Hemoglobin-based oxygen-carrying solutions: close but still so far.

MULTIPLE approaches are important when attempting to limit allogeneic blood transfusions. My interest in developing strategies to decrease bleeding and transfusion requirements started in the early 1980s, when I was evaluating perioperative anaphylaxis and noted that transfused blood was an important cause of life-threatening hypersensitivity reactions. There are multiple reasons to reduce transfusions in addition to the risk of reactions and transfusion-related diseases. Blood products are in limited supply; they incur significant costs, expose patients to a variety of potential cellular and humoral antigens, and may alone produce either proinflammatory or even immunosuppressive responses. A spectrum of immune alterations that persist for months has been reported after transfusion with allogeneic blood. Even several milliliters of plasma present in packed erythrocytes contain sufficient numbers of donor leukoagglutinin antibodies to produce transfusion-related acute lung injury. In this issue of ANESTHESIOLOGY, Lamy et al. report their multicenter randomized trial of diaspirin cross-linked human hemoglobin solutions as a potential alternative to blood transfusion after cardiac surgery. They note that administration of the hemoglobin-based oxygen-carrying (HBOC) solution was able to reduce the need for transfused allogenic packed erythrocytes. This finding is interesting in view of the relatively short half-life of diaspirin cross-linked hemoglobin, and its ability to reduce transfused blood cannot be explained on duration of action only. One of the potential mechanisms by which HBOC solutions may be effective in reducing transfused blood may be a result of the fact that in hemorrhagic conditions, replenishing lost iron is difficult. Administering either oral or intravenous iron to patients is not well tolerated, free iron is toxic, and iron-containing parenteral solutions, usually bound to dextrans, have the potential to produce anaphylactic reactions. Although the oxygen-carrying capacity of most HBOC solutions may be quite transient, they are rapidly metabolized, and free iron is potentially scavenged by multiple mechanisms to subsequently stimulate erythropoiesis and reticulocytosis. This may explain why patients were discharged with similar hematocrits in both groups, despite the reduction in transfused allogenic packed erythrocytes in the HBOC-treated patients. Unfortunately, diaspirin-linked HBOC solutions have been abandoned because of a higher mortality that was reported when studying these solutions in trauma patients. Regrettably, the trauma patient population is a heterogeneous group of patients, and similar to therapeutic trials in sepsis, trauma patients represent a group with an extremely high morbidity and mortality incidence that can potentially complicate interpreting data. As Lamy et al. report, an elective cardiac surgical population represents a better alternative, in which there is an established incidence of adverse events that can be easily quantified. Based on this consideration, there are complex regulatory issues surrounding the actual approval of artificial blood products. Do the HBOC solutions need to be as good as or better than packed erythrocytes as an oxygen carrier? I believe it is important that studies of blood substitutes demonstrate that they can reduce the need This Editorial View accompanies the following article: Lamy ML, Daily EK, Brichant J-F, Larbuisson RP, Demeyere RH, Vandermeersch EA, Lehot J-J, Parsloe MR, Berridge JC, Sinclair CJ, Baron J-F, Przybelski RJ, for the DCLHb Cardiac Surgery Trial Collaborative Group: Randomized trial of diaspirin crosslinked hemoglobin solution as an alternative to blood transfusion after cardiac surgery. ANESTHESIOLOGY 2000; 92:646–56. r