Alicja Bartkowska-Śniatkowska1, Agnieszka Bienert2, Paweł Wiczling3, Marcin Owczarek4, Jowita Rosada-Kurasińska1, Małgorzata Grześkowiak5, Jan Matysiak6, Zenon J Kokot6, Roman Kaliszan7, Edmund Grześkowiak2. 1. Department of Pediatric Anesthesiology and Intensive Therapy, Poznań University of Medical Sciences, Poznań, Poland. 2. Department of Clinical Pharmacy and Biopharmacy, Poznań University of Medical Sciences, Poznań, Poland. 3. Department of Biopharmaceutics and Pharmacodynamics, Medical University of Gdańsk, Gdańsk, Poland. Electronic address: wiczling@gumed.edu.pl. 4. Department of Anaesthesiology and Intensive Therapy, Collegium Medicum in Bydgoszcz, Bydgoszcz, Poland. 5. Department of Teaching Anesthesiology and Intensive Therapy, Poznań University of Medical Sciences, Poznań, Poland. 6. Department of Analytical Chemistry, Poznan University of Medical Sciences, Poznań, Poland. 7. Department of Biopharmaceutics and Pharmacodynamics, Medical University of Gdańsk, Gdańsk, Poland.
Abstract
BACKGROUND: Propofol is a commonly used agent in total intravenous anesthesia (TIVA). However, the link between its pharmacokinetics and pharmacodynamics has not been fully characterized in children yet. Our aim was to determine the quantitative relationship between the venous plasma concentration and bispectral index (BIS) effect in a heterogeneous group of pediatric patients undergoing various surgical procedures (ASA status I-III). METHODS: Nine male and nine female patients were anesthetized with propofol-fentanyl TIVA. Sparse venous samples for propofol concentrations assay and dense BIS measurements were collected during and after the end of infusion. Nonlinear mixed-effect modeling in NONMEM was used for data analysis. RESULTS: A three-compartment model was linked with a classical Emax model through a biophase compartment to describe the available data. All clearance and volume terms were allometrically scaled to account for the body mass difference among the patients under study. A typical patient had their PK parameters observed within the range of literature values for children. The pharmacodynamic parameters were highly variable. The EC50 of 2.80 mg/L and the biophase distribution rate constant of 3.33 min(-1) were found for a typical patient. CONCLUSIONS: The BIS values in children are highly correlated with the propofol effect compartment concentrations according to the classical Emax concentration-response relationship. Children had slightly lower sensitivity to propofol and slightly higher clearance, as compared with the adult data available in literature. The intra-patient variations in the BIS require the anesthesiologist's attention in using BIS values alone to evaluate the depth of anesthesia in children.
BACKGROUND:Propofol is a commonly used agent in total intravenous anesthesia (TIVA). However, the link between its pharmacokinetics and pharmacodynamics has not been fully characterized in children yet. Our aim was to determine the quantitative relationship between the venous plasma concentration and bispectral index (BIS) effect in a heterogeneous group of pediatric patients undergoing various surgical procedures (ASA status I-III). METHODS: Nine male and nine female patients were anesthetized with propofol-fentanyl TIVA. Sparse venous samples for propofol concentrations assay and dense BIS measurements were collected during and after the end of infusion. Nonlinear mixed-effect modeling in NONMEM was used for data analysis. RESULTS: A three-compartment model was linked with a classical Emax model through a biophase compartment to describe the available data. All clearance and volume terms were allometrically scaled to account for the body mass difference among the patients under study. A typical patient had their PK parameters observed within the range of literature values for children. The pharmacodynamic parameters were highly variable. The EC50 of 2.80 mg/L and the biophase distribution rate constant of 3.33 min(-1) were found for a typical patient. CONCLUSIONS: The BIS values in children are highly correlated with the propofol effect compartment concentrations according to the classical Emax concentration-response relationship. Children had slightly lower sensitivity to propofol and slightly higher clearance, as compared with the adult data available in literature. The intra-patient variations in the BIS require the anesthesiologist's attention in using BIS values alone to evaluate the depth of anesthesia in children.
Authors: Muhammad Ilyas; Muhammad Fasih Uddin Butt; Muhammad Bilal; Khalid Mahmood; Ali Khaqan; Raja Ali Riaz Journal: Biomed Res Int Date: 2017-03-30 Impact factor: 3.411
Authors: Heleen J Blussé van Oud-Alblas; Margreke J E Brill; Mariska Y M Peeters; Dick Tibboel; Meindert Danhof; Catherijne A J Knibbe Journal: BMC Anesthesiol Date: 2019-01-22 Impact factor: 2.217
Authors: Muhammad Ilyas; Jamshed Iqbal; Sayyar Ahmad; Ali Arshad Uppal; Waqas Ahmad Imtiaz; Raja Ali Riaz Journal: IET Syst Biol Date: 2020-04 Impact factor: 1.615