title: Study of the time course of the clinical effect of propofol compared with the time course of the predicted effect-site concentration: Performance of three pharmacokinetic-dynamic models.
abstract: BACKGROUND
  In the ideal pharmacokinetic-dynamic (PK-PD) model for calculating the predicted effect-site concentration of propofol (Ce(PROP)), for any Ce(PROP), the corresponding hypnotic effect should be constant. We compared three PK-PD models (Marsh PK with Shüttler PD, Schnider PK with fixed ke0, and Schnider PK with Minto PD) in their ability to maintain a constant bispectral index (BIS), while using the respective effect-site-controlled target-controlled infusion (TCI) algorithms.
  
  
  METHODS
  We randomized 60 patients to Group M (Marsh's model with k(e0)=0.26 min(-1)), Group S1 or Group S2 (Schnider's model with a fixed k(e0)=0.456 min(-1) or a k(e0) adapted to a fixed time-to-peak effect=1.6 min, respectively). All patients received propofol at a constant rate until loss of consciousness. The corresponding Ce(PROP), as calculated by the respective models, was set as a target for effect-site-controlled TCI. We observed BIS for 20 min. We hypothesized that BIS remains constant, if Ce(PROP) remains constant over time.
  
  
  RESULTS
  All patients in Group M woke up, one in Group S1 and none in Group S2. In Groups S1 and S2, BIS remained constant after 11 min of constant Ce(PROP), at a more pronounced level of hypnotic drug effect than intended.
  
  
  CONCLUSIONS
  Targeting Ce(PROP) at which patients lose consciousness with effect-site-controlled TCI does not translate into an immediate constant effect.
authors.affiliation: Department of Anesthesia, Ghent University Hospital, Belgium.
authors.forename: M
authors.initials: M
authors.lastname: Coppens
authors.forename: J G M
authors.initials: JG
authors.lastname: Van Limmen
authors.forename: T
authors.initials: T
authors.lastname: Schnider
authors.forename: B
authors.initials: B
authors.lastname: Wyler
authors.forename: S
authors.initials: S
authors.lastname: Bonte
authors.forename: F
authors.initials: F
authors.lastname: Dewaele
authors.forename: M M R F
authors.initials: MM
authors.lastname: Struys
authors.forename: H E M
authors.initials: HE
authors.lastname: Vereecke
mesh_terms: D000328:Adult; D000465:Algorithms; D000556:Ambulatory Surgical Procedures; D018686:Anesthetics, Intravenous / Q000008:administration & dosage / Q000097:blood* / Q000494:pharmacology; D004334:Drug Administration Schedule; D016503:Drug Delivery Systems; D004569:Electroencephalography / Q000187:drug effects; D005260:Female; D006801:Humans; D007260:Infusion Pumps; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D016343:Monitoring, Intraoperative / Q000379:methods; D015742:Propofol / Q000008:administration & dosage / Q000097:blood* / Q000494:pharmacology; D055815:Young Adult
chemical_list: D018686:Anesthetics, Intravenous; D015742:Propofol