Good correlation between necessary remifentanil concentrations in individual patients determined from sedative-analgesic interactions using pharmacokinetic simulations and the remifentanil concentrations used at anesthesiologists’ discretion

Abstract

Abstract Background Analgesic and sedative agents interact with each other, and their relationship is explained in a curve convex below. In the automated control anesthesia system based on this relationship that we developed, the dose of analgesic is adjusted with the necessary remifentanil concentration, determined with propofol-remifentanil interactions, as an estimated maximal individual concentration (esMIC). With the system, a study in patients under anesthesia management by an anesthesiologist was conducted to compare the effect-site concentration (ESC) of remifentanil administered at the anesthesiologist’s discretion and the esMIC calculated with drug-drug interactions for their relationship and to assess whether the analgesic dose administered based on esMIC is appropriate. Methods In the present study involving 20 patients, anesthesiologists changed the propofol (P) infusion rate and remifentanil (R) infusion rate to maintain BIS value of 45. The estimated target-effect-site concentration of propofol for maintaining BIS 45 and the ESC of remifentanil (ESC_R) based on the model by Minto et al. were calculated. Moreover, with these data sets, the isodynamic curve of ESC of propofol (ESC_P) for maintaining BIS 45 (Y) and ESC_R (X) was determined to be an equilateral hyperbola (Y = c/(X − a) + b). With the ESC_R at which even raising ESC_R would result in small decreases in ESC_P considered the esMIC, the ESC_R at the point at which the slope of this curve is − 1 (neutral point) and at the point of the curve where the y-component deviation of the asymptote (y = b) is 20% (esMIC20) was calculated every 6 seconds. The ESC_R at the time point of an adequate analgesic state as deemed by the anesthesiologist after anesthesia had been started for 15 minutes was compared with the esMIC20 determined by objective calculations. Results The ESC_R and esMIC20 were 11.9 ± 2.4 and 11.6 ± 2.0 ng/ml, respectively. Moreover, the median ESC_R and esMIC20 in the patients showed a very good correlation (correlation coefficient R² = 0.88, p < 0.01). Conclusions The necessary analgesic concentrations estimated with drug-drug interactions did not contradict those determined at anesthesiologists’ discretion and are considered to assure a reasonable analgesic state.