The Pulmonary and Systemic Distribution and Elimination of Perflubron From Adult Patients Treated With Partial Liquid Ventilation

To assess the pulmonary and systemicdistribution and elimination of perflubron(C8F17Br1; Liqui Vent; Alliance Pharmaceutical; San Diego, CA) during and following the period ofpartial liquid ventilation. Prospective phase, I and II clinical trial. Adult surgical, ICU. Eighteen adult patients(mean ± SEM age, 37.9 ± 3.4 years) with severe respiratoryfailure, some of whom required extracorporeal life support (72%), andwho were managed with partial liquid ventilation with perflubron. Perflubron was administered into thetrachea, and gas ventilation of the perfluorocarbon-filled lung(partial liquid ventilation) was then performed. Additional doses wereadministered daily for from 1 to 7 days, with a median cumulative doseof 31 m, L/kg (range, 3 to 60 m, L/kg). Patient blood samples were evaluated by gaschromatography for serum perflubron levels. Sequential lateral andanteroposterior radiographs were assessed, using a 5-point ratingscale, for the degree of perflubron fill following the final dose. Samples of expired gas were collected, and the rate of loss ofperflubron in the expired gas was measured by gas chromatography. Meanserum perflubron levels increased to 0.16 ± 0.05 mg/dL at 24 hfollowing administration of the initial dose. A mean maximum level of0.26 ± 0.05 mg/dL of perflubron was present in the serum 24 hfollowing the administration of the last dose. This level slowlytrended downward to 0.18 ± 0.06 mg/dL over the ensuing 7 days(p = 0.281). Perflubron elimination via expired gas occurred at amean rate of 9.4 ± 3.0 m, L/h at 1 h, and 1.0 ± 0.4 m, L/h at48 h after the last dose (p = 0.012). By radiologic evaluation, perflubron was eliminated from the lungs progressively from4.2 ± 0.2 at the time of administration of the last dose, to2.8 ± 0.3 at 4 days later (p < 0.001). Perflubron tended todistribute and remain for longer periods in the dependent regions ofthe lung when compared to the nondependent regions (96-h perflubronfill score: posterior, 3.8 ± 0.5; anterior, 1.9 ± 0.4;p = 0.004). Perflubron is eliminated ata maximum rate of 9.4 ± 3.0 m, L/h by evaporative loss from theairways and is retained in greater amounts in the dependent lungregions when compared to the nondependent lung regions. There is a lowbut measurable maximum blood concentration of 0.26 ± 0.05 mg/dL inpatients after perflubron administration, which did not decreasesignificantly after cessation of partial liquidventilation.