Partial Liquid Ventilation Group Research Articles

High-frequency oscillatory ventilation combined with partial liquid ventilation in experimental lung injury: effects on lung cell apoptosis

SummaryObjectiveTo investigate the effects of high-frequency oscillatory ventilation (HFOV) and partial liquid ventilation (PLV) on apoptosis of lung tissue induced by steam inhalation injury in rabbit.DesignA prospective, randomized, controlled, multiple-group study.SettingAn animal research laboratory centre in a university burns centre.SubjectsNew Zealand rabbits (n = 32; 2.25 ± 0.25 kg) of either sex.InterventionsThe animals were ventilated by HFOV with a mean airway pressure of 10 cm H2O, a frequency of 10 Hz, an amplitude of 20 cm H2O, an inspiratory:expiratory ratio of 1:1, and an FiO2 of 1.0. After the induction of acute lung injury (ALI) by steam inhalation, the animals were randomly divided into four groups: CMV, HFOV, CMV + PLV, HFOV + PLV group. Then they were ventilated for 4 h by CMV, HFOV, CMV + PLV and HFOV + PLV, respectively. After the experimental period, cell apoptosis and apoptosis indexes in the lung tissue were assessed with TUNEL FragELTM (Fragment End Labeling).ResultsLung tissue apoptosis indexes in HFOV group and HFOV + PLV group were lower than that of in CMV group and CMV + PLV group; between-group comparison had significant difference (P < 0.01). HFOV + PLV group showed lowest apoptosis indexes.ConclusionHFOV combined with PLV can suppress lung tissue apoptosis induced by steam inhalation.

The effect of partial liquid ventilation on inflammatory response in piglets with acute lung injury induced by lipopolysaccharide

To evaluate the effect of partial liquid ventilation (PLV) on pro-inflammatory and anti-inflammatory factors change in lipopolysaccharide (LPS)-induced piglets acute lung injury (ALI). Twelve Shanghai white piglets were randomly divided into mechanical ventilation (MV) group (n=6) and PLV group (n=6). 60 μg×kg(-1)×h(-1) LPS were intravenous infused continuously for 2 hours to induce ALI model. PLV model was set on the basis of the MV by endotracheal injection of perfluorodecalin (PFC, 10 mL/kg). The hemodynamic and respiratory parameters such as mechanics and arterial blood gas analysis were monitored at basic condition and after lung injury establishment (0, 1, 2, 4 hours). The serum levels of interleukin (IL-1β, IL-6, IL-8, IL-10) and tumor necrosis factor-α (TNF-α) were dynamically monitored by enzyme linked immunosorbent assay (ELISA). A lung injury score was used to quantify lung tissues change under light microscopic observations. Ventilation and oxygenation function were improved gradually after PFC endotracheal injection in PLV group, and there were significant difference compared with MV group at 4 hours [heart rate (HR): 144 ± 6 beats/min vs. 179 ± 9 beats/min, respiratory rate (RR): 58 ± 4 beats/min vs. 77 ± 6 beats/min, mean arterial blood pressure (MAP): 99 ± 7 mmHg vs. 75 ± 29 mmHg, dynamic lung compliance (Cdyn): 1.9 ± 0.3 mL×cmH(2)O(-1)×kg(-1) vs. 1.2 ± 0.4 mL×cmH(2)O(-1)×kg(-1), tidal volume (VT): 7.8 ± 0.4 mL/kg vs. 5.8 ± 0.9 mL/kg, mean airway resistance (Raw): 20.5 ± 6.6 cmH(2)O×L(-1)×s(-1) vs. 35.2 ± 4.0 cmH(2)O×L(-1)×s(-1), mean airway pressure (Paw): 1.0 ± 0.5 cmH(2)O vs. 3.0 ± 0.9 cmH(2)O, ventilation efficacy index (VEI): 0.18 ± 0.02 vs. 0.08 ± 0.02, pH value: 7.386 ± 0.143 vs. 7.148 ± 0.165, arterial partial pressure of oxygen (PaO(2)): 121.8 ± 12.5 mmHg vs. 73.6 ± 10.9 mmHg, arterial partial pressure of carbon dioxide (PaCO(2)): 39.6 ± 20.3 mmHg vs. 66.8 ± 23.5 mmHg, oxygenation index (PaO(2)/FiO(2)): 311 ± 35 mmHg vs. 184 ± 27 mmHg, P<0.05 or P<0.01]. All serum cytokines in both groups were significantly increased after LPS-induced ALI, and showed an elevated tendency. The serum pro-inflammatory factors of TNF-α, IL-1β, IL-6 and IL-8 in PLV group were significantly lower than those in MV group at 4 hours (TNF-α: 98.4 ± 21.1 ng/L vs. 178.0 ± 55.0 ng/L, IL-1β: 142.0 ± 38.0 ng/L vs. 226.0 ± 55.0 ng/L, IL-6: 763.0 ± 282.0 ng/L vs. 1 303.0 ± 260.0 ng/L, IL-8: 1 183.0 ± 403.0 ng/L vs. 1 876.0 ± 232.0 ng/L, P<0.05 or P<0.01). There was no significant difference in serum anti-inflammatory factor of IL-10 between PLV and MV groups at 4 hours (292.0 ± 40.0 ng/L vs. 208.0 ± 82.0 ng/L, P>0.05). The ratio of TNF-α/IL-10 in PLV group was significantly decreased compared with MV group at 2 hours (0.58 ± 0.13 vs. 1.13 ± 0.54, P<0.05). The ratio of IL-6/IL-10 in PLV group was significantly decreased compared with MV group at 4 hours (2.72 ± 1.27 vs. 7.17 ± 3.08, P<0.01). Microscopic changes in intra-alveolar and interstitial inflammation, hemorrhage and edema were better in PLV group than those in MV group. The lung injury score of PLV group was lower than MV group (independent lung regions: 9.8 ± 0.8 vs. 11.8 ± 1.0, t=3.956, P=0.003; dependent lung regions: 5.0 ± 0.6 vs. 14.7 ± 2.3, t=10.127, P=0.000). PLV can significantly reduce the levels of pro-inflammatory factors and the ratio of pro-inflammatory/anti-inflammatory factor, which may contribute to the protective effects of PLV on ALI.

