Perfluorocarbons

Perfluorocarbons (Riess 1991) are simply constructed molecules derived from hydrocarbons by replacing all the hydrogen atoms with fluorine. Some of these compounds also contain a bromide atom to provide radio-opacity.

Perfluorocarbons are insoluble in water and therefore have to be emulsified. They are not metabolized in the organism but are rapidly (within a few hours) phagocytized by cells of the reticuloendothelial system. In a second slow phase (within a few weeks), they are redistributed to the blood, transported to the lungs, and finally exhaled.

The most important physicochemical feature of perfluorocarbons is that oxygen is highly soluble in them. The relationship between PO2 and oxygen content in perfluorocarbon solutions is linear, rather than sigmoidal as is the case in blood. At high oxygen partial pressures, achieved by 100 per cent oxygen ventilation, the oxygen content is higher in whole blood than in perfluorocarbons; in the presence of a high PO2 gradient between arterial blood and tissues, oxygen release to tissues is comparable for blood and perfluorocarbons. For example, 100 g of perfluoro-octyl bromide (perflubron), a second-generation perfluorocarbon, can deliver 15 ml of oxygen in the presence of an arterial PO2 of 600 mmHg and an estimated tissue PO2 of 38 mmHg (PO2 gradient DPO2 = 562 mmHg). This amount of oxygen is approximately equivalent to the amount of oxygen delivered by one unit (450 ml) of blood with a hemoglobin concentration of 14 g/dl.

In theory, intravenously administered perfluorocarbon emulsion should effectively replace the oxygen transport function of red blood cells lost during anemia, thereby preserving tissue oxygenation and organ function. However, the first clinical trials using a 20 per cent weight per volume (w/v) emulsion (Fluosol-DA) have failed. Despite a high intravenous dose, Fluosol-DA 20 per cent was incapable of preserving adequate tissue oxygenation in severly anemic surgical patients who had refused homologous blood transfusion. Six of eight patients died ( Gould eLaL 198.6).

One reason for the lack of efficacy of Fluosol-DA 20 per cent is shown schematically in Fig,, 1. The oxygen transport capacity of a perfluorocarbon emulsion depends on the concentration of the perfluorocarbon compound in the emulsion and is reflected by the slope of the corresponding straight line. The higher the slope, the more oxygen is dissolved for the same increase in PO2 and the higher is the oxygen transport capacity of the emulsion. As Fig 1 indicates, the oxygen transport capacity of

Fluosol-DA 20 per cent is low because of its low perfluorocarbon concentration. This is the main reason for the failure of the emulsion in clinical studies.

Fig. 1 Relationship between PO2 and oxygen content in whole blood (sigmoidal relationship) and perfluorocarbon emulsions (linear relationship). The oxygen transport capacity of the perfluorocarbon emulsions (slopes of the straight lines) increases with increasing perfluorocarbon concentration.

Production of perfluorocarbon emulsions at higher concentrations was not feasible for many years because of technical difficulties. However, new preparations containing up to 90 per cent w/v perfluorocarbon (perflubron) are being tested experimentally and clinically, and the initial results appear promising ( Wahr ef a/

1996). Low dosages of perflubron do not seem to cause serious side-effects. Animal experiments have shown that the oxygen transport capacity is high enough to preserve tissue oxygenation and organ function even at very low hematocrits (8 per cent).

Artificial blood substitutes which can replace the oxygen transport capacity of lost red blood cells in anemic patients are being investigated with the aim of reducing the costs and risks of homologous transfusion. Free hemoglobin solutions increase the hemoglobin-bound fraction of the arterial oxygen content, and perfluorocarbons increase the physically dissolved fraction. Because of the special properties of these two types of oxygen-carrying blood substitute (short intravascular half-life, requirement of 100 per cent oxygen ventilation in the case of perfluorocarbons), they are presently being evaluated in controlled clinical studies of intentional intraoperative dilutional anemia.

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