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

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Author:
No author available
Journal Title:
Chinese Medical Journal
Issue:
15
DOI:
10.3760/cma.j.issn.0366-6999.2012.15.007
Key Word:
sevoflurane;remifentanil;response surface;the observer's assessment of alertness/sedation;bispectral index

Abstract: 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.

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