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 OAA/S.Sevoflurene alone could produce OAA/S ≤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 OAA/S score was ≥3 even when the remifentanil cencentration 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 between 60 and 40.Conclusions The response surface method can analyze the pharmacodynamic interactions between remifentanil and sevoflurane qualitatively and quantitatively.Within the range of our study (remifentanil ≤10 ng/ml,sevoflurane ≤3.4％),the two drugs produced synergistic effects on OAA/S but had no interactive effect on BIS.A guideline of BIS between 40 and 60 may cause excessive anesthesia when opioids are used to maintain anesthesia.