Effect of partial liquid ventilation on lung function in oleic acidinduced lung injury model of piglets

Background Pediatric patients are susceptible to lung injury that does not respond to traditional therapies. Partial liquid ventilation (PLV) has been developed as an alternative ventilatory strategy for treating severe lung injury. The aim of this study is to investigate the effect of PLV on lung function in immature piglets. Methods Acute lung injury was induced in 12 Chinese immature piglets by oleic acid (OA). The animals were randomly assigned to two groups (n=6 each group): (1) conventional mechanical ventilation (MV) group and (2) PLV with FC-77 (10 ml/kg) group. Mean arterial blood pressure (MAP), mean pulmonary arterial pressure (MPAP), central venous pressure (CVP), left atrial pressure (LAP), systemic vascular resistance (SVR), pulmonary vascular resistance (PVR), cardiac output (CO), mean pressure of airway (Paw), dynamic lung compliance (Cydn), and arterial blood gases were measured during the observation period. Results No piglet died in either group with severe lung injury. After four hours of ventilation, pH in the MV group gradually decreased to lower than 7.20, while in the PLV group, pH also gradually decreased but remained higher than 7.20 (P &lt;0.05). Partial pressure of oxygen in artery (PaO2) decreased in both groups, but with a significant difference between the PLV group and MV group (P &lt;0.05). Partial pressure of carbon dioxide in artery (PaCO2) increased in both groups, but with a significant difference between the PLV group and MV group (P &lt;0.05). Paw increased in both groups, but was not significantly different (P &gt;0.05). Cydn decreased in both groups, but without a significant difference (P &gt;0.05). At four hours, heart rate (HR) and MAP in both groups decreased. MPAP in both groups increased, and there was a significant difference between the two groups (P &lt;0.05). CVP was stable in both groups. At four hours, PVR and LAP were increased in both groups. CO was decreased in both groups (P &lt;0.05). SVR was stable during the observation time. Conclusion PLV did not improve outcome in changes of lung function.

A comparison of conventional surfactant treatment and partial liquid ventilation on the lung volume of injured ventilated small lungs

As an alternative to surfactant therapy (ST), partial liquid ventilation (PLV) with perfluorocarbons (PFC) has been considered as a treatment for acute lung injury (ALI) in newborns. The instilled PFC is much heavier than the instilled surfactant and the aim of this study was to investigate whether PLV, compared to ST, increases the end-expiratory volume of the lung (VL). Fifteen newborn piglets (age <12 h, mean weight 678 g) underwent saline lung lavage to achieve a surfactant depletion. Thereafter animals were randomized to PLV (n = 8), receiving PFC PF5080 (3M, Germany) at 30 mL kg−1, and ST (n = 7) receiving 120 mg Curosurf®. Blood gases, hemodynamics and static compliance were measured initially (baseline), immediately after ALI, and after 240 min mechanical ventilation with either technique. Subsequently all piglets were killed; the lungs were removed in toto and frozen in liquid N2. After freeze-drying the lungs were cut into lung cubes (LCs) with edge lengths of 0.7 cm, to calculate VL. All LCs were weighed and the density of the dried lung tissue was calculated. No statistically significant differences between treatment groups PLV and ST (means ± SD) were noted in body weight (676 ± 16 g versus 679 ± 17 g; P = 0.974) or lung dry weight (1.64 ± 0.29 g versus 1.79 ± 0.48 g; P = 0.48). Oxygenation index and ventilatory efficacy index did not differ significantly between both groups at any time. VL (34.28 ± 6.13 mL versus 26.22 ± 8.1 mL; P < 0.05) and the density of the dried lung tissue (48.07 ± 5.02 mg mL−1 versus 69.07 ± 5.30 mg mL−1; P < 0.001), however, differed significantly between the PLV and ST groups. A 4 h PLV treatment of injured ventilated small lungs increased VL by 30% and decreased lung density by 31% compared to ST treatment, indicating greater lung distension after PLV compared to ST.

