Cortínez Luis I, Anderson Brian J
Departamento de Anestesiología, Hospital Clínico de la Pontificia Universidad Católica de Chile, Santiago, Chile.
Department of Anaesthesiology, Auckland University, Auckland, New Zealand.
Curr Opin Anaesthesiol. 2018 Aug;31(4):415-422. doi: 10.1097/ACO.0000000000000619.
The use of conventional pharmacokinetic parameters sets 'models' derived from nonobese patients has proven inadequate to administer intravenous anesthetics in the obese population and is commonly associated with higher than anticipated plasma propofol concentrations when used with target (plasma or effect site) controlled infusion pumps. In this review we will describe recent modeling strategies to characterize the disposition of intravenous anesthetics in the obese patient and will show clinically relevant aspects of new model's performance in the obese population.
Because clearance of a drug increases in a nonlinear manner with weight, nonlinear relationships better scale infusion rates between lean and obese individuals. Allometric concepts have been successfully used to describe size-related nonlinear changes in clearances. Other nonlinear scaling options include the use of descriptors such as body surface area, lean body weight, fat-free mass, and normal fat mass. Newer pharmacokinetic models, determined from obese patient data, have been developed for propofol and remifentanil using allometric concepts and comprehensive size descriptors.
Pharmacokinetic models to perform target-controlled infusion in the obese population should incorporate descriptors that reflect with greater precision the influence of body composition in volumes and clearances of each drug. It is our hope that commercially available pumps will soon incorporate these new models to improve the performance of this technique in the obese population.
事实证明，使用源自非肥胖患者的传统药代动力学参数所建立的“模型”，不足以用于肥胖人群的静脉麻醉给药，并且在与目标（血浆或效应部位）控制输注泵联用时，通常会导致血浆丙泊酚浓度高于预期。在本综述中，我们将描述近期用于表征肥胖患者静脉麻醉药处置情况的建模策略，并展示新模型在肥胖人群中性能的临床相关方面。
由于药物清除率随体重呈非线性增加，非线性关系能更好地按比例确定瘦人与肥胖个体之间的输注速率。异速生长概念已成功用于描述清除率中与体型相关的非线性变化。其他非线性缩放选项包括使用诸如体表面积、瘦体重、去脂体重和正常脂肪量等描述符。已利用异速生长概念和综合体型描述符，根据肥胖患者数据为丙泊酚和瑞芬太尼开发了更新的药代动力学模型。
用于肥胖人群进行靶控输注的药代动力学模型应纳入能更精确反映身体组成对每种药物的容积和清除率影响的描述符。我们希望市售输注泵很快能纳入这些新模型，以改善该技术在肥胖人群中的性能。
