• Br J Anaesth · May 2018

    Pharmacokinetic-pharmacodynamic model for propofol for broad application in anaesthesia and sedation.

    • D J Eleveld, P Colin, A R Absalom, and Struys M M R F MMRF Department of Anesthesiology, University Medical Center Groningen, Groningen, The Netherlands; Department of Anesthesia and Peri-operative Medicine, G.
    • Department of Anesthesiology, University Medical Center Groningen, Groningen, The Netherlands. Electronic address: d.j.eleveld@umcg.nl.
    • Br J Anaesth. 2018 May 1; 120 (5): 942-959.

    BackgroundPharmacokinetic (PK) and pharmacodynamic (PD) models are used in target-controlled-infusion (TCI) systems to determine the optimal drug administration to achieve a desired target concentration in a central or effect-site compartment. Our aim was to develop a PK-PD model for propofol that can predict the bispectral index (BIS) for a broad population, suitable for TCI applications.MethodsPropofol PK data were obtained from 30 previously published studies, five of which also contained BIS observations. A PK-PD model was developed using NONMEM. Weight, age, post-menstrual age (PMA), height, sex, BMI, and presence/absence of concomitant anaesthetic drugs were explored as covariates. The predictive performance was measured across young children, children, adults, elderly, and high-BMI individuals, and in simulated TCI applications.ResultsOverall, 15 433 propofol concentration and 28 639 BIS observations from 1033 individuals (672 males and 361 females) were analysed. The age range was from 27 weeks PMA to 88 yr, and the weight range was 0.68-160 kg. The final model uses age, PMA, weight, height, sex, and presence/absence of concomitant anaesthetic drugs as covariates. A 35-yr-old, 170 cm, 70 kg male (without concomitant anaesthetic drugs) has a V1, V2, V3, CL, Q2, Q3, and ke0 of 6.28, 25.5, 273 litres, 1.79, 1.75, 1.11 litres min-1, and 0.146 min-1, respectively. The propofol TCI administration using the model matches well with recommendations for all age groups considered for both anaesthesia and sedation.ConclusionsWe developed a PK-PD model to predict the propofol concentrations and BIS for broad, diverse population. This should be useful for TCI in anaesthesia and sedation.Copyright © 2018 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.

      Pubmed     Full text   Copy Citation     Plaintext  

      Add institutional full text...

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

    Notes

     
    Knowledge, pearl, summary or comment to share?
    300 characters remaining
    help        
    You can also include formatting, links, images and footnotes in your notes
    • Simple formatting can be added to notes, such as *italics*, _underline_ or **bold**.
    • Superscript can be denoted by <sup>text</sup> and subscript <sub>text</sub>.
    • Numbered or bulleted lists can be created using either numbered lines 1. 2. 3., hyphens - or asterisks *.
    • Links can be included with: [my link to pubmed](http://pubmed.com)
    • Images can be included with: ![alt text](https://bestmedicaljournal.com/study_graph.jpg "Image Title Text")
    • For footnotes use [^1](This is a footnote.) inline.
    • Or use an inline reference [^1] to refer to a longer footnote elseweher in the document [^1]: This is a long footnote..

    hide…