【罂粟摘要】全麻中应用Elevel模型输注丙泊酚药代-药效学模型的前瞻性临床验证

全麻中应用Elevel模型输注丙泊酚药代-药效学模型的前瞻性临床验证翻译：佟睿 | 编辑：佟睿 | 审校：曹莹

背景

靶控输注(TCI)系统结合了药代动力学(PK)或药代-药效学(PK-PD)模型，可用于指导给药。现有的模型是根据选定人群的数据所开发，严格地说，这些数据仅限于这些人群使用。最近，异丙酚PK-PD模型被开发出来，适用于广泛的人群范围。这项研究的目的是在接受全身麻醉的儿童、成人、老年受试者和肥胖成年人中前瞻性地验证这一模型。

方法

纳入四组进行试验，每组的25名受试者按年龄和体重分层。受试者接受按Elevel模型进行靶控输注的丙泊酚，双频指数(BIS)控制在40-60。分别于丙泊酚开始输注后5、10、20、30、40、60min及此后每隔30min采集动脉血样本，最多10份。连续记录BIS。使用Varvel标准评估预测性能。

结果

从药代动力学上看，Eleveld模型在儿童、成人和肥胖成人中的偏差小于±20%，但在老年受试者中的偏差较大(-27%)。各组间精密度均<30%。从药物效应学上看，各组的偏移和摆动均小于5个BIS单位，测量精度均接近10个BIS单位。麻醉医生为了使术中BIS值达到40-60的目标，使用效应目标浓度约为年龄调整后Ce50的85-140%。

结论

Eleveld模式输注丙泊酚的PK-PD模型在临床麻醉使用TCI时，对动脉血药浓度和BIS预测的精确度<30%，总体偏差较低。

Prospective clinical validation of the Eleveld propofol pharmacokinetic-pharmacodynamic model in general anaesthesia

ABSTRACT

Background: Target-controlled infusion (TCI) systems incorporating pharmacokinetic (PK) or PK-pharmacodynamic (PKPD) 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.

Methods: 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.

Results: 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 Ce50.

Conclusions: 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.

原始文献来源：

Remco Vellinga1, Laura N. Hannivoort1, Michele Introna, et al. Prospective clinical validation of the Eleveld propofol pharmacokinetic-pharmacodynamic model in general anaesthesia.[J].BJ Anaesth., 2021 Feb; 126 (2): 386-394.