Su Hong, Eleveld Douglas J, Struys Michel M R F, Colin Pieter J
Department of Anesthesiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Department of Anesthesiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands; Department of Basic and Applied Medical Sciences, Ghent University, Ghent, Belgium.
Br J Anaesth. 2022 May;128(5):806-816. doi: 10.1016/j.bja.2022.01.022. Epub 2022 Mar 3.
The 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.
Mean 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.
The mechanistic model consisted of three turnover equations representing total peripheral resistance (TPR), stroke volume (SV), and HR. Propofol-induced changes were implemented by E 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, 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.
We developed a mechanism-based pharmacodynamic model for propofol-induced changes in MAP, TPR, SV, and HR as a potential approach for predicting haemodynamic alterations.
NCT02043938.
静脉麻醉药丙泊酚的不良血流动力学效应已广为人知，但很少有实证模型探究其剂量反应关系。有证据表明，全身麻醉期间的低血压与术后死亡率相关。我们开发了一种基于机制的模型，该模型定量表征了全身麻醉期间丙泊酚诱导的血流动力学效应的大小。
36名健康志愿者通过使用施奈德药代动力学模型的靶控输注以递增和递减方式接受丙泊酚，可获得其平均动脉压（MAP）、心率（HR）和脉压（PP）测量值。基于斯内尔德模型探索了一种机制性药效学模型。为了评估该模型的性能，我们开发了MAP、HR和PP的实证模型。
该机制模型由代表总外周阻力（TPR）、每搏输出量（SV）和HR的三个周转方程组成。丙泊酚诱导的变化通过E模型作用于TPR和SV周转方程的零级生成速率。丙泊酚诱导TPR和SV变化的估计50%有效浓度分别为2.96和0.34μg/ml。基于机制的模型与实证模型的拟合优度无明显差异。模拟结果表明，基于机制的模型的预测与先前发表的MAP和HR观察结果相似。
我们开发了一种基于机制的药效学模型来描述丙泊酚诱导的MAP、TPR、SV和HR变化，作为预测血流动力学改变的一种潜在方法。
NCT02043938。
