₂O increase; 95% confidence interval [95% CI], 1.21–1.85). When modeled together in ExPress, ΔΔP (aHR, 1.42; 95% CI, 1.14–1.78) was more strongly associated with mortality than ΔPa_O2/FI_O2 (aHR, 0.95 per 25 mm Hg increase; 95% CI, 0.90–1.00). Conclusions: Reduced DP following protocolized ventilator changes was more strongly and consistently associated with lower mortality than was increased Pa_O2/FI_O2, making ΔΔP more informative about benefit from ventilator adjustments. Our results reinforce the primacy of ΔP, rather than oxygenation, as the key variable associated with outcome.