Fuentes Ricardo, Cortínez Luis Ignacio, Contreras Víctor, Ibacache Mauricio, Anderson Brian J
División Anestesiología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago de Chile, Chile.
Department of Anesthesiology, University of Auckland, Auckland, New Zealand.
Paediatr Anaesth. 2018 Dec;28(12):1078-1086. doi: 10.1111/pan.13486. Epub 2018 Oct 11.
Propofol and remifentanil are commonly combined during total intravenous anesthesia. The impact of remifentanil in this relationship is poorly quantified in children. Derivation of an integrated pharmacokinetic and pharmacodynamic propofol model, containing remifentanil pharmacodynamic interaction information, enables propofol effect-site target-controlled infusion in children with a better prediction of its hypnotic effect when both drugs are combined.
We designed this study to derive an integrated propofol pharmacokinetic-pharmacodynamic model in children and to describe the pharmacodynamic interaction between propofol and remifentanil on the electroencephalographic bispectral index effect.
Thirty children (mean age: 5.45 years, range 1.3-11.9; mean weight: 23.5 kg, range 8.5-61) scheduled for elective surgery with general anesthesia were studied. After sevoflurane induction, maintenance of anesthesia was based on propofol and remifentanil. Blood samples to measure propofol concentration were collected during anesthesia maintenance and up to 6 hours in the postoperative period. Bispectral index data were continuously recorded throughout the study. A pharmacokinetic-pharmacodynamic model was developed using population modeling. The Greco model was used to examine the pharmacokinetic-pharmacodynamic interaction between propofol and remifentanil for BIS response RESULTS: Propofol pharmacokinetic data from a previous study in 53 children were pooled with current data and simultaneously analyzed. Propofol pharmacokinetics were adequately described by a three-compartment distribution model with first-order elimination. Theory-based allometric relationships based on TBW improved the model fit. The Greco model supported an additive interaction between propofol and remifentanil. Remifentanil showed only a minor effect in BIS response.
We have developed an integrated propofol pharmacokinetic-pharmacodynamic model that can describe the pharmacodynamic interaction between propofol and remifentanil for BIS response. An additive interaction was supported by our modeling analysis.
丙泊酚和瑞芬太尼在全静脉麻醉中常联合使用。在儿童中，瑞芬太尼在这种联合使用关系中的影响量化不足。推导一个包含瑞芬太尼药效学相互作用信息的丙泊酚药代动力学和药效学综合模型，能够在两种药物联合使用时，更好地预测丙泊酚在儿童效应室靶控输注时的催眠效果。
我们设计本研究以推导儿童丙泊酚药代动力学-药效学综合模型，并描述丙泊酚和瑞芬太尼对脑电图双谱指数效应的药效学相互作用。
对30例计划接受全身麻醉择期手术的儿童（平均年龄：5.45岁，范围1.3 - 11.9岁；平均体重：23.5kg，范围8.5 - 61kg）进行研究。七氟醚诱导后，麻醉维持采用丙泊酚和瑞芬太尼。在麻醉维持期间及术后长达6小时采集血样以测定丙泊酚浓度。在整个研究过程中持续记录双谱指数数据。使用群体建模开发药代动力学-药效学模型。采用Greco模型研究丙泊酚和瑞芬太尼对BIS反应的药代动力学-药效学相互作用。结果：将先前在53例儿童中进行的一项研究的丙泊酚药代动力学数据与当前数据合并并同时分析。丙泊酚药代动力学可用具有一级消除的三室分布模型充分描述。基于总体重的理论异速生长关系改善了模型拟合。Greco模型支持丙泊酚和瑞芬太尼之间存在相加相互作用。瑞芬太尼在BIS反应中仅显示出较小的影响。
我们开发了一个丙泊酚药代动力学-药效学综合模型，该模型能够描述丙泊酚和瑞芬太尼对BIS反应的药效学相互作用。我们的建模分析支持相加相互作用。
