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接受体外膜肺氧合治疗的儿童的药物暴露模式:迈向优先开展未来药理学研究的一步。

Patterns of Medication Exposure in Children on Extracorporeal Membrane Oxygenation: A Step in Prioritizing Future Pharmacologic Studies.

作者信息

Thibault Céline, Collier Hailey, Naim Maryam Y, Heichel Jenna, Schwartz Emily, Zuppa Athena F

机构信息

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

Center for Clinical Pharmacology, Children's Hospital of Philadelphia, Philadelphia, PA.

出版信息

Crit Care Explor. 2019 Sep 16;1(9):e0045. doi: 10.1097/CCE.0000000000000045. eCollection 2019 Sep.

Abstract

UNLABELLED

To identify medications administered to pediatric patients on extracorporeal membrane oxygenation and to review the available pharmacokinetics and pharmacodynamics literature for the most commonly administered medications.

DESIGN

Retrospective single-center study.

SETTING

ICUs at Children's Hospital of Philadelphia.

PATIENTS

Pediatric patients supported by extracorporeal membrane oxygenation between October 1, 2014, and September 30, 2018.

INTERVENTIONS

None.

MEASUREMENTS AND MAIN RESULTS

Drug exposure was described according to age group (< 1 mo, 1 mo to < 2 yr, 2 to < 12 yr, and > 12 yr) and ICU (cardiac, neonatal, pediatric). The association of drug exposure with patient's characteristics was examined using one-way analysis of variance for categorical variables and linear regression for continuous variables. All pharmacokinetics and pharmacodynamics literature for the 50 most commonly administered medications on extracorporeal membrane oxygenation was reviewed, with inclusion of studies that reported dosing regimens in conjunction with pharmacokinetics or pharmacodynamics data. A total of 179 different medications were administered to 254 children. Cumulative drug exposure increased with the duration of extracorporeal membrane oxygenation from a median (interquartile) of 10 drugs (6-14) at 1 week to 31 drugs (21-45) at 5 weeks following cannulation. There were significant differences in total drug exposure between age groups and ICUs. With exclusion of in vitro studies, published literature was available to support the use of 40% (20/50) of the most commonly administered medications. Dosing guidance was available for 20% (10/50) of medications and was primarily based on simulations and retrospective studies focusing on neonates and infants.

CONCLUSIONS

This study highlights specific needs for future pharmacokinetics and pharmacodynamics studies. Dosing guidelines are essential to optimize the care of critically ill children supported by extracorporeal membrane oxygenation.

摘要

未标注

确定接受体外膜肺氧合治疗的儿科患者所使用的药物,并回顾最常用药物的现有药代动力学和药效学文献。

设计

回顾性单中心研究。

地点

费城儿童医院的重症监护病房。

患者

2014年10月1日至2018年9月30日期间接受体外膜肺氧合支持的儿科患者。

干预措施

无。

测量指标及主要结果

根据年龄组(<1个月、1个月至<2岁、2至<12岁、>12岁)和重症监护病房类型(心脏、新生儿、儿科)描述药物暴露情况。使用分类变量的单因素方差分析和连续变量的线性回归来检验药物暴露与患者特征之间的关联。回顾了体外膜肺氧合治疗中50种最常用药物的所有药代动力学和药效学文献,纳入了报告给药方案并结合药代动力学或药效学数据的研究。共有179种不同药物用于254名儿童。随着体外膜肺氧合持续时间的延长,累积药物暴露量增加,插管后1周时中位数(四分位间距)为10种药物(6 - 14种),5周时为31种药物(21 - 45种)。年龄组和重症监护病房类型之间的总药物暴露存在显著差异。排除体外研究后,有发表的文献支持40%(20/50)的最常用药物的使用。20%(10/50)的药物有给药指导,主要基于针对新生儿和婴儿的模拟研究和回顾性研究。

结论

本研究突出了未来药代动力学和药效学研究的特定需求。给药指南对于优化接受体外膜肺氧合支持的危重症儿童的治疗至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7606/7063935/3660e938fd7d/cc9-1-e0045-g002.jpg

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