title: Prediction of distribution volume of vancomycin in critically ill patients using extravascular lung water and pulmonary vascular permeability indices.
abstract: OBJECTIVE
  Alterations in distribution volume affect the concentrations of hydrophilic drugs in plasma and tissues at the time of initial therapy. When the distribution volume of hydrophilic antimicrobials is increased in critically ill patients with a serious infection, antimicrobial concentrations are reduced, which may adversely affect the efficacy of antimicrobial therapy. A transpulmonary thermodilution technique system (PiCCO) enables measurements of pulmonary vascular permeability index (PVPI) and extravascular lung water index (EVLWI), which are related to pulmonary edema and pulmonary vascular permeability, respectively. In addition, those indices may also be related to the distribution volume of hydrophilic antimicrobials. The aim of this study was to investigate the relationships of PVPI and EVLWI with the distribution volume of vancomycin (Vss), as well as to establish a method for estimating Vss for planning an appropriate initial dose for individual patients.
  
  
  METHODS
  Seven patients were administered vancomycin intravenously and underwent extended hemodynamic monitoring with the PiCCO system in the intensive care unit (ICU) from April 2009 to March 2011. Vss was calculated using the Bayesian method, and the relationships of PVPI and EVLWI with Vss were investigated.
  
  
  RESULTS
  The relationship between Vss/actual body weight (ABW) and median EVLWI on days when blood levels were measured was significant (r = 0.900, p = 0.0057), whereas the relationship between Vss/ABW and PVPI was not significant (r = 0.649, p = 0.1112).
  
  
  CONCLUSIONS
  EVLWI determined by the PiCCO system is useful to predict Vss and should lead to more effective vancomycin therapy for critically ill patients at the initial stage.
authors.affiliation: Department of Clinical Evaluation of Drug Efficacy, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan.
authors.forename: Masaharu
authors.initials: M
authors.lastname: Imaura
authors.forename: Haruko
authors.initials: H
authors.lastname: Yokoyama
authors.forename: Tomoki
authors.initials: T
authors.lastname: Kohyama
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nagafuchi
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kohata
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takahashi
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Yamada
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D001499:Bayes Theorem; D002199:Capillary Permeability; D016638:Critical Illness; D015633:Extravascular Lung Water / Q000378:metabolism*; D005260:Female; D006439:Hemodynamics; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007564:Japan; D008168:Lung / Q000098:blood supply*; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D008991:Monitoring, Physiologic; D011654:Pulmonary Edema / Q000097:blood / Q000378:metabolism*; D012189:Retrospective Studies; D013815:Thermodilution; D014018:Tissue Distribution; D014640:Vancomycin / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin