ABSTRACT
AIM: To investigate the effect of cytokine adsorption in patients receiving extracorporeal cardiopulmonary resuscitation (ECPR) after cardiac arrest. METHODS: CYTER was a single-centre, open-label, randomised, controlled trial. Patients selected for ECPR at the University Medical Center Freiburg (Freiburg, Germany) were assigned to extracorporeal membrane oxygenation (ECMO) support with or without cytokine adsorption (1:1) using the CytoSorb adsorber, incorporated into the ECMO, replaced every 24 hours, and removed after 72 hours. The primary endpoint was serum interleukin (IL)-6 concentration at 72 hours (intention-to-treat analysis). Secondary endpoints included 30-day survival, vasopressor support and biomarkers of end-organ injury. RESULTS: Of 50 patients enrolled in the trial, 26 (52%) were treated with cytokine adsorption and 24 (48%) without. Nine patients were excluded (informed consent could not be obtained); 41 patients were therefore included in the primary analysis. Median IL-6 levels (IQR) decreased from 408.0(93.4-906.5) to 324.0 (134.3-4617.3) pg/mL and increased from 133.0 (56.2-528.5) to 241.0 (132.8-718.0) pg/mL in the cytokine adsorption and control group, respectively (linear regression for treatment [cytokine adsorption vs control]: p = 0.48). Three (14%) of 22 patients treated with cytokine adsorption and 8 (42%) of 19 patients treated without cytokine adsorption survived to day 30 (HR = 1.85, 95% CI 0.86-4.01; p = 0.10). Vasopressor support and NSE, S100b, troponin T, CRP and PCT levels were similar between groups. CONCLUSION: Cytokine adsorption in patients receiving ECPR did not reduce serum IL-6 and had no significant effect on survival, vasopressor support, or biomarkers of injury. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT03685383.
Subject(s)
Cardiopulmonary Resuscitation , Extracorporeal Membrane Oxygenation , Post-Cardiac Arrest Syndrome , Adsorption , Cytokines , Humans , Retrospective Studies , Treatment OutcomeABSTRACT
BACKGROUND: We sought to clarify the benefit of cytokine adsorption in patients with COVID-19 supported with venovenous extracorporeal membrane oxygenation (ECMO). METHODS: We did a single-centre, open-label, randomised, controlled trial to investigate cytokine adsorption in adult patients with severe COVID-19 pneumonia requiring ECMO. Patients with COVID-19 selected for ECMO at the Freiburg University Medical Center (Freiburg, Germany) were randomly assigned (1:1) to receive cytokine adsorption using the CytoSorb device or not. Randomisation was computer-generated, allocation was concealed by opaque, sequentially numbered sealed envelopes. The CytoSorb device was incorporated into the ECMO circuit before connection to the patient circuit, replaced every 24 h, and removed after 72 h. The primary endpoint was serum interleukin-6 (IL-6) concentration 72 h after initiation of ECMO analysed by intention to treat. Secondary endpoints included 30-day survival. The trial is registered with ClinicalTrials.gov (NCT04324528) and the German Clinical Trials Register (DRKS00021300) and is closed. FINDINGS: From March 29, 2020, to Dec 29, 2020, of 34 patients assessed for eligibility, 17 (50%) were treated with cytokine adsorption and 17 (50%) without. Median IL-6 decreased from 357·0 pg/mL to 98·6 pg/mL in patients randomly assigned to cytokine adsorption and from 289·0 pg/mL to 112·0 pg/mL in the control group after 72 h. One patient in each group died before 72 h. Adjusted mean log IL-6 concentrations after 72 h were 0·30 higher in the cytokine adsorption group (95% CI -0·70 to 1·30, p=0·54). Survival after 30 days was three (18%) of 17 with cytokine adsorption and 13 (76%) of 17 without cytokine adsorption (p=0·0016). INTERPRETATION: Early 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. FUNDING: None.
