Effect of Lowering VT on Mortality in Acute Respiratory Distress Syndrome Varies with Respiratory System Elastance

Rationale: If the risk of ventilator-induced lung injury in acute respiratory distress syndrome (ARDS) is causally determined by driving pressure rather than by V-T, then the effect of ventilation with lower V-T on mortality would be predicted to vary according to respiratory system elastance (Ers). Objectives: To determine whether the mortality benefit of ventilation with lower V-T varies according to Ers. Methods: In a secondary analysis of patients from five randomized trials of lower-versus higher-V-T ventilation strategies in ARDS and acute hypoxemic respiratory failure, the posterior probability of an interaction between the randomized V-T strategy and Ers on 60-day mortality was computed using Bayesian multivariable logistic regression. Measurements and Main Results: Of 1,096 patients available for analysis, 416 (38%) died by Day 60. The posterior probability that the mortality benefit from lower-V-T ventilation strategies varied with Ers was 93% (posterior median interaction odds ratio, 0.80 per cm H2O/[ml/kg]; 90% credible interval, 0.63-1.02). Ers was classified as low (<2 cm H2O/[ml/kg], n=321, 32%), intermediate (2-3 cm H2O/[ml/kg], n=475, 46%), and high (>3 cm H2O/[ml/kg], n=224, 22%). In these groups, the posterior probabilities of an absolute risk reduction in mortality >= 1% were 55%, 82%, and 92%, respectively. The posterior probabilities of an absolute risk reduction >= 5% were 29%, 58%, and 82%, respectively. Conclusions: The mortality benefit of ventilation with lower V-T in ARDS varies according to elastance, suggesting that lungprotective ventilation strategies should primarily target driving pressure rather than V-T.

Automated summary

The mortality benefit of ventilation with lower V-T in ARDS varies according to elastance, suggesting that lung-protective ventilation strategies should primarily target driving pressure rather than V-T.