Current development and use of hemoglobin-based oxygen-carrying (HBOC) solutions

Abstract

Objective: To review the human and veterinary literature on the current development and use of hemoglobin-based oxygen-carrying solutions. Human data synthesis: Hemoglobin-based oxygen-carrying (HBOC) solutions have been developed extensively over the last 3 decades. Early problems associated with pure hemoglobin and cytoskeleton residues have been resolved with chemical modification of the hemoglobin tetramer resulting in effective oxygen-carrying molecules of either human or bovine origin. The limited availability of human red blood cells and concerns of disease transmission, the difficulty in mass production of genetically produced hemoglobin solutions (recombinant hemoglobin), and the wide availability of bovine blood have resulted in the development of bovine-derived HBOC solutions. Research efforts have been directed toward determining the effects of HBOC solutions on tissue perfusion as the target uses of HBOC solutions in human medicine are the perioperative period, shock, and trauma fluid resuscitation. The most controversial issues regarding the cardiovascular effects of HBOC solutions surround increased vasoactivity. Some HBOC formulations have been removed from advanced clinical trials due to intense vasoactivity resulting in increased morbidity. There are currently 3 HBOC solutions in the latter stages of phase III clinical trials: Hemolink®, a Hemopure®, b and PolyHeme®. c The hemoglobin source of Hemopure® is bovine, and the hemoglobin source for Hemolink® and Polyheme® is human. Veterinary data synthesis: The only HBOC solution that has gained approval from the FDA is the veterinary product Oxyglobin®. d Oxyglobin® is 13 g/dL of ultrapurified, polymerized hemoglobin solution of bovine origin in a modified lactated Ringer's solution. There is a significant colloid effect and it also provides a plasma source of oxygen-carrying capacity. The solution is stable at room temperature for 3 years; there is no special preparation required prior to use and no cross-match is required prior to administration (contains no cell membranes). Veterinary publications on the use of Oxyglobin® include laboratory investigations in dogs, cats, and horses for use as a resuscitation fluid and for the treatment of anemia. Clinical use of Oxyglobin® in dogs, cats, birds, horses, and other mammalian species has been reported in several publications. Conclusion: The search for a safe, effective HBOC solution for use in human medicine is ongoing. Soon, there will be one or several products approved for use in the perioperative period and/or for the treatment of shock and trauma. The practice of veterinary emergency and critical care has been provided a unique opportunity to apply the use of an HBOC solution (Oxyglobin®) to various aspects of perfusion and oxygen-carrying needs. Continued clinical experience and research is essential in understanding the use of HBOC solutions in veterinary medicine. © Veterinary Emergency and Critical Care Society 2003.