Response surface analysis of sevoflurane-remifentanil interactions on consciousness during anesthesia  

作　　者：WANG Hui-ling YANG Lu GUO Xiang-yang ZHANG Li-ping BI Shan-shan LU Wei 

机构地区：[1]Department of Anesthesiology, Peking University Third Hospital,Beijing 100191, China [2]Peking University School of Pharmaceutical Science, Beijing100191, China

出　　处：《Chinese Medical Journal》2012年第15期2682-2687,共6页中华医学杂志（英文版）

基　　金：The National Natural Science Foundation Youth Fund of China

摘　　要：Background Recently, the combination of sevoflurane and remifentanil has been widely used in general anesthesia. In this study, we investigated the sevoflurane-remifentanil pharmacodynamic interactions at clinical concentrations using the observer＇s assessment of alertness/sedation （OAA/S） and the bispectral index （BIS） by response surface analysis. Methods Totally 65 American Society of Anesthesiologists （ASA） I patients age 20 to 50 years old were included in this study. Patients were randomly assigned to be anesthetized with different target end-tidal sevoflurane concentrations that ranged from 0.2% to 3.4% in increments of 0.2%. The end-tidal sevoflurane concentration was maintained constant throughout the study. Remifentanil was infused with a target controlled infusion （TCI） system at increasing step-wise concentrations from 1 ng/ml to 10 ng/ml. The values of OAA/S and BIS at different sevoflurane-remifentanil concentration combinations were measured. The pharmacodynamic interactions between sevoflurane and remifentanil were analyzed by a response surface method. The three-dimensional response surfaces were constructed with Minitab Software. Model parameters were estimated with NONMEM program. Results Sevoflurane and remifentanil acted synergistically on OANS. Sevoflurane alone could produce OANS 〈1 at a minimal alveolar concentration （MAC） of 0.93%. When used in combination with remifentanil at 1, 3, 6, and 10 ng/ml, the corresponding sevoflurane MACs were reduced to 0.79%, 0.58%, 0.48%, and 0.38%, with reductions of 17.2%, 37.6%, 48.4%, and 62.0% from baseline, respectively. In patients administered remifentanil alone, the OANS score was 〉3 even when the remifentanil concentration reached 10 ng/ml. BIS was closely associated with the sevoflurane concentration and the remifentanil concentration did not noticeably influence the relationship between the sevoflurane concentration and BIS. A sevoflurane concentration of （1.04＋0.19）% to （1.81＋0.21）% could maintain a BIS betBackground Recently, the combination of sevoflurane and remifentanil has been widely used in general anesthesia. In this study, we investigated the sevoflurane-remifentanil pharmacodynamic interactions at clinical concentrations using the observer＇s assessment of alertness/sedation （OAA/S） and the bispectral index （BIS） by response surface analysis. Methods Totally 65 American Society of Anesthesiologists （ASA） I patients age 20 to 50 years old were included in this study. Patients were randomly assigned to be anesthetized with different target end-tidal sevoflurane concentrations that ranged from 0.2% to 3.4% in increments of 0.2%. The end-tidal sevoflurane concentration was maintained constant throughout the study. Remifentanil was infused with a target controlled infusion （TCI） system at increasing step-wise concentrations from 1 ng/ml to 10 ng/ml. The values of OAA/S and BIS at different sevoflurane-remifentanil concentration combinations were measured. The pharmacodynamic interactions between sevoflurane and remifentanil were analyzed by a response surface method. The three-dimensional response surfaces were constructed with Minitab Software. Model parameters were estimated with NONMEM program. Results Sevoflurane and remifentanil acted synergistically on OANS. Sevoflurane alone could produce OANS 〈1 at a minimal alveolar concentration （MAC） of 0.93%. When used in combination with remifentanil at 1, 3, 6, and 10 ng/ml, the corresponding sevoflurane MACs were reduced to 0.79%, 0.58%, 0.48%, and 0.38%, with reductions of 17.2%, 37.6%, 48.4%, and 62.0% from baseline, respectively. In patients administered remifentanil alone, the OANS score was 〉3 even when the remifentanil concentration reached 10 ng/ml. BIS was closely associated with the sevoflurane concentration and the remifentanil concentration did not noticeably influence the relationship between the sevoflurane concentration and BIS. A sevoflurane concentration of （1.04＋0.19）% to （1.81＋0.21）% could maintain a BIS bet

关 键 词：SEVOFLURANE REMIFENTANIL response surface  the observer＇s assessment of alertness/sedation bispectral index 

分 类 号：R614[医药卫生—麻醉学]