Generic placeholder image

Current Reviews in Clinical and Experimental Pharmacology

Editor-in-Chief

ISSN (Print): 2772-4328
ISSN (Online): 2772-4336

Research Article

Drug Utilization in Critically Ill Adults with Augmented Renal Clearance Compared to Normal Renal Clearance: Implications for use of Antimicrobials with Predominant Renal Excretion

Author(s): Kannan Sridharan*, Sheikh A.A. Pasha, Ali M. Qader, Hasan M.S.N. Hasan and Mohamed M. El Seirafi

Volume 16, Issue 2, 2021

Published on: 10 August, 2020

Page: [174 - 181] Pages: 8

DOI: 10.2174/1574884715666200810095225

Price: $65

Abstract

Background: Critically ill adults have Augmented Renal Clearance, (ARC) decreasing the systemic circulation of drugs with predominant renal elimination. The phenomenon of ARC is crucial for antimicrobial drugs as it hinders the therapeutic response and aids the development of antimicrobial resistance. The present study was conducted to assess the impact of ARC on an Intensive Care Unit (ICU) of a tertiary care hospital.

Methods: This was a prospective observational study carried out in critically ill patients with normal serum creatinine without any history of renal disease. Details on their demographic characteristics, clinical diagnoses, laboratory parameters including trough levels of vancomycin and gentamicin, ICU length of stay, and clinical outcomes (discharged alive/death) were obtained. Creatinine clearance (Crcl) was estimated from 24-hour urine creatinine. Monte Carlo simulation test with 100000 iterations was used for predicting serum vancomycin trough levels with the observed Crcl.

Results: Eighty patients were recruited in the study of which 52.5% had ARC. Patients in younger age and body weight were observed with a trend to have ARC. No significant differences were observed in any of the drug classes prescribed between patients with and without ARC, including the systemic antimicrobials. Although the observed serum trough levels of vancomycin in patients with ARC did not differ significantly from those without ARC, Monte Carlo simulation predicted that 90% of patients with ARC were likely to have trough levels between 5.63 and 7.85 mg/dl, while those without ARC may have it between 7.75 to 9.82 mg/dl.

Conclusion: A significant proportion of critically ill adults exhibit ARC and such patients are more likely to achieve lower trough concentrations of vancomycin than recommended. All critically ill adults with normal serum creatinine have to be screened for ARC using urine creatinine as soon as possible for appropriate adjustment in the dosage regimen of antimicrobials with predominant renal elimination.

Keywords: Augmented renal clearance, normal renal function, drug utilization study, sepsis, vancomycin, subarachnoid hemorrhage.

