Perfluorocarbons: Knowledge gained from clinical trials

Research into potential use of perfluorocarbons for liquid ventilation and as oxygen delivery agents in humans has been underway since the 1960s. While partial liquid ventilation with perfluorocarbons showed promise in animal models and early human investigation, randomized controlled human trials failed to show benefit and an elevated rate of adverse events. Initial approval of Fluosol-DA (Green Cross Corporation, Osaka, Japan) by the United States Food and Drug Administration as an oxygen delivery agent for use in high-risk coronary angioplasty represents the only approved application of these compounds to supplement tissue oxygenation, but the compound was rendered obsolete and removed from the market with the development of advanced angioplasty catheters in the 1990s. Second-generation perfluorocarbons were developed with a higher capacity to increase the amount of oxygen dissolved in the fluid phase of blood. Early clinical trials of perflubron emulsion in non-cardiac and cardiac surgery were promising, but dose restriction and the requirement for high inspired oxygen concentration to maximize oxygen delivery for prolonged periods of time limited the clinical utility as a replacement for the oxygen carrying capacity of red blood cells. Identification of excess serious adverse events in treated patients resulted in discontinuation of pivotal clinical trials. Continued research investigating different formulations of perfluorocarbons has shown promise in animal studies, but continued research is necessary to prove safety and efficacy in humans.