Ultra-Protective Ventilation Reduces Biotrauma in Patients on Venovenous Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome*

Introduction: Ventilator settings for patients with severe acute respiratory distress syndrome supported by venovenous extracorporeal membrane oxygenation are currently set arbitrarily. The impact on serum and pulmonary biotrauma markers of the transition to ultra-protective ventilation settings following extracorporeal membrane oxygenation implantation, and different mechanical ventilation strategies while on extracorporeal membrane oxygenation were investigated. Design: Randomized clinical trial. Settings: Nine-month monocentric study. Patients: Severe acute respiratory distress syndrome patients on venovenous extracorporeal membrane oxygenation. Interventions: After starting extracorporeal membrane oxygenation, patients were switched to the bi-level positive airway pressure mode with 1 second of 24 cm H 2 O high pressure and 2 seconds of 12 cm H 2 O low pressure for 24 hours. A computer-generated allocation sequence randomized patients to receive each of the following three experimental steps: 1) high pressure 24 cm H 2 O and low pressure 20 cm H 2 O (very high positive end-expiratory pressure–very low driving pressure); 2) high pressure 24 cm H 2 O and low pressure 5 cm H 2 O (low positive end-expiratory pressure–high driving pressure); and 3) high pressure 17 cm H 2 O and low pressure 5 cm H 2 O (low positive end-expiratory pressure–low driving pressure). Plasma and bronchoalveolar lavage soluble receptor for advanced glycation end-products, plasma interleukin-6, and monocyte chemotactic protein-1 were sampled preextracorporeal membrane oxygenation and after 12 hours at each step. Measurements and Main Results: Sixteen patients on ECMO after 7 days (1–11 d) of mechanical ventilation were included. “Ultra-protective” mechanical ventilation settings following ECMO initiation were associated with significantly lower plasma sRAGE, interleukin-6, and monocyte chemotactic protein-1 concentrations. Plasma sRAGE and cytokines were comparable within each on-ECMO experimental step, but the lowest bronchoalveolar lavage sRAGE levels were obtained at minimal driving pressure. Conclusions: ECMO allows ultra- protective ventilation, which combines significantly lower plateau pressure, tidalvolume, and driving pressure. This ventilation strategy significantly limited pulmonary biotrauma, which couldtherefore decrease ventilator-induced lung injury. However, the optimal ultra-protective ventilation strategy once ECMO is initiated remains undetermined and warrants further investigations. ( Crit Care Med 2019; 47:1505–1512)