Graphical Abstract
[1]
Barletta JF. The importance of empiric antibiotic dosing in critically ill trauma patients: Are we under-dosing based on augmented renal clearance and inaccurate renal clearance estimates? J Trauma Acute Care Surg 2016; 81(6): 1115-21.
[http://dx.doi.org/10.1097/TA.0000000000001211] [PMID: 27533906]
[2]
Mahmoud SH, Shen C. Augmented renal clearance in critical illness: An important consideration in drug dosing. Pharmaceutics 2017; 9(3): E36.
[http://dx.doi.org/10.3390/pharmaceutics9030036] [PMID: 28926966]
[3]
Cook AM, Hatton-Kolpek J. Augmented renal clearance. Pharmacotherapy 2019; 39(3): 346-54.
[http://dx.doi.org/10.1002/phar.2231] [PMID: 30723936]
[4]
De Waele JJ, Dumoulin A, Janssen A, Hoste EA. Epidemiology of augmented renal clearance in mixed ICU patients. Minerva Anestesiol 2015; 81(10): 1079-85.
[PMID: 25697881]
[5]
Claus BO, Hoste EA, Colpaert K, Robays H, Decruyenaere J, De Waele JJ. Augmented renal clearance is a common finding with worse clinical outcome in critically ill patients receiving antimicrobial therapy. J Crit Care 2013; 28(5): 695-700.
[http://dx.doi.org/10.1016/j.jcrc.2013.03.003] [PMID: 23683557]
[6]
Hobbs AL, Shea KM, Roberts KM, Daley MJ. Implications of augmented renal clearance on drug dosing in critically ill patients: A focus on antibiotics. Pharmacotherapy 2015; 35(11): 1063-75.
[http://dx.doi.org/10.1002/phar.1653] [PMID: 26598098]
[7]
Tsai D, Udy AA, Stewart PC, et al. Prevalence of augmented renal clearance and performance of glomerular filtration estimates in Indigenous Australian patients requiring intensive care admission. Anaesth Intensive Care 2018; 46(1): 42-50.
[http://dx.doi.org/10.1177/0310057X1804600107] [PMID: 29361255]
[8]
Di Giantomasso D, May CN, Bellomo R. Vital organ blood flow during hyperdynamic sepsis. Chest 2003; 124(3): 1053-9.
[http://dx.doi.org/10.1378/chest.124.3.1053] [PMID: 12970037]
[9]
Bilbao-Meseguer I, Rodríguez-Gascón A, Barrasa H, Isla A, Solinís MÁ. Augmented renal clearance in critically ill patients: A systematic review. Clin Pharmacokinet 2018; 57(9): 1107-21.
[http://dx.doi.org/10.1007/s40262-018-0636-7] [PMID: 29441476]
[10]
Liu N, Zhang B, Liu Y, Tang J, Dong D, Gu Q. Clinical study of vancomycin for appropriate dosing in severe infective patients with augmented renal clearance. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2018; 30(7): 646-51.
[PMID: 30045791]
[11]
Chu Y, Luo Y, Jiang M, et al. Application of vancomycin in patients with augmented renal clearanceEuropean Journal of Hospital Pharmacy Published Online First 2019.
[http://dx.doi.org/10.1136/ejhpharm-2018-001781]
[12]
He J, Mao E, Jing F, et al. PK/PD of vancomycin in patients with severe acute pancreatitis combined with augmented renal clearance. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2017; 29(9): 810-4.
[PMID: 28936957]
[13]
Jacobs A, Taccone FS, Roberts JA, et al. β-lactam dosage regimens in septic patients with augmented renal clearance. Antimicrob Agents Chemother 2018; 62(9): e02534-17.
[http://dx.doi.org/10.1128/AAC.02534-17] [PMID: 29987138]
[14]
Udy AA, Lipman J, Jarrett P, et al. Are standard doses of piperacillin sufficient for critically ill patients with augmented creatinine clearance? Crit Care 2015; 19: 28.
[http://dx.doi.org/10.1186/s13054-015-0750-y] [PMID: 25632974]
[15]
Carlier M, Carrette S, Roberts JA, et al. Meropenem and piperacillin/tazobactam prescribing in critically ill patients: Does augmented renal clearance affect pharmacokinetic/pharmacodynamic target attainment when extended infusions are used? Crit Care 2013; 17(3): R84.
[http://dx.doi.org/10.1186/cc12705] [PMID: 23642005]
[16]
Shahbaz H, Gupta M. Creatinine ClearanceStatPearls. Treasure Island, FL: StatPearls Publishing 2019.https://www.ncbi.nlm. nih.gov/books/NBK544228/ [Accessed on July 5 2019].
[17]
Sridharan K, Al Daylami A, Ajjawi R, Al-Ajooz H, Veeramuthu S. Clinical pharmacokinetics of vancomycin in critically ill children. Eur J Drug Metab Pharmacokinet 2019; 44(6): 807-16.
[http://dx.doi.org/10.1007/s13318-019-00568-6] [PMID: 31301023]
[18]
Antibiotics for early-onset neonatal infection: Antibiotics for the prevention and treatment of early-onset neonatal infection. NICE clinical guidelines, No. 149. National Collaborating Centre for Women’s and Children’s Health (UK). In: London: RCOG Press 2012.
[19]
Austin SR, Wong YN, Uzzo RG, Beck JR, Egleston BL. Why Summary Comorbidity Measures Such As the Charlson Comorbidity Index and Elixhauser Score Work. Med Care 2015; 53(9): e65-72.
