title: Pharmacodynamic interaction between propofol and remifentanil regarding hypnosis, tolerance of laryngoscopy, bispectral index, and electroencephalographic approximate entropy.
abstract: BACKGROUND
  The purpose of this investigation was to describe the pharmacodynamic interaction between propofol and remifentanil for probability of no response to shaking and shouting, probability of no response to laryngoscopy, Bispectral Index (BIS), and electroencephalographic approximate entropy (AE).
  
  
  METHODS
  Twenty healthy volunteers received either propofol or remifentanil alone and then concurrently with a fixed concentration of remifentanil or propofol, respectively, via a target-controlled infusion. Responses to shaking and shouting and to laryngoscopy were assessed multiple times after allowing for plasma effect site equilibration. The raw electroencephalogram and BIS were recorded throughout the study, and AE was calculated off-line. Response surfaces were fit to the clinical response data using logistic regression or hierarchical response models. Response surfaces were also estimated for BIS and AE. Surfaces were visualized using three-dimensional rotations. Model parameters were estimated with NONMEM.
  
  
  RESULTS
  Remifentanil alone had no appreciable effect on response to shaking and shouting or response to laryngoscopy. Propofol could ablate both responses. Modest remifentanil concentrations dramatically reduced the concentrations of propofol required to ablate both responses. The hierarchical response surface described the data better than empirical logistic regression. BIS and AE are more sensitive to propofol than to remifentanil.
  
  
  CONCLUSIONS
  Remifentanil alone is ineffective at ablating response to stimuli but demonstrates potent synergy with propofol. BIS and AE values corresponding to 95% probability of ablating response are influenced by the combination of propofol and remifentanil to achieve this endpoint, with higher propofol concentrations producing lower values for BIS and AE.
authors.affiliation: Department of Anesthesia, Inselspital.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Bouillon
authors.forename: Jörgen
authors.initials: J
authors.lastname: Bruhn
authors.forename: Lucian
authors.initials: L
authors.lastname: Radulescu
authors.forename: Corina
authors.initials: C
authors.lastname: Andresen
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Shafer
authors.forename: Carol
authors.initials: C
authors.lastname: Cohane
authors.forename: Steven L
authors.initials: SL
authors.lastname: Shafer
mesh_terms: D000328:Adult; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions / Q000502:physiology; D004357:Drug Synergism; D004569:Electroencephalography / Q000187:drug effects* / Q000379:methods; D019277:Entropy; D005260:Female; D006801:Humans; D006990:Hypnosis / Q000379:methods*; D007828:Laryngoscopy / Q000379:methods*; D016015:Logistic Models; D008297:Male; D010880:Piperidines / Q000493:pharmacokinetics* / Q000494:pharmacology; D015742:Propofol / Q000493:pharmacokinetics* / Q000494:pharmacology; D011446:Prospective Studies; D000077208:Remifentanil
chemical_list: D010880:Piperidines; D000077208:Remifentanil; D015742:Propofol