Venovenous Extracorporeal CO2 removal to support ultraprotective ventilation in moderate-severe ARDS: A systematic review and meta-analysis of the literature
Authors: Worku Elliott , Brodie Daniel , Ling Ryan Ruiyang , Ramanathan Kollengode , Combes Alain , Shekar Kiran 
Published: October 2021

AbstractBackgroundA strategy that limits tidal volumes and inspiratory pressures, improves outcomes in patients with the acute respiratory distress syndrome (ARDS). Extracorporeal carbon dioxide removal (ECCO2R) may facilitate ultra-protective ventilation. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of venovenous ECCO2R in supporting ultra-protective ventilation in moderate-to-severe ARDS.MethodsMEDLINE and EMBASE were interrogated for studies (2000-2021) reporting venovenous ECCO2R use in patients with moderate-to-severe ARDS. Studies reporting ≥10 adult patients in English language journals were included. Ventilatory parameters after 24 hours of initiating ECCO2R, device characteristics, and safety outcomes were collected. The primary outcome measure was the change in driving pressure at 24 hours of ECCO2R therapy in relation to baseline. Secondary outcomes included change in tidal volume, gas exchange, and safety data.ResultsTen studies reporting 421 patients (PaO2:FiO2 141.03mmHg) were included. Extracorporeal blood flow rates ranged from 0.35-1.5 L/min. Random effects modelling indicated a 3.56 cmH2O reduction (95%-CI: 3.22-3.91) in driving pressure from baseline (p<0.001) and a 1.89 ml/kg (95%-CI: 1.75-2.02, p<0.001) reduction in tidal volume. Oxygenation, respiratory rate and PEEP remained unchanged. No significant interactions between driving pressure reduction and baseline driving pressure, partial pressure of arterial carbon dioxide or PaO2:FiO2 ratio were identified in metaregression analysis. Bleeding and haemolysis were the commonest complications of therapy.ConclusionsVenovenous ECCO2R permitted significant reductions in ΔP in patients with moderate-to-severe ARDS. Heterogeneity amongst studies and devices, a paucity of randomised controlled trials, and variable safety reporting calls for standardisation of outcome reporting.Prospective evaluation of optimal device operation and anticoagulation in high quality studies is required before further recommendations can be made.Key MessagesWhat is the Key Question?In adult patients with moderate-to-severe acute respiratory distress syndrome (ARDS), can venovenous extracorporeal carbon dioxide removal (ECCO2R) support ultraprotective lung ventilation beyond the current standard for protective ventilation in ARDS?What is the bottom line?Systematic review of available data on venovenous ECCO2R shows that it can reduce driving pressure in ventilated patients with moderate-to-severe ARDS, supporting ultraprotective ventilation. Prospective measurement of mechanical power, and greater emphasis on safety and patient-centred outcomes is needed.Why read on?This is the first systematic review to exclusively address venovenous ECCO2R use in the moderate-to-severe ARDS cohort. We report the degree of lung protection achieved with venovenous ECCO2R devices, along with factors potentially limiting widespread adoption.