Perfluorocarbon-associated Gas Exchange Research Articles

The Effect of High Frequency Jet Ventilation with Partial Liquid Ventilation in Saline Lavaged Lung Injury in the Rabbit

Background: Morbidity and mortality rates from acute respiratory failure remain noteworthy despite advances in conventional ventilatory techniques and improvements in supportive care. Repeated, the large tidal volume breaths during positive pressure mechanical ventilation lead to destruction of alveoli and pulmonary capillaries. Moreover, the overdistention of terminal lung units is considered as an important mechanism of ventilator induced lung injury. High frequency ventilation (HFV) is a technique involving a small tidal volume, and a higher than physiologic respiratory rate. Partial liquid ventilation (PLV), also known as perfluorocarbon-associated gas exchange, is a new technique for respiratory support. This study was designed to compare conventional mechanical ventilation (CMV) and high frequency jet ventilation (HFJV), in combination with PLV. Methods: Twenty rabbits were anesthetized with xylazine, ketamine and vecuronium. We studied rabbits with lung injury induced by saline lavage. Animal were randomized into one of two treatment groups. Ventilator parameters included the following;CMV: of 1.0, respiratory rate 20-30 breaths/min, I/E ratio 1：1; HFJV: respiratory rate 2 Hz, driving pressure 2psi. Animals were briefly disconnected from the ventilator and lungs were lavaged with warmed saline. This procedure was repeated until . Mean arterial pressure, cardiac index and systemic vascular resistance was differed significantly. Although there were no qualitative histological differences between lungs ventilated with HFJV on CMV, the lower lobes of all PLV-treated animals were damaged less than the upper lobes, but without statical significance. Conclusions: PLV-HFJV produced a more efficient gas exchange than PLV-CMV. No significant difference was observed in the pulmonary pathologies of the groups.

Liquid ventilation

Liquid ventilation

Perfluorohexane attenuates proinflammatory and procoagulatory response of activated monocytes and alveolar macrophages.

A number of studies have demonstrated the effectiveness of liquid ventilation with perfluorocarbons in improving pulmonary function in acute respiratory distress syndrome. Although it is known that perfluorocarbon-associated gas exchange facilitates lung mechanics and oxygenation, the complete mechanism by which perfluorocarbons exert their beneficial effects in acute lung injury still remains unclear. Possibly, an influence of perfluorocarbons on proinflammatory and procoagulant features of monocytic cells present in the alveolar space, such as alveolar macrophages (AMs), may be involved. Therefore, we examined in an in vitro model the effects of perfluorocarbon on both activated mononuclear blood cells (MBCs) and AMs by monitoring the expression of interleukin (IL)-1 beta, tumor necrosis factor (TNF)alpha, and tissue factor (TF). Mononuclear blood cells, obtained from peripheral blood of healthy volunteers, or AMs from diagnostic bronchoalveolar lavage were stimulated by incubation with lipopolysaccharide in the presence of different amounts of perfluorohexane, which was devoid of cytotoxicity. Using both video-enhanced contrast and electron microscopy, the authors observed that perfluorohexane droplets were phagocytosed by activated monocytes as well as by in vitro--cultured AMs within 1--3 h. After lipopolysaccharide stimulation of monocytes or AMs, we observed a down-regulation of TF mRNA and a significant inhibition (P < 0.05) of cellular TF antigen by perfluorohexane. In addition, the concentration of both IL-1 beta and TNF alpha in the supernatant of lipopolysaccharide-stimulated MBC was significantly decreased (P < 0.01) by perfluorohexane compared with controls without perfluorohexane. By preincubation of lipopolysaccharide-containing medium with perfluorohexane, the authors could exclude that the inhibitory effect of perfluorohexane was caused by binding or sequestering limited amounts of lipopolysaccharide. Taken together, our results demonstrate an interference of perfluorohexane with the expression of the procoagulant protein TF on monocytes and AMs as well as with the release of proinflammatory cytokines by MBCs. These effects may contribute to the protective role of liquid ventilation with perfluorocarbons in injuries associated with local activation of inflammatory processes.

