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Propofol pharmacokinetic and pharmacodynamic profile and its electroencephalographic interaction with remifentanil in
Ricardo Fuentes1, Luis Ignacio Cortínez1, Víctor Contreras1
1División Anestesiología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago de Chile, Chile.
Insights
This study developed an integrated propofol pharmacokinetic-pharmacodynamic model for children, quantifying remifentanil
Area of Science:
- Anesthesiology and Pharmacology
- Pediatric Anesthesia
- Pharmacokinetic/Pharmacodynamic Modeling
Background:
- Propofol and remifentanil are frequently combined for total intravenous anesthesia.
- The interaction between these agents in pediatric populations is not well understood.
- Accurate modeling is needed to predict hypnotic effects during combined administration.
Purpose of the Study:
- To develop an integrated propofol pharmacokinetic-pharmacodynamic (PK/PD) model in children.
- To characterize the pharmacodynamic interaction between propofol and remifentanil.
- To assess the impact on the Bispectral Index (BIS).
Main Methods:
- Population PK/PD modeling was used, integrating data from 30 children.
- Propofol concentrations and BIS data were collected during anesthesia and postoperatively.
- The Greco model analyzed the propofol-remifentanil interaction on BIS response.
Main Results:
- A three-compartment propofol PK model with allometric scaling was established.
- The Greco model indicated an additive interaction between propofol and remifentanil.
- Remifentanil demonstrated a minimal effect on the BIS response.
Conclusions:
- An integrated propofol PK/PD model was successfully developed for pediatric patients.
- The model quantifies the additive pharmacodynamic interaction between propofol and remifentanil.
- This model can improve the prediction of hypnotic effects during combined anesthesia.
Background:
Propofol and remifentanil are commonly combined during total intravenous anesthesia. The impact of remifentanil in this relationship is poorly quantified in children. Derivation of an integrated pharmacokinetic and pharmacodynamic propofol model, containing remifentanil pharmacodynamic interaction information, enables propofol effect-site target-controlled infusion in children with a better prediction of its hypnotic effect when both drugs are combined.
Aims:
We designed this study to derive an integrated propofol pharmacokinetic-pharmacodynamic model in children and to describe the pharmacodynamic interaction between propofol and remifentanil on the electroencephalographic bispectral index effect.
Methods:
Thirty children (mean age: 5.45 years, range 1.3-11.9; mean weight: 23.5 kg, range 8.5-61) scheduled for elective surgery with general anesthesia were studied. After sevoflurane induction, maintenance of anesthesia was based on propofol and remifentanil. Blood samples to measure propofol concentration were collected during anesthesia maintenance and up to 6 hours in the postoperative period. Bispectral index data were continuously recorded throughout the study. A pharmacokinetic-pharmacodynamic model was developed using population modeling. The Greco model was used to examine the pharmacokinetic-pharmacodynamic interaction between propofol and remifentanil for BIS response RESULTS: Propofol pharmacokinetic data from a previous study in 53 children were pooled with current data and simultaneously analyzed. Propofol pharmacokinetics were adequately described by a three-compartment distribution model with first-order elimination. Theory-based allometric relationships based on TBW improved the model fit. The Greco model supported an additive interaction between propofol and remifentanil. Remifentanil showed only a minor effect in BIS response.
Conclusion:
We have developed an integrated propofol pharmacokinetic-pharmacodynamic model that can describe the pharmacodynamic interaction between propofol and remifentanil for BIS response. An additive interaction was supported by our modeling analysis.
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