Perfluorocarbon Enhanced Gas Exchange
The Easy Way

Michael P. Hlastala, Ph.D. and Jennifer E. Souders, M.D.

University of Washington, Seattle, Washington

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Early studies into gas exchange while breathing liquid began with the primary goal of developing a means for submarine emergency escape by breathing saline as a respired medium having minimal nitrogen partial pressure. Breathing air at hyperbaric pressures would expose the diver to very high nitrogen partial pressures and a significant risk of decompression sickness. Early work with liquid ventilation (1) showed that hypercapnia was the most significant limitation of liquid breathing with saline because of its low carbon dioxide solubility.

In the early 1990s, several groups brought liquid breathing into the clinical realm of lung disease treatment using perfluorocarbons (PFCs) with enhanced CO₂ solubility to provide a new strategy for the treatment of respiratory distress syndrome (RDS). Space limitations prevent a detailed discussion of all of the important references. The study of Kandler and coworkers (2) in this issue of the American Journal of Respiratory and Critical Care Medicine (pp. 31-35) brings PFC technology to its greatest level of sophistication. A brief discussion of methods for PFC administration helps to illustrate the importance of an aerosol delivery approach.

A significant positive step was the use of PFC-associated gas exchange (3), now termed partial liquid ventilation (PLV). A volume of PFC equivalent to the normal functional residual capacity (30 ml/kg) is instilled into the trachea with a superimposed volume-regulated gas ventilation (fraction of inspired oxygen [FI_O2] = 1.0). In the presence of lung injury, gas exchange is improved during PLV (4) because of the combined effects of reduced surface tension and improved delivery of O₂ to edematous areas of the lung. These studies evaluated the efficiency of gas exchange using measures of O₂ and CO₂ exchange efficiency, such as Pa_O2, Pa_CO2, and AaPO₂. Using the multiple inert gas elimination technique in the normal lung, the gas exchange limitations are found to be due to increased shunt and increased aAPCO₂ resulting from the low solubility of CO₂ in PFC (8). With the large PFC volumes in PLV, CO₂ exchange deteriorates due to diffusion limitation through the PFC fluid layer (9).

One complication of PLV results from the high density of PFC, which is distributed predominantly to the dependent regions of the lung (10). Although gas is distributed to all lung regions, more ventilation was found in the nondependent regions. Thus PLV may work through a combined redistribution of blood flow and ventilation toward the nondependent regions serving to improve alveolar volume/cardiac output (_A/) matching in the nondependent regions of the lung.

Creative use of small amounts of PFC can exhibit similar or superior therapeutic consequences. The use of vaporized PFC (individual molecules in the gas phase) has been described by Bleyl and colleagues (11). These investigators introduced perfluorohexane (chosen for its optimal vapor pressure, 177 mm Hg) through two vaporizers in series to oleic acid-injured sheep. They showed an improvement of oxygenation during the treatment interval. This improvement was sustained past the treatment phase. Peak arterial PO₂ levels were reached 2 h after the end of the treatment period with no residual PFC. The important observation was that vaporized PFC had a significant effect in improving animal status without requiring a large liquid PFC volume to be introduced into the lungs. These findings showed that the surface tension-reducing properties of PFC could be provided by introducing PFC in the vapor form.

The most recent innovative step by Kandler and coworkers in this issue of the Journal is the novel use of aerosols (small droplets of PFC in the gas phase) to increase the PFC content in inspired gas (2). This approach allows a greater volume of PFC to be delivered to the lung surface than with vaporization while introducing less PFC volume than with either full or partial liquid ventilation. A major advantage of aerosols is that PFC is delivered to the alveolar surface in a relatively uniform manner without the density-dependent distribution of PFC to dependent regions of the lungs. This study evaluated the effect of aerosolized PFC (FC77) with a surfactant-depleted piglet lung model. The authors compared aerosol-PFC with three other ventilation modes: PLV at functional residual capacity (FRC), PLV at low lung volume, and intermittent mandatory ventilation, and showed that aerosol-PFC provided the best gas exchange and improved dynamic compliance. The maximum Pa_O2 was found in the aerosol-PFC group up to 6 h after completion of treatment. The improvement of gas exchange was as effective as PLV and persisted for a longer time. No adverse effects were seen with aerosolized PFC.

A significant advantage of both the vaporized and aerosolized methods over PLV is the more uniform distribution of surface-tension reduction independent of the density-dependent distribution of PFC during PLV. However, the Kandler method (2) has significant advantages that sets it apart from even vaporization as an improvement in the manner of administration of PFC. First, the method of aerosol administration does not carry the same potential for lung injury. Second, there is a considerable advantage for acceptability and ease of use for treatment of injured lungs in the critical care environment. Minimal training will be necessary for personnel to safely and competently administer aerosolized PFC. In addition, the equipment will remain simple to use and inexpensive, and this increases accessibility of the technique. Third, the simplicity of equipment and ease of use make this therapy more portable, potentially expanding its use outside of the intensive care unit. Fourth, unlike vaporization, this method is not limited by the vapor pressure of the PFC that is used. Therefore, more types of PFC could be suitable, perhaps specific to particular lung injuries. Further research is needed to evaluate this promising treatment modality and to optimize its efficiency. Kandler and coworkers may have simplified the administration of PFC to the point that we will see a renewed interest in using these chemicals to treat acutely injured lungs.

	References

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