Vandemoortele Ophélie, Hannivoort Laura N, Vanhoorebeeck Florian, Struys Michel M R F, Vereecke Hugo E M
Department of Anaesthesia and Reanimation, UZ Leuven, 3000 Leuven, Belgium.
Department of Anesthesiology, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands.
J Clin Med. 2022 Apr 28;11(9):2487. doi: 10.3390/jcm11092487.
Target controlled infusion (TCI) is a clinically-available and widely-used computer-controlled method of drug administration, adjusting the drug titration towards user selected plasma- or effect-site concentrations, calculated according to pharmacokinetic-pharmacodynamic (PKPD) models. Although this technology is clinically available for several anaesthetic drugs, the contemporary commercialised PKPD models suffer from multiple limitations. First, PKPD models for anaesthetic drugs are developed using deliberately selected patient populations, often excluding the more challenging populations, such as children, obese or elderly patients, of whom the body composition or elimination mechanisms may be structurally different compared to the lean adult patient population. Separate PKPD models have been developed for some of these subcategories, but the availability of multiple PKPD models for a single drug increases the risk for invalid model selection by the user. Second, some models are restricted to the prediction of plasma-concentration without enabling effect-site controlled TCI or they identify the effect-site equilibration rate constant using methods other than PKPD modelling. Advances in computing and the emergence of globally collected databases has allowed the development of new "general purpose" PKPD models. These take on the challenging task of identifying the relationships between patient covariates (age, weight, sex, etc) and the volumes and clearances of multi-compartmental pharmacokinetic models applicable across broad populations from neonates to the elderly, from the underweight to the obese. These models address the issues of allometric scaling of body weight and size, body composition, sex differences, changes with advanced age, and for young children, changes with maturation and growth. General purpose models for propofol, remifentanil and dexmedetomidine have appeared and these greatly reduce the risk of invalid model selection. In this narrative review, we discuss the development, characteristics and validation of several described general purpose PKPD models for anaesthetic drugs.
靶控输注（TCI）是一种临床可用且广泛应用的计算机控制给药方法，它根据药代动力学-药效学（PKPD）模型，朝着用户选定的血浆或效应室浓度调整药物滴定。尽管这项技术在临床上可用于多种麻醉药物，但当代商业化的PKPD模型存在多种局限性。首先，麻醉药物的PKPD模型是使用特意挑选的患者群体开发的，通常排除了更具挑战性的群体，如儿童、肥胖或老年患者，这些人群的身体组成或消除机制与瘦体重成年患者群体相比可能在结构上有所不同。已经为其中一些亚类别开发了单独的PKPD模型，但针对单一药物有多个PKPD模型增加了用户选择无效模型的风险。其次，一些模型仅限于预测血浆浓度，无法实现效应室控制的TCI，或者它们使用PKPD建模以外的方法确定效应室平衡速率常数。计算技术的进步和全球收集数据库的出现使得新的“通用”PKPD模型得以开发。这些模型承担了一项具有挑战性的任务，即确定患者协变量（年龄、体重、性别等）与适用于从新生儿到老年人、从体重过轻到肥胖的广泛人群的多室药代动力学模型的容积和清除率之间的关系。这些模型解决了体重和体型的异速生长缩放、身体组成、性别差异、老年变化以及幼儿的成熟和生长变化等问题。丙泊酚、瑞芬太尼和右美托咪定的通用模型已经出现，这些模型大大降低了选择无效模型的风险。在这篇叙述性综述中，我们讨论了几种已描述的麻醉药物通用PKPD模型的开发、特点和验证。
