Cefotaxime administration is recommended in doses of 3-12 g/day in adults with a Glomerular Filtration Rate (GFR) > 5 mL/min. This study aimed to assess the impact of renal function and obesity on cefotaxime concentrations in intensive care unit (ICU) patients. A retrospective cohort study was conducted on consecutive ICU patients receiving continuous cefotaxime infusion between 2020 and 2022 [IRBN992021/CHUSTE]. Doses were not constant; consequently, a concentration-to-dose ratio (C/D) was considered. Statistical analysis was performed to assess the relationship between cefotaxime concentrations, renal function, and obesity. A total of 70 patients, median age 61 years, were included, with no significant difference in cefotaxime concentrations between obese and non-obese patients. However, concentrations varied significantly by GFR, with underdosing prevalent in patients with normal to increased renal function and overdosing in those with severely impaired renal function. Adjustment of cefotaxime dosing according to GFR was associated with improved target attainment. Cefotaxime dosing in critically ill patients should consider renal function, with higher initial doses required in patients with normal to increased GFR and lower doses in those with severely impaired renal function. Therapeutic drug monitoring may aid in optimising dosing regimens. Prospective studies are warranted to validate these findings and inform clinical practice.

BACKGROUND: Several studies report lack of meropenem pharmacokinetic/pharmacodynamic (PK/PD) target attainment (TA) and risk of therapeutic failure with intermittent bolus infusions in intensive care unit (ICU) patients. The aim of this study was to describe meropenem TA in an ICU population and the clinical response in the first 72 h after therapy initiation.
METHODS: A prospective observational study of ICU patients ≥18 years was conducted from 2014 to 2017. Patients with normal renal clearance (NRC) and augmented renal clearance (ARC) and patients on continuous renal replacement therapy (CRRT) were included. Meropenem was administered as intermittent bolus infusions, mainly at a dose of 1 g q6h. Peak, mid, and trough levels were sampled at 24, 48, and 72 h after therapy initiation. TA was defined as 100% T > 4× MIC or trough concentration above 4× MIC. Meropenem PK was estimated using traditional calculation methods and population pharmacokinetic modeling (P-metrics®). Clinical response was evaluated by change in C-reactive protein (CRP), Sequential Organ Failure Assessment (SOFA) score, leukocyte count, and defervescence.
RESULTS: Eighty-seven patients were included, with a median Simplified Acute Physiology (SAPS) II score 37 and 90 days mortality rate of 32%. Median TA was 100% for all groups except for the ARC group with 45.5%. Median CRP fell from 175 (interquartile range [IQR], 88-257) to 70 (IQR, 30-114) (p < .001) in the total population. A reduction in SOFA score was observed only in the non-CRRT groups (p < .001).
CONCLUSIONS: Intermittent meropenem bolus infusion q6h gives satisfactory TA in an ICU population with variable renal function and CRRT modality, except for ARC patients. No consistent relationship between TA and clinical endpoints were observed.

Children undergoing allogeneic hematopoietic stem cell transplantation (HSCT) are prone to developing acute kidney injury (AKI). Markers of kidney damage: kidney injury molecule (KIM)-1, interleukin (IL)-18, and neutrophil gelatinase-associated lipocalin (NGAL) may ease early diagnosis of AKI. The aim of this study was to assess serum concentrations of KIM-1, IL-18, and NGAL in children undergoing HSCT in relation to classical markers of kidney function (creatinine, cystatin C, estimated glomerular filtration rate (eGFR)) and to analyze their usefulness as predictors of kidney damage with the use of artificial intelligence tools. Serum concentrations of KIM-1, IL-18, NGAL, and cystatin C were assessed by ELISA in 27 children undergoing HSCT before transplantation and up to 4 weeks after the procedure. The data was used to build a Random Forest Classifier (RFC) model of renal injury prediction. The RFC model established on the basis of 3 input variables, KIM-1, IL-18, and NGAL concentrations in the serum of children before HSCT, was able to effectively assess the rate of patients with hyperfiltration, a surrogate marker of kidney injury 4 weeks after the procedure. With the use of the RFC model, serum KIM-1, IL-18, and NGAL may serve as markers of incipient renal dysfunction in children after HSCT.

