Center for Clinical Pharmacology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Division of Pediatric Critical Care Medicine, Department of Pediatrics, CHU Sainte-Justine, Montreal, Qc, Canada.
Blood Purif. 2024 Jun;53(6):520-526. doi: 10.1159/000534828. Epub 2024 Feb 28.
Extracorporeal life support (ECLS), including extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT), are life-saving therapies for critically ill children. Despite this, these modalities carry frustratingly high mortality rates. One driver of mortality may be altered drug disposition due to a combination of underlying illness, patient-circuit interactions, and drug-circuit interactions. Children receiving ECMO and/or CRRT routinely receive 20 or more drugs, and data supporting optimal dosing is lacking for most of these medications. The Pediatric Paracorporeal and Extracorporeal Therapies Summit (PPETS) gathered an international group of experts in the fields of ECMO, CRRT, and other ECLS modalities to discuss the current state of these therapies, disseminate innovative support strategies, share clinical experiences, and foster future collaborations. Here, we summarize the conclusions of PPETS and put forward a pathway to optimize pharmacokinetic (PK) research in this population. We must prioritize specific medications for in-depth study to improve drug use in ECLS and patient outcomes. Based on frequency of use, potential for adverse outcomes if dosed inappropriately, and lack of existing PK data, a list of high priority drugs was compiled for future research. Researchers must additionally reconsider study designs, emphasizing pooling of resources through multi-center studies and the use of innovative PK modeling techniques. Finally, the integration of validated PK models into clinical practice must be streamlined to deliver optimal medication use at the bedside. Focusing on the proposed list of highlighted medications and key methodological considerations will maximize the impact of future research.
体外生命支持（ECLS），包括体外膜氧合（ECMO）和连续肾脏替代治疗（CRRT），是危重症儿童的救命治疗方法。尽管如此，这些方法的死亡率仍然令人沮丧地高。死亡率的一个驱动因素可能是由于潜在疾病、患者-回路相互作用和药物-回路相互作用的综合影响，导致药物处置发生改变。接受 ECMO 和/或 CRRT 的儿童通常接受 20 种或更多的药物，而这些药物中的大多数缺乏最佳剂量的数据支持。儿科体外和体外治疗峰会（PPETS）汇集了 ECMO、CRRT 和其他 ECLS 模式领域的国际专家，讨论这些治疗方法的现状，传播创新的支持策略，分享临床经验，并促进未来的合作。在这里，我们总结了 PPETS 的结论，并提出了优化该人群药代动力学（PK）研究的途径。我们必须优先考虑对特定药物进行深入研究，以改善 ECLS 中的药物使用和患者结局。根据使用频率、如果剂量不当可能产生不良后果的可能性以及缺乏现有 PK 数据，为未来研究编制了一份高优先级药物清单。研究人员还必须重新考虑研究设计，强调通过多中心研究汇集资源，并使用创新的 PK 建模技术。最终，必须简化将经过验证的 PK 模型集成到临床实践中的流程，以在床边提供最佳药物使用。专注于拟议的重点药物清单和关键方法学考虑因素将最大限度地提高未来研究的影响。
