Remifentanil-sevoflurane interaction models of circulatory response to laryngoscopy and circulatory depression

Sevoflurane and remifentanil are commonly combined to produce the hypnotic and analgesic effects required for clinical anaesthesia. Previous studies have characterized interactions between several i.v. drugs and inhalation agents. Aiming to extend this effort, we developed two new mathematical models to characterize the interactions manner and strength between sevoflurane and remifentanil.

Sixty-five adult Chinese patients undergoing elective operations received a target-controlled infusion of remifentanil (0-10 ng ml(-1)) and inhaled sevoflurane (0.3-3.4 vol.%) at various randomly selected target concentration pairs. After reaching pseudo-steady-state drug levels, the circulatory response to laryngoscopy and any circulatory depression (a side-effect) were observed for each pair of target concentrations. The pharmacodynamic interactions between sevoflurane and remifentanil were investigated by response surface methodology. NONMEM software was used to estimate the model parameters.

The response surface models revealed significant synergy between sevoflurane and remifentanil. When the target remifentanil concentration was increased from 0 to 10 ng ml(-1), the C50, sevo decreased from 2.6 to 0.38 vol.% for the prevention of circulatory response to laryngoscopy and from 3.53 to 1.46 vol.% for the induction of circulatory depression.

The new models can be used to characterize the interactions between these two drugs both qualitatively and quantitatively. Remifentanil significantly decreased the amount of sevoflurane required to eliminate patient response to clinical stimuli, thus reducing the likelihood of side-effects, specifically circulatory depression.