OBJECTIVES: Randomized controlled trials of partial liquid ventilation in acute respiratory distress syndrome have been negative. Reasons for this failure may reside in the use of too large doses of perfluorocarbon. The objective was to evaluate whether various doses of perflubron affect ventilation-induced injury in edematous lungs in different ways. DESIGN: Prospective, controlled animal study. SETTING: Research laboratory of a university. SUBJECTS: Male Wistar rats weighing 300+/-20 g. INTERVENTIONS: Separate groups of rats were injected with alpha-naphtylthiourea to produce mild permeability pulmonary edema. They were then given 0, 7 (low), 13 (moderate), or 20 mL/kg (near functional residual capacity) perflubron doses and mechanically ventilated with a large (33 mL/kg) tidal volume for 15 mins. MEASUREMENTS AND MAIN RESULTS: 125I-albumin distribution space was used to assess lung microvascular permeability. Quasi-static respiratory system pressure-volume curves were analyzed. Administration of low and moderate perflubron doses significantly improved respiratory mechanics and reduced the ventilator-induced permeability alterations to the level observed in rats that were not ventilated. By contrast, a perflubron dose that was near functional residual capacity increased end-inspiratory plateau pressure and aggravated the permeability alterations due to high tidal volume ventilation. CONCLUSIONS: Near functional residual capacity but not low perflubron dose worsens ventilation-induced lung injury of preinjured lungs. This may provide some explanation for the negative results of the recent clinical trials, and it stresses the importance of the amount of perflubron used for partial liquid ventilation.
OBJECTIVES: Randomized controlled trials of partial liquid ventilation in acute respiratory distress syndrome have been negative. Reasons for this failure may reside in the use of too large doses of perfluorocarbon. The objective was to evaluate whether various doses of perflubron affect ventilation-induced injury in edematous lungs in different ways. DESIGN: Prospective, controlled animal study. SETTING: Research laboratory of a university. SUBJECTS: Male Wistar rats weighing 300+/-20 g. INTERVENTIONS: Separate groups of rats were injected with alpha-naphtylthiourea to produce mild permeability pulmonary edema. They were then given 0, 7 (low), 13 (moderate), or 20 mL/kg (near functional residual capacity) perflubron doses and mechanically ventilated with a large (33 mL/kg) tidal volume for 15 mins. MEASUREMENTS AND MAIN RESULTS: 125I-albumin distribution space was used to assess lung microvascular permeability. Quasi-static respiratory system pressure-volume curves were analyzed. Administration of low and moderate perflubron doses significantly improved respiratory mechanics and reduced the ventilator-induced permeability alterations to the level observed in rats that were not ventilated. By contrast, a perflubron dose that was near functional residual capacity increased end-inspiratory plateau pressure and aggravated the permeability alterations due to high tidal volume ventilation. CONCLUSIONS: Near functional residual capacity but not low perflubron dose worsens ventilation-induced lung injury of preinjured lungs. This may provide some explanation for the negative results of the recent clinical trials, and it stresses the importance of the amount of perflubron used for partial liquid ventilation.
Authors: Ryan A Orizondo; Charlene Irvin Babcock; Mario L Fabiilli; Leonid Pavlovsky; J Brian Fowlkes; John G Younger; Keith E Cook Journal: J Aerosol Med Pulm Drug Deliv Date: 2014-01-29 Impact factor: 2.849