Alan Parent

Liquid ventilation improves pulmonary function, gas exchange, and lung injury in a model of respiratory failure.

ObjectiveThe authors evaluated gas exchange, pulmonary function, and lung histology during perfluorocarbon liquid ventilation (LV) when compared with gas ventilation (GV) in the setting of severe respiratory failure. BackgroundThe efficacy of LV in the setting of respiratory failure has been evaluated in premature animals with surfactant deficiency. However, very little work has been performed in evaluating the efficacy of LV in older animal models of the adult respiratory distress syndrome (ARDS). MethodsA stable model of lung injury was induced in 12 young sheep weighing 16.4 ± 3.0 kg using right atrial injection of 0.07 mL/kg of oleic acid followed by saline pulmonary lavage and bjjugular venovenous extracorporeal life support (ECLS). For the first 30 minutes on ECLS, all animals were ventilated with gas. Animals were then ventilated with either 15 mL/kg gas (GV, n = 6) or perflubron([PFC], LV, n = 6) over the ensuing 2.5 hours. Subsequently, ECLS was discontinued in five of the GV animals and five of the LV animals, and GV or LV continued for 1 hour or until death. Main FindingsPhysiologic shunt (Qps/Q1) was significantly reduced in the LV animals when compared with the GV animals (LV = 31 ± 10%; GV = 93 ± 4%; p < 0.001) after 3 hours of ECLS. At the same time point, pulmonary compliance (Cγ) was significantly increased in the LV group when compared with the GV group (LV = 1.04 ± 0.19 mL/cm H2O/kg; GV = 0.41 ± 0.02 mL/cm H2O/kg; p < 0.001). In addition, the ECLS flow rate required to maintain the PaO2 in the 50− to 80-mm Hg range was substantially and significantly lower in the LV group when compared with that of the GV group (LV =14 ± 5 mL/kg/min; GV = 87 ± 15 mL/kg/min; p < 0.001). All of the GV animals died after discontinuation of ECLS, whereas all the LV animals demonstrated effective gas exchange without extracorporeal support for 1 hour (p < 0.01). Lung biopsy light microscopy demonstrated a marked reduction in alveolar hemorrhage, lung fluid accumulation, and inflammatory infiltration in the LV group when compared with the GV animals.

Development and application of a simplified liquid ventilator

OBJECTIVE Perfluorocarbon liquid ventilation has been shown to have advantages over conventional gas ventilation in premature newborn and lung-injured animals. To simplify the process of liquid ventilation, we adapted an extra-corporeal life-support circuit as a time-cycled, volume-limited liquid ventilator. DESIGN Laboratory study that involved sequential application of gas and liquid ventilation in normal cats and in lung-injured sheep. SETTING A research laboratory at a university medical center. SUBJECTS Eight normal cats weighing 2.7 to 3.8 kg (mean 3.1 +/- 0.5), and four lung-injured young sheep weighing 10.4 to 22.5 kg (mean 15.9 +/- 5.0). INTERVENTIONS Normal cats were supported with traditional gas ventilation for 1 hr (respiratory rate 20 breaths/min, peak inspiratory pressure 12 cm H2O, positive end-expiratory pressure 4 cm H2O, and FIO2 1.0). The lungs were then filled with perfluorocarbon (30 mL/kg) and tidal volume liquid ventilation was instituted, utilizing a newly developed liquid ventilation device. Liquid ventilatory settings were 4 secs for inspiration time, 8 secs for expiration time, 5 breaths/min for respiratory rate, and 15 to 20 mL/kg for tidal volume. Liquid ventilation utilizing this device was also applied to sheep after induction of severe lung injury by right atrial injection of 0.07 mL/kg of oleic acid, followed by saline pulmonary lavage. Extracorporeal life support was instituted to provide a stable model of lung injury. For the first 30 mins of extracorporeal support, all animals were ventilated with gas. Animals were then ventilated with 15 mL/kg of perfluorocarbon over the ensuing 2.5 hrs. MEASUREMENTS AND MAIN RESULTS In normal cats, mean PaO2 values after 1 hr of liquid or gas ventilation were 275 +/- 90 (SD) torr (36.7 +/- 10.4 kPa) in the liquid-ventilated animals and 332 +/- 78 torr (44.3 +/- 10.4 kPa) in the gas-ventilated animals (NS). Mean PaCO2 values were 40.5 +/- 5.7 torr (5.39 +/- 0.31 kPa) in the liquid-ventilated animals and 37.6 +/- 2.3 torr (5.01 +/- 0.31 kPa) in the gas-ventilated animals (NS). Mean arterial pH values were 7.35 +/- 0.07 in the liquid-ventilated animals and 7.34 +/- 0.04 in the gas-ventilated animals (NS). No significant changes in heart rate, mean arterial pressure, lung compliance, or right atrial venous oxygen saturation were observed during liquid ventilation when compared with gas ventilation. In the lung-injured sheep, an increase in physiologic shunt from 15 +/- 7% to 66 +/- 9% was observed with induction of lung injury during gas ventilation. Liquid ventilation resulted in a significant reduction in physiologic shunt to 31 +/- 10% (p < .001). In addition, the extracorporeal blood flow rate required to maintain the PaO2 in the 50 to 80 torr (6.7 to 10.7 kPa) range was substantially and significantly (p < .001) lower during liquid ventilation than during gas ventilation (liquid ventilation 15 +/- 5 vs. gas ventilation 87 +/- 15 mL/min/kg). CONCLUSIONS Liquid ventilation can be performed successfully utilizing this simple adaptation of an extracorporeal life-support circuit. This modification to an existing extracorporeal circuit may allow other centers to apply this new investigational method of ventilation in the laboratory or clinical setting.

