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External Validation of a Pharmacokinetic Model of Propofol for Target-Controlled Infusion in Children under Two Years Old

Journal of Korean Medical Science 2020년 35권 11호 p.70 ~ 70
 ( Ji Sang-Hwan ) - Seoul National University Hospital Department of Anesthesiology and Pain Medicine

이지현 ( Lee Ji-Hyun ) - Seoul National University Hospital Department of Anesthesiology and Pain Medicine
조주연 ( Cho Joo-Youn ) - Seoul National University College of Medicine and Hospital Department of Clinical Pharmacology and Therapeutics
 ( Kim Hwa-Suk ) - Seoul National University College of Medicine and Hospital Department of Clinical Pharmacology and Therapeutics
장영은 ( Jang Young-Eun ) - Seoul National University Hospital Department of Anesthesiology and Pain Medicine
김은희 ( Kim Eun-Hee ) - Seoul National University Hospital Department of Anesthesiology and Pain Medicine
김진태 ( Kim Jin-Tae ) - Seoul National University Hospital Department of Anesthesiology and Pain Medicine
김희수 ( Kim Hee-Soo ) - Seoul National University Hospital Department of Anesthesiology and Pain Medicine

Abstract


Background: Previously, a linked pharmacokinetic-pharmacodynamic model (the Kim model) of propofol with concurrent infusion of remifentanil was developed for children aged 2?12 years. There are few options for pharmacokinetic-pharmacodynamic model of propofol for children under two years old. We performed an external validation of the Kim model for children under two years old to evaluate whether the model is applicable to this age group.

Methods: Twenty-four children were enrolled. After routine anesthetic induction, a continuous infusion of 2% propofol and remifentanil was commenced using the Kim model. The target effect-site concentration of propofol was set as 2, 3, 4, and 5 μg/mL, followed by arterial blood sampling after 10 min of each equilibrium. Population estimates of four parameters?pooled bias, inaccuracy, divergence, and wobble?were used to evaluate the performance of the Kim model.

Results: A total of 95 plasma concentrations were used for evaluation of the Kim model. The population estimate (95% confidence interval) of bias was ?0.96% (?8.45%, 6.54%) and that of inaccuracy was 21.0% (15.0%?27.0%) for the plasma concentration of propofol.

Conclusion: The pooled bias and inaccuracy of the pharmacokinetic predictions are clinically acceptable. Therefore, our external validation of the Kim model indicated that the model can be applicable to target-controlled infusion of propofol in children younger than 2 years, with the recommended use of actual bispectral index monitoring in clinical settings that remifentanil is present.

키워드

Anesthesiology; Pediatrics; Population Pharmacokinetics; Modeling & Simulation
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