Partial liquid ventilation (PLV)

Partial liquid ventilation using PFCs is a relatively new therapeutic approach for the treatment of acute lung injury (ALI) and ARDS. Partial liquid ventilation combines the intrapulmonary application of an oxygen carrying liquid with conventional gas ventilation and was firstly introduced by Fuhrman in 1991 as perfluorocarbon associated gas exchange (PAGE). Today mostly the term partial liquid ventilation (PLV) is used. To our current knowledge the PFCs instilled into the lungs during the procedure are not metabolized in the human body due to their mostly unbranched carbon chains and their extremely stable fluorine-carbon bonds. PFCs are nearly totally eliminated via exhalation; only a very small amount of about 1% is eliminated via transpiration and unchanged biliary excretion. The unique physialchemical properties of PFCs allow the transport of reasonable amounts of oxygen and carbon dioxide. Additionally, these properties are responsible for the preferential distribution of the liquid to otherwise atelectatic, non aerated and ventilated areas, thus inducing lung recruitment. Gas transport to these regions and/or a redistribution of pulmonary blood flow result in an improvement of gas exchange by improved V/Q matching. Additionally PFCs can reduce the inflammatory reaction of the alveolar environment. The mechanisms responsible for these anti-inflammatory properties are currently unknown. Numerous animal studies have demonstrated the efficacy of PLV in various species and in different models of lung injury. In the US and Canada, clinical studies with patients of all ages have been performed using the PFC perflubron (LiquiVent®, Alliance Pharmaceutical, San Diego, CA). First results of a randomized controlled multicenter phase I–II study in 90 adult patients have been presented in 1997; this study was published definitively in 1998. PLV can be combined with other therapeutic interventions for the treatment of severe pulmonary failure. Studies combining PLV with different ventilator patterns including high frequency oscillation ventilation (HFOV) have been performed. Additionally, the combined application with surfactant or the use in combination with inhaled nitric oxide and inhaled or instilled prostaglandin (PGE1) has been investigated. In 1998, a new randomized controlled multicenter study was started in the US and Canada which was been extended to Europe in 1999 and is currently underway.

Partial liquid ventilation

Partial liquid ventilation (PLV) is a relatively new therapeutic approach to acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS). The idea of combining the intrapulmonary application of an oxygen-carrying substance and positive pressure ventilation was introduced by Fuhrman in 1991 and originally called perfluorocarbon-associated gas exchange (PAGE). Nowadays, the technique is mostly known as partial liquid ventilation (PLV). The efficacy of PVL treatment has been demonstrated in numerous animal studies in different models of lung injury. The results of those studies led to multicenter phase I-II studies in patients of all age groups in the United States and Canada. Recently, the first randomized, controlled study in 90 adult patients suffering from ALI and ARDS was completed and first results have been published. Comparison of overall mortality and number of ventilator-free days (VFD's) in a 28-day period showed no differences between PLV and conventionally treated patients. A post-hoc stratification by age (< 55 years) demonstrated a tendency to lower mortality (PLV 25.6%; CMV 36.8%) and a significant increase of VFD (PLV 8.95 days; CMV 4.11 days; p = 0.03) in PLV when compared to conventionally treated patients. Perfluorocarbons (PFCs) are chemically stable and inert. They are mostly eliminated via exhalation (> 99%). The unique physicochemical properties of PFCs permit access to atelectatic, non-ventilated lung areas, enhance gas exchange and decrease inflammation. The dense PFCs prevent the endexpiratory collapse of alveoli and reestablish functional residual capacity (FRC). Comparable to positive endexpiratory pressure (PEEP), these effects have been described as "liquid or fluid PEEP". These properties offer a new approach to the underlying pathophysiology of ALI and ARDS. In addition, the combination with other therapeutic approaches to ALI and ARDS like high-frequency oscillations (HFO), inhaled nitric oxide (NO) therapy, and surfactant replacement can be considered and is already the subject of recent publications. However, combination therapy is still experimental and further investigation is necessary to evaluate efficacy and potential risks. Many questions still exist which need to be answered by experimental as well as human pilot studies. Based on these studies, the results of ongoing human trials can be assessed properly and new multicenter trials can be planned effectively.

