Venovenous extracorporeal membrane oxygenation in patients with acute covid-19 associated respiratory failure: comparative effectiveness study

Abstract

Objective To estimate the effect of extracorporeal membrane oxygenation (ECMO) compared with conventional mechanical ventilation on outcomes of patients with covid-19 associated respiratory failure. Design Observational study. Setting 30 countries across five continents, 3 January 2020 to 29 August 2021. Participants 7345 adults admitted to the intensive care unit with clinically suspected or laboratory confirmed SARS-CoV-2 infection. Interventions ECMO in patients with a partial pressure of arterial oxygen to fraction of inspired oxygen (PaO 2 /FiO 2 ) ratio <80 mm Hg compared with conventional mechanical ventilation without ECMO. Main outcome measure The primary outcome was hospital mortality within 60 days of admission to the intensive care unit. Adherence adjusted estimates were calculated using marginal structural models with inverse probability weighting, accounting for competing events and for baseline and time varying confounding. Results 844 of 7345 eligible patients (11.5%) received ECMO at any time point during follow-up. Adherence adjusted mortality was 26.0% (95% confidence interval 24.5% to 27.5%) for a treatment strategy that included ECMO if the PaO 2 /FiO 2 ratio decreased <80 mm Hg compared with 33.2% (31.8% to 34.6%) had patients received conventional treatment without ECMO (risk difference –7.1%, 95% confidence interval –8.2% to –6.1%; risk ratio 0.78, 95% confidence interval 0.75 to 0.82). In secondary analyses, ECMO was most effective in patients aged <65 years and with a PaO 2 /FiO 2 <80 mm Hg or with driving pressures >15 cmH 2 O during the first 10 days of mechanical ventilation. Conclusions ECMO was associated with a reduction in mortality in selected adults with covid-19 associated respiratory failure. Age, severity of hypoxaemia, and duration and intensity of mechanical ventilation were found to be modifiers of treatment effectiveness and should be considered when deciding to initiate ECMO in patients with covid-19.

Bleeding and thrombotic events in patients with severe COVID-19 supported with extracorporeal membrane oxygenation: a nationwide cohort study

“…This may reflect a higher disease severity, nutritional deficiencies, increased inflammation and endothelial activation. This may also help to explain the reported association between survival and duration of MV before ECMO in both COVID and non-COVID patients [17,18,46]. Finally, a high fibrinogen level (≥ 6 g/L) was associated with greater odds of thrombosis.…”

“…Since the beginning of the SARS-CoV-2 pandemic, ECMO has been widely used for acute respiratory distress syndrome (ARDS) related to coronavirus disease 2019 (COVID-19) and, to a lesser extent, for COVID-19-associated circulatory failure [14][15][16][17][18]. Immunothrombosis is thought to be a key mechanism contributing to the pathogenesis of severe COVID-19 and to its high reported thrombotic risk [19][20][21].…”

Respiratory indications for ECMO: focus on COVID-19

“…In a larger emulated target trial, the COVID-19 Critical Care Consortium [ 42 ] studied 7345 patients with COVID-19-related acute respiratory failure; 844 patients received ECMO. In patients with PaO 2 /FiO 2 < 80 mmHg, ECMO support reduced hospital mortality by 7.1% (95% CI 6.1–8.1%) compared to conventional mechanical ventilation without ECMO (RR 0.78, 95% CI 0.75–0.82).…”

“…Similarly, in a large cohort of ECMO patients in Germany, Karagiannidis et al observed the lowest in-hospital mortality rate in patients who had been mechanically ventilated ≤ 3 days before ECMO initiation [ 51 ]. In an emulated target trial, Urner et al found that ECMO was most effective if initiated early, and certainly within the first 10 days of IMV [ 42 ]. Finally, in another emulated target trial, ECMO was associated with a mortality benefit when initiated within four days of IMV [ 40 ].…”

“…However, other analytic approaches are being used. Recently, three target trial emulations have been performed analyzing the efficacy of mechanical ventilation with ECMO compared to mechanical ventilation alone in patients with severe COVID-19-related ARDS [40][41][42]. This approach may allow causal inferences similar to those from a randomized trial [43,44].…”