Very Low Driving-Pressure Ventilation in Patients With COVID-19 Acute Respiratory Distress Syndrome on Extracorporeal Membrane Oxygenation: A Physiologic Study

J Cardiothorac Vasc Anesth. 2023 Mar;37(3):423-431. doi: 10.1053/j.jvca.2022.11.033. Epub 2022 Nov 28.


Objectives: To determine in patients with acute respiratory distress syndrome (ARDS) on venovenous extracorporeal membrane oxygenation (VV ECMO) whether reducing driving pressure (ΔP) would decrease plasma biomarkers of inflammation and lung injury (interleukin-6 [IL-6], IL-8, and the soluble receptor for advanced glycation end-products sRAGE).

Design: A single-center prospective physiologic study.

Setting: At a single university medical center.

Participants: Adult patients with severe COVID-19 ARDS on VV ECMO.

Interventions: Participants on VV ECMO had the following biomarkers measured: (1) pre-ECMO with low-tidal-volume ventilation (LTVV), (2) post-ECMO with LTVV, (3) during low-driving-pressure ventilation (LDPV), (4) after 2 hours of very low driving-pressure ventilation (V-LDPV, main intervention ΔP = 1 cmH2O), and (5) 2 hours after returning to LDPV.

Main measurements and results: Twenty-six participants were enrolled; 21 underwent V-LDPV. There was no significant change in IL-6, IL-8, and sRAGE from LDPV to V-LDPV and from V-LDPV to LDPV. Only participants (9 of 21) with nonspontaneous breaths had significant change (p < 0.001) in their tidal volumes (Vt) (mean ± SD), 1.9 ± 0.5, 0.1 ± 0.2, and 2.0 ± 0.7 mL/kg predicted body weight (PBW). Participants with spontaneous breathing, Vt were unchanged-4.5 ± 3.1, 4.7 ± 3.1, and 5.6 ± 2.9 mL/kg PBW (p = 0.481 and p = 0.065, respectively). There was no relationship found when accounting for Vt changes and biomarkers.

Conclusions: Biomarkers did not significantly change with decreased ΔPs or Vt changes during the first 24 hours post-ECMO. Despite deep sedation, reductions in Vt during V-LDPV were not reliably achieved due to spontaneous breaths. Thus, patients on VV ECMO for ARDS may have higher Vt (ie, transpulmonary pressure) than desired despite low ΔPs or Vt.

Keywords: COVID-19; acute respiratory distress syndrome; biomarkers; extracorporeal membrane oxygenation; low driving pressure ventilation; ventilator-induced lung injury.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Biomarkers
  • COVID-19* / complications
  • COVID-19* / therapy
  • Extracorporeal Membrane Oxygenation*
  • Humans
  • Interleukin-6
  • Interleukin-8
  • Prospective Studies
  • Receptor for Advanced Glycation End Products
  • Respiration, Artificial
  • Respiratory Distress Syndrome* / therapy


  • Interleukin-6
  • Receptor for Advanced Glycation End Products
  • Interleukin-8
  • Biomarkers