Continuous Renal Replacement Therapy Modalities Research Articles

Continuous renal replacement therapy with vitamin E-coated polysulfone hemofilter reduces inflammatory responses in a porcine lipopolysaccharide-treated model.

Biological invasions may promote the onset of systemic inflammatory response syndrome in patients eligible for continuous renal replacement therapy (CRRT), leading to poor prognosis. Hence, we aimed to examine the inflammatory reactions in circulation using vitamin E-coated polysulfone hollow fiber membrane (ViLIFE). Lipopolysaccharides were intravenously administered to pigs (2 μg/kg/30 min) to establish an acute inflammation model. Extracorporeal circulation was performed for 6 h in continuous venovenous hemodiafiltration mode using a hemofilter for CRRT filled with a polysulfone hollow fiber membrane or ViLIFE, and the differences in inflammatory reactions were evaluated. The ViLIFE group exhibited low platelet and cytokine levels (p < 0.05 vs. sham-CRRT group). Additionally, the ViLIFE group had lower lactate and high mobility group box 1 levels than the other groups. ViLIFE represents a promising CRRT modality that can inhibit the inflammatory response in circulation and inhibit further biological invasions.

An Integrative Risk Assessment Approach to Enhancing Patient Safety in Continuous Renal Replacement Therapy (CRRT)

Continuous Renal Replacement Therapy (CRRT) serves as an intervention strategy for the management of acute kidney injury (AKI) in critically ill patients. However, owing to its complex nature and the potential for complications, the implementation of CRRT demands continuous monitoring to prevent patient safety risks. This study aims to identify and validate prevalent risks linked to CRRT within a real-world clinical setting, intending to propose preventive measures grounded in expert insights. To systematically categorize and visually depict the risks, their consequences, preventive measures, and recovery controls, our study employed the Bowtie method in conjunction with the Systems Engineering Initiative for Patient Safety (SEIPS) model. In addition to considering patient-related factors that exhibit variability among critically ill individuals, our key findings showed that the most influential risks impacting the effective delivery of CRRT are incidents of clotted filters, bleeding risks arising from the necessity of anticoagulation for filter efficacy, vascular catheter-related bloodstream infections, variations in proficiency levels among healthcare professionals regarding CRRT modalities, especially in operating the CRRT machines, high nursing workload, frequent nursing turnover, occurrences of hypophosphatemia, variability in CRRT prescribing patterns, and issues related to communication among stakeholders. This research sheds light on the primary risks associated with CRRT and provides practical and viable strategies for effective management. Furthermore, the Bowtie diagram developed as part of this study serves as a valuable tool for visually representing the healthcare system and facilitating the identification of system-related risks within healthcare settings.

#2507 Enhancing critical care nephrology: analyzing continuous renal replacement therapy with a citrate-based anticoagulation focus

