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克服危重症成人患者 ECMO 期间药物最佳剂量的障碍。

Overcoming barriers to optimal drug dosing during ECMO in critically ill adult patients.

机构信息

a Faculty of Medicine , University of Queensland Centre for Clinical Research (UQCCR), The University of Queensland , Brisbane , Australia.

b School of Pharmacy , International Islamic University Malaysia , Kuantan , Malaysia.

出版信息

Expert Opin Drug Metab Toxicol. 2019 Feb;15(2):103-112. doi: 10.1080/17425255.2019.1563596. Epub 2019 Jan 3.

Abstract

One major challenge to achieving optimal patient outcome in extracorporeal membrane oxygenation (ECMO) is the development of effective dosing strategies in this critically ill patient population. Suboptimal drug dosing impacts on patient outcome as patients on ECMO often require reversal of the underlying pathology with effective pharmacotherapy in order to be liberated of the life-support device. Areas covered: This article provides a concise review of the effective use of antibiotics, analgesics, and sedative by characterizing the specific changes in PK secondary to the introduction of the ECMO support. We also discuss the barriers to achieving optimal pharmacotherapy in patients on ECMO and also the current and potential research that can be undertaken to address these clinical challenges. Expert opinion: Decreased bioavailability due to sequestration of drugs in the ECMO circuit and ECMO induced PK alterations are both significant barriers to optimal drug dosing. Evidence-based drug choices may minimize sequestration in the circuit and would enable safety and efficacy to be maintained. More work to characterize ECMO related pharmacodynamic alterations such as effects of ECMO on hepatic cytochrome system are still needed. Novel techniques to increase target site concentrations should also be explored.

摘要

在体外膜肺氧合(ECMO)中实现最佳患者预后的一个主要挑战是为这一危重病患者人群制定有效的剂量方案。药物剂量不足会影响患者的预后,因为 ECMO 患者通常需要有效的药物治疗来逆转潜在的病理,从而摆脱生命支持设备。

涵盖领域

本文通过描述 ECMO 支持引入后 PK 发生的特定变化,简要综述了抗生素、镇痛药和镇静剂的有效使用。我们还讨论了在 ECMO 患者中实现最佳药物治疗的障碍,以及目前和潜在的研究,以解决这些临床挑战。

专家意见

药物在 ECMO 回路中的隔离导致生物利用度降低和 ECMO 诱导的 PK 改变,都是实现最佳药物剂量的重大障碍。基于证据的药物选择可能会最大限度地减少回路中的隔离,并能够维持安全性和疗效。仍需要更多的工作来描述与 ECMO 相关的药效学改变,例如 ECMO 对肝细胞色素系统的影响。还应探索增加靶位浓度的新技术。

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