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In previous studies, researchers suggested a beneficial role of hemofiltration performed during cardiopulmonary bypass in children. This study was performed to assess both clinical effects and inflammatory mediator removal by high-volume, zero-fluid balance ultrafiltration during rewarming (Z-BUF).Twenty children undergoing cardiac surgery were assigned randomly to Z-BUF or a control group. Plasma C3a, interleukin (IL)-1, IL-6, IL-8, IL-10, tumor necrosis factor, myeloperoxidase, and leukocyte count were measured before (T1) and after (T2) hemofiltration and 24 h later (T3). The intensive care unit staff was blinded to the patient's group. Postoperative alveolar-arterial oxygen gradient, time to extubation, body temperature, and postoperative blood loss were monitored.Ultrafiltration rate was 4,972 (3,183-6,218) mL/m2 (median [minimum-maximum]) in the Z-BUF group, where significant reductions were observed in postoperative blood loss, time to extubation (10.8 [9-18] vs. 28.2 [15-58] h) and postoperative alveolar-arterial oxygen gradient (320 [180-418] vs. 551 [485-611] mmHg at T3). In the Z-BUF group, significant removal of tumor necrosis factor, IL-10, myeloperoxidase, and C3a were observed at T2. Interleukin 1, IL-6, IL-8, and myeloperoxidase were decreased at T3, suggesting earlier removal of factor(s) that may trigger their release.These results suggest that hemofiltration exerts some beneficial clinical effects that are not due to water removal. The role of the early removal of factors triggering the inflammatory response, rather than a direct removal of cytokines, deserves further investigation.