Randomized trial of diaspirin cross-linked hemoglobin solution as an alternative to blood transfusion after cardiac surgery

Background: Risks associated with transfusion of allogeneic blood have prom pted development of methods to avoid orreduce blood transfusions. New oxyge n-carrying compounds such as diaspirin cross-linked hemoglobin (DCLHb) coul d enable more patients to avoid allogeneic blood transfusion. Methods: The efficacy, safety, hemodynamic effects, and plasma persistence of DCLHb were investigated in a randomized, active-control, single-blind, m ulticenter study in post-cardiac bypass surgery patients. Of 1,956 screened patients, 209 were determined to require a blood transfusion and met the i nclusion criteria during the 24-h post-cardiac bypass period. These patient s were randomized to receive up to three 250-ml infusions of DCLHb (n = 104 ) or three units of packed erythrocytes (pRBCs; n = 105), Further transfusi ons of pRBCs or whole blood were permitted, if indicated. Primary efficacy end points were the avoidance of blood transfusion through hospital dischar ge or 7 days postsurgery, whichever came first, and a reduction in the numb er of units of pRBCs transfused during this same time period, Various labor atory, physiologic, and hemodynamic parameters were monitored to define the safety and pharmacologic effect of DCLHb in this patient population, Results: During the period from the end of cardiopulmonary bypass surgery t hrough postoperative day 7 or hospital discharge, 20 of 104 (19%) DCLHb rec ipients did not receive a transfusion of pRBCs compared with 100% of contro l patients (P < 0.05). The overall number of pRBCs administered during the 7-day postoperative period was not significantly different. Mortality was s imilar between the DCLHb (6 of 104 patients) and the control (8 of 105 pati ents) groups. Hypertension, jaundice/hyperbilirubinemia, increased serum gl utamic oxalo-acetic transaminase, abnormal urine, and hematuria were report ed more frequently in the DCLHb group, and there was one case of renal fail ure in. each group. The hemodynamic effects of DCLHb, included a consistent and slightly greater increase in systemic and pulmonary vascular resistanc e with associated increases in systemic and pulmonary arterial pressures co mpared with pRBC, Cardiac output values decreased more In the DCLHb group p atients after the first administration than the control group patients, At 24 h postinfusion, the plasma hemoglobin level was less than one half the m aximal level for arty amount of DCLHb Infused. Conclusions: Administration of DCLHb allowed a significant number (19%) of cardiac surgery patients to avoid exposure to erythrocytes postoperatively.