Michael C. Overbeck

Efficacy of perfluorocarbon partial liquid ventilation in a large animal model of acute respiratory failure

OBJECTIVE To demonstrate the efficacy of partial perfluorocarbon liquid ventilation in large animal model of acute respiratory failure. DESIGN Prospective, randomized, controlled trial. SETTING Animal laboratory at a university medical center. SUBJECTS Ten adult sheep, weighing 53.0 +/- 2.8 kg. INTERVENTIONS After assessment of baseline physiologic data, acute respiratory failure was induced by right atrial injection of oleic acid (0.2 mL/kg). Five animals (partial liquid ventilation group) underwent sequential intratracheal dosing of 10 mL/kg of perflubron at 30-min intervals to the following cumulative doses: 10, 20, 30, 40, and 50 mL/kg. The remaining five animals were gas ventilated (control group). Physiologic data were assessed at 30-min intervals in both groups for the 2.5-hr experimental period or until death. MEASUREMENTS AND MAIN RESULTS When compared with control animals, intratracheal perfluorocarbon instillation resulted in significant improvements in arterial oxygen saturation (arterial oxygen saturation after 50 mL/kg: partial liquid ventilation, 96 +/- 3%; control, 55 +/- 8%; p = .001) and physiologic shunt (physiologic shunt after 50 mL/kg dose: partial liquid ventilation, 2 +/- 8%; control, 64 +/- 5%; p = .004). Oxygen delivery improved with perfluorocarbon instillation, but this improvement was not significant. No significant difference in pulmonary compliance was observed during partial liquid ventilation when compared with controls (pulmonary compliance: partial liquid ventilation, 0.43 +/- 0.04 mL/ cm H2O/kg; control, 0.53 +/- 0.03 mL/cm H2O/kg; p = .102). CONCLUSIONS Partial liquid ventilation with perflubron provides effective improvement in gas exchange in an adult animal model of respiratory failure.

Distribution of pulmonary blood flow and total lung water during partial liquid ventilation in acute lung injury

BACKGROUND Gas exchange is improved during partial liquid ventilation (PLV) with perfluorocarbon in animal models of acute lung injury. The mechanisms are not fully defined. We hypothesize that redistribution of pulmonary blood flow (PBF) along with redistribution of, and decrease in, total lung water (TLW) during PLV may improve oxygenation. METHODS We characterized PBF and TLW in anesthetized adult dogs by using positron emission tomography with H2(15)O. Measurements of gas exchange, PBF, and TLW were made before and after acute lung injury was induced with intravenous oleic acid. The same measurements were made during PLV (with 30 ml/kg perfluorocarbon) and compared with gas ventilated (GV) controls. RESULTS Oxygenation was significantly improved during PLV. PBF redistributed from the dependent zone of the lung to the nondependent zones, thus potentially improving ventilation/perfusion relationships. However, a similar pattern of PBF redistribution was observed during GV such that there was no significant difference between groups. TLW redistributed in a similar pattern during PLV. By quantitative measurements, PLV ameliorated the continued accumulation of TLW compared with GV animals. CONCLUSIONS We conclude that PBF and TLW redistribution and attenuation of increases in TLW may contribute to the improvement in gas exchange during PLV in the setting of acute lung injury.

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.

Partial liquid ventilation provides effective gas exchange in a large animal model

PURPOSE The purpose of this study was to show the ability of partial liquid ventilation (PLV) to sustain gas exchange in normal large (50 to 70 kg) adult animals. METHODS Ten adult sheep (53.7 +/- 2.8 kg) were anesthetized and mechanically ventilated. Sequential dosing of perflubron (LiquiVent, Alliance Pharmaceutical Corp, San Diego, CA) was performed to cumulative doses of 10 mL/kg, 20 mL/kg, 40 mL/kg, and 60 mL/kg. Physiological data were assessed at baseline and after each dose. Five animals were rotated through the left decubitus, right decubitus, supine, and prone positions while five animals remained prone throughout the experiment. RESULTS PaO2 and PaCO2 did not change significantly from baseline during administration of perflubron except for the PaO2 in rotated animals when supine (rotated-supine PaO2: baseline = 519 +/- 64 mm Hg; 60 mL/kg = 380 +/- 109 mm Hg, P = .0131). In both groups, static lung compliance (CT) decreased steadily with each successive perflubron instillation (nonrotated CT: baseline = 1.55 +/- 0.22 mL/cm H2O/kg; 60 mL/kg = 0.52 +/- 0.10 ml/cmH2O/kg, P = .0003). CONCLUSIONS These data show that during PLV in this normal animal model, effective gas exchange is sustained and CT decreases with increasing perflubron dose.