Augmented renal clearance in critically ill patients with cancer (ARCCAN Study): A prospective observational study evaluating prevalence and risk factors

Nazer, Lama; Abusara, Aseel; Kamal, Yasmeen

doi:10.1002/prp2.747

Cited by 8 publications

(7 citation statements)

References 23 publications

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“…However, Baptista et al monitored trough concentrations rather than AUCs 32 . Given that ARC is common in critically ill patients with cancer, the association between ARC and vancomycin AUC is important when empirically initiating vancomycin therapy 33 …”

Section: Discussionmentioning

confidence: 99%

Vancomycin therapeutic monitoring by measured trough concentration versus Bayesian‐derived area under the curve in critically ill patients with cancer

Abusara

Abdelrahman

Habash

et al. 2022

Pharmacology Res & Perspec

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The updated vancomycin guideline and recent studies suggested that trough concentrations may result in underestimation of the actual area under the curve (AUC), leading to excessive dosing and nephrotoxicity. With limited data available on critically ill cancer patients, this study aimed to compare the two methods in this patient population. This was a 5-year retrospective study on patients treated with vancomycin in the intensive care unit (ICU) of a comprehensive cancer center. The measured trough concentration was compared to Bayesian-derived AUC/minimum-inhibitoryconcentration (MIC), considering MIC as 1. Trough concentrations of 15-20 mg/L and AUC of 400-600 mg h/L were considered the targeted goal. Multivariate analysis was performed to identify factors associated with an AUC below the targeted goal. During the study period, 316 patients were included. The mean age was 54 years ±16 (SD); most patients had solid tumors (75%), and 11% had neutropenia. A targeted goal AUC and trough were recorded in 128 (41%) patients and in 64 (20%) patients, respectively.Of the 128 patients with targeted goal AUC, 31 (24%) had targeted goal trough concentrations and 91 (71%) had trough concentrations below 15 mg/L. Furthermore, among the patients with targeted goal trough concentration (n = 64), 33 (52%) had higher than targeted goal AUC. Augmented renal clearance (ARC), defined as a calculated creatinine-clearance ≥130 ml/min, was associated with an AUC below the targeted goal. In a cohort of critically ill patients with cancer, over two-thirds of the patients with a targeted goal Bayesian AUC/MIC had trough concentrations below the targeted goal. ARC was associated with AUC below the targeted goal.

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Section: Discussionmentioning

confidence: 99%

Vancomycin therapeutic monitoring by measured trough concentration versus Bayesian‐derived area under the curve in critically ill patients with cancer

Abusara

Abdelrahman

Habash

et al. 2022

Pharmacology Res & Perspec

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“…ARC may occur due to a variety of factors ( Figure 1 ). Younger age has been a significant predictor of ARC in univariate and multivariate analyses ( Kawano et al, 2016 ; Barletta et al, 2017 ; Mulder et al, 2019 ; Nei et al, 2020 ; Nazer et al, 2021 ). Some studies have also found that lower disease severity ( Udy et al, 2013 ; Huttner et al, 2015 ; Kawano et al, 2016 ; Udy et al, 2017b ; Nei et al, 2020 ), trauma ( Udy et al, 2013 ; Campassi et al, 2014 ; Huttner et al, 2015 ; Ruiz et al, 2015 ; Nei et al, 2020 ), and ICH ( Nei et al, 2020 ) are independent risk factors associated with ARC.…”

Section: Definition Epidemiology and Risk Factors Of Augmented Renal ...mentioning

confidence: 99%

“…Besides, febrile neutropenia was investigated to be an independent risk factor for ARC in critically ill patients (OR 5.86, 95% CI 1.98 ± 66, p = 0.0030) ( Hirai et al, 2016 ), but there is a lack of further studies to confirm this result. Other risk factors that may promote the development of ARC include male sex ( Udy et al, 2013 ; Barletta et al, 2017 ; Mulder et al, 2019 ), fluid therapy ( Mulder et al, 2019 ; Dhondt et al, 2020 ), mechanical ventilation ( Udy et al, 2014 ; Nazer et al, 2021 ), higher cardiac index (CI) ( Udy et al, 2013 ; Barletta et al, 2016 ), use of vasopressor drugs ( Udy et al, 2010c ; Nazer et al, 2021 ), and less frequent use of furosemide ( Campassi et al, 2014 ; Nazer et al, 2021 ). However, these factors were not subsequently confirmed in multivariate analyses.…”

Section: Definition Epidemiology and Risk Factors Of Augmented Renal ...mentioning

confidence: 99%

“…Studies suggest that enhanced RBF through dilatation of the afferent glomerular arterioles after impaired renal autoregulation and protein loading are the main mechanisms involved in RFR mobilization ( Samoni et al, 2016 ). SIRS in combination with greater RFR has been suggested as a possible mechanism for the development of ARC for severe infections ( Campassi et al, 2014 ; Nazer et al, 2021 ).…”

Section: Pathophysiological Mechanisms Of Arc For Severe Infectionsmentioning

confidence: 99%

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Augmented Renal Clearance in Severe Infections—An Important Consideration in Vancomycin Dosing: A Narrative Review

Xiao

Zhang

et al. 2022

Front. Pharmacol.

