Propofol reduces perioperative remifentanil requirements in a synergistic manner: response surface modeling of perioperative remifentanil-propofol interactions

Anesthesiology. 2003 Aug;99(2):347-59. doi: 10.1097/00000542-200308000-00016.


Background: Remifentanil is often combined with propofol for induction and maintenance of total intravenous anesthesia. The authors studied the effect of propofol on remifentanil requirements for suppression of responses to clinically relevant stimuli and evaluated this in relation to previously published data on propofol and alfentanil.

Methods: With ethics committee approval and informed consent, 30 unpremedicated female patients with American Society of Anesthesiologists physical status class I or II, aged 18-65 yr, scheduled to undergo lower abdominal surgery, were randomly assigned to receive a target-controlled infusion of propofol with constant target concentrations of 2, 4, or 6 microg/ml. The target concentration of remifentanil was changed in response to signs of inadequate anesthesia. Arterial blood samples for the determination of remifentanil and propofol concentrations were collected after blood-effect site equilibration. The presence or absence of responses to various perioperative stimuli were related to the propofol and remifentanil concentrations by response surface modeling or logistic regression, followed by regression analysis. Both additive and nonadditive interaction models were explored.

Results: With blood propofol concentrations increasing from 2 to 7.3 microg/ml, the C(50) of remifentanil decreased from 3.8 ng/ml to 0 ng/ml for laryngoscopy, from 4.4 ng/ml to 1.2 ng/ml for intubation, and from 6.3 ng/ml to 0.4 ng/ml for intraabdominal surgery. With blood remifentanil concentrations increasing from 0 to 7 ng/ml, the C(50) of propofol for the return to consciousness decreased from 3.5 microg/ml to 0.6 microg/ml.

Conclusions: Propofol reduces remifentanil requirements for suppression of responses to laryngoscopy, intubation, and intraabdominal surgical stimulation in a synergistic manner. In addition, remifentanil decreases propofol concentrations associated with the return of consciousness in a synergistic manner.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Algorithms
  • Anesthesia, General*
  • Anesthetics, Intravenous* / administration & dosage
  • Anesthetics, Intravenous* / pharmacokinetics
  • Computer Simulation
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Female
  • Humans
  • Intubation, Intratracheal
  • Laryngoscopy
  • Middle Aged
  • Models, Biological
  • Piperidines* / administration & dosage
  • Piperidines* / pharmacokinetics
  • Propofol* / administration & dosage
  • Propofol* / pharmacokinetics
  • Remifentanil


  • Anesthetics, Intravenous
  • Piperidines
  • Remifentanil
  • Propofol