During partial liquid ventilation perfluorocarbons are instilled into the airways from where they subsequently evaporate via the bronchial system. This process is influenced by multiple factors, such as the physicochemical properties of the perfluorocarbons (especially vapour pressure), the instilled volume, intrapulmonary perfluorocarbon distribution, postural positioning and ventilatory settings (especially minute ventilation and level of end-expiratory pressure) [1-6]. Only small amounts cross the alveolo-capillary membranes and are stored in intra- and extrathoracic lymph-nodes as well as in other organs indicating systemic distribution .
The eliminated volume has to be replaced intermittently or continuously to maintain sufficient intrapulmonary perfluorocarbon filling for therapeutic effects during partial liquid ventilation. As perfluorocarbons are expensive and may contribute to environmental pollution it is of interest to minimize unnecessary perfluorocarbon loss.
One method may be the use of a closed breathing system in which the expired gas containing perfluorocarbon vapour is cleared of CO2 and returned to the inspiratory limb of the respirator after addition of oxygen. Previous experiments suggested a relevant saving in dose . The elimination of perfluorocarbons may also be reduced by heat-and-moisture-exchangers. These devices minimize heat and evaporative water loss from the respiratory system and have also been suggested to reduce evaporative loss of perfluorocarbon . A third measure may be the use of a sodalime absorber. As these absorbers not only bind CO2 but also conserve heat and humidity we hypothesize that they reduce perfluorocarbon elimination to a similar extent as heat-and-moisture-exchangers.
We compared the effects of these three measures on evaporative perfluorocarbon loss. We studied isolated lungs to control all other factors influencing perfluorocarbon elimination, especially the perfluorocarbon volume present within the lungs.
Material and methods
The study was performed in accordance with the National Institute of Health guidelines of laboratory animal care (NIH publication No. 86-23, revised 1985) and with approval of the local District Animal Investigation Committee. Adult male Wistar rats with a mean body weight of 390 ± 51 g were anaesthetized with 500 mg kg−1 ketamine (Ketavet; Jacoby Pharmazeutika GmbH, Hallein, Austria) injected intraperitoneally. Their trachea was intubated with a cannula (18G; B. Braun, Melsungen, Germany). Following midline sternotomy, trachea, heart and lungs were removed en bloc and suspended from a force transducer. The isolated lungs were inflated for a short time period with positive pressures (20 cmH2O) until any visible atelectases had resolved. Subsequently, the lungs were allowed to deflate again and were then ventilated with a small animal ventilator (Harvard Apparatus, Edenbridge, UK) using the following respiratory settings: a tidal volume of 10 mL kg−1, a respiratory rate of 40 breaths min−1, zero end-expiratory pressure, an inspiration/expiration ratio of 1: 1, and 21% oxygen. These respiratory settings resulted in a mean fresh gas flow of 156 mL min−1 during ventilation with an open breathing system. During ventilation with a closed breathing system fresh gas flow was reduced to a basal rate of less than 1 mL min−1. Following instrumentation the lungs were covered with a thin plastic foil (Plus, Mühlheim, Germany) to reduce drying of the pleura.
Perfluorocarbon (10 mL kg−1) was instilled via a side port of the tracheal cannula into the airways just above the carina. The compound used (FC-77; 3M, Neuss, Germany) had the following characteristics: chemical structure C8F18, specific gravity 1.77g mL−1, surface tension 15 dyn cm−1, vapour pressure 5.9 kPa at 25°C and dynamic viscosity 1.4 mPa s−1.
Evaporative perfluorocarbon loss was determined by measuring changes in lung weight with a force transducer (model FT 03; Grass Instruments, Quincy, MA, USA). This transducer was calibrated before and after each experiment and had the following specifications: stability ± 1%, resolution as high as 25 000: 1 and drift <50 mg h−1.
Only lungs without signs of air or liquid leaks (loss of airway pressure when ventilation was stopped in inspiration or liquid accumulation in the plastic foil covering the lung) were included in the experimental protocol.
The isolated lungs were randomized to 5 groups by drawing numbers: Lungs of Group 1 (n = 6) were ventilated with an open breathing system, while lungs of Group 2 (n = 6) were ventilated with a closed circuit system. For this purpose, the exhaust limb of the ventilator was connected to the gas inlet via silicone hoses and a gas reservoir. Lungs of Group 3 (n = 6) were ventilated with an open breathing system with a heat-and-moisture-exchanger (Humid-Vent micro+, Gibeck, Indianapolis, USA) placed between the Y-piece and the tracheal cannula. Lungs of Group 4 (n = 6) were ventilated with an open breathing system with a sodalime absorber (3.3 g, Dräger-Sorb 800, Drägerwerk AG, Lübeck, Germany) placed between the Y-piece and the tracheal cannula. Lungs of Group 5 (n = 6) were ventilated with a closed breathing system in combination with a heat-and-moisture-exchanger and a sodalime absorber. Lungs were ventilated for 12 h or until all perfluorocarbon had been eliminated.
