• Remco Vellinga, Laura N Hannivoort, Michele Introna, Daan J Touw, Anthony R Absalom, Douglas J Eleveld, and Struys Michel M R F MMRF Department of Anesthesiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Department of Basic and A.
• Department of Anesthesiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. Electronic address: r.vellinga@umcg.nl.
• Br J Anaesth. 2021 Feb 1; 126 (2): 386-394.

BackgroundTarget-controlled infusion (TCI) systems incorporating pharmacokinetic (PK) or PK-pharmacodynamic (PK-PD) models can be used to facilitate drug administration. Existing models were developed using data from select populations, the use of which is, strictly speaking, limited to these populations. Recently a propofol PK-PD model was developed for a broad population range. The aim of the study was to prospectively validate this model in children, adults, older subjects, and obese adults undergoing general anaesthesia.MethodsThe 25 subjects included in each of four groups were stratified by age and weight. Subjects received propofol through TCI with the Eleveld model, titrated to a bispectral index (BIS) of 40-60. Arterial blood samples were collected at 5, 10, 20, 30, 40, and 60 min after the start of propofol infusion, and every 30 min thereafter, to a maximum of 10 samples. BIS was recorded continuously. Predictive performance was assessed using the Varvel criteria.ResultsFor PK, the Eleveld model showed a bias < ±20% in children, adults, and obese adults, but a greater bias (-27%) in older subjects. Precision was <30% in all groups. For PD, the bias and wobble were <5 BIS units and the precision was close to 10 BIS units in all groups. Anaesthetists were able to achieve intraoperative BIS values of 40-60 using effect-site target concentrations about 85-140% of the age-adjusted Ce50.ConclusionsThe Eleveld propofol PK-PD model showed predictive precision <30% for arterial plasma concentrations and BIS predictions with a low (population) bias when used in TCI in clinical anaesthesia practice.Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.

This article appears in the collection: Comparing propofol TCI pharmacokinetic models.

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