Cytokine Adsorption in ECMO Negatively Affects Survival in Severe COVID-19

In patients with severe COVID-19 supported with venovenous extracorporeal membrane oxygenation (ECMO), the early initiation of cytokine adsorption does not reduce serum interleukin-6 (IL-6) compared with no initiation of cytokine adsorption, and may negatively affect survival, according to study results published in The Lancet Respiratory Medicine.

Severe COVID-19 is associated with uncontrolled cytokine response and COVID-19-related acute respiratory distress syndrome (ARDS) is associated with an increase in serum IL-6 concentrations, leading to worse outcomes in this patient group. While previous studies suggest that cytokine adsorption can reduce IL-6 levels and provide similarly promising results in ARDS in patients without COVID-19, the benefits in patients with COVID-19 who are supported with ECMO is unclear.

A team of investigators in Germany conducted a single-center, open-label, randomized, controlled trial (CYCOV; ClinicalTrials.gov Identifier: NCT04324528; German Clinical Trials Identifier: DRKS00021300) to characterize the efficacy of extracorporeal cytokine adsorption in patient with severe COVID-19 pneumonia receiving venovenous ECMO and to observe changes in IL-6 levels.

Patients with COVID-19 receiving ECMO were randomly assigned (1:1) to either undergo cytokine adsorption using a CytoSorb device or not. The device was incorporated into the ECMO circuit and replaced every 24 hours and removed after 72 hours. The main outcome of the study was the IL-6 concentration after 72 hours following the initiation of ECMO. Secondary outcomes included 30-day survival.

Of the 34 patients included in the study (median age, 61 years; 26% women), 17 patients were randomly assigned to the cytokine adsorption group, while 17 patients were randomly assigned to the control group.

After 72 hours, the median IL-6 concentration declined from 357.0 pg/mL to 98.6 pg/mL in the cytokine adsorption group and declined from 289.0 pg/mL to 112.0 pg/mL in the control group. No significant differences in IL-6 concentrations were observed in the 2 groups after 72 hours of ECMO.

The 30-day survival among patients in the control group was 76%; however, the 30-day survival among patients in the cytokine adsorption group was significantly reduced to 18% (P =.0016). Additional multiple regression analyses with mediation variables also suggested that the effect of treatment was statistically significant in all models. The only mediation variable with significant effects on survival was the change in neutrophil levels from baseline to 72 hours of ECMO.

Finally, in single and multiple Cox regression analyses of survival time following ECMO initiation, cytokine adsorption was significantly associated with harmful effects on survival (hazard ratio, 6.46; P =.0075).

The significance out these outcomes led the investigators to stop recruitment for the next portion of the analysis, which would have been a multicenter study (CYCOV-II; ClinicalTrials.gov Identifier: NCT04385771).

“Our results do not allow us to draw conclusions about treatment with cytokine adsorption in patients with COVID-19 without venovenous ECMO, nor do they allow us to draw conclusions about treatment with cytokine adsorption in patients with venovenous ECMO for ARDS of causes other than COVID-19,” the authors noted.

“Therefore, early cytokine adsorption should be avoided in patients with COVID-19 requiring venovenous ECMO support,” concluded the investigators.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

Reference

Supady 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, randomised, controlled trial. Lancet Respir Med. Published online May 14, 2021. doi:10.1016/S2213-2600(21)00177-6