Burns, Trauma and Critical Care Research Centre, University of Queensland, Brisbane, Queensland, Australia.
Curr Pharm Biotechnol. 2011 Dec;12(12):2020-9. doi: 10.2174/138920111798808446.
In-hospital and intensive care unit mortality rates for sepsis remain un-acceptably high, and have prompted the publication of international guidelines on best practice. Crucial to this is the application of early appropriate antibacterial therapy, in the correct dose. However, antibacterial regimes in this setting have largely been extrapolated from those in healthy volunteers, and fail to consider the unique pathophysiology and treatment provided to this population. As such, augmented renal clearance (ARC) - the enhanced renal elimination of circulating solute - is likely to be one of the more common physiological changes encountered in this setting, although to date remains largely under-appreciated. Significantly this may alter the pharmacokinetics of many routinely prescribed agents in this setting, pre-disposing to subtherapeutic levels or treatment failure. This review paper examines this phenomenon in detail, providing a summary of the likely underlying mechanisms, those patients at greatest risk, and the implications for antibacterial dosing in the critically ill.
脓毒症患者的住院和重症监护病房死亡率仍然高得令人无法接受，这促使国际上发布了最佳实践指南。这方面的关键是应用早期适当的抗菌治疗，并使用正确的剂量。然而，该领域的抗菌方案在很大程度上是从健康志愿者中推断出来的，并未考虑到为该人群提供的独特病理生理学和治疗方法。因此，增强的肾清除率（ARC）——即循环溶质的增强肾脏清除率——可能是该领域中更常见的生理变化之一，尽管迄今为止，这种变化在很大程度上仍未被充分认识。重要的是，这可能会改变许多常规处方药物在这种情况下的药代动力学，导致治疗水平不足或治疗失败。本文详细探讨了这一现象，总结了可能的潜在机制、风险最大的患者以及对重症患者抗菌药物剂量的影响。
