Hemoadsorption to Reduce Plasma Free Hemoglobin during Cardiac Surgery: Results of REFRESH I Pilot Study

OBJECTIVE: Generation of plasma free hemoglobin (pfHb) and activated complement during complex cardiac surgery contributes to end-organ dysfunction. This prospective, multi-center REFRESH I (REduction in FREe Hemoglobin) randomized controlled trial (RCT) evaluated the safety and feasibility of CytoSorb hemoadsorption therapy to reduce these factors during prolonged cardiopulmonary bypass (CPB). METHODS: Eligible patients underwent elective, non-emergent complex cardiac surgery with expected CPB duration ≥ 3h. Exclusions included single procedures including primary CABG, single valves, transplant, and LVAD extraction. TREATMENT used two parallel 300 ml CytoSorb hemoadsorption cartridges in a side circuit during CPB. CONTROL was standard of care. RESULTS: Of 52 enrolled patients, 46 underwent surgery (Safety group, n=23 vs Control, n=23), and 38 were evaluated for pfHb reduction (EFFICACY group, n=18 vs CONTROL, n=20). Type and number of SAEs (44 vs 43 CONTROL) were similar, as was 30-day mortality. Transient reduction in platelets during CPB was observed in both groups, especially TREATMENT, but returned to pre-treatment levels after CPB without bleeding. Peak pfHb was positively correlated with CPB length (p=0.01) but the high variability of pfHb, due to the broad surgical procedure mix, prevented detection of changes in pfHb in the overall EFFICACY population. However, the valve replacement surgery subgroup (8 vs 10 CONTROL) had the highest peak pfHb levels, and TREATMENT demonstrated significant pfHb reductions vs CONTROL (p≤0.05) in CPB ≥ 3h. In the EFFICACY group, C3a and C5a were significantly reduced by treatment throughout surgery. CONCLUSIONS: Intraoperative hemoadsorption with CytoSorb was safe and feasible in this randomized, controlled pilot study during complex cardiac surgery. Treatment with CytoSorb resulted in significant reductions in pfHb during valve replacement surgery and reductions in C3a and C5a in the overall EFFICACY group. Future studies will target complex cardiac surgery patients with prolonged CPB to assess hemoadsorption effect on end-organ dysfunction and outcomes