Augmented renal clearance: Implications for antibacterial dosing in the critically Ill

Udy, Andrew A., Roberts, Jason A., Boots, Robert J., Paterson, David L. and Lipman, Jeffrey (2010) Augmented renal clearance: Implications for antibacterial dosing in the critically Ill. Clinical Pharmacokinetics, 49 1: 1-16. doi:10.2165/11318140-000000000-00000

Author Udy, Andrew A.
Roberts, Jason A.
Boots, Robert J.
Paterson, David L.
Lipman, Jeffrey
Title Augmented renal clearance: Implications for antibacterial dosing in the critically Ill
Journal name Clinical Pharmacokinetics   Check publisher's open access policy
ISSN 0312-5963
Publication date 2010-01-01
Sub-type Critical review of research, literature review, critical commentary
DOI 10.2165/11318140-000000000-00000
Volume 49
Issue 1
Start page 1
End page 16
Total pages 16
Place of publication Auckland, New Zealand
Publisher ADIS Press International
Collection year 2011
Language eng
Subject 1115 Pharmacology and Pharmaceutical Sciences
Abstract The prescription of pharmaceuticals in the critically ill is complicated by a paucity of knowledge concerning the pharmacokinetic implications of the underlying disease state. Changes in organ function can be dramatic in this population, both as a consequence of the primary pathophysiology and in response to clinical interventions provided. Vascular tone, fluid status, cardiac output and major organ blood flow can be significantly altered from baseline, influencing the volume of distribution and clearance of many commonly prescribed agents. Although measurable endpoints can be used to titrate doses for many drugs in this setting (such as sedatives), for those agents with silent pharmacodynamic indices, enhanced excretory organ function can result in unexpectedly low plasma concentrations, leading to treatment failure. This is particularly relevant to the use of antibacterials in the critically ill, where inadequate, inappropriate and/or delayed prescription can have significant effects on morbidity and mortality. Augmented renal clearance (ARC) refers to enhanced renal elimination of circulating solute and is being described with increasing regularity in the critically ill. However, defining this process in terms of current measures of renal function is problematic, as although the glomerular filtration rate (GFR) is largely considered the best index of renal function, there is no consensus on an upper limit of normal. In addition, the most readily available and accurate estimate of the GFR at the bedside is still widely debated. From a pharmacokinetic point of view, ARC can result in elevated renal elimination and subtherapeutic plasma concentrations of pharmaceuticals, although whether this process solely involves augmented filtration (as opposed to enhanced tubular secretion and/or reabsorption) remains uncertain. The primary contributors to this process are likely to be the innate immune response to infection and inflammation (with its associated systemic and haemodynamic consequences), fluid loading and use of vasoactive medications. The resultant increase in cardiac output and renal blood flow prompts enhanced glomerular filtration and drug elimination. Current evidence suggests that young patients without pre-existing co-morbidity or organ dysfunction who present with trauma are most likely to manifest ARC. As this phenomenon has received little attention in the literature, dose modification has rarely been considered. However, with increasing data supporting the concept, and many investigators demonstrating subtherapeutic concentrations of drugs in the critically ill, consideration of ARC and alternative dosing regimens is now mandatory, both to improve the likelihood of treatment success and to reduce the rate of development of antibacterial resistance. Copyright (c) 2000-2010
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
Collections: UQ Centre for Clinical Research Publications
Official 2011 Collection
School of Medicine Publications
School of Pharmacy Publications
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Citation counts: TR Web of Science Citation Count  Cited 118 times in Thomson Reuters Web of Science Article | Citations
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Created: Sun, 31 Jan 2010, 00:04:43 EST