Department of Anesthesiology, Fukushima Medical University, 1 Hikarigaoka, Fukushima, Fukushima, Japan.
Curr Opin Anaesthesiol. 2023 Aug 1;36(4):414-421. doi: 10.1097/ACO.0000000000001280. Epub 2023 Jun 8.
Understanding the changes in drug disposition of intravenous anesthetics in patients with obesity and administering appropriate doses are critical to avoid intraoperative awareness with recall because of underdosing and over-sedation and delayed emergence due to overdosing. Pharmacokinetic simulation or target-controlled infusion (TCI) using models that have been adapted to patients with obesity are necessary to select appropriate dosing regimens. This review aimed to describe the pharmacokinetic concepts underpinning the use of intravenous anesthetics, including propofol, remifentanil, and remimazolam, in patients with obesity.
In the last 5 years, a series of pharmacokinetic models for propofol, remifentanil, and remimazolam that were estimated from populations that included obese patients have been published. These new pharmacokinetic models can be considered 'second generation' compared with earlier models in that they expand the range of covariate effects (e.g. the extremes of body weight and age) accounted for by the models. The predictive performances of each pharmacokinetic model have been shown in the literature to be within clinically acceptable limits. Among them, the propofol model by Eleveld et al. has been externally validated and has shown reasonable predictive accuracy.
Pharmacokinetic simulations or TCI using pharmacokinetic models that account for the influence of obesity on a drug's disposition are essential to predict plasma/effect-site concentrations of intravenous anesthetics and understand the temporal profile of drug concentrations and effect in patients with obesity, particularly severe obesity.
了解肥胖患者静脉麻醉药物处置的变化,并给予适当的剂量非常重要,这可以避免因剂量不足导致术中知晓和回忆,以及因剂量过大导致过度镇静和苏醒延迟。需要使用针对肥胖患者进行了调整的药代动力学模拟或靶控输注(TCI),以选择合适的剂量方案。本综述旨在描述静脉麻醉药物(包括丙泊酚、瑞芬太尼和雷米佐胺)在肥胖患者中的应用所基于的药代动力学概念。
在过去 5 年中,已经发表了一系列针对肥胖患者的丙泊酚、瑞芬太尼和雷米佐胺的药代动力学模型,这些模型是通过包含肥胖患者的人群估算得到的。与早期模型相比,这些新的药代动力学模型可以被认为是“第二代”模型,因为它们扩展了模型所考虑的协变量效应范围(例如体重和年龄的极端值)。文献中已经证明了每种药代动力学模型的预测性能均在临床可接受的范围内。其中,Eleveld 等人的丙泊酚模型已经过外部验证,显示出合理的预测准确性。
药代动力学模拟或 TCI 使用考虑肥胖对药物处置影响的药代动力学模型对于预测静脉麻醉药物的血浆/效应部位浓度以及了解肥胖患者药物浓度和效应的时间过程非常重要,尤其是严重肥胖患者。