The pulmonary and systemic distribution and elimination of perflubron from adult patients treated with partial liquid ventilation

To assess the pulmonary and systemic distribution and elimination of perflubron (C(8)F(17)Br(1); LiquiVent; Alliance Pharmaceutical; San Diego, CA) during and following the period of partial 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 respiratory failure, some of whom required extracorporeal life support (72%), and who were managed with partial liquid ventilation with perflubron.

Perflubron was administered into the trachea, and gas ventilation of the perfluorocarbon-filled lung (partial liquid ventilation) was then performed. Additional doses were administered daily for from 1 to 7 days, with a median cumulative dose of 31 mL/kg (range, 3 to 60 mL/kg).

Patient blood samples were evaluated by gas chromatography for serum perflubron levels. Sequential lateral and anteroposterior radiographs were assessed, using a 5-point rating scale, for the degree of perflubron fill following the final dose. Samples of expired gas were collected, and the rate of loss of perflubron in the expired gas was measured by gas chromatography. Mean serum perflubron levels increased to 0.16 +/- 0.05 mg/dL at 24 h following administration of the initial dose. A mean maximum level of 0.26 +/- 0.05 mg/dL of perflubron was present in the serum 24 h following the administration of the last dose. This level slowly trended downward to 0.18 +/- 0.06 mg/dL over the ensuing 7 days (p = 0.281). Perflubron elimination via expired gas occurred at a mean rate of 9.4 +/- 3.0 mL/h at 1 h, and 1.0 +/- 0.4 mL/h at 48 h after the last dose (p = 0.012). By radiologic evaluation, perflubron was eliminated from the lungs progressively from 4.2 +/- 0.2 at the time of administration of the last dose, to 2.8 +/- 0.3 at 4 days later (p < 0.001). Perflubron tended to distribute and remain for longer periods in the dependent regions of the lung when compared to the nondependent regions (96-h perflubron fill score: posterior, 3.8 +/- 0.5; anterior, 1.9 +/- 0.4; p = 0.004).

Perflubron is eliminated at a maximum rate of 9.4 +/- 3.0 mL/h by evaporative loss from the airways and is retained in greater amounts in the dependent lung regions when compared to the nondependent lung regions. There is a low but measurable maximum blood concentration of 0.26 +/- 0.05 mg/dL in patients after perflubron administration, which did not decrease significantly after cessation of partial liquid ventilation.