Effects of different mechanical ventilation methods on morphology of type II alveolar epithelium cell in newborn piglets with acute lung injury

Objective To investigate the effects of 3 different ventilation methods, including conventional mechanical ventilation(CMV), high-frequency oscillatory ventilation(HFOV) and partial liquid ventilation(PLV), on the morphology of type Ⅱ alveolar epithelium cell(ACEⅡ) of newborn piglet with acute lung injury(ALI). Methods Twenty-four less than 3-day-old newborn piglets were enrolled.After ALI was established with saline lavage(38 ℃, 0.035 L/kg), newborn piglets were randomly assigned to 4 study groups: control group(n=6, no ventilation), CMV group(n=6), HFOV group(n=6), and PLV group(n=6, 38 ℃, 0.018 L/kg). Piglets in the 4 groups were sacrificed after being ventilated for 24 hours, and the number, area, density of fluorescence of ACEⅡ were detected. Results Through 24 hours mechanical ventilation, the numbers of ACEⅡ in CMV group, HFOV group and PLV group remained were 30±5, 52±5, 81±7, respectively, while areas of fluorescence were 340.40±47.50, 329.69±124.50, 295.55±109.30, respectively, and there were significant differences among the 3 groups, and the population mean of density of fluorescence had significant difference among the 3 groups.The number of ACEⅡremains was lowest in CMV group compared with HFOV group(P=0.026) and PLV group(P=0.000), and the density of fluorescence of ACEⅡ was lowest in CMV group compared with HFOV group(P=0.001) and PLV group(P=0.002). Conclusions Different mechanical ventilations have various effects for ACEⅡ, and CMV is the most harmful mechanical ventilation on ACEⅡ, while PLV is the least harmful. Key words: Mechanical ventilation; Type Ⅱ alveolar epithelium cell; Morphology; Newborn piglet

Cerebral blood flow is not affected during perfluorocarbon dosing with volume-controlled ventilation

Perfluorocarbon administration increases cerebral blood flow. This can be mitigated by preventing a rise in carbon dioxide by adjusting pressure-controlled ventilation. Volume-controlled ventilation should prevent increases in arterial carbon dioxide and cerebral blood flow. This study aims to determine if cerebral blood flow is increased during administration of 10 mL/kg of perfluorocarbon while using volume-controlled ventilation. Two New Zealand white rabbits, ventilated with volume-control, were each allocated to six dosing events where each dosing event was randomly allocated to one of two dosing strategies: a control group - given a sham dose of air (10 mL/kg) over 20 min; or a partial liquid ventilation group - given 10 mL/kg FC-77 slowly over 20 min. Data were recorded for 1 min before and 30 min after the start of each dosing event. No adjustment of ventilation (except fraction of inspired oxygen) was allowed during each dosing event. There were no significant changes over time and no differences between groups for carotid blood flow (P = 0.48 at the end of the dose). There were slight increases in cortical cerebral blood flow in both groups; there was no statistically significant difference between groups (P = 0.56 at end dose and P = 0.49 at time of maximum difference). There was no difference between groups for the variability in carotid blood flow or cortical cerebral blood flow. Cerebral blood flow was not significantly increased during administration of a dose of 10 mL/kg of perfluorocarbon during commencement of partial liquid ventilation when using volume-controlled ventilation.

