Partial liquid ventilation: Effect of initial dose and redosing strategy in acute lung injury.

Abstract

OBJECTIVE: Partial liquid ventilation (PLV) with perfluorochemicals has been shown to be effective in treating acute respiratory failure in animal studies and human trials. To determine the influences of perfluorochemicals on initial dose and redosing strategy, we studied their effects on gas exchange, pulmonary mechanics, and lung architecture. DESIGN: After lung injury was induced by repeated warm saline lavages, the animals were instilled endotracheally with different doses of perflubron during 5-10 mins in PLV-treated groups. The animals were randomized to five groups: PLV-12S (12 mL/kg perflubron, single dose), PLV-12M (12 mL/kg perflubron, multiple replacement doses), PLV-18S (18 mL/kg perflubron, single dose), PLV-18M (18 mL/kg perflubron, multiple replacement doses), and the control group (conventional mechanical ventilation only). Ventilator settings were kept constant during the 4-hr experiment. SETTING: An animal laboratory affiliated with Temple University School of Medicine. SUBJECTS: Twenty-eight New Zealand White juvenile rabbits (weight, 1.96 +/- 0.03 kg). INTERVENTIONS: Physiologic data were recorded every 30 mins. A constant volume (1.3 mL/kg/hr) of perflubron was replaced hourly in the PLV-12M and PLV-18M groups. The perflubron in the expired gas was measured with a thermal detector device. The hourly evaporative loss rate and the estimated residual perfluorochemical amount were calculated and analyzed. Histologic examinations of the lungs were performed. MEASUREMENTS AND MAIN RESULTS: All animals in the PLV-treated groups (PLV-12S, n = 4; PLV-12M, n = 5, PLV-18S, n = 5; PLV-18M, n = 4) demonstrated improvements in gas exchange and respiratory compliance that were significantly (p <.05) better than the control group (n = 8). However, the PLV-12S group demonstrated progressive deterioration after the initial improvement. The loss rate of perflubron did not differ among the PLV-treated groups (1.17 +/- 0.03 mL/kg/hr), but the residual perfluorochemical volume in the lungs decreased progressively and significantly in the PLV-12S and PLV-18S groups as a function of time (p <.05). Histologic examination showed good alveolar protection in the PLV-12M, PLV-18S, and PLV-18M groups. CONCLUSIONS: We conclude that the low initial dose (12 mL/kg, about two thirds the functional residual capacity volume of rabbits) of perflubron required hourly replacement to maintain the effects of PLV. With a high initial dose of 18 mL/kg perflubron (equal to a full functional residual capacity volume in rabbits), the responses are potentiated in both single and multiple dosing groups up to 4 hrs.