Opioid-Volatile Pharmacodynamic Interaction: A Response Surface Analysis With Sufentanil And Sevoflurane As Prototypes

BackgroundCombining a hypnotic and an analgesic to produce sedation, analgesia, and surgical immobility required forclinical anesthesia is more common than administration of a volatile anesthetic alone. The aim of this study was to apply response surface methods to characterize the interactions between sufentanil and sevoflurane.Methods:patients, study design and drug delivery:Based on parallel slices design, sixty-two patients were randomly assigned to inhale a specific end-tidal concentration of sevoflurane (0.5-3.5 vol%) and a target-controlled infusion of sufentanil (0.05-0.5 ng/ml) at various target concentration pairs. After reaching pseudo-steady state drug levels, when the patients got the Observer's Assessment of Alertness/Sedation score zero and response to a laryngoscopy stimulation were observed for each target concentration pair. Response surface pharmacodynamic interaction models were built using the Logit modeling method.ResultsSufentanil synergistically decreased the amount of sevoflurane necessary to produce analgesia. NONMEM estimated the average of the model parameters for laryngoscopy of C50sevo,C50sufen are 1.61% and 4.24ng/ml respectively. ConclusionResponse surface analyses demonstrate a synergistic interaction between sufentanil and sevoflurane for the analgesic endpoint.