Effects of mechanical ventilation method on inflammatory factors and pulmonary surfactant associated protein A of bronchoalveolar lavage fluid in newborn piglets with acute lung injury

Objective To investigate the effects of 3 different ventilation methods, including conventional mechanical ventilation (CMV), high frequency oscillatory ventilation(HFOV) and partial liquid ventilation (PLV), on the changes of inflammatory factors and pulmonary surfactant associated protein A(SP-A) in bronchoalveolar lavage fluid(BALF) in newborn piglets with acute lung injury(ALI). Methods Twenty-four newborn piglets, no more than 3 days old, were enrolled.After ALI made with saline lavage(38 ℃, 35 mL/kg), newborn piglets were randomly assigned to 4 groups: control group (n=6, no ventilation), CMV group(n=6), HFOV group(n=6), and PLV group(n=6). Piglets were sacrificed after being ventilated for 24 h. Tumor necrosis factor-α(TNF-α), interleukin-8(IL-8), interleukin-1(IL-1) and SP-A in BALF were measured quantitatively by using enzyme-linked immunosorbent assay. Results In 3 groups using different ventilation methods, the population mean of TNF-α, IL-8, IL-1 and SP-A were statistically diffe-rent(all P=0.000). SP-A in PLV group and HFOV group were higher than that in CMV group (all P<0.05), while IL-8, IL-1 and TNF-α in PLV group were lower than those in CMV group (all P<0.05), IL-8 and TNF-α in PLV group were lower than those in HFOV group (all P<0.05), IL-8 and TNF-α in HFOV group were lower than those in CMV group (all P<0.05). Conclusions Pulmonary inflammatory reaction was different in 3 ventilation groups.Compared with CMV and HFOV, PLV attenuated inflammatory reaction, so it could increase the expression of SP-A and decrease the degradation of SP-A. Key words: Mechanical ventilation method; Bronchoalveolar lavage fluid; Inflammatory factor; Pulmonary surfactant associated protein A

Partial liquid ventilation for the prevention of mortality and morbidity in paediatric acute lung injury and acute respiratory distress syndrome.

Acute lung injury and acute respiratory distress syndrome are syndromes of severe respiratory failure. Children with acute lung injury or acute respiratory distress syndrome have high mortality and the survivors have significant morbidity. Partial liquid ventilation is proposed as a less injurious form of respiratory support for these children. Uncontrolled studies in adults have shown improvements in gas exchange and lung compliance with partial liquid ventilation. A single uncontrolled study in six children with acute respiratory syndrome showed some improvement in gas exchange during three hours of partial liquid ventilation. This review was originally published in 2004, updated in 2009 and again in 2012. To assess whether partial liquid ventilation reduces mortality or morbidity, or both, in children with acute lung injury or acute respiratory distress syndrome. In this updated review, we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 11); CINAHL (Cumulative Index to Nursing & Allied Health Literature) via Ovid (1982 to November 2011); Ovid MEDLINE (1950 to November 2011); and Ovid EMBASE (1982 to November 2011). The search was last performed in August 2008. We included randomized controlled trials (RCTs) which compared partial liquid ventilation with other forms of ventilation in children (aged 28 days to 18 years) with acute lung injury or acute respiratory distress syndrome. Trials had to report one or more of the following: mortality; duration of mechanical ventilation, respiratory support, oxygen therapy, stay in the intensive care unit, or stay in hospital; infection; long-term cognitive impairment, neurodevelopmental progress, or other long-term morbidities. We independently evaluated the quality of the relevant studies and extracted the data from the included studies. Only one study enrolling 182 patients (reported as an abstract in conference proceedings) was identified and found eligible for inclusion; the authors reported only limited results. The trial was stopped prematurely and was, therefore, under-powered to detect any significant differences and at high risk of bias. The only available outcome of clinical significance was 28-day mortality. There was no statistically significant difference between groups, with a relative risk for 28-day mortality in the partial liquid ventilation group of 1.54 (95% confidence interval 0.82 to 2.9). There is no evidence from RCTs to support or refute the use of partial liquid ventilation in children with acute lung injury or acute respiratory distress syndrome. Adequately powered, high quality RCTs are still needed to assess its efficacy. Clinically relevant outcome measures should be assessed (mortality at discharge and later, duration of both respiratory support and hospital stay, and long-term neurodevelopmental outcomes). The studies should be published in full.

60 Comparison Between Aerosolized Perfluorocarbon and Partial Liquid Ventilation in Preterm Lambs With Severe Respiratory Distress Syndrome

Background and aimPerfluorocarbon (PFC) aerosolization is feasible; however, it is unknown whether aerosolization is better than Partial Liquid Ventilation (PLV).Methods18 preterm lambs were randomly assigned to receive aerosolized PFC (10...

