• Hong Su, Douglas J Eleveld, StruysMichel M R FMMRFDepartment of Anesthesiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands; Department of Basic and Applied Medical Sciences, Ghent University, Ghent, Belgium., and Pieter J Colin.
• Department of Anesthesiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
• Br J Anaesth. 2022 May 1; 128 (5): 806-816.

BackgroundThe adverse haemodynamic effects of the intravenous anaesthetic propofol are well known, yet few empirical models have explored the dose-response relationship. Evidence suggests that hypotension during general anaesthesia is associated with postoperative mortality. We developed a mechanism-based model that quantitatively characterises the magnitude of propofol-induced haemodynamic effects during general anaesthesia.MethodsMean arterial pressure (MAP), heart rate (HR) and pulse pressure (PP) measurements were available from 36 healthy volunteers who received propofol in a step-up and step-down fashion by target-controlled infusion using the Schnider pharmacokinetic model. A mechanistic pharmacodynamic model was explored based on the Snelder model. To benchmark the performance of this model, we developed empirical models for MAP, HR, and PP.ResultsThe mechanistic model consisted of three turnover equations representing total peripheral resistance (TPR), stroke volume (SV), and HR. Propofol-induced changes were implemented by Emax models on the zero-order production rates of the turnover equations for TPR and SV. The estimated 50% effective concentrations for propofol-induced changes in TPR and SV were 2.96 and 0.34 μg ml-1, respectively. The goodness-of-fit for the mechanism-based model was indistinguishable from the empirical models. Simulations showed that predictions from the mechanism-based model were similar to previously published MAP and HR observations.ConclusionsWe developed a mechanism-based pharmacodynamic model for propofol-induced changes in MAP, TPR, SV, and HR as a potential approach for predicting haemodynamic alterations.Clinical Trial RegistrationNCT02043938.Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.

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