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体外膜肺氧合支持下儿童使用右美托咪定:利用既往发表模型进行药代动力学数据探索

Dexmedetomidine in Children on Extracorporeal Membrane Oxygenation: Pharmacokinetic Data Exploration Using Previously Published Models.

作者信息

Thibault Céline, Zuppa Athena F

机构信息

Department of Anesthesiology and Critical Care Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, United States.

出版信息

Front Pediatr. 2022 Jun 27;10:924829. doi: 10.3389/fped.2022.924829. eCollection 2022.

Abstract

BACKGROUND

Dexmedetomidine is a sedative and analgesic increasingly used in children supported with extracorporeal membrane oxygenation (ECMO). No data is available to describe the pharmacokinetics (PK) of dexmedetomidine in this population.

METHODS

We performed a single-center prospective PK study. Children <18 years old, supported with ECMO, and on a dexmedetomidine infusion as part of their management were prospectively included. PK samples were collected. Dexmedetomidine dosing remained at the discretion of the clinical team. Six population PK models built in pediatrics were selected. Observed concentrations were compared with population predicted concentrations using the PK models.

RESULTS

Eight children contributed 30 PK samples. None of the PK models evaluated predicted the concentrations with acceptable precision and bias. Four of the six evaluated models overpredicted the concentrations. The addition of a correction factor on clearance improved models' fit. Two of the evaluated models were not applicable to our whole population age range because of their structure.

CONCLUSION

Most of the evaluated PK models overpredicted the concentrations, potentially indicating increased clearance on ECMO. Population PK models applicable to a broad spectrum of ages and pathologies are more practical in pediatric critical care settings but challenging to develop.

摘要

背景

右美托咪定是一种镇静镇痛药,越来越多地用于接受体外膜肺氧合(ECMO)支持的儿童。目前尚无数据描述右美托咪定在该人群中的药代动力学(PK)。

方法

我们进行了一项单中心前瞻性PK研究。前瞻性纳入年龄<18岁、接受ECMO支持且作为治疗一部分接受右美托咪定输注的儿童。采集PK样本。右美托咪定的给药由临床团队自行决定。选择了六个儿科建立的群体PK模型。使用PK模型将观察到的浓度与群体预测浓度进行比较。

结果

八名儿童提供了30个PK样本。所评估的PK模型均未以可接受的精度和偏差预测浓度。六个评估模型中有四个高估了浓度。在清除率上添加校正因子改善了模型的拟合度。由于结构原因,六个评估模型中有两个不适用于我们的全人群年龄范围。

结论

大多数评估的PK模型高估了浓度,这可能表明ECMO上清除率增加。适用于广泛年龄和病理情况的群体PK模型在儿科重症监护环境中更实用,但开发具有挑战性。

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