Perfluorocarbon Dosing when Starting Partial Liquid Ventilation: Haemodynamics and Cerebral Blood Flow in Preterm Lambs

Background: Very preterm neonates can have severe lung disease and are prone to brain injury if cerebral blood flow fluctuates. Partial liquid ventilation (PLV) may benefit the lung disease, but it is unknown whether the administration of intratracheal perfluorocarbon when starting PLV affects haemodynamics or cerebral blood flow. Objectives: To determine if haemodynamics or cerebral blood flow are affected in preterm lambs receiving a dose of perfluorocarbon when starting PLV. Methods: Sixteen preterm lambs were randomised to either PLV or conventional mechanical ventilation. An intratracheal loading dose of 30 ml/kg of perfluorocarbon liquid (PLV group) or air (sham group) was instilled over 20 min. Data were collected continuously for 30 min from the start of dosing. Results: Cortical cerebral blood flow velocity, measured continuously with laser Doppler, was increased in the PLV group during the administration of perfluorocarbon and immediately thereafter (p = 0.0026); the highest mean increase in the PLV group was 27%. There was no difference in cortical cerebral blood flow variability (p = 0.96). There was a slightly lower mean arterial blood pressure in the PLV group; the heart rate did not differ between groups. The PaCO₂ was higher in the PLV group at 30 min – the difference between groups was not statistically significant (difference between means = 5.5 mm Hg, 95% confidence interval –2.7 to 13.7). Conclusions: Preterm lambs receiving a dose of tracheal perfluorocarbon at the start of PLV have an increased cortical cerebral blood flow velocity, but no change in cortical cerebral blood flow variability.

Partial liquid ventilation confers protection against acute lung injury induced by endotoxin in juvenile piglets

To investigate the effect of partial liquid ventilation (PLV) at low inflation pressures on acute lung injury (ALI), endotoxin was administered to healthy anesthetized juvenile piglets. The animals were randomly assigned to two groups, n=6 each: (1) conventional mechanical ventilation (MV) and (2) PLV with perfluorodecalin (10 mL kg(-1)). Compared with MV, PLV improved each cardiopulmonary variable measured. These variables included pulse contour cardiac output, heart rate, blood pH, breathing rate, both partial pressure of arterial oxygen (PaO2) and PaO2/FIO2 (fraction of inspired oxygen), partial pressure of arterial carbon dioxide (PaCO2), dynamic lung compliance, tidal volume, and ventilation efficacy index. Lung morphology also showed less damage in the PLV group, even in non-dependent regions (P<0.05). Our data support the hypothesis that PLV can decrease pulmonary damage, improve gas exchange and cardiac output, and may lead to a better prognosis in endotoxin-induced ALI.

Effects of perfluorochemical evaporative properties on oxygenation during partial liquid ventilation

The physical-chemical properties of perfluorochemical (PFC) liquids have been shown to influence physiological and cellular responses during partial liquid ventilation (PLV). The aim of this study is to compare the relationship between patho-physiological endpoints and the physical properties of three PFC liquids used in treating acute lung injury. A total of 18 juvenile rabbits were randomized into conventional mechanical ventilation or PLV groups after lung saline lavages. Three PFC liquids, including Flutec perfluoro-1,3,5-trimethylcyclohexane (PP4; vapor pressure, 28.8 mmHg at 37 degrees C), Perfluorodecalin (PFD; vapor pressure, 13.6 mmHg at 37 degrees C), and Perflubron (PFB; vapor pressure, 10.4 mmHg at 37 degrees C) were used for PLV with no replacement for 4 h. A thermal detector was used to measure PFC loss rate. Physiological measurements and evaporative loss rate of PFC were done every 30 min, and lung histology was examined. The mean evaporative loss rate was significantly higher in the PP4 group (4.75 +/- 0.24 mL/kg per h) than in either the PFD (1.43 +/- 0.11 mL/kg per h) or the PFB (1.18 +/- 0.05 mL/kg per h) group (P < 0.05). The oxygenation of PFD and PFB was maintained good for 4 h, however, the PP4 group showed a fast deterioration since 2 h post-treatment due to fast dropping of the residual PP4 amount in lungs. Histology showed good alveolar integrity in the PFD and PFB groups. The effects of PLV are directly influenced by the evaporative property of the PFC liquid. With no replacement over 4 h, PLV effects could be maintained with utilizing a PFC liquid with low, rather than high, vapor pressure. PFC with high vapor pressure has a high loss rate and low residual volume that causes poor maintenance on oxygenation during PLV. Therefore, measuring PFC loss rate is important in future studies and clinical application of PLV.

Effects of vaporized perfluorohexane and partial liquid ventilation on regional distribution of alveolar damage in experimental lung injury

To determine whether the patterns of distribution of histological effects of vaporized perfluorohexane (PFH) and partial liquid ventilation (PLV) differ significantly in acute lung injury. Experimental study in an animal research laboratory. Eighteen pigs. After induction of acute lung injury by means of infusion of oleic acid animals were randomly assigned to PFH, PLV, or gas ventilation (GV) groups. Six hours thereafter animals were killed, and lung tissue samples were taken for analysis. Histopathological analysis revealed less damage with PFH than with GV or PLV in the nondependent and central regions. PFH and PLV showed less injury in the dependent regions than GV. GV and PFH were associated with less histological damage in the nondependent than the dependent regions, whereas PLV presented the opposite pattern. Morphometric analysis showed increased aeration in nondependent than dependent regions with PFH and GV. PLV led to more aeration in the periphery than in central areas. PFH was associated with a more homogeneous attenuation of alveolar damage across the lungs, although this therapy had more pronounced effects in nondependent zones. PLV showed the opposite pattern, with more important reduction in alveolar damage in dependent lung regions. Interestingly, reduction in alveolar damage with PFH was as effective as with PLV in dependent zones. Our findings suggest that vaporized perfluorocarbon could be advantageous as adjunctive therapy in the treatment of acute lung injury.

