Perfluorocarbon-based red blood cell substitutes.

Abstract

Since our review 5 years ago, a new generation of PFC emulsion has been developed and is undergoing extensive testing. This new generation is the result of the application of physicochemical principles, applied to both the choice of the PFC itself and the emulsifier, as well as advances in emulsion-producing technology. The efficacy of PFCs in general for oxygen transporting capability has been fully recognized, as exemplified by the limited license issued to Fluosol. The latter also represents the recognition of the relative absence of major toxicity of PFCs in general. The development of new products owes much to the lessons learned during the past 20 years and to advances made in the physical chemistry of PFCs. These advances now permit the rational selection or design of the most appropriate PFC and the design of emulsifiers best suited for the purpose. Perflubron represents a clear advance over the Fluosol-DA-type formulation. It is only one but the most advanced of the second-generation products. At least three other commercial entities (Hema-Gen/PFC, Green Cross, Adamantech) are also developing products based on the above principles. Five years ago we concluded that, in spite of the enormous complexity of PFC emulsions as large volume parenterals, they have shown remarkable biocompatibility. The advances in the past 5 years have confirmed this conclusion. The advances occurring during the past 5 years show that the application of the proper technology can lead to product improvement, and that PFC preparations with significant transfusional and nontransfusional potential are, in fact, feasible. It remains to be seen whether high PFC-content emulsion can be successfully deployed in initial, prehospital resuscitation situations. The high PFC content will reduce the absolute requirement for the maintenance of FIO2 > 0.8 in the case of Fluosol-DA for optimal efficacy. The second-generation products also seem to lend themselves to intraoperative use, because they can be removed from the blood postoperatively by plasmapheresislike methods. They are also suitable in combination with autologous blood donation/transfusion. All of these potential applications are in various stages of exploration and, if found to be efficacious, will likely conserve the supply of whole blood and blood components. The nontransfusional applications, particularly those in diagnostic imaging, seem to show substantial promise. Because they involve smaller doses than transfusional applications, they may enter clinical use earlier. The applications in radiation and chemotherapy of malignant diseases represent an intermediate position between the transfusional and nontransfusional uses.(ABSTRACT TRUNCATED AT 400 WORDS)