title: Randomized trial of diaspirin cross-linked hemoglobin solution as an alternative to blood transfusion after cardiac surgery. The DCLHb Cardiac Surgery Trial Collaborative Group.
abstract: BACKGROUND
  Risks associated with transfusion of allogeneic blood have prompted development of methods to avoid or reduce blood transfusions. New oxygen-carrying compounds such as diaspirin cross-linked hemoglobin (DCLHb) could 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, multicenter study in post-cardiac bypass surgery patients. Of 1,956 screened patients, 209 were determined to require a blood transfusion and met the inclusion criteria during the 24-h post-cardiac bypass period. These patients were randomized to receive up to three 250-ml infusions of DCLHb (n = 104) or three units of packed erythrocytes (pRBCs; n = 105). Further transfusions of pRBCs or whole blood were permitted, if indicated. Primary efficacy end points were the avoidance of blood transfusion through hospital discharge or 7 days postsurgery, whichever came first, and a reduction in the number of units of pRBCs transfused during this same time period. Various laboratory, 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 through postoperative day 7 or hospital discharge, 20 of 104 (19%) DCLHb recipients did not receive a transfusion of pRBCs compared with 100% of control patients (P < 0.05). The overall number of pRBCs administered during the 7-day postoperative period was not significantly different. Mortality was similar between the DCLHb (6 of 104 patients) and the control (8 of 105 patients) groups. Hypertension, jaundice/hyperbilirubinemia, increased serum glutamic oxalo-acetic transaminase, abnormal urine, and hematuria were reported more frequently in the DCLHb group, and there was one case of renal failure in each group. The hemodynamic effects of DCLHb included a consistent and slightly greater increase in systemic and pulmonary vascular resistance with associated increases in systemic and pulmonary arterial pressures compared with pRBC. Cardiac output values decreased more in the DCLHb group patients after the first administration than the control group patients. At 24 h postinfusion, the plasma hemoglobin level was less than one half the maximal level for any amount of DCLHb infused.
  
  
  CONCLUSIONS
  Administration of DCLHb allowed a significant number (19%) of cardiac surgery patients to avoid exposure to erythrocytes postoperatively.
authors.affiliation: Department of Anesthesia and Intensive Care Medicine of the University of Liège, Centre Hospitalier Universitaire, Belgium. mlamy@chu.ulg.ac.be
authors.forename: M L
authors.initials: ML
authors.lastname: Lamy
authors.forename: E K
authors.initials: EK
authors.lastname: Daily
authors.forename: J F
authors.initials: JF
authors.lastname: Brichant
authors.forename: R P
authors.initials: RP
authors.lastname: Larbuisson
authors.forename: R H
authors.initials: RH
authors.lastname: Demeyere
authors.forename: E A
authors.initials: EA
authors.lastname: Vandermeersch
authors.forename: J J
authors.initials: JJ
authors.lastname: Lehot
authors.forename: M R
authors.initials: MR
authors.lastname: Parsloe
authors.forename: J C
authors.initials: JC
authors.lastname: Berridge
authors.forename: C J
authors.initials: CJ
authors.lastname: Sinclair
authors.forename: J F
authors.initials: JF
authors.lastname: Baron
authors.forename: R J
authors.initials: RJ
authors.lastname: Przybelski
mesh_terms: D000368:Aged; D001241:Aspirin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D001802:Blood Substitutes / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001803:Blood Transfusion; D006348:Cardiac Surgical Procedures; D005260:Female; D006400:Hematocrit; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006454:Hemoglobins / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D007552:Isotonic Solutions; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000201:enzymology; D017701:Reticulocyte Count; D000077331:Ringer's Solution; D016037:Single-Blind Method
chemical_list: D001802:Blood Substitutes; D006454:Hemoglobins; D007552:Isotonic Solutions; D000077331:Ringer's Solution; C083478:diaspirin-cross-linked hemoglobin; D001241:Aspirin