VAPORIZED PERFLUOROHEXANE VS. PARTIAL LIQUID VENTILATION IN EXPERIMENTAL LUNG INJURY

It is currently not known whether vaporized perfluorohexane may be superior to partial liquid ventilation (PLV) for the therapy of acute lung injury. In this work, we aimed at comparing the effects of both therapies in oleic acid induced lung injury. Lung injury was induced in thirty anesthetized and mechanically ventilated pigs by means of central venous infusion of oleic acid. Animals were assigned to one of the following groups: 1) control or gas ventilation (GV); 2) 2.5 % perfluorohexane vapor; 3) 5 % perfluorohexane vapor; 4) 10 % perfluorohexane vapor and 5) PLV with perfluorooctane (30 ml/kg). Two hours after randomization, lungs were recruited and positive end-expiratory pressure was adjusted to obtain minimal elastance (open lung approach). Ventilation was continued during 4 additional hours, when animals were killed for lung histologic examination. Gas exchange and elastance were comparable among vaporized perfluorohexane, PLV and GV before the open lung approach was used and improved in a similar fashion in all groups after positive end-expiratory pressure was adjusted to optimal elastance (p < 0.05). A similar behavior was observed in the functional residual capacity in animals treated with vaporized perfluorohexane and GV. Lung resistance improved after recruitment (p < 0.05), but values were higher in the perfluorohexane 10 % and PLV groups, as compared to GV (p < 0.05). Interestingly, positive end-expiratory pressure values required to obtain minimal elastance were lower with 5 % perfluorohexane than PLV and GV (p <0.05). Diffuse alveolar damage was significantly lower in the 5 % and 10 % perfluorohexane vapor groups, as compared to PLV and GV (p < 0.05). Analysis of distribution of effects revealed that alveolar damage was lower with 5 % perfluorohexane than with GV or PLV in the non-dependent (p<0.001 and p<0.0001, respectively), as well as in central regions (p<0.0001 and p<0.001, respectively). In peripheral regions, 5 % perfluorohexane led to reduced alveolar damage (p<0.05), as compared to GV. In dependent regions, alveolar damage was lower with 5 % perfluorohexane and PLV as compared to GV (p<0.0001). Gas ventilated and animals treated with 5 % perfluorohexane showed less alveolar damage in the non-dependent as compared to dependent regions (p<0.001 and p<0.05, respectively), whereas PLV presented the opposite pattern (p<0.05). Oxidative stress was decreased with 5 % perfluorohexane as compared to GV (p<0.05). None of these perfluorcarbon therapies improved gas exchange or lung mechanics, as compared to GV. However, the use of 5 % vaporized perfluorohexane permitted to reduce pressures needed to stabilize the lungs and was associated with better histologic findings than PLV and GV. Whereas PLV led to more pronounced effects in dependent than in non-dependent regions, 5 % vaporized perfluorohexane showed the opposite pattern. Despite this gravity-related characteristic, 5 % vaporized perfluorohexane attenuated alveolar damage as efficiently as PLV in dependent regions and also reduced the oxidative stress in the lungs. Vaporized perfluorohexane may prove an alternative to PLV to reduce alveolar damage in acute lung injury.

Comparative Effects of Vaporized Perfluorohexane and Partial Liquid Ventilation in Oleic Acid– induced Lung Injury

