The quest for a red blood cell substitute

Perfluorocarbons have been the most extensively tested class of artificial blood substitute compounds. Results of PFC use in the treatment of severe anemia in Jehovah's Witnesses have been disappointing, but they may be occasionally useful. Their major utility may prove to be in conditions of abnormal microvascular circulation and in serving as chemo and radiation-sensitizers. The PFCs themselves may have significant direct toxic effects in addition to the potential toxicity of high levels of oxygen and oxygen radicals at sites of inflammation or disease. Polymerized P-SFH solutions and encapsulated Hgb hold more promise than does FDA-20 for tissue oxygen delivery. However, few toxicity studies and no human clinical trials have been done using Hgb solutions or liposome-encapsulated hemoglobins. These methods may permit safe use of outdated hemoglobin that currently is wasted. Investigations of all these substances have focused on their oxygen carrying and delivery properties. Future investigations must look at other RBC properties such as carbon dioxide transport and acid buffering. In addition, the efficacy of these blood substitutes must be tested when multiple stresses on the oxygen transport system are present. Unfortunately, combinations of anemia, cardiac dysfunction, and respiratory failure do occur in clinical situations The potential exists for the development of new PFCs with greater oxygen-carrying capacity and/or longer half-lives. These newer PFCs will hold even greater potential for use in ischemic diseases and in tumor therapy. Hemoglobin solutions may prove very useful in treating acute anemia, both in patients who refuse RBC transfusions and in outlying locations such as accident sites or on battlefields. Finally, the use of artificial blood substitutes to restore intravascular volume has the potential to provide two clinical benefits. The first benefit is the persistence of these substances in the circulation for longer periods than the half-lives of albumin or crystalloid. The second benefit is the additional oxygen transport. It will be important to test the hypothesis that improvement in oxygen transport and oxygen consumption in critically ill patients leads to improved clinical outcomes. If this theory is given credence, then finding new blood substitutes that do not tax the already stressed national blood banking system will become even more important. The habit of accepting a hematocrit of 30% in the ICU patient needs to be questioned. Further studies on the optimal hematocrit for patients with respiratory failure or multisystem organ failure need to be carried out. Barlett⁵³ emphasized out lack of attention to oxygen transport by RBCs in his ''Critical Carol,'' an essay in which the ghost of the physiologist Ernest Starling visits a physician caring for Charles Cratchit, a typical ICU patient, on Christmas Eve. Starling comments to the physician on the ''habit of using anemia as a treatment . . . you bleed poor Charlie every day and leave him with a hematocrit of 32. You are a modern day intensive care leech.'' The physician's response is ''I resent being compared to a leech. This patient is not anemic . . . Charlie's hematocrit is 32% . . . I mean it's, it's not anemic for a critically ill patient. Most of our critically ill patients have hematocrits in the 30s.'' Although artificial blood substitutes may not immediately replace red blood cell transfusion, they focus our attention on oxygen delivery and oxygen consumption in critically ill patients. While artificial blood substitutes are being tested and perfected over the next decade, the utility of maintaining hematocrits of 35%, 40%, or even 45% in the critically ill patient should be rapidly determined.