Blood remains, from a physiologic perspective, the ideal resuscitation agent, but there are substantial practical limitations to its routine use. Although the potential for disease transmission has been significantly reduced by modern donor screening techniques, it has not been completely eliminated. 17 Other concerns include the limited availability of blood products; the cost of collection, storage and transfusion; a limited shelf-life; and the existence of religious prohibitions against the transfusion of blood products. These issues have led researchers to search for alternative agents that can safely and effectively deliver oxygen to the cells. 18 To date the use of stoma-free hemoglobin as well as pyridoxalated-hemoglobin-polyoxyethylene (PHP) conjugate represent examples of hemoglobin-based substitutes under investigation. Hemoglobin solutions became of interest during World War II owing to practical difficulties of blood storage and compatibility testing on the battlefield. Their use was ultimately rejected due to their short half-lives and the frequent occurrence of significant hypotension. Subsequent research was directed at the modification of these solutions to eliminate side effects such as renal failure and bleeding abnormalities. Currently, although some modified hemoglobin solutions may be effective at restoring blood pressure and cardiac index, their clinical efficacy remains limited by their short half-lives and potential toxic effects. 19 Hemoglobin has been identified as a neurotoxin and has been shown to promote vasoconstriction, platelet adhesion, and free radical damage.
Perfluorocarbons (PFCs) have also been investigated as possible blood substitute candidates because of their high oxygen solubility. Unfortunately, new PFC emulsions produce toxic effects on the lung in a dose-dependent fashion, thereby severely limiting their ability to improve oxygen-carrying capacity. Because of these problems, blood substitutes are not currently recommended as an alternative to blood transfusion in the treatment of hemorrhagic shock. The importance of developing a safe and effective blood substitute is not diminished, however, and this remains a fertile area for future research.
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