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Response surface modelling of the pharmacodynamic interaction between propofol and remifentanil in patients undergoing anaesthesia
Author(s) -
Choe SangMin,
Choi ByungMoon,
Lee YongHun,
Lee SooHan,
Lee EunKyung,
Kim KiSeong,
Noh GyuJeong
Publication year - 2017
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.12677
Subject(s) - remifentanil , propofol , anesthesia , pharmacodynamics , muscle rigidity , medicine , approximate entropy , electroencephalography , psychology , pharmacokinetics , psychiatry , pattern recognition (psychology) , cognitive psychology
Summary 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 ( EEG s) 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 EEG s 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 C 50 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.