Pharmacokinetics and pharmacodynamics of propofol in children undergoing different types of surgeries.
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.
['Bartkowska-Śniatkowska|Alicja|A|', 'Bienert|Agnieszka|A|', 'Wiczling|Paweł|P|', 'Owczarek|Marcin|M|', 'Rosada-Kurasińska|Jowita|J|', 'Grześkowiak|Małgorzata|M|', 'Matysiak|Jan|J|', 'Kokot|Zenon J|ZJ|', 'Kaliszan|Roman|R|', 'Grześkowiak|Edmund|E|']
D000293:Adolescent D018686:Anesthetics, Intravenous D002648:Child D002675:Child, Preschool D056805:Consciousness Monitors D005260:Female D005283:Fentanyl D006801:Humans D007223:Infant D008297:Male D008954:Models, Biological D017711:Nonlinear Dynamics D015742:Propofol
Propofol Children Total intravenous anesthesia Bispectral index Pharmacokinetic and pharmacodynamics modeling