It is currently not known whether vaporized perfluorohexane is superior to partial liquid ventilation (PLV) for therapy of acute lung injury. In this study, the authors compared the effects of both therapies in oleic acid-induced lung injury. Lung injury was induced in 30 anesthetized and mechanically ventilated pigs by means of central venous infusion of oleic acid. Animals were assigned to one of the following groups: (1) control or gas ventilation (GV), (2) 2.5% perfluorohexane vapor, (3) 5% perfluorohexane vapor, (4) 10% perfluorohexane vapor, or (5) PLV with perfluorooctane (30 ml/kg). Two hours after randomization, lungs were recruited and positive end-expiratory pressure was adjusted to obtain minimal elastance. Ventilation was continued during 4 additional hours, when animals were killed for lung histologic examination. Gas exchange and elastance were comparable among vaporized perfluorohexane, PLV, and GV before the open lung approach was used and improved in a similar fashion in all groups after positive end-expiratory pressure was adjusted to optimal elastance (P < 0.05). A similar behavior was observed in functional residual capacity (FRC) in animals treated with vaporized perfluorohexane and GV. Lung resistance improved after recruitment (P < 0.05), but values were higher in the 10% perfluorohexane and PLV groups as compared with GV (P < 0.05). Interestingly, positive end-expiratory pressure values required to obtain minimal elastance were lower with 5% perfluorohexane than with PLV and GV (P < 0.05). In addition, diffuse alveolar damage was significantly lower in the 5% and 10% perfluorohexane vapor groups as compared with PLV and GV (P < 0.05). Although the use of 5% vaporized perfluorohexane permitted the authors to reduce pressures needed to stabilize the lungs and was associated with better histologic findings than were PLV and GV, none of these perfluorocarbon therapies improved gas exchange or lung mechanics as compared with GV.

Effect of low???bias flow oscillation with partial liquid ventilation on fluoroscopic image analysis, gas exchange, and lung injury

To evaluate the effect of low-bias flow oscillation (LBFO) with partial liquid ventilation (PLV) on perfluorochemical evaporation, histopathology, and oxidative tissue damage in an animal model of acute lung injury. Prospective, randomized animal study. Research laboratory of a health sciences university. Twelve New Zealand White rabbits. Juvenile rabbits were anesthetized, paralyzed, and ventilated through a tracheostomy with either high-frequency oscillatory ventilation or LBFO. Lung injury was induced by repeated saline lavage, after which perflubron was instilled through a side port of the endotracheal tube. Lateral fluoroscopic images were performed at baseline and at various postfill intervals of animals in the high-frequency oscillatory ventilation-PLV and LBFO-PLV groups. The images were digitalized for computer analysis of the Lung Lucency Index, a surrogate marker of perflubron evaporation. Histopathologic evaluation was performed using a lung-injury scoring system. Malondialdehyde was measured in lung homogenates to assess oxidative damage. There were no significant differences in gas exchange and ventilator settings between groups throughout the experiment. At 300 mins, the high-frequency oscillatory ventilation-PLV group had a significantly higher Lung Lucency Index compared with the LBFO-PLV group in both dependent and nondependent lung regions (a high Lung Lucency Index correlates with increased perflubron loss). Malondialdehyde measurements were not different between groups. Animals treated with LBFO-PLV had a lower histopathologic lung-injury score compared with high-frequency oscillatory ventilation-PLV. LBFO-PLV is a viable mode of ventilation in a model of acute lung injury and is associated with significant preservation of perflubron in comparison with high-frequency oscillatory ventilation-PLV. The lower evaporative losses during LBFO-PLV were associated with improved histology scores.

Partial Liquid Ventilation in Adult Patients with Acute Respiratory Distress Syndrome

Despite recent clinical trials demonstrating improved outcome in acute respiratory distress syndrome (ARDS), mortality remains high. Partial liquid ventilation (PLV) using perfluorocarbons has been shown to improve oxygenation and decrease lung injury in various animal models. To determine if PLV would have an impact on outcome in patients with ARDS. Patients with ARDS were randomized to (1) conventional mechanical ventilation (CMV; n=107), (2) "low-dose" perfluorocarbon (10 ml/kg; n=99), and (3) "high-dose" perfluorocarbon (20 ml/kg; n=105). Patients in all three groups were ventilated using volume ventilation, Vt <or= 10 ml/kg predicted body weight, rate <or= 25/min, inspiratory-to-expiratory ratio <or= 1:1, Fi(O(2)) >or= 0.5, and positive end-expiratory pressure >or= 13 cm H(2)O. The 28-d mortality in the CMV group was 15%, versus 26.3% in the low-dose (p=0.06) and 19.1% in the high-dose (p=0.39) PLV groups. There were more ventilator-free days in the CMV group (13.0+/-9.3) compared with both the low-dose (7.4+/-8.5; p<0.001) and high-dose (9.9+/-9.1; p=0.043) groups. There were more pneumothoraces, hypoxic episodes, and hypotensive episodes in the PLV patients. PLV at both high and low doses did not improve outcome in ARDS compared with CMV and cannot be recommended for patients with ARDS.

