Response surface modelling of the pharmacodynamic interaction between propofol and remifentanil in patients undergoing anaesthesia

Sang Min Choe, Byung Moon Choi, Yong Hun Lee, Soo Han Lee, Eun Kyung Lee, Ki Seong Kim, Gyu Jeong Noh

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


This study describes the pharmacodynamic interaction between propofol and remifentanil. Sixty patients who were scheduled for elective surgery under general anaesthesia (30 males/30 females) were enrolled. Patients were randomly allocated to receive one of 15 combinations of drug levels. Baseline electroencephalograms (EEGs) were recorded for 5 minutes prior to administering the drugs. Patients received a target-controlled infusion at one of four predefined doses of propofol (high, 3 μg/mL; medium, 1.5 μg/mL; low, 0.5 μg/mL; or no drug) and of remifentanil (high, 6 or 8 ng/mL; medium, 4 ng/mL; low, 2 ng/mL; or no drug). The occurrence of muscle rigidity, apnoea, and loss of consciousness (LOC) was monitored, and EEGs were recorded during the drug administration phase. Electroencephalographic approximate entropy (ApEn) and temporal linear mode complexity (TLMC) parameters at baseline and under steady state conditions were calculated off-line. Response surfaces were developed to map the interaction between propofol and remifentanil to the probability of occurrence for quantal responses (muscle rigidity, apnoea, LOC) and ApEn and TLMC measurements. Model parameters were estimated using non-linear mixed effects modelling. The response surface revealed infra-additive and synergistic effects for muscle rigidity and apnoea, respectively. The effects of the combined drugs on LOC and EEG parameters (eg, ApEn and TLMC) were additive. The C50 estimates of remifentanil (ng/mL) and propofol (μg/mL) were 9.11 and 130 000 for muscle rigidity, 8.99 and 6.26 for apnoea, 13.9 and 3.04 for LOC, 23.4 and 10.4 for ApEn, and 14.8 and 6.51 for TLMC, respectively. The probability of occurrence for muscle rigidity declined when propofol was combined with remifentanil.

Original languageEnglish
Pages (from-to)30-40
Number of pages11
JournalClinical and Experimental Pharmacology and Physiology
Issue number1
StatePublished - 1 Jan 2017

Bibliographical note

Funding Information:
The authors are grateful to Ki-Seong Kim (Research Associate, Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology) for generating the 3D figures.

Publisher Copyright:
© 2016 John Wiley & Sons Australia, Ltd


  • interaction
  • propofol
  • remifentanil


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