Burns, Trauma and Critical Care Research Centre, University of Queensland, UQ Centre for Clinical Research, Brisbane, Australia.
Critical Care Research Group, Brisbane, Australia.
Crit Care Resusc. 2017 Oct;19(Suppl 1):8-14.
Significant interactions between drugs, extracorporeal membrane oxygenation (ECMO) circuits and critical illness may affect the pharmacokinetic properties of antibiotics in critically ill patients receiving ECMO.
To describe the pharmacokinetic properties of ciprofloxacin during ECMO by integrating pre-clinical findings (ie, ex vivo and in vivo ovine models) to a critically ill patient.
DESIGN, PARTICIPANTS AND INTERVENTION: An ex vivo model of an ECMO circuit was used to describe ciprofloxacin concentration changes over 24 hours. An in vivo ovine model of ECMO was used to describe the population pharmacokinetic properties of ciprofloxacin in three different groups of sheep, and to investigate sources of pharmacokinetic variability. In the final phase, data from a 39-year-old critically ill man was used to validate the findings from the ovine pharmacokinetic model.
In the ex vivo model of ECMO circuits, the median concentrations of ciprofloxacin at baseline and at 24 hours after ciprofloxacin infusion were similar. The time course of ciprofloxacin in the in vivo ovine on ECMO model was adequately described by a two-compartment model. The final population primary parameter mean estimates were: clearance (CL), 0.21 L/kg/h (SD, 0.09 L/kg/h) and volume of distribution (V), 0.84 L/kg (SD, 0.12 L/kg). In the critically ill ECMO patient, the primary pharmacokinetic parameter estimates were: CL, 0.15 L/kg/h and V, 0.99 L/kg.
We provide preliminary evidence that ciprofloxacin dosing in ECMO patients should remain in line with the recommended dosing strategies for critically ill patients not receiving ECMO.
药物、体外膜肺氧合（ECMO）回路和危重病之间的显著相互作用可能会影响接受 ECMO 的危重病患者中抗生素的药代动力学特性。
通过将临床前发现（即体外和体内绵羊模型）整合到接受 ECMO 的危重病患者中，描述环丙沙星在 ECMO 期间的药代动力学特性。
设计、参与者和干预措施：使用 ECMO 回路的体外模型来描述 24 小时内环丙沙星的浓度变化。使用 ECMO 的体内绵羊模型来描述三种不同绵羊组中环丙沙星的群体药代动力学特性，并研究药代动力学变异性的来源。在最后阶段，使用一名 39 岁危重病男性的数据来验证绵羊药代动力学模型的发现。
在 ECMO 回路的体外模型中，环丙沙星在基线和环丙沙星输注后 24 小时的中位数浓度相似。在 ECMO 模型中，绵羊体内环丙沙星的时间过程由两室模型充分描述。最终群体主要参数均值估计值为：清除率（CL），0.21 L/kg/h（SD，0.09 L/kg/h）和分布容积（V），0.84 L/kg（SD，0.12 L/kg）。在接受 ECMO 的危重病患者中，主要药代动力学参数估计值为：CL，0.15 L/kg/h 和 V，0.99 L/kg。
我们提供了初步证据表明，在接受 ECMO 的危重病患者中，环丙沙星的剂量应与未接受 ECMO 的危重病患者的推荐剂量策略保持一致。