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Vancomycin is a hydrophilic antibiotic widely used in severe infections, including bacteremia and central nervous system (CNS) infections caused by Gram-positive bacteria such as methicillin-resistant Staphylococcus aureus (MRSA), coagulase-negative staphylococci and enterococci. Appropriate antimicrobial dosage regimens can help achieve the target exposure and improve clinical outcomes. However, vancomycin exposure in serum and cerebrospinal fluid (CSF) is challenging to predict due to rapidly changing pathophysiological processes and patient-specific factors. Vancomycin concentrations may be decreased for peripheral infections due to augmented renal clearance (ARC) and increased distribution caused by systemic inflammatory response syndrome (SIRS), increased capillary permeability, and aggressive fluid resuscitation. Additionally, few studies on vancomycin’s pharmacokinetics (PK) in CSF for CNS infections. The relationship between exposure and clinical response is unclear, challenging for adequate antimicrobial therapy. Accurate prediction of vancomycin pharmacokinetics/pharmacodynamics (PK/PD) in patients with high interindividual variation is critical to increase the likelihood of achieving therapeutic targets. In this review, we describe the interaction between ARC and vancomycin PK/PD, patient-specific factors that influence the achievement of target exposure, and recent advances in optimizing vancomycin dosing schedules for severe infective patients with ARC.

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“…Recent investigations have shown that critically ill, septic [5], febrile neutropenic [6], and hematologic malignant patients [7] have an increase in renal clearance, a condition called augmented renal clearance (ARC). ARC is a pathological condition associated with enhancing renally excreted drugs' filtration, such as that of antipseudomonal beta-lactams, aminoglycosides, and vancomycin [8].…”

Section: Introductionmentioning

confidence: 99%

Augmented Renal Clearance and Hypoalbuminemia-Induced Low Vancomycin Trough Concentrations in Febrile Neutropenic Patients With Hematological Malignancies

Alzahrani¹,

Hakami²,

AlAzmi³

et al. 2022

Cureus

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Introduction: Vancomycin administration in individuals with hematological malignancy or neutropenia is associated with a suboptimal trough concentration. Nonetheless, most studies did not distinguish whether low vancomycin trough concentrations were due to hematological malignancies or neutropenia. This study aimed to determine the association between types of hematological malignancy and febrile neutropenia with low vancomycin concentrations.Methods: The present retrospective chart review study was conducted by using clinical data adopted from computerized physician order entries (BestCare®) for all of the patients who received intravenous vancomycin treatment between January 2017 and December 2020 at King Abdulaziz Medical City in Jeddah.Results: Out of the 296 patients, 217 were included. There was no significant association between the type of hematological malignancy and the incidence of a low trough concentration (p > 0.05), while a significant association between febrile neutropenia and the incidence of a low trough concentration was observed (p < 0.05). Furthermore, the predictors for a low trough among febrile neutropenic patients were creatinine clearance (CrCI) and a low albumin concentration. In addition, there was a significant association between febrile neutropenia and augmented renal clearance (p < 0.05).Conclusions: The findings of this study conclude that febrile neutropenia is associated with low vancomycin concentrations. Interestingly, augmented renal clearance was observed in most of the febrile neutropenia patients with a significant association, which is considered the main driver for a low trough in neutropenic patients.

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Augmented renal clearance in critically ill patients with cancer (ARCCAN Study): A prospective observational study evaluating prevalence and risk factors

Cited by 8 publications

References 23 publications

Vancomycin therapeutic monitoring by measured trough concentration versus Bayesian‐derived area under the curve in critically ill patients with cancer

Vancomycin therapeutic monitoring by measured trough concentration versus Bayesian‐derived area under the curve in critically ill patients with cancer

Augmented Renal Clearance in Severe Infections—An Important Consideration in Vancomycin Dosing: A Narrative Review

Augmented Renal Clearance and Hypoalbuminemia-Induced Low Vancomycin Trough Concentrations in Febrile Neutropenic Patients With Hematological Malignancies

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