The Efficacy of Partial Liquid Ventilation in Lung Protection During Hypotension and Cardiac Arrest: Preliminary Study of Lung Transplantation Using Non–heart–beating Donors

Because of the shortage of suitable brain-dead donors, the use of non-heart-beating donor lungs has been investigated experimentally. However, no effective lung protection method has been developed. In this study, we preliminarily investigated the protective effect of partial liquid ventilation (PLV) on a non-heart-beating rabbit lung. We used 20 male rabbits (mean weight, 3.7 kg) and divided them into 3 groups: the conventional ventilation (control) group, the PLV without cooling group, and the PLV with cooling group. After initially measuring donor cardiopulmonary function, we maintained hypotension at <50 mm Hg for 1 hour followed by 2-hour cardiac arrest. During this time, we used either conventional ventilation or PLV with or without cooling (4 degrees C) for ventilation, and we evaluated the changes in arterial blood gas analysis, pulmonary resistance and elastance, tissue interleukin-8 (IL-8) concentration, and histologic damage. We found no significant difference in arterial oxygen concentration or in carbon dioxide tension among the 3 groups in the hypotensive phase. Pulmonary elastance increased after perfusion of preservation solution in the control group. However, we found no change in elastance in the PLV groups, which was less than that in the control group. Histologic evaluation after perfusion of preservation solution revealed that alveolar structure was damaged significantly less and cell infiltration was milder in the PLV groups than in the control group. Although IL-8 concentrations in the controls increased after cardiac arrest, IL-8 in the PLV groups remained at baseline concentrations during the study period. In this experimental model of hypotension and cardiac arrest, PLV suppresses lung injury when compared with gas-controlled ventilation.

Effect of partial liquid ventilation and nebulized perfluorocarbon on CT lung density distribution: randomized controlled study of experimental lung injury

Perfluorocarbon (PFC) liquid can improve gas exchange in acute lung injury. How PFC aerosol is distributed in the lung is unknown. We induced lung injury in rabbits with saline lavage, followed by mechanical ventilation in the supine position. The animals were divided into three groups: a control group, a group treated with partial liquid ventilation and a group given nebulized perfluorocarbon (PF 5080). We made CT image slices of the excised lungs. In the apical, middle and caudal slices we defined three regions of interest, from anterior to posterior, and noted the mean attenuation of each area. We also studied two rabbits which had not received lung injury or mechanical ventilation. Group means were different between the normal rabbits and all three study groups. There was a difference between the control and partial liquid ventilation groups, and between the partial liquid ventilation and nebulized groups, but no difference between the nebulized and control groups. Within each treatment group, there was no regional difference in the distribution of density. PF 5080 is not deposited in large amounts by aerosol. Less PFC was found in the lungs after partial liquid ventilation than expected. Within treatment groups, lung densities indicate less gravitational and regional differences than found in other studies.

Partial liquid ventilation for the prevention of mortality and morbidity in paediatric acute lung injury and acute respiratory distress syndrome.

Acute lung injury, and acute respiratory distress syndrome, are syndromes of severe respiratory failure. Children with acute lung injury or acute respiratory syndrome have high mortality and significant morbidity. Partial liquid ventilation is proposed as a less injurious form of respiratory support for these children. Uncontrolled studies in adults have shown improvement in gas exchange and lung compliance with partial liquid ventilation A single uncontrolled study in six children with acute respiratory syndrome showed some improvement in gas exchange during three hours of partial liquid ventilation. To assess whether partial liquid ventilation reduces either mortality or morbidity, or both, in children with acute lung injury or acute respiratory syndrome. We searched The Cochrane Central Register of Controlled Trials (CENTRAL), The Cochrane Library issue 2, 2003; MEDLINE (1966 to April 2003); and CINAHL (1982 to April 2003); intensive care journals and conference proceedings; reference lists and 'grey literature'. Randomized controlled trials which compared partial liquid ventilation with other forms of ventilation, in children (28 days - 18 years) with acute lung injury or acute respiratory syndrome, reporting one or more of the following: mortality; duration of mechanical ventilation, respiratory support, oxygen therapy, stay in the intensive care unit, or stay in hospital; infection; or long term cognitive impairment or neurodevelopmental progress or other long term morbidities. Two reviewers independently evaluated the quality of the relevant studies and extracted the data from the included studies. Only one study enrolling 182 patients (only reported as an abstract in conference proceedings) was identified and found eligible for inclusion: the authors report only limited results. The trial was stopped prematurely and therefore under-powered to detect any significant differences. The only outcome of clinical significance available was 28 day mortality: there was no statistically significant difference between groups with a relative risk for 28 day mortality in the partial liquid ventilation group of 1.54 (95% confidence intervals of 0.82 to 2.9). There is no evidence from randomized controlled trials to support or refute the use of partial liquid ventilation in children with acute lung injury or acute respiratory syndrome: adequately powered, high quality randomized controlled trials are still needed to assess its efficacy. Clinically relevant outcome measures should be assessed (mortality at discharge and later, duration of respiratory support and hospital stay, and long-term neurodevelopmental outcomes) and the studies should be published in full.