Hemoglobin-based oxygen carriers: first, second or third generation? Human or bovine? Where are we now?

This article discusses current efforts to develop hemoglobin-based oxygen carriers as blood substitutes in light of the worldwide shortage of safe and viable allogeneic donor blood. There are now viable approaches to modify the intrinsic biologic properties of hemoglobin to produce improved hemoglobin-based oxygen carriers. Polymerized hemoglobin preparations have proved most successful in clinical trials due to their improved side effect profile. The goal is to evaluate blood substitutes with enhanced intravascular retention, reduced osmotic activity, and attenuated hemodynamic derangements such as vasoconstriction. Although not without substantial morbidity and mortality, the current safety of allogeneic blood transfusion demands that comparative studies show minimal adverse effects as well as efficacy and potential for novel applications.