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Liquid ventilation.

Partial liquid ventilation (PLV) developed considerably in the clinical and experimental fields during the past few years. In addition to improved oxygenation and lung mechanics by perfluorocarbon (PFC) administration, recent animal studies have tried to optimize PLV by evaluating the most appropriate ventilatory mode to use during PLV and by adjusting the best level of positive end-expiratory pressure (PEEP). Other pathophysiological aspects of acute lung injury that may be positively affected by liquid ventilation have been studied, including regional blood flow redistribution, reduction in ventilator-induced lung injury, and antiinflammatory properties of PFC. Although the precise dosing of PFC is debated, evidence from several experimental studies supports the use of smaller doses of PFC because larger doses increase the occurrence of baro- and volutrauma. In the clinical field, after promising data from preliminary studies, an international randomized controlled trial is on the verge of completion.

Fluorocarbons↗

High-frequency oscillatory ventilation with partial liquid ventilation in a model of acute respiratory failure.

OBJECTIVE: To determine whether there is an improvement in oxygenation when partial liquid ventilation and high-frequency oscillatory ventilation are combined in the treatment of acute lung injury, compared with high-frequency oscillatory ventilation alone. DESIGN: Controlled animal trial. SETTING: Research laboratory in a university setting. SUBJECTS: Ten 3-kg piglets. INTERVENTIONS: Anesthetized piglets underwent high-frequency oscillatory ventilation, with mean airway pressure of 20 cm H2O, before induction of acute lung injury with repeated saline lavage. When PaO2 values were < 100 torr (< 13.3 kPa), five animals were randomized to receive escalating doses (3, 15, and 30 mL/kg) of perflubron at 60-min intervals. The other five animals remained on high-frequency oscillatory ventilation only. Sham dosing was performed at 60-min intervals in these animals. Arterial blood gases were obtained in both groups at baseline, after injury, and after perflubron and sham doses. MEASUREMENTS AND MAIN RESULTS: Statistically significant improvements in oxygenation were demonstrated in animals that received 3 mL/kg of perflubron with high-frequency oscillatory ventilation compared with animals receiving high-frequency oscillatory ventilation alone (253 +/- 161 vs. 90 +/- 30 torr [33.65 +/- 21.46 vs. 12.0 +/- 4.0 kPa], p < .05). Improvements in oxygenation with additional administration of perflubron were not greater than the improvements seen in the high-frequency oscillatory ventilation-only group. PaCO2 and pH were similar in both groups at all times. No hemodynamic compromise occurred in either group of animals. CONCLUSIONS: The combination of low-dose perflubron with high-frequency oscillatory ventilation leads to more rapid improvement in arterial oxygenation than high-frequency oscillatory ventilation alone, in a piglet model of acute lung injury. Although the group receiving high-frequency oscillatory ventilation alone eventually achieved PaO2 values that were equivalent to the group receiving high-frequency ventilation and perflubron, the combination of perflubron with high-frequency oscillatory ventilation may permit effective oxygenation and ventilation at lower mean airway pressures by facilitating alveolar expansion and decreasing intrapulmonary shunt.

Analysis of Variance↗

[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.

Blood Gas Analysis↗

Treatment of pulmonary hypertension and hypoxia due to oleic acid induced lung injury with intratracheal prostaglandin E1 during partial liquid ventilation.

BACKGROUND: Partial liquid ventilation using perfluorocarbon liquids may be of therapeutic benefit in patients with acute respiratory failure. This study investigated the effects of prostaglandin E1 (PGE1) delivered intratracheally during partial liquid ventilation on lung function and pulmonary circulation in rabbits with acute respiratory distress syndrome. METHODS: Lung injury was induced by intravenous oleic acid in adult Japanese white rabbits, 1 h after which they were divided into four groups of 10 animals. Group 1 received mechanical ventilation alone, group 2 received aerosolized PGE1 (5 microg followed by 0.1 microg x kg(-1) x min(-1)) under mechanical ventilation combined with 5 cm H2O positive end-expiratory pressure, and groups 3 and 4 received partial liquid ventilation with 15 ml/kg perflubron. Group 4 received a 5-microg bolus followed by 0.1 microg x kg(-1) x min(-1) PGE1 instilled intratracheally (not by aerosol) in combination with partial liquid ventilation. Measurements were performed at 30-min intervals for 120 min after lung injury. RESULTS: After lung injury, hypoxemia, hypercapnia, acidosis, and pulmonary hypertension developed in all animals and were sustained in groups 1 and 2 throughout the experiment. The partial pressure of oxygen in arterial blood of animals in group 3 improved with initiation of treatment, with statistical significance achieved at the 30 and 60 min time points as compared with controls. Group 4 animals had immediate and sustained increases in the partial pressure of oxygen in arterial blood that were significant compared with all other groups during the experiment. Statistically significant reductions in mean pulmonary artery pressure were seen only in group 4 animals compared with all other groups. CONCLUSIONS: These results suggest that PGE1 delivered intratracheally during partial liquid ventilation may be a useful therapeutic strategy for patients with the acute respiratory distress syndrome.