In addition, control lungs (n = 8) were either gas ventilated without instillation of perfluorocarbon (n = 4) or received perfluorocarbon without subsequent ventilation (n = 4) to exclude relevant effects of gas ventilation or ventilation-independent perfluorocarbon loss (e.g. via the pleura) on weight measurements.
Data are presented as mean ± standard deviation. Elimination half-lives were calculated as time intervals between perfluorocarbon instillation and the time when 50% of the initial weight increase had been eliminated. ANOVA and Bonferroni's test were used to test differences in means for statistical significance. An alpha adjusted P < 0.05 was considered significant.
During partial liquid ventilation lung weight decreased in an almost linear fashion (Fig. 1). Weight loss of perfluorocarbon-filled lungs, which were not ventilated, was less than 0.01g h−1 indicating that only negligible amounts of perfluorocarbon were lost independent of ventilation. Weight loss of gas-ventilated control lungs without perfluorocarbons was also negligible (<0.01g h−1) implying that the observed changes in weight predominantly reflected evaporative loss of perfluorocarbon via the airways of the lungs.
Elimination half-lives differed significantly between groups (Fig. 2). The shortest half-life was observed with an open system (1.2 ± 0.07 h). The effects on elimination half-life were most significant with a closed breathing system (6.4 ± 0.9 h, P < 0.01), followed by a sodalime absorber (5.0 ± 0.6 h, P < 0.01) and a heat-and-moisture-exchanger (4.5 ± 0.8 h, P < 0.01). The combination of all three measures showed no statistically significant additional effects when compared to the use of a closed breathing system alone (7.1 ± 0.8 h, P < 0.05).
The aim of our study was to study the effects of open and closed breathing systems, a heat-and-moisture-exchanger and a sodalime absorber on perfluorocarbon evaporation during partial liquid ventilation. When compared to an open breathing system all other measures showed a significant reduction in perfluorocarbon loss.
Our measurements were performed in isolated lungs, which allowed us to control ventilation-independent effects on perfluorocarbon elimination. Specifically, we compared the effects on evaporative loss at the same intrapulmonary perfluorocarbon content. For this purpose, the rat lungs were suspended from a force transducer allowing gravimetric determinations of perfluorocarbon elimination with high precision. In control experiments we excluded any decrease in lung weight during gas ventilation (e.g. due to exhaled water vapour) or decrease following perfluorocarbon instillation without subsequent ventilation (e.g. due to ventilation-independent transpleural loss of perfluorocarbon). Half-lives of perfluorocarbon elimination were used to compare effects on elimination rates because the interval between instillation and the time point at which half of the instilled amount of perfluorocarbon had been eliminated could be determined exactly.
The vapour pressure of the instilled perfluorocarbon compound (FC-77), a major determinant of evaporative loss, was 5.9 kPa at 25°C. We expect shorter elimination half-life when perfluorocarbon compounds with higher vapour pressures are used and vice versa. However, qualitative effects of the studied measures on the rate of evaporation should be similar for different perfluorocarbon compounds.
Consistent with our hypothesis and with a previous observation  perfluorocarbon evaporation significantly decreased in a closed circle system. Compared to partial liquid ventilation in an open breathing system elimination half-life increased by a factor of five. The finding that elimination was not reduced to zero may be explained by a redistribution of perfluorocarbon vapour within the breathing system (tubing, Y-piece, small animal ventilator and the gas reservoir). This redistribution can be reduced by reducing the gas volume in which perfluorocarbons can evaporate.
Although to a lesser extent, perfluorocarbon elimination half-life is also increased in open circle systems containing an incorporated heat-and-moisture-exchanger or a sodalime absorber. Heat-and-moisture-exchangers are used to minimize water vapour from the airways during mechanical ventilation. The exhaled water vapour condenses within the exchanger and is subsequently returned to the airways during inspiration. We observed a fourfold increase in perfluorocarbon elimination half-life with the heat-and-moisture-exchanger and assume that perfluorocarbon vapour is stored and released in a similar manner.
Sodalime absorbers are used to remove carbon dioxide from closed breathing systems. Their specific effects on perfluorocarbon elimination have not been studied before. Interestingly, sodalime absorbers also reduced perfluorocarbon loss to the same extent as heat-and-moisture-exchangers. The underlying mechanism by which the absorber reduces evaporation might be explained by absorption of perfluorocarbon vapour to the sodalime granula followed by a delayed release.
Interestingly, both measures, heat-and-moisture-exchangers and sodalime absorbers, conserve perfluorocarbon vapour more effectively in the first hours of partial liquid ventilation than a closed breathing system. This effect may be explained by an initial redistribution of perfluorocarbon vapour in a closed breathing system.
In conclusion, we have demonstrated that evaporative perfluorocarbon loss can be reduced effectively with closed breathing systems, followed by the use of sodalime absorbers and heat-and-moisture-exchangers.
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