The use of perfluorocarbon-associated gas exchange to improve ventilation and decrease mortality after inhalation injury in a neonatal swine model

Patients with tracheobronchial disease frequently require mechanical ventilation during therapy and experience iatrogenic complications such as barotrauma and volutrauma. The purpose of this study was to determine whether perfluorocarbon-associated gas exchange (PAGE) results in lower ventilatory pressures and more efficient ventilation than that provided by conventional ventilation after tracheobronchial mucosal injury caused by smoke inhalation in neonatal piglets. Ten piglets were used for this prospective, randomized study. After administration of a severe smoke inhalation injury, the piglets were randomly assigned to either the perfluorocarbon or control groups. Group 1 served as the control population and received standard (time-cycled, volume-limited) mechanical ventilation. Ventilator settings were adjusted to maintain physiological pH and P o 2 at the lowest tidal volume, rate, and end-expiratory pressure possible throughout the study period. Group 2 was administered intratracheal perfluorocarbon as well as identical mechanical ventilation to attain the same physiological pH and P o 2. Oxygenation index, peak and mean airway pressures, and arterial blood gas levels were measured throughout the study period and subjected to statistical analysis. Histological comparison of airway and parenchymal tissues confirmed identical patterns of smoke injury in both groups. Carbon monoxide levels were the same in both groups. There was significant barotrauma and volutrauma in the control group, but none in the PAGE group. All controls died from 13 to 17 hours after injury; one PAGE pig died at 23 hours with all others surviving past 24 hours ( P = .0021). Peak, plateau, and mean airway pressures were all significantly higher ( P < .05) past 12 hours after injury and continued to increase until death in the controls. Arterial blood gases showed significantly ( P < .05) decreased pH, P o 2, and elevated P co 2 levels in the control group past 12 hours after injury. The oxygenation index was significantly elevated ( P < .05) in the control group past 12 hours after injury. PAGE shows potential for improving ventilation and survival immediately after severe smoke inhalation injury and may have clinical applications in other nonhomogeneous lung injuries.

ADJUNCTS TO MECHANICAL VENTILATION

Adjunctive ventilatory strategies have been developed to improve oxygenation and carbon dioxide (CO2) removal during mechanical ventilation of critically ill patients. These techniques allow clinicians to attain their clinical goals at lower levels of ventilatory support. In this article, the authors discuss extracorporeal CO2 removal, venovenous intravena caval oxygenator, and tracheal gas insufflation as adjuncts to CO2 removal and nitric oxide, surfactant replacement therapy, perfluorocarbon-associated gas exchange, and prone positioning as adjuncts to oxygenation.

A.146 Perfluorocarbon-associated gas exchange with small volumes of FC 3280 increases survival time in experimental ARDS

A.146 Perfluorocarbon-associated gas exchange with small volumes of FC 3280 increases survival time in experimental ARDS

Perfluorocarbon-associated gas exchange in normal and acid-injured large sheep

We hypothesized that a) perfluorocarbon-associated gas exchange could be accomplished in normal large sheep; b) the determinants of gas exchange would be similar during perfluorocarbon-associated gas exchange and conventional gas ventilation; c)in large animals with lung injury, perfluorocarbon-associated gas exchange could be used to enhance gas exchange without adverse effects on hemodynamics; and d) the large animal with lung injury could be supported with an FIO2 of <1.0 during perfluorocarbon-associated gas exchange. Prospective, observational animal study and prospective randomized, controlled animal study. An animal laboratory in a university setting. Thirty adult ewes. Five normal ewes (61.0 +/- 4.0 kg) underwent perfluorocarbon-associated gas exchange to ascertain the effects of tidal volume, end-inspiratory pressure, and positive end-expiratory pressure (PEEP) on oxygenation. Respiratory rate, tidal volume, and minute ventilation were studied to determine their effects on CO2 clearance. Sheep, weighing 58.9 +/- 8.3 kg, had lung injury induced by instilling 2 mL/kg of 0.05 Normal hydrochloric acid into the trachea. Five minutes after injury, PEEP was increased to 10 cm H2O. Ten minutes after injury, sheep with Pao2 values of <100 torr (<13.3 kPa) were randomized to continue gas ventilation (control, n=9) or to institute perfluorocarbon-associated gas exchange (n=9) by instilling 1.6 L of unoxygenated perflubron into the trachea and resuming gas ventilation. Blood gas and hemodynamic measurements were obtained throughout the 4-hr study. Both tidal volume and end-inspiratory pressure influenced oxygenation in normal sheep during perfluorocarbon-associated gas exchange. Minute ventilation determined CO2 clearance during perfluorocarbon-associated gas exchange in normal sheep. After acid aspiration lung injury, perfluorocarbon-associated gas exchange increased PaO2 and reduced intrapulmonary shunt fraction. Hypoxia and intrapulmonary shunting were unabated after injury in control animals. Hemodynamics were not influenced by the institution of perfluorocarbon-associated gas exchange. Tidal volume and end-inspiratory pressure directly influence oxygenation during perfluorocarbon-associated gas exchange in large animals. Minute ventilation influences clearance of CO2. In adult sheep with acid aspiration lung injury, perfluorocarbon-associated gas exchange at an FIO2 of <1.0 supports oxygenation and improves intrapulmonary shunting, without adverse hemodynamic effects, when compared with conventional gas ventilation.