Animals↗

Current status of liquid ventilation.

Perfluorochemical liquid has been used experimentally to enhance mechanical ventilation for the past 30 years. Liquid ventilation is one of the most extensively studied revolutionary medical therapies being considered for use in practice. Since 1989, when the first human neonates were treated with perfluorochemical liquid, more than 500 human patients--neonate, pediatric, and adult--have been treated with liquid ventilation as part of clinical trials. However, most of the clinically relevant information known to the medical field about liquid ventilation still comes from the laboratory. This paper seeks to briefly present current information available from studies involving liquid ventilation, both laboratory-based and clinical trials, as well as to inform the reader on patient management. In addition, we attempt to elucidate future directions.

Animals↗

Partial liquid ventilation in critically ill infants receiving extracorporeal life support. Philadelphia Liquid Ventilation Consortium.

OBJECTIVES: To demonstrate that a period of partial liquid ventilation (PLV) with perflubron improves pulmonary function, without adverse events, in a select group of critically ill infants receiving extracorporeal life support (ECLS) with a high likelihood of mortality. METHODS: This was an open-label, noncontrolled, phase I and II trial of PLV in two infants with congenital diaphragmatic hernia and four infants with acute respiratory distress syndrome (ARDS) who were failing to improve while receiving ECLS. PLV was performed by instilling and maintaining a functional residual capacity of sterile perflubron for 4 to 96 hours. RESULTS: Four infants were successfully weaned off ECLS for at least 3 days, and two infants (both with ARDS) are long-term survivors after PLV. All infants demonstrated lung recruitment and improved lung compliance, and there were no adverse events related to PLV. CONCLUSIONS: The study suggests that perflubron PLV is safe, improves lung function, and recruits lung volume in critically ill infants receiving ECLS. PLV therapy for infants with ARDS seems to have a great deal of promise. Based on this and other phase I and II trials, studies of PLV on selected full-term infants before ECLS have been initiated.

Emulsions↗

A closed rebreathing system for dose maintenance during Partial Liquid Ventilation.

Partial Liquid Ventilation (PLV), a treatment for acute respiratory failure in which the lungs are filled, either partially or to functional residual capacity (FRC), with perfluorochemical (PFC) liquid while the patient is on mechanical gas ventilation, has progressed to clinical trials using the PFC perflubron (PFB). Because gas expired during PLV is laden with PFB vapor, PFB is lost via evaporation, which increases dose consumption and necessitates periodic redosing. A device has been developed to minimize evaporative loss by confining PFC vapor to a gas volume breathed by the patient, which is isolated from the ventilator. This closed rebreathing system works with the ventilator such that after the lung is filled with PFB, the patient is connected to the rebreathing system, with breathing still "driven" by the ventilator. The rebreathing system consists of two gas circuits, or compartments, separated by a flexible bag (in a box) partition. One compartment is in gas communication with the lung, while the second communicates with the ventilator. The O2 level on the patient side is matched to that on the ventilator side by sensing gas concentrations and by feedback control of O2 introduction. Similarly, air is introduced into the patient side under pressure-based feedback control to maintain a constant gas volume. On inspiration, the ventilator delivers the tidal volume (breath) into the box surrounding the bag, which, in turn, is transmitted through the bag to the lung. On expiration, the process is reversed. Unidirectional circulation of gas in the rebreathing circuit is achieved via check valves, and expired CO2 is removed by a barium hydroxide lime cartridge. Airway humidification is maintained by captive water vapor in the system and water vapor from the CO2 absorber. It is recommended that flow, pressure, O2, and CO2 levels be monitored at the patient "Y," i.e., the proximal end of the endotracheal tube. Performance data from both in-vitro experiments and in-vivo PLV experiments in pigs are presented. The authors conclude that with the closed rebreathing system, the dose can be safely maintained with fewer redosing procedures, and an approximately 90% savings in dose is achieved.