Total liquid ventilation with perfluorocarbons increases pulmonary end-expiratory volume and compliance in the setting of lung atelectasis

OBJECTIVE To compare compliance and end-expiratory lung volume during reexpansion of normal and surfactant-deficient ex vivo atelectatic lungs with either gas or total liquid ventilation. DESIGN Controlled, animal study using an ex vivo lung preparation. SETTING A research laboratory at a university medical center. SUBJECTS Thirty-six adult cats, weighing 2.5 to 4.0 kg. INTERVENTIONS Heparin (300 U/kg) was administered, cats were killed, and lungs were excised en bloc. Normal lungs and saline-lavaged, surfactant-deficient lungs were allowed to passively collapse and remain atelectatic for 1 hr. Lungs then were placed in a plethysmograph and ventilated for 2 hrs with standardized volumes of either room air or perfluorocarbon. Static pulmonary compliance and end-expiratory lung volume were measured every 30 mins. MEASUREMENTS AND MAIN RESULTS Reexpansion of normal atelectatic lungs with total liquid ventilation was associated with an 11-fold increase in end-expiratory lung volume when compared with the increase in end-expiratory lung volume observed with gas ventilation (total liquid ventilation 50 +/- 14 mL, gas ventilation 4 +/- 9 mL, p < .0001). The difference was even more pronounced in the surfactant-deficient lungs with an approximately 19-fold increase in end-expiratory lung volume observed in the total liquid ventilated group, compared with the gas ventilated group (total liquid ventilation 44 +/- 17 mL, gas ventilation 2 +/- 8 mL, p = .0001). Total liquid ventilation was associated with an increase in pulmonary compliance when compared with gas ventilation in both normal and surfactant-deficient lungs (normal: gas ventilation 6 +/- 1 mL/cm H2O, total liquid ventilation 14 +/- 4 mL/cm H2O, p < .0001; surfactant-deficient: gas ventilation 4 +/- 1 mL/cm H2O, total liquid ventilation 9 +/- 3 mL/cm H2O, p < .01). CONCLUSIONS End-expiratory lung volume and static compliance are increased significantly following attempted reexpansion with total liquid ventilation when compared with gas ventilation in normal and surfactant-deficient, atelectatic lungs. The ability of total liquid ventilation to enhance recruitment of atelectatic lung regions may be an important means by which gas exchange is improved during total liquid ventilation when compared with gas ventilation in the setting of respiratory failure.

Oxygen dynamics during partial liquid ventilation in a sheep model of severe respiratory failure.

BACKGROUND We evaluated the relationship of dose of perflubron and gas tidal volume to oxygen dynamics during partial liquid ventilation in the setting of respiratory failure. METHODS Lung injury was induced in 16 sheep by using right atrial injection of 0.15 ml/kg oleic acid. Animals were ventilated with 15 ml/kg gas tidal volume and stabilized. Animals were then divided into three groups: (1) gas ventilation with a tidal volume of 15 ml/kg (control, GV, n = 5); (2) partial liquid ventilation at a gas tidal volume of 15 ml/kg with 10 ml/kg incremental pulmonary dosage of perflubron from 10 to 50 ml/kg (best fill, BF, n = 6); (3) administration of 35 ml/kg perflubron pulmonary dose with 5 ml/kg incremental increase in gas tidal volume from 10 to 30 ml/kg (best tidal volume, BTV, n = 5). RESULTS Arterial oxygen saturation increased with increasing dose of perflubron and gas tidal volume (BF, p = 0.01; BTV, p = 0.001). A simultaneous trend toward a reduction in cardiac index was observed with increasing dose of perflubron (BF, p = 0.01). Maximal increase in mixed venous oxygen saturation was observed in the BF and BTV groups at a cumulative perflubron dose of 40 ml/kg and a gas tidal volume of 20 ml/kg, respectively. CONCLUSIONS In this sheep lung injury model oxygenation improves with incremental increases in perflubron dose or gas tidal volume, and the mixed venous oxygen saturation appears to be optimal at a cumulative perflubron dose of 40 ml/kg and a gas tidal volume of 20 ml/kg.