title: The pulmonary and systemic distribution and elimination of perflubron from adult patients treated with partial liquid ventilation.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  Prospective phase I and II clinical trial.
  
  
  METHODS
  Adult surgical ICU.
  
  
  METHODS
  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.
  
  
  METHODS
  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).
  
  
  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 ventilation.
authors.affiliation: Department of Surgery, University of Michigan Medical Center, Ann Arbor, MI, USA.
authors.forename: C
authors.initials: C
authors.lastname: Reickert
authors.forename: T
authors.initials: T
authors.lastname: Pranikoff
authors.forename: M
authors.initials: M
authors.lastname: Overbeck
authors.forename: E
authors.initials: E
authors.lastname: Kazerooni
authors.forename: K
authors.initials: K
authors.lastname: Massey
authors.forename: R
authors.initials: R
authors.lastname: Bartlett
authors.forename: R
authors.initials: R
authors.lastname: Hirschl
mesh_terms: D000328:Adult; D003287:Contrast Media / Q000493:pharmacokinetics*; D005466:Fluorocarbons / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D006842:Hydrocarbons, Brominated; D021061:Liquid Ventilation; D008875:Middle Aged; D011446:Prospective Studies; D011659:Pulmonary Gas Exchange; D012131:Respiratory Insufficiency / Q000503:physiopathology / Q000628:therapy*
chemical_list: D003287:Contrast Media; D005466:Fluorocarbons; D006842:Hydrocarbons, Brominated; C003072:perflubron