Animals↗

Adjunctive therapy to mechanical ventilation: surfactant therapy, liquid ventilation, and prone position.

Acute lung injury and acute respiratory distress syndrome are associated with significant morbidity and mortality in critically ill patients. Although lung protective mechanical ventilation is the only therapy shown to reduce mortality and development of organ failure, several biologic pathways have been identified and provided an opportunity for therapeutic interventions. No pharmacologic or adjunctive treatments are available. Clinical studies demonstrated that prone position results in significant and clinically relevant improvement in oxygenation and ventilation, which persist when patients are returned to supine position; the beneficial response is not limited to patients turned early in disease course. Few complications are associated with prone ventilation. Clinical experience suggests that prone ventilation may protect the lung from potential detrimental effects of mechanical ventilation. Further studies are needed.

Humans↗

Positive end-expiratory pressure improves gas exchange and pulmonary mechanics during partial liquid ventilation.

Partial liquid ventilation (PLV) with perflubron (PFB) has been proposed as an adjunct to the current therapies for the acute respiratory distress syndrome (ARDS). Because PFB has been also referred to as "liquid PEEP," distributing to the most gravity-dependent regions of the lung, less attention has been paid to the amount of applied positive end-expiratory pressure (PEEP). We hypothesized that higher PEEP levels than currently applied are needed to optimize gas exchange, and that the lower inflection point (LIP) of the pressure-volume curve could be used to estimate the amount of PEEP needed when the lung is filled with PFB. Lung injury was induced in 23 sheep by repeated lung lavage with warmed saline until the PaO2/FIO2 ratio fell below 150. Five sheep were used to investigate the change of the LIP when the lung was filled with PFB in increments of 5 ml/kg/body weight to a total of 30 ml/kg/body weight. To evaluate the impact of PEEP set at LIP +1 cm H2O we randomized an additional 15 sheep to three groups with different doses (7.5 ml, 15 ml, 30 ml/kg/body weight) of PFB. In random order a PEEP of 5 cm H2O or PEEP at LIP +1 cm H2O was applied. The LIP decreased with incremental filling of PFB to a minimum at 10 ml (p < 0.05). Increasing PEEP from below LIP to LIP +1 cm H2O at 15 and 30 ml/kg resulted in an improvement in PaO2 from 152 +/- 36 to 203 +/- 68 (NS) and 193 +/- 57 to 298 +/- 80 (p < 0.05), respectively. Pulmonary shunt, and ratio of dead space volume to tidal volume (VD/VT) decreased, and static lung compliance increased with PEEP at LIP +1 cm H2O (p < 0.05). No changes were observed in hemodynamics. We conclude that increasing the dose of PFB shifts the LIP to the left, and that setting PEEP at LIP +1 cm H2O improves gas exchange at moderate to high doses of PFB.

Analysis of Variance↗

Perfluorocarbon protects lung epithelial cells from neutrophil-mediated injury in an in vitro model of liquid ventilation therapy.

Liquid ventilation with perfluorocarbon has been effective in improving gas exchange and pulmonary function in the setting of acute respiratory failure. How improvement is brought about remains unknown. In the present study, we examined perfluorocarbon for effects on neutrophil function and for effects on neutrophil-epithelial cell interactions that could underlie its in vivo activity. Exposure of neutrophils in vitro to perfluorocarbon followed by washing did not interfere with their ability to generate oxidants or release proteolytic enzymes upon subsequent stimulation. Likewise, such treatment did not interfere with subsequent adhesion of the neutrophils to monolayers of epithelial cells or with neutrophil-induced injury to these cells. In contrast, when perfluorocarbon was added to neutrophils and epithelial cells together and the neutrophils then stimulated, it reduced their adhesive interaction with the target cells and concomitantly reduced target cell injury. In companion studies, cells were obtained by bronchial lavage of perfluorocarbon-treated patients with acute respiratory distress syndrome (ARDS) and analyzed for oxidant production. Oxidant-generating capacity by the cells obtained from the bronchial lavage fluid was similar to that of peripheral blood neutrophils. These data are consistent with the suggestion that perfluorocarbon protects cells in vitro from neutrophil-mediated injury, at least in part, by acting as a mechanical barrier. These findings are consistent with a potential mechanism of action in vivo.

