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.

The new advanced membrane gas exchanger.

Current membrane oxygenators are constructed for patients with a body surface under 2.2 m(2). If the body surface exceeds 2.5 m(2), commercially available devices may not allow adequate oxygenation during cardiopulmonary bypass. To address this, a hollow-fiber oxygenator with an enlarged contact surface of 1.81 m(2) was tested. In an experimental set-up, six calves of mean weight 85.4 ± 3 kg were connected to cardiopulmonary bypass. They were randomly assigned to a standard oxygenator (n = 3; ADMIRAL, Euroset, Medola, Italy) with a surface of 1.35 m(2) or to an enlarged surface oxygenator (n = 3; AMG, Euroset). Blood samples were taken before bypass, after 10 min on bypass, and after 1, 2, 5 and 6 h of perfusion. Analysis of variance was used for repeated measurements. The mean flow rate was 6.5 l/min for 6 h. The total oxygen transfer at 6 h was significantly higher in the high-surface group (P < 0.05). Blood trauma, evaluated by plasma hemoglobin and lactate dehydrogenase levels, did not detect any significant hemolysis. Thrombocytes and white blood cell count profiles showed no significant differences between the two groups at 6 h of perfusion (P = 0.06 and 0.80, respectively). At the end of testing, no clot deposition was found in the oxygenator, and there was no evidence of peripheral emboli. The results suggest that the new oxygenator allows very good gas transfer and may be used for patients with a large body surface area.