[http://dx.doi.org/10.1097/MLR.0b013e318297429c] [PMID: 23703645]
[20]
Tomasa Irriguible TM. Augmented renal clearance: Much more is better? Med Intensiva 2018; 42(8): 500-3.
[http://dx.doi.org/10.1016/j.medin.2018.02.004] [PMID: 29551234]
[21]
Dahyot-Fizelier C, Marchand S, Lipman J. Is augmented renal clearance the Holy Grail of antibiotic therapy failure in ventilator-acquired pneumonia? Anaesth Crit Care Pain Med 2018; 37(1): 5-6.
[http://dx.doi.org/10.1016/j.accpm.2017.12.003] [PMID: 29362162]
[22]
Udy AA, Roberts JA, Boots RJ, Paterson DL, Lipman J. Augmented renal clearance: Implications for antibacterial dosing in the critically ill. Clin Pharmacokinet 2010; 49(1): 1-16.
[http://dx.doi.org/10.2165/11318140-000000000-00000] [PMID: 20000886]
[23]
Campassi ML, Gonzalez MC, Masevicius FD, et al. Augmented renal clearance in critically ill patients: incidence, associated factors and effects on vancomycin treatment. Rev Bras Ter Intensiva 2014; 26(1): 13-20.
[http://dx.doi.org/10.5935/0103-507X.20140003] [PMID: 24770684]
[24]
Barletta JF, Mangram AJ, Byrne M, et al. Identifying augmented renal clearance in trauma patients: Validation of the augmented renal clearance in trauma intensive care scoring system. J Trauma Acute Care Surg 2017; 82(4): 665-71.
[http://dx.doi.org/10.1097/TA.0000000000001387] [PMID: 28129261]
[25]
Avedissian SN, Rhodes NJ, Kim Y, Bradley J, Valdez JL, Le J. Augmented renal clearance of aminoglycosides using population-based pharmacokinetic modelling with Bayesian estimation in the paediatric ICU. J Antimicrob Chemother 2019; 75(1): 162-9.
[http://dx.doi.org/10.1093/jac/dkz408] [PMID: 31648297]
[26]
Avedissian SN, Bradley E, Zhang D, et al. Augmented renal clearance using population-based pharmacokinetic modeling in critically ill pediatric patients. Pediatr Crit Care Med 2017; 18(9): e388-94.
[http://dx.doi.org/10.1097/PCC.0000000000001228] [PMID: 28640009]
[27]
Morbitzer KA, Rhoney DH, Dehne KA, Jordan JD. Enhanced renal clearance and impact on vancomycin pharmacokinetic parameters in patients with hemorrhagic stroke. J Intensive Care 2019; 7: 51.
[http://dx.doi.org/10.1186/s40560-019-0408-y] [PMID: 31832200]
[28]
Minkutė R, Briedis V, Steponavičiūtė R, Vitkauskienė A, Mačiulaitis R. Augmented renal clearance-An evolving risk factor to consider during the treatment with vancomycin. J Clin Pharm Ther 2013; 38(6): 462-7.
[http://dx.doi.org/10.1111/jcpt.12088] [PMID: 23924288]
[29]
Waineo MF, Kuhn TC, Brown DL. The pharmacokinetic/pharmacodynamic rationale for administering vancomycin via continuous infusion. J Clin Pharm Ther 2015; 40(3): 259-65.
[http://dx.doi.org/10.1111/jcpt.12270] [PMID: 25865426]
[30]
Jacobs A, Taccone FS, Roberts JA, et al. β-lactam dosage regimens in septic patients with augmented renal clearance. Antimicrob Agents Chemother 2018; 62(9): pii: e02534.
[31]
Wu CC, Tai CH, Liao WY, et al. Augmented renal clearance is associated with inadequate antibiotic pharmacokinetic/pharmacodynamic target in Asian ICU population: A prospective observational study. Infect Drug Resist 2019; 12: 2531-41.
[http://dx.doi.org/10.2147/IDR.S213183] [PMID: 31496765]
[32]
Adnan S, Ratnam S, Kumar S, et al. Select critically ill patients at risk of augmented renal clearance: experience in a Malaysian intensive care unit. Anaesth Intensive Care 2014; 42(6): 715-22.
[http://dx.doi.org/10.1177/0310057X1404200606] [PMID: 25342403]
[33]
Aitullina A, Krūmiņa A, Svirskis Š, Purviņa S. Colistin use in patients with extreme renal function: From dialysis to augmented clearance. Medicina (Kaunas) 2019; 55(2): 33.
[http://dx.doi.org/10.3390/medicina55020033] [PMID: 30709064]
[34]
Bragadottir G, Redfors B, Ricksten SE. Assessing Glomerular Filtration Rate (GFR) in critically ill patients with acute kidney injury--true GFR versus urinary creatinine clearance and estimating equations. Crit Care 2013; 17(3): R108.
[http://dx.doi.org/10.1186/cc12777] [PMID: 23767877]
[35]
Declercq P, Gijsen M, Meijers B, et al. Reliability of serum creatinine-based formulae estimating renal function in non-critically ill surgery patients: Focus on augmented renal clearance. J Clin Pharm Ther 2018; 43(5): 695-706.
[http://dx.doi.org/10.1111/jcpt.12695] [PMID: 29733108]
[36]
Lee B, Kim J, Park JD, Kang HM, Cho YS, Kim KS. Predicting augmented renal clearance using estimated glomerular filtration rate in critically-ill children. Clin Nephrol 2017; 88(9): 148-55.
[http://dx.doi.org/10.5414/CN109216] [PMID: 28699888]

Rights & Permissions Print Export Cite as
© 2024 Bentham Science Publishers | Privacy Policy