BACKGROUND: This study aimed to determine the impact of augmented renal clearance (ARC) on anticoagulation therapy in critically ill patients with coronavirus disease 2019 (COVID-19).
METHODS: This retrospective cohort study included adult patients with severe COVID-19 with ARC who had been treated at our hospital between 2020 and 2021. We measured the estimated glomerular filtration rate calculated by the Chronic Kidney Disease Epidemiology Collaboration formula (eGFRCKD-EPI) every morning, and ARC condition was defined as eGFRCKD-EPI ≥ 130 mL/min/1.73 m2. Multivariate regression analysis with Huber-White sandwich estimator was performed to examine the association of unfractionated heparin (UH) dosage between blood test timings with activated partial thromboplastin time (APTT) compared with and without ARC.
RESULTS: We identified 38 enrolled patients: seven and 31 in the ARC and non-ARC groups, respectively. In the ARC coexisting condition, a higher dose of UH, which corresponded to the total dose in 24 h from the previous day, was required to achieve the same APTT prolongation, with a significant difference (p < 0.001).
CONCLUSIONS: Our study suggests that careful monitoring and consideration of higher UH doses in critically ill patients with COVID-19 is necessary because anticoagulation failure can occur during ARC.

UNASSIGNED: We aimed to study the prevalence of augmented renal clearance (ARC) and validate the utility of ARC and ARCTIC scores. We also aimed to assess the correlation and agreement between estimated GFR (eGFR-EPI) and 8-hour measured creatinine clearance (8 hr-mCLcr).
UNASSIGNED: This was a prospective, observational study done in the mixed medical-surgical intensive care unit (ICU) and 90 patients were recruited. 8 hr-mCLcr, ARC, and ARCTIC scores and eGFR-EPI were calculated for all patients. ARC was said to be present if 8 hr-mCLcr was ≥ 130 mL/min.
UNASSIGNED: Four patients were excluded from the analysis. The prevalence of ARC was 31.4%. The sensitivity, specificity, and positive and negative predictive values of ARC and ARCTIC scores were found to be 55.6, 84.7, 62.5, 80.6, and 85.2, 67.8, 54.8, and 90.9 respectively. AUROC for ARC and ARCTIC scores were 0.802 and 0.765 respectively. A strong positive correlation and poor agreement were observed between eGFR-EPI and 8 hr-mCLcr.
UNASSIGNED: The prevalence of ARC was significant and the ARCTIC score showed good potential as a screening tool to predict ARC. Lowering the cut-off of ARC score to ≥5 improved its utility in predicting ARC. Despite its poor agreement with 8 hr-mCLcr, eGFR-EPI with a cut-off ≥114 mL/min showed utility in predicting ARC.
UNASSIGNED: Kanna G, Patodia S, Annigeri RA, Ramakrishnan N, Venkataraman R. Prevalence of Augmented Renal Clearance (ARC), Utility of Augmented Renal Clearance Scoring System (ARC score) and Augmented Renal Clearance in Trauma Intensive Care Scoring System (ARCTIC score) in Predicting ARC in the Intensive Care Unit: Proactive Study. Indian J Crit Care Med 2023;27(6):433-443.

BACKGROUND: Augmented renal clearance (ARC) remains poorly evaluated in ICU. The objective of this study is to provide a full description of ARC in ICU including prevalence, evolution profile, risk factors and outcomes.
METHODS: This was a retrospective, single-center, observational study. All the patients older than 18 years admitted for the first time in Medical ICU, Bichat, University Hospital, APHP, France, between January 1, 2017, and November 31, 2020 and included into the Outcomerea database with an ICU length of stay longer than 72 h were included. Patients with chronic kidney disease were excluded. Glomerular filtration rate was estimated each day during ICU stay using the measured creatinine renal clearance (CrCl). Augmented renal clearance (ARC) was defined as a 24 h CrCl greater than 130 ml/min/m2.
RESULTS: 312 patients were included, with a median age of 62.7 years [51.4; 71.8], 106(31.9%) had chronic cardiovascular disease. The main reason for admission was acute respiratory failure (184(59%)) and 196(62.8%) patients had SARS-COV2. The median value for SAPS II score was 32[24; 42.5]; 146(44%) and 154(46.4%) patients were under vasopressors and invasive mechanical ventilation, respectively. The overall prevalence of ARC was 24.6% with a peak prevalence on Day 5 of ICU stay. The risk factors for the occurrence of ARC were young age and absence of cardiovascular comorbidities. The persistence of ARC during more than 10% of the time spent in ICU was significantly associated with a lower risk of death at Day 30.
CONCLUSIONS: ARC is a frequent phenomenon in the ICU with an increased incidence during the first week of ICU stay. Further studies are needed to assess its impact on patient prognosis.