Perfluorocarbon-associated gas exchange improves oxygenation, lung mechanics, and survival in a model of adult respiratory distress syndrome

To compare the effectiveness of perfluorocarbon-associated gas exchange to volume controlled positive pressure breathing in supporting gas exchange, lung mechanics, and survival in an acute lung injury model. A prospective, randomized study. A university medical school laboratory approved for animal research. Neonatal piglets. Eighteen piglets were randomized to receive perfluorcarbon-associated gas exchange with perflubron (n=10) or volume controlled continuous positive pressure breathing (n=8) after acute lung injury was induced by oleic acid infusion (0.15 mL/kg iv). Arterial and venous blood gases, hemodynamics, and lung mechanics were measured every 15 mins during a 3-hr study period. All animals developed a metabolic and a respiratory acidosis during the infusion of oleic acid. Following randomization, the volume controlled positive pressure breathing group developed a profound acidosis (p<.05), while pH did not change in the perfluorocarbon-associated gas exchange group. Within 15 mins of initiating perfluorocarbon-associated gas exchange, oxygenation increased from a PaO2 of 52 +/- 12 torr (6.92 +/- 1.60 kPa) to 151 +/- 93 torr (20.0 +/- 12.4 kPa) and continued to improve throughout the study (p<.05). Animals that received volume controlled positive pressure breathing remained hypoxic with no appreciable change in PaO2. Although both groups developed hypercarbia during oleic acid infusion, PaCO2, steadily increased over time in the control group (p<.01). Static lung compliance significantly increased postrandomization (60 mins) in the animals supported by perflurocarbon-associated gas exchange (p<.05), whereas it remained unchanged over time in the volume controlled positive pressure breathing group. However, survival was significantly higher in the perfluorocarbon-associated gas exchange group with eight (80%) of ten animals surviving the entire study period. Only two (25%) of the eight animals in the volume controlled positive pressure breathing group were alive at the end of the study period (log-rank statistic, p=.013). Perflurocarbon-associated gas exchange enhanced gas exchange, pulmonary mechanics, and survival in this model of acute lung injury.

Perfluorocarbon-associated gas exchange improves pulmonary mechanics, oxygenation, ventilation, and allows nitric oxide delivery in the hypoplastic lung congenital diaphragmatic hernia lamb model

To determine the efficacy of perfluorocarbon-associated gas exchange and the effects of inhaled nitric oxide during perfluorocarbon-associated gas exchange in the congenital diaphragmatic hernia lamb model. Prospective, nonrandomized, controlled, nonhuman trial. Animal research facility. Fetal lambs of 16 time-dated pregnant ewes, at 80 days gestation (term 140 to 145 days). The congenital diaphragmatic hernia lamb model was created in 16 animals. Twelve animals survived to be studied. All animals were mechanically ventilated for 4 hrs with a time-cycled, pressure-limited ventilator. Perfluorocarbon-associated gas exchange was started after 15 mins of ventilation (n = 6). Blood gases were analyzed at 30 mins and then hourly. The perfluorocarbon-associated gas exchange animals had dynamic compliance and tidal volumes measured. After 1 hr, inhaled nitric oxide (80 parts per million) was delivered to the perfluorocarbon-associated gas exchange animals for 10 mins. All blood gas parameters, including pH (6.72 +/- 0.06 vs. 7.14 +/- 0.07), PCO2 (186 +/- 12 vs. 70.5 +/- 16.7 torr [24.8 +/- 1.6 vs. 9.5 +/- 2.1 kPa]), and PO2 (48 +/- 17 vs. 156 +/- 48 torr [6.4 +/- 2.3 vs. 20.8 +/- 6.4 kPa]) were significantly improved in the perfluorocarbon-associated gas exchange-treated group at 4 hrs (p < .005). Dynamic compliance (0.13 +/- 0.02 vs. 0.32 +/- 0.06 mL/cm H2O/kg) and tidal volume (3.5 +/- 0.35 vs. 7.22 +/- 0.61 mL/kg) were also significantly (p < .001) increased in the perfluorocarbon-associated gas exchange group. In the perfluorocarbon-associated gas exchange animals, nitric oxide caused a significant (p < .05) increase in oxygenation and a reduction in pulmonary hypertension. This effect was reversed by stopping the inhaled nitric oxide. Perfluorocarbon-associated gas exchange significantly improved gas exchange, dynamic compliance, and tidal volumes. Furthermore, inhaled nitric oxide can be effectively delivered during perfluorocarbon-associated gas exchange to reduce pulmonary hypertension and enhance oxygenation.

