Choi Gordon, Gomersall Charles D, Tian Qi, Joynt Gavin M, Freebairn Ross, Lipman Jeffrey
Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China.
Crit Care Med. 2009 Jul;37(7):2268-82. doi: 10.1097/CCM.0b013e3181aab3d0.
To outline the concepts involved in optimizing antibacterial dosing in critically ill patients with acute renal failure undergoing continuous renal replacement therapy (CRRT), provide a strategy for optimizing dosing, and summarize the data required to implement the strategy.
MEDLINE search from February 1986 to 2008.
Optimal dosing of antibacterials is dependent on achieving pharmacokinetic targets associated with maximal killing of bacteria and improved outcomes. The initial dose is dependent on the volume of distribution. Maintenance doses are dependent on clearance. Both should be adjusted according to the pharmacokinetic target associated with optimal bacterial killing, when known. The volume of distribution of some antibacterials is altered by critical illness or acute renal failure or both. Clearance by CRRT is dependent on the dose and mode of CRRT and the sieving or saturation coefficient of the drug. Both sieving and saturation coefficient are related to the plasma protein binding and thus may be altered in renal failure.
Appropriate dose calculation requires knowledge of the pharmacokinetic target and the usual minimum inhibitory concentration of the suspected organism in the patient's locality (or if unavailable, the break point for the organism), published pharmacokinetic data (volume of distribution, non-CRRT clearance) on critically ill patients receiving CRRT (which may differ substantially from noncritically ill patients or those without renal failure), the sieving or saturation coefficient of the relevant drug in critically ill patients, the dose and mode of CRRT being used, and the actual dose of CRRT that is delivered. This large number of variables results in considerable inter- and intrapatient heterogeneity in dose requirements. This article provides basic principles and relevant data to guide the clinician in prescribing individualized dosing regimes.
概述在接受持续肾脏替代治疗（CRRT）的急性肾衰竭重症患者中优化抗菌药物给药方案所涉及的概念，提供优化给药的策略，并总结实施该策略所需的数据。
1986年2月至2008年的MEDLINE检索。
抗菌药物的最佳给药取决于实现与最大程度杀灭细菌及改善预后相关的药代动力学目标。初始剂量取决于分布容积。维持剂量取决于清除率。当已知时，两者均应根据与最佳细菌杀灭相关的药代动力学目标进行调整。某些抗菌药物的分布容积会因危重病或急性肾衰竭或两者共同作用而改变。CRRT的清除率取决于CRRT的剂量和模式以及药物的筛过或饱和系数。筛过系数和饱和系数均与血浆蛋白结合有关，因此在肾衰竭时可能会改变。
合适的剂量计算需要了解药代动力学目标、患者所在地区疑似病原体的通常最低抑菌浓度（或若无此数据，则为该病原体的折点）、已发表的关于接受CRRT的重症患者的药代动力学数据（分布容积、非CRRT清除率）（这可能与非重症患者或无肾衰竭患者有很大差异）、重症患者中相关药物的筛过或饱和系数、所使用的CRRT剂量和模式以及实际实施的CRRT剂量。如此众多的变量导致患者之间和患者自身的剂量需求存在相当大的异质性。本文提供了基本原则和相关数据，以指导临床医生制定个体化给药方案。
