title: Propofol and remifentanil pharmacodynamic interaction during orthopedic surgical procedures as measured by effects on bispectral index.
abstract: OBJECTIVE
  To identify and quantify the interaction between propofol and remifentanil during surgical procedures with a bispectral index (BIS) of 50 that was chosen as a continuous surrogate measure for "adequate depth" of anesthesia.
  
  
  METHODS
  Prospective, open-label study.
  
  
  METHODS
  Department of orthopedics of a university hospital.
  
  
  METHODS
  20 patients undergoing orthopedic surgery.
  
  
  METHODS
  Anesthesia was induced and maintained with propofol and remifentanil, both administered by target-controlled infusion (TCI). Initial target concentrations of propofol (1.5-8 microg/mL) and remifentanil (2-15 ng/mL) were chosen and alternated in order to maintain the BIS between 45 and 55. If constant target concentrations had been maintained for 20 minutes and the BIS did not depart from the desired range, blood samples were taken to determine propofol concentrations, and the BIS value was recorded. Isobolographic interaction models were fitted to the infusion rates of remifentanil and propofol, predicted target concentrations of both drugs, and measured propofol concentrations versus predicted remifentanil concentrations.
  
  
  RESULTS
  The isobole for the interaction of propofol and remifentanil in the concentration range investigated (propofol 1.5-8 microg/mL and remifentanil 1-30 ng/mL) is a concave up hyperbola ((0.15. C(prop))(3.13). C(rem) = 1) with C(prop) = propofol plasma concentration [microg/mL] and C(rem) = remifentanil blood concentration [ng/mL]). Use of predicted (=TCI target) concentrations or the respective infusion rates did not alter the general shape of the interaction isobole.
  
  
  CONCLUSIONS
  The interaction between propofol and remifentanil for maintenance of a BIS value between 45 and 55 during surgery is synergistic. This finding applies regardless of whether measured concentrations (for propofol), predicted concentrations of the infusion device, or infusion rates are used as model input. Notably, the interaction isobole of the (clinically readily available) infusion rates provides a useful dosing recommendation for the coadministration of propofol and remifentanil during maintenance of anesthesia.
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, University of, Bonn, Germany. Heiko.Roepcke@ukb.uni-bonn.de
authors.forename: H
authors.initials: H
authors.lastname: Röpcke
authors.forename: M
authors.initials: M
authors.lastname: Könen-Bergmann
authors.forename: M
authors.initials: M
authors.lastname: Cuhls
authors.forename: T
authors.initials: T
authors.lastname: Bouillon
authors.forename: A
authors.initials: A
authors.lastname: Hoeft
mesh_terms: D000328:Adult; D000368:Aged; D000465:Algorithms; D018686:Anesthetics, Intravenous / Q000097:blood / Q000493:pharmacokinetics*; D004347:Drug Interactions; D004569:Electroencephalography / Q000187:drug effects*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016343:Monitoring, Intraoperative; D019637:Orthopedic Procedures; D010880:Piperidines / Q000097:blood / Q000493:pharmacokinetics*; D015742:Propofol / Q000097:blood / Q000493:pharmacokinetics*; D011446:Prospective Studies; D000077208:Remifentanil
chemical_list: D018686:Anesthetics, Intravenous; D010880:Piperidines; D000077208:Remifentanil; D015742:Propofol