title: Optimizing intrapulmonary perfluorocarbon distribution: fluoroscopic comparison of mode of ventilation and body position.
abstract: OBJECTIVE
  Partial liquid ventilation with the perfluorochemical, perflubron, has been shown to improve lung mechanics and enhance gas exchange in the treatment of severe acute lung injury. However, the most effective strategy to provide optimal intrapulmonary distribution of perflubron has not been fully accessed. The objective of this study was to examine the effect of body position (supine vs. rotational) and mode of ventilation (conventional mechanical ventilation [CMV] vs. high-frequency oscillatory ventilation [HFOV]) on perflubron distribution and oxygenation improvement.
  
  
  METHODS
  Prospective, randomized, animal trial.
  
  
  METHODS
  Research laboratory at a university medical center.
  
  
  METHODS
  Twenty healthy piglets (4.5-6.6 kg).
  
  
  METHODS
  Subjects underwent repetitive saline lavage to achieve a uniform degree of lung injury and then were randomized to either CMV or were converted to HFOV. Within each ventilator group, animals were randomized to supine positioning (S) or rotational positioning with alternation between supine and prone position (R) during incremental dosing of three 5-mL/kg doses of perflubron.
  
  
  RESULTS
  Arterial blood gas tensions, hemodynamic variables, and the oxygenation index were recorded after each dose of 5 mL/kg. Lateral cinefluoroscopic images after each dose were digitized for computer analysis of density. A density index was calculated for a 2-cm2 window in three dorsal and three ventral lung regions. Uniformity of distribution was calculated by comparing the mean density among the six regions. Oxygenation improvements were compared between groups. There were no significant differences in hemodynamic variables or gas exchange after lung injury in the four groups. Rotational positioning produced significantly more uniform perflubron distribution during both CMV and HFOV. This effect was independent of the mode of ventilation. The mean ventral density index was affected by rotating position and HFOV mode of ventilation after 10 mL/kg of perflubron, and rotating position was affected only after 15 mL/kg of perflubron. There was a significant reduction in the oxygenation index from baseline to end lavage in both CMV groups, as well as all of the animals that were rotated.
  
  
  CONCLUSIONS
  Perflubron is more uniformly dispersed when dosed in a rotational fashion with alternation between supine and prone position during incremental dosing. This effect is independent of mode of ventilation. There was no relationship between oxygenation improvements and nondependent perflubron distribution. CMV and rotating dosing both led to a significant decrease in the oxygenation index after a 15 mL/kg dose of perflubron. This information has important impact on the future development of dosing strategies and clinical trial design.
authors.affiliation: Department of Anesthesia, Children's Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: S T
authors.initials: ST
authors.lastname: Bateman
authors.forename: A
authors.initials: A
authors.lastname: Doctor
authors.forename: B
authors.initials: B
authors.lastname: Price
authors.forename: M A
authors.initials: MA
authors.lastname: Murphy
authors.forename: J E
authors.initials: JE
authors.lastname: Thompson
authors.forename: D
authors.initials: D
authors.lastname: Zurakowski
authors.forename: G A
authors.initials: GA
authors.lastname: Taylor
authors.forename: J H
authors.initials: JH
authors.lastname: Arnold
mesh_terms: D000818:Animals; D001784:Blood Gas Analysis; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D016903:Drug Monitoring / Q000379:methods; D005466:Fluorocarbons / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005471:Fluoroscopy / Q000379:methods; D006439:Hemodynamics / Q000187:drug effects; D006612:High-Frequency Ventilation / Q000379:methods*; D006801:Humans; D021061:Liquid Ventilation / Q000379:methods*; D016684:Prone Position; D011446:Prospective Studies; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D011897:Random Allocation; D012121:Respiration, Artificial / Q000379:methods*; D012128:Respiratory Distress Syndrome / Q000139:chemically induced / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D015656:Respiratory Mechanics / Q000187:drug effects; D012965:Sodium Chloride; D016683:Supine Position; D013552:Swine; D007507:Therapeutic Irrigation; D014018:Tissue Distribution
chemical_list: D005466:Fluorocarbons; D012965:Sodium Chloride