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

Abstract：

: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.

journal_name

Clin Exp Pharmacol Physiol

journal_title

Clinical and experimental pharmacology & physiology

authors

Choe S,Choi BM,Lee YH,Lee SH,Lee EK,Kim KS,Noh GJ

doi

10.1111/1440-1681.12677

subject

Has Abstract

pub_date

2017-01-01 00:00:00

pages

30-40

issue

eissn

0305-1870

issn

1440-1681

journal_volume

pub_type

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