Ultra-lung-protective ventilation and biotrauma in severe ARDS patients on veno-venous extracorporeal membrane oxygenation: a randomized controlled study

Abstract

Background Ultra-lung-protective ventilation may be useful during veno-venous extracorporeal membrane oxygenation (vv-ECMO) for severe acute respiratory distress syndrome (ARDS) to minimize ventilator-induced lung injury and to facilitate lung recovery. The objective was to compare pulmonary and systemic biotrauma evaluated by numerous biomarkers of inflammation, epithelial, endothelial injuries, and lung repair according to two ventilator strategies on vv-ECMO. Methods This is a prospective randomized controlled study. Patients were randomized to receive during 48 h either ultra-lung-protective ventilation combining very low tidal volume (1–2 mL/kg of predicted body weight), low respiratory rate (5–10 cycles per minute), positive expiratory transpulmonary pressure, and 16 h of prone position or lung-protective-ventilation which followed the ECMO arm of the EOLIA trial (control group). Results The primary outcome was the alveolar concentrations of interleukin-1-beta, interleukin-6, interleukin-8, surfactant protein D, and blood concentrations of serum advanced glycation end products and angiopoietin-2 48 h after randomization. Enrollment was stopped for futility after the inclusion of 39 patients. Tidal volume, respiratory rate, minute ventilation, plateau pressure, and mechanical power were significantly lower in the ultra-lung-protective group. None of the concentrations of the pre-specified biomarkers differed between the two groups 48 h after randomization. However, a trend to higher 60-day mortality was observed in the ultra-lung-protective group compared to the control group (45 vs 17%, p = 0.06). Conclusions Despite a significant reduction in the mechanical power, ultra-lung-protective ventilation during 48 h did not reduce biotrauma in patients with vv-ECMO-supported ARDS. The impact of this ventilation strategy on clinical outcomes warrants further investigation. Trial registration Clinical trial registered with www.clinicaltrials.gov (NCT03918603). Registered 17 April 2019.

Factors associated with decreased compliance after on-site extracorporeal membrane oxygenation cannulation for acute respiratory distress syndrome: A retrospective, observational cohort study

“…Even though ultra-protective ventilation lowering VTs to 3 mL/kg of PBW may be associated with lower lung inflammation, [31] potential survival benefits have not yet been demonstrated, [32] and further VT reduction on outcomes is conflicting. [33] , [34] , [35] …”

Mechanical ventilation during pediatric extracorporeal life support

“…In one study, in which various settings were tested in 16 adults, it was found that limiting Pplat and driving pressure (DP), thereby reducing Vt to 1.5–3.3 ml/kg, resulted in significantly lower concentrations of plasma interleukin (IL) 6 and soluble receptor for advanced glycation end (sRAGE) products [18]. On the other hand, using a ventilation strategy that made use of Vt 1–2 ml/kg predicted body weight (PBW) compared with the control arm as used in the EOLIA trial did not reduce biotrauma in a more recent randomized controlled study of 39 patients with severe ARDS [19 ▪▪ ]. Obviously, using Vt <4 ml/kg PBW requires increased sweep flow to mitigate increases in the partial pressure of carbon dioxide ( P CO 2 ).…”

Ventilation during extracorporeal gas exchange in acute respiratory distress syndrome

“…The benefit of reducing TV in ARDS patients is maximized in patients with the lowest compliance (C RS ), and the highest driving pressure (DP) [ 20 ▪ ]. Guervilly et al randomized patients in the early phases of ECMO comparing the EOLIA ventilation strategy (control) with the application of a bundle treatment composed of TV 1–2 ml/kg IBW, RR 5–10 bpm, plus proning and transpulmonary positive end-expiratory pressure [ 21 ▪▪ ]. No difference in biochemical markers of biotrauma could be shown.…”