What is New in Augmented Renal Clearance in Septic Patients?
Javier Amador-Casta?eda, BHS, RRT, FCCM
| Respiratory Care Practitioner | Author | Speaker | Veteran | ESICM Representative, North America
Baptista, L., Moura, I., Silva, C.M. et al. What is New in Augmented Renal Clearance in Septic Patients?. Curr Infect Dis Rep 25, 255–272 (2023). https://doi.org/10.1007/s11908-023-00816-6
Summary of "What is New in Augmented Renal Clearance in Septic Patients?"
Abstract
Recent studies indicate that augmented renal clearance (ARC) in septic patients has significant implications for drug dosing, particularly for antibiotics. Standard renal function estimates are unreliable in critically ill patients, leading to underdosing of antimicrobials. ARC prevalence is higher than expected, necessitating new strategies for drug dosing, particularly for β-lactams, vancomycin, and fluconazole. Despite growing evidence, more research is needed to define proper antibiotic dosage regimens and understand the impact of ARC on clinical outcomes.
Key Points
1. Definition of ARC: ARC refers to an increased elimination of solutes via the kidneys, typically defined by a creatinine clearance (CLCR) ≥130 ml/min/1.73 m2, which leads to faster drug clearance.
2. Identification Challenges: Traditional equations to estimate renal function (e.g., Cockcroft-Gault, CKD-EPI) are unreliable in critically ill patients, and measured creatinine clearance (24-hour urine output) is the preferred method to identify ARC.
3. Prevalence: ARC occurs in a significant number of critically ill and septic patients, with studies reporting a prevalence ranging from 25% to 94%, depending on patient populations and geographic regions.
4. Pathophysiology: ARC may result from a hypermetabolic, inflammatory state in critically ill patients, leading to increased renal blood flow and glomerular filtration. Other mechanisms include the influence of inflammatory mediators, renal functional reserve, and tubular secretion.
5. Impact on Antimicrobial Dosing: ARC is associated with subtherapeutic levels of several antibiotics, including β-lactams, vancomycin, and fluconazole. This increases the risk of treatment failure due to insufficient drug levels.
6. Dosage Adjustments: There are recommendations for increasing total daily doses or extending infusions of antimicrobials in patients with ARC. However, specific clinical data guiding these dosage changes are still limited.
7. Clinical Outcomes: The effect of ARC on patient outcomes remains unclear, with conflicting studies on whether ARC leads to worse clinical outcomes. More research is needed to establish the relationship between ARC, drug dosing, and patient recovery.
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Conclusion
ARC is a frequent occurrence in critically ill septic patients and is associated with subtherapeutic levels of key antibiotics. Proper identification of ARC using measured creatinine clearance is essential for adjusting drug doses and ensuring therapeutic effectiveness. However, more research is required to provide clear dosage recommendations and to understand the clinical impact of ARC on patient outcomes.
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Discussion Questions
1. How does augmented renal clearance affect the pharmacokinetics of key antibiotics in septic patients?
2. What challenges exist in identifying ARC in critically ill patients, and how can they be addressed?
3. What strategies should be implemented to adjust antibiotic dosing for patients with ARC to prevent treatment failure?
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