Cardiorespiratory effects of perfluorocarbon-associated gas exchange at reduced oxygen concentrations

To determine whether reducing FIO2 during perfluorocarbon-associated gas exchange would cause deterioration of hemodynamics, lung mechanics, or gas exchange in normal piglets. A prospective, controlled animal trial. Experimental animal laboratory in a university setting. Twelve normal, anesthetized piglets, 7 to 14 days old, and weighing 3.31 +/- 0.75 kg. After the induction of anesthesia, tracheostomy and catheterization, piglets were stabilized. They were mechanically ventilated with a tidal volume of 15 mL/kg, inspiratory time of 25%, positive end-expiratory pressure of 4 cm H2O, and a respiratory rate of 20 to 28 breaths/min to obtain a baseline PaCO2 between 34 and 45 torr (4.7 and 6.0 kPa). Each animal was studied during continuous positive-pressure breathing, and during perfluorocarbon-associated gas exchange. They were ventilated at an FIO2 of 1.0 for 15 mins. FIO2 was randomly varied among 0.75, 0.5, and 0.3 every 15 mins, then returned to 1.0. At each FIO2, measurements of gas exchange, lung mechanics, and hemodynamics were made. After continuous positive-pressure breathing, perfluorocarbon-associated gas exchange was instituted by replacing the gaseous functional residual capacity of the lungs with perfluorooctylbromide. Animals were then ventilated and measurements were taken. At each FIO2, measurements of gas exchange (arterial blood gases and saturation), lung mechanics (mean airway pressure, static end-inspiratory pressure, and peak inspiratory pressure), and hemodynamics (heart rate, and mean arterial, right atrial, pulmonary artery occlusion, and pulmonary arterial pressures) were recorded. In six piglets, cardiac output was measured at each FIO2 by thermodilution. Cardiac index, indexed oxygen delivery and consumption, and indexed pulmonary vascular resistance were derived using standard formulas. Piglets were well saturated at all FIO2 settings during continuous positive-pressure breathing. However, during perfluorocarbon-associated gas exchange, arterial saturation decreased to 72% at an FIO2 of 0.3. Cardiac index and oxygen consumption were not affected by reducing FIO2 during perfluorocarbon-associated gas exchange, and were not significantly different than during continuous positive-pressure breathing. Oxygen delivery was reduced at an FIO2 of 0.3 during perfluorocarbon-associated gas exchange, but oxygen consumption remained in the flow independent portion of the curve despite arterial desaturation. Pulmonary arterial pressure was higher during perfluorocarbon-associated gas exchange than during continuous positive-pressure breathing. Pulmonary arterial pressure and indexed pulmonary vascular resistance were significantly higher during perfluorocarbon-associated gas exchange at an FIO2 of 0.3 than at any other FIO2 settings. Piglets showed no adverse effects on lung mechanics during perfluorocarbon-associated gas exchange. Hemodynamics were well supported at all FIO2 settings, and arterial blood was fully oxygenated during perfluorocarbon-associated gas exchange at an FIO2 of > or = 0.5.

