Abstract
Background: Major bleeding and allogeneic transfusion leads to negative outcomes in patients receiving cardiac surgery with cardiopulmonary bypass (CPB). Ulinastatin, a urine trypsin inhibitor, relieves systemic inflammation and improves coagulation profiles with however sparse evidence of its effects on blood loss and allogeneic transfusion in this specific population. Methods: In this prospective randomized controlled trial, 426 consecutive patients receiving open heart surgery with CPB were randomly assigned into three groups to receive ulinastatin (group U, n=142), tranexamic acid (group T, n=143) or normal saline (group C, n=141). The primary outcome was the total volume of post-operative bleeding and the secondary outcome included the volume and exposure of allogeneic transfusion, the incidence of stroke, post-operative myocardial infarction, renal failure, respiratory failure and all-cause mortality. A ten-year follow-up was carried on to evaluate long-term safety.Results: Compared with placebo, ulinastatin significantly reduced the volume of post-operative blood loss within 24 hours (688.39±393.55ml vs 854.33±434.03ml MD -165.95ml, 95%CI -262.88ml to -69.01ml, p<0.001) and the volume of allogeneic erythrocyte transfusion (2.57±3.15 unit vs 3.73±4.21 unit, MD-1.16 unit, 95%CI -2.06 units to -0.26 units, p=0.002). The bleeding and transfusion outcomes were comparable between the ulinastatin group and the tranexamic acid group. In-hospital outcomes and 10-year follow-up showed no statistical difference in mortality and major morbidity among groups. Conclusions: Ulinastatin reduced post-operative blood loss and allogeneic erythrocyte transfusion in heart surgery with CPB. The mortality and major morbidity was comparable among the groups shown by the 10-year follow-up. Trial registration: The trial was retrospectively registered on February 2, 2010. Trial registration number: https://www.clinicaltrials.gov. Identifier: NCT01060189.