Objective: To assess the pulmonary and systemic
distribution and elimination of perflubron
(C8F17Br1; LiquiVent; Alliance
Pharmaceutical; San Diego, CA) during and following the period of
partial liquid ventilation.
Design: Prospective phase
I and II clinical trial.
Setting: Adult surgical
Patients: 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.
Interventions: 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).
main results: 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).
Conclusions: 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