Perfluorocarbons for the treatment of decompression illness: how to bridge the gap between theory and practice

Decompression illness (DCI) is a complex clinical syndrome caused by supersaturation of respiratory gases in blood and tissues after abrupt reduction in ambient pressure. The resulting formation of gas bubbles combined with pulmonary barotrauma leads to venous and arterial gas embolism. Severity of DCI depends on the degree of direct tissue damage caused by growing bubbles or indirect cell injury by impaired oxygen transport, coagulopathy, endothelial dysfunction, and subsequent inflammatory processes. The standard therapy of DCI requires expensive and not ubiquitously accessible hyperbaric chambers, so there is an ongoing search for alternatives. In theory, perfluorocarbons (PFC) are ideal non-recompressive therapeutics, characterized by high solubility of gases. A dual mechanism allows capturing of excess nitrogen and delivery of additional oxygen. Since the 1980s, numerous animal studies have proven significant benefits concerning survival and reduction in DCI symptoms by intravenous application of emulsion-based PFC preparations. However, limited shelf-life, extended organ retention and severe side effects have prevented approval for human usage by regulatory authorities. These negative characteristics are mainly due to emulsifiers, which provide compatibility of PFC to the aqueous medium blood. The encapsulation of PFC with amphiphilic biopolymers, such as albumin, offers a new option to achieve the required biocompatibility avoiding toxic emulsifiers. Recent studies with PFC nanocapsules, which can also be used as artificial oxygen carriers, show promising results. This review summarizes the current state of research concerning DCI pathology and the therapeutic use of PFC including the new generation of non-emulsified formulations based on nanocapsules.