Prolonged partial liquid ventilation using conventional and high-frequency ventilatory techniques: gas exchange and lung pathology in an animal model of respiratory distress syndrome.

Abstract

OBJECTIVE: To evaluate the effect of prolonged partial liquid ventilation with perflubron (partial liquid ventilation), using conventional and high-frequency ventilatory techniques, on gas exchange, hemodynamics, and lung pathology in an animal model of lung injury. DESIGN: Prospective, randomized, controlled study. SETTING: Animal laboratory of the Infant Pulmonary Research Center, Children's Health Care-St. Paul. SUBJECTS: Thirty-six newborn piglets. INTERVENTIONS: We studied newborn piglets with lung injury induced by saline lavage. Animals were randomized into one of five treatment groups: a) conventional gas ventilation (n = 8); b) partial liquid ventilation with conventional ventilation (n = 7); c) partial liquid ventilation with high-frequency jet ventilation (n = 7); d) partial liquid ventilation with high-frequency oscillation (n = 7); and e) partial liquid ventilation with high-frequency flow interruption (n = 7). After induction of lung injury, all partial liquid ventilation animals received intratracheal perflubron to approximate functional residual capacity. After 30 mins of stabilization, animals randomized to high-frequency ventilation were changed to their respective high-frequency modes. Hemodynamics and blood gases were measured before and after lung injury, after perflubron administration, and then every 4 hrs for 20 hrs. Histopathologic evaluation was carried out using semiquantitative scoring and computer-assisted morphometric analysis on pulmonary tissue from animals surviving at least 16 hrs. MEASUREMENTS AND MAIN RESULTS: All animals developed acidosis and hypoxemia after lung injury. Oxygenation significantly (p < .001) improved after perflubron administration in all partial liquid ventilation groups. After 4 hrs, oxygenation was similar in all ventilator groups. The partial liquid ventilation-jet ventilation group had the highest pH; intergroup differences were seen at 16 and 20 hrs (p < .05). The partial liquid ventilation-oscillation group required higher mean airway pressure; intergroup differences were significant at 4 and 8 hrs (p < .05). Aortic pressures, central venous pressures, and heart rates were not different at any time point. Survival rate was significantly lower in the partial liquid ventilation-flow interruption group (p < .05). All partial liquid ventilation-treated animals had less lung injury compared with gas-ventilated animals by both histologic and morphometric analysis (p < .05). The lower lobes of all partial liquid ventilation-treated animals demonstrated less damage than the upper lobes, although scores reached significance (p < .05) only in the partial liquid ventilation-conventional ventilation animals. CONCLUSIONS: In this animal model, partial liquid ventilation using conventional or high-frequency ventilation provided rapid and sustained improvements in oxygenation without adverse hemodynamic consequences. Animals treated with partial liquid ventilation-flow interruption had a significantly decreased survival rate vs. animals treated with the other studied techniques. Histopathologic and morphometric analysis showed significantly less injury in the lower lobes of lungs from animals treated with partial liquid ventilation. High-frequency ventilation techniques did not further improve pathologic outcome.