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.

Keywords: Biotrauma; Severe ARDS; Ultra-lung-protective ventilation; Veno-venous ECMO.

Fig. 1

Study design. ECMO extracorporeal membrane oxygenation, NMB neuromuscular blocker, APRV airway pressure release ventilation, Vt tidal volume, PEEP positive end-expiratory pressure, RR respiratory rate, ACV assist controlled ventilation, BAL broncho-alveolar lavage, ABG arterial blood gas

Fig. 2

Comparisons of alveolar interleukin-1-beta, interleukin-6, interleukin-8, surfactant protein D and blood concentrations of serum advanced glycation end products and angiopoietin-2 at baseline (T0) and T + 48 h between lung-protective group and ultra-lung-protective group. sRAGE serum advanced glycation end products. The empty circles represent the outliers and the black stars represent the extreme values