Bronchoalveolar Lavage Fluid↗

Effects of exogenous surfactant on lung pressure-volume characteristics during liquid ventilation.

Total liquid ventilation (LV) lowers airway pressures and potentially reduces barotrauma in models of hyaline membrane disease. LV eliminates surface tension by eliminating the air-perfluorochemicals (PFC) interface but does not eliminate interfacial tension (IT) at the lung/PFC interface. We hypothesized that pretreatment with exogenous surfactant before LV would shift the overall pressure-volume (PV) curve to the left, compared with LV without surfactant. Sequential quasi-static PV curves were obtained in 10 excised lungs (saline, air, PFC), with one-half randomized to exogenous surfactant replacement before LV. Analysis revealed that maximal inflation pressures were reduced during LV compared with baseline air curves. Addition of exogenous surfactant to LV further reduced maximal inflation pressures. A novel approach was used to transform these PV curves to estimates of in situ IT-volume curves. Estimated maximal IT at 20 ml/kg in preterm lamb lungs on air inflation after surfactant was 51 mN/m, compared with 40 mN/m for LV alone and with 27 mN/m for the combination of surfactant and LV. We conclude that the IT-reducing properties of the PFC studied (perflubron) can be augmented through the use of exogenous surfactant.

Animals↗

The effect of mode, inspiratory time, and positive end-expiratory pressure on partial liquid ventilation.

Partial liquid ventilation (PLV) has been shown to be an effective means of improving oxygenation in the injured lung. However, little is known about how approach to ventilation during PLV affects gas exchange and pulmonary mechanics. We hypothesized that gas exchange and pulmonary mechanics would be best with positive end-expiratory pressure (PEEP) set above the lower inflection point (LIP) of the pressure-volume (P-V) curve regardless of mode of ventilation or inspiratory to expiratory time (I:E) ratio and that the efficiency of ventilation would be greatest with volume-controlled ventilation (VCV) compared with pressure-controlled ventilation (PCV) and with long inspiratory time as compared with short inspiratory time. Lung injury was induced in 14 sheep by lavage, 10 of which were studied. Sheep were then assigned to high-PEEP (Group H, n = 5) and low-PEEP (Group L, n = 5) groups. In Group H applied PEEP was set at the LIP and in Group L applied PEEP was set at 5 cm H2O after the lung was filled with perflubron (PFB). We randomly compared VCV and PCV with I:E ratios of 1:2, 1:1, and 2:1. Peak inspiratory pressure and VT were adjusted to maintain a constant end-inspiratory plateau pressure (Pplat) of about 25 cm H2O in both groups and a constant total PEEP of about 5 cm H2O in Group L and about 12 cm H2O in Group H. There were no differences in oxygenation among modes in Group H. In Group L VCV 2:1 and all of the PCV modes in Group L had a lower PaO2 than VCV 1:1 (p < 0.05). PaCO2 and VD/VT were significantly different (p < 0.05) among modes. VD/VT was highest during PCV 1:2 with PEEP of 5 cm H2O (p < 0.05). Quasi-static compliance in Group H was higher than in Group L (p < 0.05). We conclude that during low PEEP gas exchange deteriorated in VCV with long inspiratory time and in PCV. Oxygenation was enhanced during VCV 1:1 when compared with VCV at longer I:E ratios or PCV at any I:E ratio. With PEEP set at the LIP, adequate gas exchange and improved lung mechanics could be obtained in all modes assessed.

Animals↗

Partial liquid ventilation ventilates better than gas ventilation.

