Perfluorocarbons - therapeutic strategies in ARDS. From isoflurane to perfluorohexane

The introduction of Perfluorochemicals into medicine and especially into th e treatment of severe lung injury is a fascinating scientific task. Many re call the famous experiments from Clark et al.in 1966 when he demonstrated " liquidventilation with perfluorocarbons" in the mammal species for the firs t time. after this hallmark, perfluorocarbons were subsequently introduced in research of acute lung injury by the techniques of Total- and Partial-li quid-Ventilation (TLV; PLV). Perfluorocarbons (saturated organofluorids) ha ve unique chemical and physical properties which made them attractive subst ances for intraalveolar application. The strong C-F bindings in the perfluo rocarbon molecules are responsible for their chemical stability, biochemica l inertness, high capacity to dissolve respiratory gases, low surface tensi on and high vapor pressures. Furthermore, the high density of the PFC lead to radio-opacity and their distribution to dependent lung areas. The effica cy of PFC liquid, applied by TLV/PLV has been demonstrated in numerous anim al studies using different models of acute lung injury. Currently, several mechanisms of action of perfluorocarbon fluids in acute lung injury are dis cussed: recruitment of atelectatic alveoli, prevention of endexpiratory col lapse of alveoli ("liquid PEEP"), redistribution of perfusion, oxygen trans port, surfactant like effects and decrease of inflammation. Since total liq uid ventilation has been used only in experimental models of lung injury, p artial liquid ventilation has been introduced successfully into clinical tr ials (phase I-II). However, the results of the first randomised, controlled study of PLV in 90 adult patients suffering from severe respiratory failur e (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 compli cations such as liquithoraces, pneumothoraces and hypoxia. Since mammal lun gs are evolutionary specialised to gas exchange using atmospheric oxygen, t he application of liquids, even if they transport respiratory gases very we ll is not physiologic. To overcome these unwanted side effects, we develope d a technique of perfluorocarbon vaporisation in analogy to the application of inhalation anaesthetic agents. After resolving some technical issues, t his 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. T hough these results are promising, mechanisms of action, dose-efficacy rela tion, surfactant-perfluorocarbon interaction or anti-inflammatory effects o f vaporised perfluorohexane are still unclear. These questions need to be c larified before this technique can be applied clinically. However,the inhal ation of vapor, a technique already familiar to anaesthesiologists should a void risks of large amounts of fluids in the bronchoalveolar space. Further more, this technique can be administered by established anaesthetic equipme nt with the advantage of exact dosing, continuous monitoring,and demand app lication in a way near to clinical routine.