Perfluorocarbon-associated gas exchange in gastric aspiration

To test whether perfluorocarbon-associated gas exchange (gas ventilation of the perfluorocarbon-liquid filled lung) could support oxygenation better than conventional positive pressure breathing in a piglet model of gastric aspiration-induced adult respiratory distress syndrome (ARDS). Prospective, randomized, blinded, controlled study. A critical care research laboratory in a university medical school. Fourteen healthy piglets. Under alpha-chloralose anesthesia and metocurine iodide neuromuscular blockade, 14 piglets underwent tracheostomy; central venous, systemic and pulmonary arterial catheterizations; and volume-regulated continuous positive-pressure breathing. Homogenized gastric aspirate (1 mL/kg) titrated to pH of 1.0 was instilled into the tracheostomy tube of each subject at 0 min to induce ARDS. Hemodynamics, lung mechanics, and gas exchange were evaluated every 30 mins for 6 hrs. Seven piglets were treated at 60 mins by tracheal instillation of perflubron, a volume selected to approximate normal functional residual capacity, and were supported by perfluorocarbon-associated gas exchange without modifying ventilatory settings. Perflubron was added to the trachea every hour to replace evaporative losses. There was a significant difference in oxygenation over time when tested by repeated-measures analysis of variance (F test = 8.78, p < .01). On further analysis, the differences were not significant from baseline to 2.5 hrs but became increasingly significant from 2.5 to 6 hrs after injury (p < .05) in the inflammatory phase of gastric aspiration-induced ARDS. Histologic evidence for ARDS in the treated group 6 hrs after injury was lacking. In the piglet model, perfluorocarbon-associated gas exchange with perflubron facilitates oxygenation in the acute phase of gastric aspiration-induced inflammatory ARDS when compared with conventional positive-pressure breathing. Histologic and physiologic data suggest that perfluorocarbon-associated gas exchange with perflubron might prevent ARDS if instituted after aspiration in the time window before the acute inflammatory process is manifest.

Liquid ventilation: it's not science fiction anymore.

Liquid ventilation is, by all initial considerations, an unconventional concept. Decades of research, however, have found that by using perfluorocarbons, which are capable of holding high concentrations of critical gases such as oxygen and carbon dioxide, gas exchange optimal enough to support life is possible with no known toxic effects. The earliest method of liquid ventilation, tidal liquid breathing, involved infusion and active removal of tidal volumes of perfluorocarbons by a liquid ventilator for gas exchange. Recently, a new method of partial liquid breathing, called perfluorocarbon-associated gas exchange, makes the process of liquid ventilation simpler by using conventional gas ventilators. Current research is showing great promise in the use of liquid ventilation for patients with pulmonary pathology. Critical care nurses should become knowledgeable of this new mode of ventilation and be prepared to meet the special needs of this unique population.

Oxygenation during perfluorocarbon associated gas exchange in normal and abnormal lungs.

Perfluorocarbon-associated gas exchange (PAGE) has been proposed for the treatment of lung diseases characterized by high alveolar surface tension. Perflubron (perfluorooctyl bromide, LiquiVent, Alliance Pharmaceutical Corp.) is a high purity medical grade perfluorocarbon suitable for PAGE. We studied PAGE using perflubron in normal piglets and in animal models of pulmonary disease (meconium aspiration syndrome, oleic acid infusion and gastric acid aspiration as models of ARDS, and neonatal respiratory distress syndrome). All animals were studied under anesthesia. PAGE was instituted by intratracheal instillation of a volume of perflubron (generally 30 ml/kg) that approximates a normal functional residual capacity of the lung. Arterial blood gases were measured at 15 minute intervals. FiO2 during PAGE was 1.0. In normal piglets, PaO2 fell from 543 torr (during conventional gas breathing) to 363 torr (during PAGE). However, in models of lung disease, PAGE significantly enhanced PaO2.

Perfluorocarbon Associated Gas Exchange (Page): Gas Ventilation of the Perfluorocarbon Filled Lung

Throughout most of the second half of this century, progress in respiratory life support was dominated by modernization of the mechanical ventilator. We have now entered an era in which the fundamental physiology of lung function can be manipulated to improve lung performance in hope of reducing morbidity and mortality and thereby decreasing the cost of intensive care. Despite its almost alien technology, perfluorocarbon tidal liquid breathing is an effective means to support respiration in normal and surfactant deficient lungs. A second, technique, perfluorocarbon associated gas exchange (PAGE), has recently been shown effective in normal lungs and in several animal models of lung disease. Both techniques appear to improve pulmonary function when pulmonary surface tension is elevated. PAGE improves lung function and poses opportunities to reduce pulmonary morbidity and diminish the cost of intensive care.