Augmented renal clearance (ARC) is a phenomenon that has been demonstrated in many subsets of critically ill patients and is characterized by a creatinine clearance (CrCl) > 130 mL/min. Prior research has examined ARC prevalence in the presence of sepsis, traumatic brain injury, subarachnoid hemorrhage, and intracranial hemorrhage. However, to our knowledge, no studies have examined whether this phenomenon occurs in patients suffering from an acute ischemic stroke (AIS). The objective of this study was to evaluate whether patients experiencing an AIS exhibit ARC, identify potential contributing factors, and examine the precision of current renal clearance estimation methods in patients with AIS experiencing ARC.
This was a single-center prospective observational study conducted in adult patients admitted to a neurocritical intensive care unit (ICU) at a community hospital. Once consent was gained, patients with an admitting diagnosis of an AIS underwent a 24-h urine collection to assess measured CrCl. The primary end point assessed for ARC, defined as a measured CrCl > 130 mL/min. The secondary end point evaluated length of stay in the neurocritical ICU.
Twenty-eight patients met enrollment criteria, and data was analyzed for 20 patients. ARC was present in 35% of enrolled patients. Mathematical estimations of renal function were inadequate in detecting ARC manifestation. Patients experiencing ARC were associated with nonsignificantly shorter ICU length of stay.
ARC appears to manifest in patients with AIS inconsistently. Patients experiencing ARC were associated with nonsignificantly shorter ICU length of stay.

This study aimed to examine the risk factors of augmented renal clearance (ARC) and the association between ARC and vancomycin pharmacokinetic/pharmacodynamic (PK/PD) indices in Chinese adult patients. A prospective, observational, multicenter study was conducted, and 414 adult patients undergoing vancomycin therapeutic drug monitoring (TDM) were enrolled. Clinical and PK/PD data were compared between ARC and non-ARC groups. Independent risk factors were examined using a multivariate logistic regression analysis. The ARC and augmented renal clearance in trauma intensive care (ARCTIC) scoring systems were evaluated. Eighty-eight of the enrolled patients (88/414, 21.3%) had ARC before vancomycin therapy. Patients with ARC were more likely to have subtherapeutic vancomycin PK/PD indices, including trough concentration (p = 0.003) and 24 h area under the concentration−time curve (AUC24) to minimal inhibitory concentration (MIC) ratio (p < 0.001). Male sex (OR = 2.588), age < 50 years (OR = 2.713), overweight (OR = 2.072), receiving mechanical ventilation (OR = 1.785), enteral nutrition (OR = 2.317), neutrophil percentage (OR = 0.975), and cardiovascular diseases (OR = 0.281) were significantly associated with ARC. In conclusion, ARC is associated with subtherapeutic vancomycin trough concentration and AUC24/MIC; therefore, higher than routine doses may be needed. Risk factors and ARC risk scoring systems are valuable for early identification.

BACKGROUND: Augmented renal clearance is increasingly recognized in critically ill patients. This condition may lead to suboptimal dosing of renally excreted medications.
OBJECTIVE: Our primary objective was to identify demographic and clinical factors associated with augmented renal clearance in a mixed critically ill population.
METHODS: This retrospective single center observational cohort study evaluated patients admitted in a mixed adult intensive care unit for augmented renal clearance, defined as a creatinine clearance of ≥ 130 ml/min/1.73m2, through weekly 24-h urine collection. Variables associated with augmented renal clearance were identified using univariate analysis, then served as covariates in a backward stepwise logistic regression. Goodness-of-fit of the model was assessed and receiver operating characteristic curve was generated.
RESULTS: Augmented renal clearance was observed in 25.3% of the study cohort (n = 324). Age below 50 years (adjusted odds ratio 7.32; 95% CI 4.03-13.29, p < 0.001), lower serum creatinine at intensive care admission (adjusted odds ratio 0.97; 95% CI 0.96-0.99, p < 0.001) and trauma admission (adjusted odds ratio 2.26; 95% CI 1.12-4.54, p = 0.022) were identified as independent risk factors. Our model showed acceptable discrimination in predicting augmented renal clearance (Area under receiver operating characteristic curve (0.810; 95% CI 0.756-0.864, p < 0.001)).
CONCLUSIONS: We identified age below 50 years, lower serum creatinine upon intensive care admission and trauma as independent risk factors for augmented renal clearance, consistent with the literature suggesting that patients with low serum creatinine upon admission could have a higher risk of developing augmented renal clearance.

OBJECTIVE: To characterize the incidence, timing, and predictors of augmented renal clearance (ARC) in patients with traumatic brain injury (TBI).
METHODS: In 61 patients with TBI, creatinine clearance (CrCl) was prospectively measured from urine samples, over seven days. ARC was defined as a CrCl >130 mL/min/1.73 m2 in at least one day. We compared patients with and without ARC.
RESULTS: We performed 295 determinations of CrCl. ARC was present in 82% of the patients and arose in the first 2 days in 86% of them. ARC was more frequent in patients with associated injuries (100 vs. 75%, P = 0.02). There was a trend to a more aggressive resuscitation in patients with ARC but young age was the only independent predictor. Hospital length of stay was higher in ARC (15 [8-25] vs. 6 [3-19] days, P < 0.05).
CONCLUSIONS: ARC is very common and has an early appearance in patients with TBI. Young age is its main determinant.