Perfluorocarbons

General information

Oxygen carriers can be divided into two classes: synthetic perfluorocarbons and hemoglobin-based oxygen carriers, prepared from hemoglobin of human or bovine origin (see separate monograph). It is important for the laboratory medicine community to be aware of their effects on routine laboratory testing and the settings in which they might be used [ ].

The characteristics of an ideal emulsion for use as a blood substitute are absence of red cell incompatibility, absence of a risk of transmission of infectious diseases, a long duration of conservation, easy access, and rheological parameters similar to those of blood [ ].

Perfluorocarbons are synthetic molecules made of 8–10 carbon molecules with fluorine atoms replacing hydrogen atoms. They are immiscible with water and can dissolve oxygen and carbon dioxide. Perfluorocarbon emulsions are heavy, low-viscosity liquids, inert, and optically clear, with a high specific gravity and good surface tension. Their chemical and physical properties make them a suitable temporary intraoperative tool to flatten the retina during surgery, and they have gained wide acceptance in the surgical management of complicated retinal detachment [ ]. Perfluorocarbons have a transport capacity that is greater than that of blood under hyperoxic conditions [ ].

Unlike hemoglobin, which binds oxygen covalently, perfluorocarbons require a high PaO ₂ (300 mmHg) to be effective [ ]. Second-generation perfluorocarbons that have been developed include Oxygent, Oxyfluor, Oxycyte, and Perftoran. A phase III study of Oxygent was terminated because of a possible increase in strokes. Oxyfluor was associated with mild thrombocytopenia and flu-like symptoms in phase I and II trials, but its development has been ended. The flu-like symptoms may be due to immunological activation of macrophages by the particle size of the product. Perftoran was associated with hypotension and pulmonary complications in about 1% of cases in a randomized trial. Clinical experience with large volumes of Perflubron (Oxygent) yielded few adverse events, diarrhea being the most common. Perfluorocarbons interfere with laboratory assays such as CO oximetry.

The available formulations include perfluoro-octyl bromide, perfluoro-octylethane, perfluorodichloro-octane, Fluosol-DA (70% perfluorodecalin plus 30% perfluorotripropylamine), Oxygent (perflubron, perfluoro-octyl bromide) [ ], and LiquiVent (perflubron). Second-generation perfluorocarbons have been used in anemia, trauma, high blood loss surgery, perioperative hemodilution, ischemia, and organ conservation for transplantation.

Perfluorocarbon blood substitutes can cause a flu-like illness 4–6 hours after infusion [ , ]. Symptoms include back pain, malaise, flushing, and transient fever [ ]; arterial hypotension, tachycardia, a high leukocyte count, and thrombocytopenia can also occur. These symptoms are most probably cytokine-mediated, as the perfluorocarbon particles are cleared by cells of the reticuloendothelial system [ ].

The most important adverse effect of LiquiVent is intravascular passage of the perfluorocarbon. Phagocytosis by alveolar macrophages has been demonstrated by cytology. Larger doses of emulsion particles can lead to hepatic engorgement and temporary impairment of immune defences [ ].

Drug studies