EFFECT OF DIASPIRIN CROSSLINKED HEMOGLOBIN (DCLHb HemAssist™) DURING HIGH BLOOD LOSS SURGERY ON SELECTED INDICES OF ORGAN FUNCTION

Background: The safety of the hemoglobin based oxygen carrier diaspirin crosslinked hemoglobin (DCLHb) has been reported only in the low (50-200 mg/kg) dose range[Przybelski, R.J.; Daily, E.K.; Kisicki, J.C.; Mattia-Goldberg, C.; Bounds, M.J.; Colburn, W.A. Phase I study of the safety and pharmacologic effects of diaspirin crosslinked hemoglobin solution. Crit. Care Med. 1996, 24 (12), 1993-2000, Bloomfield, E.; Rady, M.; Popovich, M.; Esfandiari, S.; Bedocs, N. The use of diaspirin crosslinked hemoglobin (DCLHb™) in post-surgical critically ill patients. 1996, 95, (3A), A220.]. We conducted a randomized prospective open-label trial of DCLHb and packed red blood cells (PRBCs) in high-blood loss surgical patients to show the effect of 750 ml DCLHb (approximately 1000 mg/kg) on selected indices of organ function. Method: After institutional approval, 24 patients scheduled to undergo elective orthopedic or abdominal surgery, were randomized to receive either PRBCs or 10% DCLHb within 12 hours after the start of surgery. Patients with renal insufficiency, abnormal liver function, severe coronary artery disease (CAD) and ASA physical status≥IV were excluded. The anesthetic technique was left to the judgment of the anesthesiologist. Autologous pre-donation and intraoperative blood conservation techniques were utilized as appropriate. The indications for blood transfusion were individualized on disease state, stage of surgery, and plasma Hb concentration. Laboratory studies were obtained preoperatively and up to 28 days postoperatively. Patients were observed daily for development of jaundice, hematuria, nausea, vomiting, gastrointestinal discomfort, cardiac, respiratory, and infectious complications. Organ effects were assessed with urinalysis, creatinine clearance, electrocardiogram (ECG), and a panel of blood and serum laboratory tests. Results: The dose of DCLHb administered ranged from 680-1500 mg/kg (mean=999 mg/kg). Estimated blood loss was 27±13 ml/kg and 31±15 ml/kg in the control and DCLHb groups, respectively. Fewer PRBCs (1.9±1.2 vs. 3.4±2.4 units, P=0.06) were transfused to DCLHb patients on the operative day although this difference was no longer apparent later on. In the DCLHb group, 4/12 patients avoided any allogeneic PRBC transfusion vs. none in the control group (P=0.09). Systolic, diastolic and mean blood pressure increased moderately after DCLHb for a period of 24-30 hours. There were no occurrences of cardiac ischemia, myocardial infarction,