Augmented renal clearance: implications for antibacterial dosing in the critically ill

Area of Science:

• Pharmacology
• Nephrology
• Critical Care Medicine

Background:

• Drug pharmacokinetics in critically ill patients are complex due to altered organ function.
• Changes in vascular tone, fluid status, cardiac output, and organ blood flow impact drug distribution and clearance.
• Silent pharmacodynamic indices can lead to treatment failure if drug concentrations are subtherapeutic.

Purpose of the Study:

• To explore the phenomenon of augmented renal clearance (ARC) in critically ill patients.
• To discuss the challenges in defining and measuring ARC.
• To highlight the implications of ARC for drug dosing, particularly antibacterials.

Main Methods:

• Review of existing literature on pharmacokinetics in critical illness and ARC.
• Discussion of factors contributing to ARC, including immune response, fluid loading, and vasoactive medications.
• Analysis of current measures of renal function and their limitations in assessing ARC.

Main Results:

• Augmented renal clearance (ARC) is increasingly observed in critically ill patients, characterized by enhanced renal elimination.
• Defining and measuring ARC is problematic due to lack of consensus on upper limits of normal glomerular filtration rate (GFR).
• ARC can lead to subtherapeutic drug concentrations, especially for antibacterials, potentially causing treatment failure.

Conclusions:

• Consideration of ARC and alternative dosing regimens is mandatory for critically ill patients.
• Optimizing drug dosing in the presence of ARC can improve treatment success and reduce antibacterial resistance.
• Younger patients with trauma and without comorbidities are more likely to exhibit ARC.