Perfluorocarbon-associated gas exchange (partial liquid ventilation) in respiratory distress syndrome A prospective, randomized, controlled study

To determine the efficacy of perfluorocarbon-associated gas exchange (partial liquid ventilation) in respiratory distress syndrome. Prospective, randomized, controlled study. State University of New York at Buffalo, School of Medicine and Biomedical Sciences. Eleven premature lambs with respiratory distress syndrome, delivered by cesarean section. Five lambs were supported by conventional mechanical ventilation alone. Six lambs were switched to perfluorocarbon-associated gas exchange after 60 to 90 mins of conventional mechanical ventilation. Perfluorocarbon-associated gas exchange was accomplished by instilling a volume of liquid perfluorocarbon equivalent to normal functional residual capacity (30 mL/kg) into the trachea, performing 3 to 4 mins of tidal liquid ventilation, and, at end-expiration, with liquid functional residual capacity of 30 mL/kg remaining in the lung, reconnecting the animal to the volume ventilator for gas tidal volumes. Serial arterial blood gases and lung mechanics were measured. While receiving conventional ventilation, all animals developed progressive hypoxemia, hypercarbia, and acidosis. However, in the perfluorocarbon-associated gas exchange group, within 5 mins of the initiation of perfluorocarbon-associated gas exchange, mean PaO2 increased four-fold, from 59 +/- 6 torr (7.9 +/- 0.8 kPa) during conventional ventilation to 250 +/- 28 torr (33.3 +/- 3.7 kPa; p < .05) during perfluorocarbon-associated gas exchange, and this increase was sustained at 60 mins of perfluorocarbon-associated gas exchange (268 +/- 38 torr; 35.7 +/- 5.1 kPa; p < .05). Mean PaCO2 decreased progressively from 62 +/- 4 torr (8.3 +/- 0.5 kPa) during conventional ventilation to 38 +/- 3.3 torr (5.1 +/- 0.4 kPa) at 60 mins of perfluorocarbon-associated gas exchange (p < .05). Mean pH concomitantly increased. Dynamic compliance increased three-fold within 15 mins of instituting perfluorocarbon-associated gas exchange, from 0.31 +/- 0.02 mL/cm H2O during conventional ventilation to 0.90 +/- 0.11 mL/cm H2O during perfluorocarbon-associated gas exchange, and this increase was sustained at 60 mins of perfluorocarbon-associated gas exchange (p < .05). Mean peak expiratory flow and mean expiratory resistance were essentially unchanged during perfluorocarbon-associated gas exchange as compared with conventional ventilation in the same group. We conclude that perfluorocarbon-associated gas exchange, which employs liquid functional residual capacity and gas tidal volumes delivered by a conventional ventilator, can facilitate oxygenation and CO2 removal, and dramatically improve lung mechanics in the premature lamb with respiratory distress syndrome.

Perfluorocarbon-associated gas exchange

Liquid ventilation with oxygenated perfluorocarbon eliminates surface tension due to pulmonary air/fluid interfaces, and improves pulmonary function and gas exchange in surfactant deficiency. In liquid ventilation, perfluorocarbon is oxygenated, purged of CO2, and cycled into and out of the lungs using an investigational device. A new approach, perfluorocarbon-associated gas exchange, uses a conventional ventilator and combines features of liquid ventilation and continuous positive-pressure breathing. In 13 normal piglets, a volume of perfluorocarbon equivalent to the normal functional residual capacity (30 mL/kg) was instilled into the trachea, left in situ, and volume-regulated gas ventilation (FIO2 1.0) was resumed. For 1 hr, perfluorocarbon was continuously bubble-oxygenated within the lungs, where it directly participated in gas exchange. PaO2 and PaCO2 averaged 401 +/- 51 and 40 +/- 4 torr (53.6 +/- 6.8 and 5.3 +/- 0.5 kPa), respectively. Peak airway pressure during perfluorocarbon-associated gas exchange (22 +/- 2 cm H2O at 1 hr) and during continuous, positive-pressure breathing (23 +/- 4 cm H2O) were nearly identical. Venous oxygen saturation and pH were normal (73 +/- 8% and 7.43 +/- 0.05, respectively, at 1 hr). Perfluorocarbon-associated gas exchange was uniformly well tolerated, and its efficiency approached that of continuous positive-pressure breathing. Applications of perfluorocarbon technology to lung disease may not be limited by existing instrumentation.

Perfluorocarbon-associated gas exchange

Perfluorocarbon-associated gas exchange