From isoflurane to perfluorohexane? Perfluorocarbons--therapeutic strategies in acute lung failure

Abstract

The introduction of Perfluorochemicals into medicine and especially into the treatment of severe lung injury is a fascinating scientific task. Many recall the famous experiments from Clark et al. in 1966 when he demonstrated "liquidventilation with perfluorocarbons" in the mammal species for the first time. After this hallmark, perfluorocarbons were subsequently introduced in research of acute lung injury by the techniques of Total- and Partial-Liquid-Ventilation (TLV; PLV). Perfluorocarbons (saturated organofluorids) have unique chemical and physical properties which made them attractive substances for intraalveolar application. The strong C-F bindings in the perfluorocarbon molecules are responsible for their chemical stability, biochemical inertness, high capacity to dissolve respiratory gases, low surface tension and high vapor pressures. Furthermore, the high density of the PFC lead to radio-opacity and their distribution to dependent lung areas. The efficacy of PFC liquid, applied by TLV/PLV has been demonstrated in numerous animal studies using different models of acute lung injury. Currently, several mechanisms of action of perfluorocarbon fluids in acute lung injury are discussed: recruitment of atelectatic alveoli, prevention of endexpiratory collapse of alveoli ("liquid PEEP"), redistribution of perfusion, oxygen transport, surfactant like effects and decrease of inflammation. Since total liquid ventilation has been used only in experimental models of lung injury, partial liquid ventilation has been introduced successfully into clinical trials (phase I-II). However, the results of the first randomised, controlled study of PLV in 90 adult patients suffering from severe respiratory failure (ALI/ARDS) showed no differences between PLV and conventional treatment. Furthermore, the instillation of relatively large amounts of liquid into the lungs poses several technical challenges and may be associated with complications such as liquithoraces, pneumothoraces and hypoxia. Since mammal lungs are evolutionary specialised to gas exchange using atmospheric oxygen, the application of liquids, even if they transport respiratory gases very well is not physiologic. To overcome these unwanted side effects, we developed a technique of perfluorocarbon vaporisation in analogy to the application of inhalation anaesthetic agents. After resolving some technical issues, this application technique was used successfully in an animal model of acute lung injury. Vaporisation of perfluorohexane in a concentration of 18 Vol.% of inspired gas improved significantly oxygenation and lung compliance. Though these results are promising, mechanisms of action, dose-efficacy relation, surfactant-perfluorocarbon interaction or anti-inflammatory effects of vaporised perfluorohexane are still unclear. These questions need to be clarified before this technique can be applied clinically. However, the inhalation of vapor, a technique already familiar to anaesthesiologists should avoid risks of large amounts of fluids in the bronchoalveolar space. Furthermore, this technique can be administered by established anaesthetic equipment with the advantage of exact dosing, continuous monitoring, and demand application in a way near to clinical routine.