Partial liquid ventilation (PLV) improves oxygenation in several models of lung injury. However, PLV has only been compared with conventional gas ventilation (GV) with low PEEP. Both PLV and GV can markedly improve oxygenation when PEEP is set above the lower corner pressure (Plc) on the inspiratory pressure-volume (P-V) curve of the total respiratory system. We questioned if the use of PEEP set above the Plc during PLV and GV would result in similar gas exchange. Lung injury was induced in 12 sheep by saline lavage before randomization to PLV (n = 6) or GV (n = 6). Animals in the PLV group were filled with perflubron (22 ml/kg) until a meniscus at the teeth was observed. Both groups were then ventilated with pressure control (FI(O(2)), 1.0; rate, 20/min; I:E, 1:1) and PEEP (1 cm H(2)O above the Plc on the inspiratory P-V curve). Peak inspiratory pressure (PIP) was limited to 35 cm H(2)O. Animals were ventilated for 5 h and then killed for histologic examinations. All 12 animals survived the 5-h ventilation period. After increasing PEEP above Plc, Pa(O(2)) increased significantly (p < 0.01) in both the GV and the PLV groups, but it did not differ significantly between groups (p = 0.86) at any time during the experiment. Pa(CO(2)) and VD/VT in GV increased markedly throughout the experiment after increasing PEEP (p < 0.001), but there was no significant change in Pa(CO(2)) in PLV (p = 0.13). Mean arterial blood pressure, mean pulmonary artery pressure, pulmonary artery occlusion pressure, and central venous pressure, increased and SVR decreased in GV (p < 0.05). The extent and the severity of lung injury in the dependent regions was greater in the GV group (p < 0.05). Both PLV and GV improved oxygenation, but PLV resulted in better ventilation than GV while preserving lung structure when PEEP was set 1 cm H(2)O above the Plc and PIP limited to 35 cm H(2)O.

Animals↗

Liquid ventilation.

Research on using liquid ventilation to provide artificial respiration in mammals has been ongoing since the 1960s. The development of inert perfluorocarbon (PFC) liquids with high oxygen and carbon dioxide solubility has made gas exchange with liquid ventilation possible. In 1991 the technique of partial liquid ventilation was introduced where PFC are instilled into the lungs whilst continuing with conventional mechanical ventilation. Partial liquid ventilation has been shown to improve gas exchange and lung function with decreased secondary lung injury, in animal models of acute lung injury and surfactant deficiency. It has been used in uncontrolled trials in preterm neonates, and preliminary results are available from a randomized controlled trial of partial liquid ventilation in paediatric acute respiratory distress syndrome. Perfluorocarbons can also be used to deliver drugs to the lungs, to lavage inflammatory exudate and debris from the lungs, and as an intrapulmonary X-ray contrast medium. Many questions about partial liquid ventilation remain unanswered particularly with regard to the dose of PFC required, its ideal method of administration and the long-term effects. Partial liquid ventilation promises to be an exciting new therapy for infants and children with a variety of respiratory problems. The technique requires ongoing research and experimentation.

Acute Disease↗

Comparison of perfluorochemical fluids used for liquid ventilation: effect of endotracheal tube flow resistance.

Neonatal endotracheal tubes with small inner diameters are associated with increased resistance regardless of the medium used for assisted ventilation. During liquid ventilation (LV) reduced interfacial tension and pressure drop along the airways result in lower alveolar inflation pressure compared with gas ventilation (GV). This is possible by optimizing liquid ventilation strategies to overcome the resistive forces associated with liquid density (rho) and viscosity (mu) of these fluids. Knowledge of the effect of rho, mu, and endotracheal tube (ETT) size on resistance is essential to optimize LV strategies. To evaluate these physical properties, three perfluorochemical (PFC) fluids with a range of kinematic viscosities (FC-75 = 0.82, LiquiVent = 1.10, APF-140 = 2.90) and four different neonatal ETT tubes (Mallincrokdt Hi-Lo Jet ID 2.5, 3.0, 3.5, and 4.0 mm) were studied. Under steady-state flow, flow and pressure drop across the ETTs were measured simultaneously. Resistance was calculated by dividing pressure drop by flow, and both pressure-flow and resistance-flow relationships were plotted. Also, pressure drop and resistance were each plotted as a function of kinematic viscosity at flows of 0.01 L.s-1 for all four ETT sizes. Data demonstrated a quadratic relationship with respect to pressure drop versus flow, and a linear relationship with resistance versus flow: both were significantly correlated (R = 0.92; P < 0.01) and were inversely related to ETT size. Additionally, there was a significant correlation between pressure drop or resistance and kinematic viscosity (R = 0.99; P < 0.01). For LV in neonates these data can be used to select the optimum ETT size and PFC liquid depending OR the chosen ventilation strategy.

Airway Resistance↗

Evaluation of work of breathing in spontaneously breathing animals during partial liquid ventilation.

