The Association Between Daily Driving Pressures and Mortality in Patients Supported With Veno-venous Extracorporeal Membrane Oxygenation for Acute Respiratory Distress Syndrome

Rationale: The association between daily driving pressure (ΔP) and the mortality of mechanically ventilated patients is established. It remains unclear whether this association holds for patients supported with veno-venous extracorporeal membrane oxygenation (vv-ECMO), who are receiving very low volume and pressure mechanical ventilation strategies.This study aimed to measure the associations of daily dynamic ΔP, static ΔP, transpulmonary pressure, and respiratory effort (ΔPES) with 28-day mortality in patients with severe ARDS supported with vv-ECMO.Methods: Respiratory variables were collected from 115 consecutive patients with severe ARDS supported with vv- ECMO at the Toronto General Hospital ICU during the first 24 hours after vv-ECMO deployment and then daily. In a subgroup of 40 consecutive patients, ΔPES and transpulmonary pressure were measured daily. The primary outcome was all-cause 28-day-mortality. Bayesian Joint Models for longitudinal and time-to-event outcomes were used to measure the association of a change in either daily dynamic ΔP, static ΔP, transpulmonary pressure, or daily exposure to excessive (> 14 cmH2O) or too low (< 6 cmH2O) ΔPES with 28-day mortality. Thresholds for excessive and too low ΔPES were data-derived based on 30th and 60th percentiles of ΔPES values in the population. Models were adjusted for age, sex, and severity of illness at baseline, as measured by respiratory system compliance, SOFA score, and APACHE II score. P-values represent the tail probabilities that the estimates contain the zero-effect value.Results: Of 115 patients, receiving very low tidal volume and pressure ventilation, 24% died within the first 28 days of vv-ECMO support. Each daily increase in dynamic ΔP was associated with a 1.17-fold increased hazard of death (Hazard ratio [HR]: 1.17, 95% credible intervals [CrI], 95% CrI: 1.06 to 1.29). No association was observed between daily static or transpulmonary ΔP and outcomes (Figure 1). Exposure to excessive or too low ΔPES during mechanical ventilation was associated with an increased hazard of death (HR: 2.02, 95% CrI: 0.99 to 4.43, p = 0.053; and HR: 1.73, 95% CrI: 1.21 to 2.84, p = 0.004 respectively).Conclusion: Patients with severe ARDS supported with vv-ECMO remain at risk of ventilator-induced lung injury, despite treatment with currently established ultraprotective mechanical ventilation strategies. Dynamic ΔP and ΔPES may represent tailoring variables to mitigate further lung injury and to guide mechanical ventilation during vv-ECMO support