Cytokine adsorption and ECMO in patients with COVID-19
Authors: Pasquale Nardelli, Marina Pieri, Evgeny Fominskiy, Anna Mara Scandroglio
Journal: The Lancet Respiratory Medicine (2021)

Cytokine adsorption during extracorporeal membrane oxygenation (ECMO) has been a subject of interest over the past decade. As a cytokine storm was proposed among pathogenetic mechanisms of severe COVID-19, interest in control of cytokines increased dramatically during the pandemic. Therefore, the trial by Alexander Supady and colleagues1Supady A Weber E Rieder M et al.Cytokine adsorption in patients with severe COVID-19 pneumonia requiring extracorporeal membrane oxygenation (CYCOV): a single centre, open-label, randomized, controlled trial.Lancet Respir Med. 2021; 9: 755-762Summary Full Text Full Text PDF PubMed Scopus (124) Google Scholar is timely and offers interesting insights, but their findings must be carefully discussed before conclusions can be applied to clinical practice. The manuscript reports the results of a small, single-centre, unblinded trial with small block sized randomisation that might have failed in balancing the two groups at baseline. Patients receiving cytokine adsorption were more frequently in shock and required substantially more norepinephrine support (0·15 μg/kg per min [0·04–0·22] vs 0·03 μg/kg per min [0·00–0·36]) and over 3 L of fluids during the first 72 h, had a more severe acute respiratory distress syndrome (ratio of the partial pressure of oxygen in arterial blood to the fractional concentration of oxygen in inspired air was 62·7 [48·5–72·7] vs 84·2 [59·9–95·6] mmHg) and had higher concentrations of inflammation (ie, higher concentrations of C-reactive protein, ferritin, and D-dimers). In our clinical experience, adsorption filters have a shorter lifespan in patients with COVID-19; however, the trial reports an extremely high rate of adsorber thrombosis. Unfortunately, no anticoagulation protocol, nor activated prothrombin time value was reported in the study. Furthermore, the authors investigated ten secondary outcomes despite only enrolling 17 patients, meaning the chance of false-positive findings is high. Therefore, the observed mortality difference could be attributed to chance rather than to a treatment effect. Finally, the trial enrolled patients treated in two different intensive care units between March and December, 2020—a period of time in which clinical management of COVID-19 was not standardised.2Pan H Peto R et al.WHO Solidarity Trial ConsortiumRepurposed antiviral drugs for COVID-19 —interim WHO solidarity trial results.N Engl J Med. 2021; 384: 497-511Crossref PubMed Scopus (1686) Google Scholar In our opinion, cytokine adsorption efficacy should not be assessed in terms of interleukin-6 concentration alone. Its effects are wide and can be more properly assessed in terms of shock control (eg, reduction of inotropic requirements and shock laboratory parameters).3Scandroglio AM Pieri M Nardelli P et al.Impact of CytoSorb on kinetics of vancomycin and bivalirudin in critically ill patients.Artif Organs. 2021; (published online March 9.)https://doi.org/10.1111/aor.13952Crossref PubMed Scopus (12) Google Scholar Moreover, patients on ECMO rarely benefit from or are rarely harmed by a single treatment: outcome is the result of comprehensive intensive management, by which the strategy of therapy is supported by mechanical circulatory support and associated devices. The reported causes of death reflect the importance and outcome of intensive care in general (including more than 6 L of fluids per patient) rather than device-related thromboembolic complications. To date, inflammation control and immunomodulation in patients who are critically ill and mechanically supported are not yet based on strong clinical evidence. For instance, the adsorption of antibiotics and clinically relevant drugs by the filter is currently still under investigation. However, a single, small trial should not steward worldwide clinical practice. More data arising from large, multicentre trials on cytokine adsorption are unquestionably needed and should not be delayed by these negative results; however, the growing body of non-randomised evidence cannot simply be overlooked. We declare no competing interests. Cytokine adsorption in patients with severe COVID-19 pneumonia requiring extracorporeal membrane oxygenation (CYCOV): a single centre, open-label, randomised, controlled trialEarly initiation of cytokine adsorption in patients with severe COVID-19 and venovenous ECMO did not reduce serum IL-6 and had a negative effect on survival. Cytokine adsorption should not be used during the first days of ECMO support in COVID-19. Full-Text PDF Cytokine adsorption and ECMO in patients with COVID-19 – Author's replyWe thank Andrey Rybalko, Pasquale Nardelli, and their colleagues for critically discussing the results from our CYCOV trial1 and raising valid points. Full-Text PDF Cytokine adsorption and ECMO in patients with COVID-19We read with interest the CYCOV trial by Alexander Supady and colleagues,1 in which the authors describe extracorporeal membrane oxygenation (ECMO) support in patients with severe COVID-19 combined with cytokine adsorption. The authors conclude that cytokine adsorption during the first 72 h of ECMO support did not result in reduced interleukin (IL)-6 concentrations after 72 h, that cytokine adsorption was associated with an increased mortality risk within 30 days after initiation of ECMO, and that early cytokine adsorption should be avoided in patients with COVID-19 requiring venovenous ECMO support. Full-Text PDF