BACKGROUND: Partial liquid ventilation improves lung mechanics and gas exchange in paralyzed mechanically ventilated animals. OBJECTIVE: Examine the work of breathing (WOB) in a spontaneously breathing animal model during partial liquid ventilation with and without the use of pressure-support ventilation (PSV). METHODS: This was a prospective study including 6 lambs (mean weight 10.9 +/- 1.3 kg). Baseline measurements, including total work of breathing (WOB(T)), elastic work of breathing (WOB(E)), and resistive work of breathing (WOB(R)), were obtained using pressure-controlled synchronized intermittent mandatory ventilation with positive end-expiratory pressure of 5 cm H(2)O at PSV levels of 0, 5, and 10 cm H(2)O. The animals' lungs were filled with perflubron through an endotracheal tube, in 10-20 mL aliquots, until filled, approximately 30 mL/kg or functional residual capacity. Repeat measurements were obtained at 10 mL/kg, 20 mL/kg, and full. Perflubron was then allowed to evaporate from the lungs and repeat measurements were obtained 3 additional times, with at least a 1 hour separation between phases, for up to 7 hours after the lungs were filled. RESULTS: No differences were detected in WOB(T), WOB(R), or WOB(E) between the gas-filled lung and the lung filled to functional residual capacity with perflubron. However, compared to the gas-filled lung, WOB(T) and WOB(R) were higher during the filling (p < 0.05) and evaporative phases (p < 0.05). The PSV level affected WOB. Work of breathing was least at PSV 10 cm H(2)O. CONCLUSION: In this pilot study of healthy animals breathing spontaneously with perflubron-filled lungs, there was an acceptable amount of WOB, which decreased with the addition of PSV. However, WOB increased when the perflubron level was not maintained at functional residual capacity.

Airway Resistance↗

Measurement of changes in respiratory mechanics during partial liquid ventilation using jet pulses.

OBJECTIVE: To compare the changes in respiratory mechanics within the breathing cycle in healthy lungs between gas ventilation and partial liquid ventilation using a special forced-oscillation technique. DESIGN: Prospective animal trial. SETTINGS: Animal laboratory in a university setting. SUBJECTS: A total of 12 newborn piglets (age, <12 hrs; mean weight, 725 g). INTERVENTIONS: After intubation and instrumentation, lung mechanics of the anesthetized piglets were measured by forced-oscillation technique at the end of inspiration and the end of expiration. The measurements were performed during gas ventilation and 80 mins after instillation of 30 mL/kg perfluorocarbon PF 5080. MEASUREMENTS AND MAIN RESULTS: Brief flow pulses (width, 10 msec; peak flow, 16 L/min) were generated by a jet generator to measure the end-inspiratory and the end-expiratory respiratory input impedance in the frequency range of 4-32 Hz. The mechanical variables resistance, inertance, and compliance were determined by model fitting, using the method of least squares. At least in the lower frequency range, respiratory mechanics could be described adequately by an RIC single-compartment model in all piglets. During gas ventilation, the respiratory variables resistance and inertance did not differ significantly between end-inspiratory and end-expiratory measurements (mean [sd]: 4.2 [0.7] vs. 4.1 [0.6] kPa x L(-1) x sec, 30.0 [3.2] vs. 30.7 [3.1] Pa x L(-1) x sec2, respectively), whereas compliance decreased during inspiration from 14.8 (2.0) to 10.2 (2.4) mL x kPa(-1) x kg(-1) due to a slight lung overdistension. During partial liquid ventilation, the end-inspiratory respiratory mechanics was not different from the end-inspiratory respiratory mechanics measured during gas ventilation. However, in contrast to gas ventilation during partial liquid ventilation, compliance rose from 8.2 (1.0) to 13.0 (3.0) mL x kPa(-1) x kg(-1) during inspiration. During expiration, when perfluorocarbon came into the upper airways, both resistance and inertance increased considerably (mean with 95% confidence interval) by 34.3% (23.1%-45.8%) and 104.1% (96.0%-112.1%), respectively. CONCLUSIONS: The changes in the respiratory mechanics within the breathing cycle are considerably higher during partial liquid ventilation compared with gas ventilation. This dependence of lung mechanics from the pulmonary gas volume hampers the comparability of dynamic measurements during partial liquid ventilation, and the magnitude of these changes cannot be detected by conventional respiratory-mechanical analysis using time-averaged variables.

Airway Resistance↗