Cytokine clearance with CytoSorb® during cardiac surgery: a pilot randomized controlled trial.
BACKGROUND
Cardiopulmonary bypass (CPB) is often associated with degrees of complex inflammatory response mediated by various cytokines. This response can, in severe cases, lead to systemic hypotension and organ dysfunction. Cytokine removal might therefore improve outcomes of patients undergoing cardiac surgery. CytoSorb® (Cytosorbents, NJ, USA) is a recent device designed to remove cytokine from the blood using haemoadsorption (HA). This trial aims to evaluate the potential of CytoSorb® to decrease peri-operative cytokine levels in cardiac surgery.


METHODS
We have conducted a single-centre pilot randomized controlled trial in 30 patients undergoing elective cardiac surgery and deemed at risk of complications. Patients were randomly allocated to either standard of care (n = 15) or CytoSorb® HA (n = 15) during cardiopulmonary bypass (CPB). Our primary outcome was the difference between the two groups in cytokines levels (IL-1a, IL-1b, IL-2, IL-4, IL-5, IL-6, IL-10, TNF-α, IFN-γ, MCP-1) measured at anaesthesia induction, at the end of CPB, as well as 6 and 24 h post-CPB initiation. In a consecutive subgroup of patients (10 in HA group, 11 in control group), we performed cross-adsorber as well as serial measurements of coagulation factors' activity (antithrombin, von Willebrand factor, factor II, V, VIII, IX, XI, and XII).


RESULTS
Both groups were similar in terms of baseline and peri-operative characteristics. CytoSorb® HA during CPB was not associated with an increased incidence of adverse event. The procedure did not result in significant coagulation factors' adsorption but only some signs of coagulation activation. However, the intervention was associated neither with a decrease in pro- or anti-inflammatory cytokine levels nor with any improvement in relevant clinical outcomes.


CONCLUSIONS
CytoSorb® HA during CPB was not associated with a decrease in pro- or anti-inflammatory cytokines nor with an improvement in relevant clinical outcomes. The procedure was feasible and safe. Further studies should evaluate the efficacy of CytoSorb® HA in other clinical contexts.


TRIAL REGISTRATION
ClinicalTrials.gov NCT02775123 . Registered 17 May 2016.
['Poli|Elettra C|EC|', 'Alberio|Lorenzo|L|', 'Bauer-Doerries|Anna|A|', 'Marcucci|Carlo|C|', 'Roumy|Aurélien|A|', 'Kirsch|Matthias|M|', 'De Stefano|Eleonora|E|', 'Liaudet|Lucas|L|', 'Schneider|Antoine G|AG|http://orcid.org/0000-0003-0576-7094']
D000328:Adult D000368:Aged D000369:Aged, 80 and over D002315:Cardiopulmonary Bypass D018932:Chemokine CCL2 D016207:Cytokines D005260:Female D006440:Hemofiltration D006801:Humans D016753:Interleukin-10 D053582:Interleukin-1alpha D053583:Interleukin-1beta D007376:Interleukin-2 D015847:Interleukin-4 D015848:Interleukin-5 D015850:Interleukin-6 D008297:Male D008657:Metabolic Clearance Rate D008875:Middle Aged D010865:Pilot Projects D011183:Postoperative Complications D014409:Tumor Necrosis Factor-alpha
Cytokines CytoSorb® Haemoadsorption Coagulation factors Cardio-pulmonary bypass