The Influence of Age on the Dynamic Relationship Between End-Tidal Sevoflurane Concentrations and Bispectral Index

BACKGROUND: Age is an important determinant of the pharmacokinetic profile of inhaled anesthetics. The influence of age on the dynamic profile of sevoflurane's effect has not been well described. We performed this study to characterize the influence of age and other covariates on the dynamic relationship between sevoflurane end-tidal concentration (C(ET)) and its effect measured by bispectral index (BIS). METHODS: Fifty patients, aged 3-71 yr, scheduled for minor surgery were prospectively studied. The BIS and sevoflurane C(ET) were continuously measured during the study period. During maintenance of anesthesia and after stable BIS values of 60-65 were obtained, the inspired concentration of sevoflurane was increased to 5 vol % for 5 min or until BIS <40 and then decreased. The dynamic relationship between sevoflurane C(ET) and its effect as measured by BIS during this transition period were modeled with an inhibitory E(max) model using a population pharmacokinetic-pharmacodynamic approach with NONMEM V. A predictive check method was used to validate the final model. RESULTS: The sensitivity to sevoflurane's effect as measured by BIS expressed in the C(50) [steady-state C(ET) eliciting half of maximum response (I(max))] increased with age. The speed of change of sevoflurane's effect, expressed as the effect-site equilibration half-life (t(1/2) k(e0)), increased at older ages. The predictive check analysis confirmed the adequacy of the model. CONCLUSIONS: Age significantly affects the dynamic relationship between sevoflurane C(ET) and its effect measured with BIS

The Influence of Age on the Dynamic Relationship Between End-Tidal Sevoflurane Concentrations and Bispectral Index

BACKGROUND: Age is an important determinant of the pharmacokinetic profile of inhaled anesthetics. The influence of age on the dynamic profile of sevoflurane's effect has not been well described. We performed this study to characterize the influence of age and other covariates on the dynamic relationship between sevoflurane end-tidal concentration (C(ET)) and its effect measured by bispectral index (BIS). METHODS: Fifty patients, aged 3-71 yr, scheduled for minor surgery were prospectively studied. The BIS and sevoflurane C(ET) were continuously measured during the study period. During maintenance of anesthesia and after stable BIS values of 60-65 were obtained, the inspired concentration of sevoflurane was increased to 5 vol % for 5 min or until BIS <40 and then decreased. The dynamic relationship between sevoflurane C(ET) and its effect as measured by BIS during this transition period were modeled with an inhibitory E(max) model using a population pharmacokinetic-pharmacodynamic approach with NONMEM V. A predictive check method was used to validate the final model. RESULTS: The sensitivity to sevoflurane's effect as measured by BIS expressed in the C(50) [steady-state C(ET) eliciting half of maximum response (I(max))] increased with age. The speed of change of sevoflurane's effect, expressed as the effect-site equilibration half-life (t(1/2) k(e0)), increased at older ages. The predictive check analysis confirmed the adequacy of the model. CONCLUSIONS: Age significantly affects the dynamic relationship between sevoflurane C(ET) and its effect measured with BIS