Department of Anesthesiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Department of Anesthesiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Br J Anaesth. 2021 Feb;126(2):386-394. doi: 10.1016/j.bja.2020.10.027. Epub 2020 Dec 13.
Target-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.
The 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.
For 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 Ce.
The 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.
采用药代动力学（PK）或 PK-药效动力学（PK-PD）模型的靶控输注（TCI）系统可用于辅助给药。现有的模型是使用来自特定人群的数据开发的，严格来说，这些模型的使用仅限于这些人群。最近，为广泛的人群范围开发了一种丙泊酚 PK-PD 模型。该研究的目的是前瞻性验证该模型在接受全身麻醉的儿童、成人、老年患者和肥胖成人中的适用性。
每个年龄和体重亚组包括 25 名受试者。受试者通过 TCI 输注丙泊酚，采用 Eleveld 模型，靶浓度设定为 40-60。在开始输注丙泊酚后 5、10、20、30、40 和 60 分钟，以及之后每 30 分钟采集一次动脉血样，最多采集 10 个样本。连续记录 BIS。使用 Varvel 标准评估预测性能。
对于 PK，Eleveld 模型在儿童、成人和肥胖成人中表现出<±20%的偏倚，但在老年患者中表现出更大的偏倚（-27%）。所有组的精度均<30%。对于 PD，偏倚和摆动均<5 BIS 单位，所有组的精度均接近 10 BIS 单位。麻醉医师能够通过使用效应部位目标浓度约为年龄校正 Ce 的 85-140%，在术中实现 40-60 的 BIS 值。
Eleveld 丙泊酚 PK-PD 模型在临床麻醉实践中用于 TCI 时，其动脉血浆浓度和 BIS 预测的预测精度<30%，人群偏倚较低。
