Purpose

Adequate dosing of antimicrobials is critical to properly treat infections and limit development of resistance and adverse effects. Limited guidance exist for antimicrobial dosing adjustments in patients requiring extracorporeal membrane oxygenation (ECMO) therapy, particularly in the pediatric population. A systematic review was conducted to delineate the pharmacokinetics (PK) and pharmacodynamics (PD) of antimicrobials in critically ill neonates and children requiring ECMO therapy.

Methods

Medline, EMBASE, Global Health and All EBM Reviews databases were queried. Grey literature was examined. All clinical studies reporting PK/PD parameters of antimicrobials in critically ill pediatric patients treated with ECMO were included, except for case reports and congress abstracts. Two independent reviewers applied the inclusion and exclusion criteria. Reviewers were then paired to independently extract data and evaluate the methodological quality of studies using the ROBINS-I tool and the compliance with ClinPK reporting guidelines. Patient and study characteristics, key PK/PD findings, details of ECMO circuits and co-treatments were summarized qualitatively. Broad dosing recommendations were formulated based on the available data for specific antimicrobials.

Results

Twenty-nine clinical studies were included; most were observational and uncontrolled. Patient characteristics and co-treatments were often missing. The effect of ECMO on PK/PD parameters of antimicrobials varied depending on the drugs and population studied. It was only possible to formulate dosing recommendations for a few antimicrobials given the paucity of data, its overall low quality and heterogeneity in reporting.

Conclusion

Limited data exists on the PK/PD of antimicrobials during ECMO therapy in the pediatric population. Rigorously designed population PK studies are required to establish empiric dosing guidelines for antimicrobials in patients requiring this therapeutic modality. The use of therapeutic drug monitoring for antimicrobials in pediatric patients on ECMO should be encouraged to optimize dosing.

Trial Registry

PROSPERO registration number: CRD42018099992 (Registered: July 24th 2018).

中文翻译：

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危重儿科患者体外膜氧合期间常用抗菌药物的药代动力学：系统评价

目的

足够剂量的抗菌药物对于正确治疗感染并限制耐药性和不良反应的发展至关重要。对于需要体外膜肺氧合 (ECMO) 治疗的患者（尤其是儿科人群）的抗菌药物剂量调整指导有限。进行了一项系统评价，以描述抗菌药物在需要 ECMO 治疗的危重新生儿和儿童中的药代动力学 (PK) 和药效学 (PD)。

方法

查询了 Medline、EMBASE、Global Health 和所有 EBM 评论数据库。检查了灰色文献。除病例报告和会议摘要外，所有报告接受 ECMO 治疗的危重儿科患者抗菌药物 PK/PD 参数的临床研究均纳入其中。两名独立评审员应用了纳入和排除标准。然后审稿人配对独立提取数据并使用 ROBINS-I 工具评估研究的方法学质量以及对 ClinPK 报告指南的遵守情况。定性总结了患者和研究特征、关键 PK/PD 结果、ECMO 回路和联合治疗的详细信息。根据特定抗菌药物的现有数据制定了广泛的剂量建议。

结果

纳入了 29 项临床研究；大多数是观察性的且不受控制的。患者特征和联合治疗经常缺失。ECMO 对抗菌药物 PK/PD 参数的影响因所研究的药物和人群而异。由于数据缺乏、总体质量低且报告的异质性，只能为少数抗菌药物制定剂量建议。

结论

关于儿科人群 ECMO 治疗期间抗菌药物的 PK/PD 的数据有限。需要严格设计的群体 PK 研究来为需要这种治疗方式的患者建立抗菌药物的经验剂量指南。应鼓励对使用 ECMO 的儿科患者使用治疗药物监测抗菌药物，以优化剂量。

试验登记处

PROSPERO注册号：CRD42018099992（注册日期：2018年7月24日）。