Abstract Background and Aims Continuous renal replacement therapy (CRRT) is pivotal for managing acute kidney injury (AKI) unstable patients. However, questions persist regarding prescription and the role of anticoagulation. This study aims to examine CRRT practices, focus on citrate-based anticoagulation and clarify contraindications. Method This study comprises a retrospective analysis of a patient cohort requiring CRRT and admitted to the Postoperative Intensive Care Unit and Burn Unit. Inclusion criteria involved the need for CRRT and adult age, with exclusion criteria based on treatment duration (&amp;lt;48 hours), reducing the initial cohort from 256 to 176 patients. Clinical variables, including gender, age, underlying pathology, CRRT modality, and anticoagulation type, were characterized. Subsequently, the association between anticoagulation type and clot formation within 48 hours and in-hospital mortality was investigated. Furthermore, an analysis of citrate-based CRRT was conducted, evaluating laboratory values (Table 1) at the beginning and 48 hours using the Wilcoxon test, and their correlation with clot development and mortality. Additionally, we used a logistic regression model to explore the relationship between AST, ALT, and lactate values with citrate accumulation. Finally, a survival analysis was conducted. Results The sample consisted of 66.5% males and 33.5% females, with an average age of 59.48 years. Reasons for admission are depicted in Fig. 1. CRRT modalities were 20.5% HDVVC, 76.1% HDFVVC, and 3.4% HFVVC. Anticoagulation included 35.2% none, 28.4% heparin, 33.5% citrate, and 2.8% alprostadil. Filter clotting occurred in 29.1% withing 48 hours. Heparin was associated with a 5.4-fold increased risk of clotting compared to citrate. Mortality was 63.3%, with no anticoagulation type showing a significant association. Parameters at CRRT initiation and 48 hours for citrate-based CRRT patients and Wilcoxon test results are presented in Table 1. Only 5.1% had filter clotting &amp;lt;48 hours, and no baseline parameters were significantly associated with an increased clotting risk. There was one case of citrate intoxication due to a programming error, which was not included. 76.81% had CaT/CaI &amp;lt;2.1, and 7.25% had CaT/CaI &amp;gt;2.1, requiring technique adjustments. Aminotransferases and lactate values, often considered as contraindications for citrate, were analyzed: The average AST and ALT values were 188.53 IU/l and 108.08 IU/l, respectively. When AST levels exceeded 5 times the normal range and ALT levels exceeded 3 times the normal range, a statistically significant association with CaT/CaI &amp;gt;2.1 at the 48-hour mark of CRRT utilization was observed (p &amp;lt; 0.001 for both).The average lactic acid value was 1.74 mg/dl. Having a lactic acid level &amp;gt;4 was associated (p &amp;lt; 0.05) with a higher risk of developing CaT/CaI &amp;gt;2.1. 54.2% of the sample died. No baseline parameters were significantly associated with it. At 48 hours, higher bicarbonate levels and metabolic alkalosis were associated with increased mortality (p &amp;lt; 0.05). The median survival time was 11 days (±4.38). Conclusion This study supports the use of citrate-based anticoagulation in CRRT, as no cases of citrate intoxication (CaT/CaI &amp;gt;2.5) were found. Nonetheless, a significantly elevated AST (&amp;gt;5 times normal), ALT (&amp;gt;3 times normal), and lactate (&amp;gt;4 mg/dl), were associated with a higher risk of citrate accumulation (CaT/CaI &amp;gt;2.1). Customized approaches and preventive measures to mitigate the development of metabolic alkalosis are essential for optimizing patient outcomes.

#916 Outcomes of renal replacement therapy in ICU adult patients with acute kidney injury: a retrospective cohort study

Abstract Background and Aims Continuous renal replacement therapy (CRRT) and sustained low-efficiency dialysis (SLED) are usually used for critically ill patients with acute kidney injury when indicated. Most studies done throughout the years showed no statistically significant difference in outcomes between the two modalities. Thus, this study aims to determine the outcomes and associated factors of both CRRT and SLED in patients with AKI. Hence, this will allow us to determine our competency as an institution in using CRRT and SLED to formulate recommendations and protocols in the future. Method We conducted a retrospective cohort study of patients who developed acute kidney injury and underwent either SLED or CRRT in the ICU of a tertiary hospital in Makati City, Metro Manila. Patients who are on maintenance hemodialysis, who underwent both sustained low-efficiency dialysis and continuous replacement therapy, and who did not complete or tolerate 1 session of SLED or 24 hours of CRRT were excluded in the study. Key outcomes investigated were all-cause mortality at 30 days and dialysis dependence at 30 days after initiation of treatment. Results Eighty-four patients who were initiated with either SLED (N=48) or CRRT (N=36). There was a significant difference in terms of all-cause mortality between modalities 20 (42%) for SLED and 33 (92%) for CRRT, p-value=0.000). Among variables used in the study, higher vasopressor requirement (aOR 2.78, 95% CI: 1.47-5.25, p=0.002) and age (aOR 2.21, 95% CI: 1.13-4.33, p=0.021) at initiation were associated with higher likelihood of mortality across modalities. Thirteen patients (28%) who underwent SLED were dependent on dialysis at 30 days. Baseline serum creatinine (aOR 3.21 95% CI: 1.17-8.79, p=0.023) and serum creatinine at initiation (aOR 4.11, 95% CI: 1.43-22.56, p=0.014) were identified to be associated with dialysis dependence. Sub-analysis of the CRRT group showed continuous veno-venous hemodialysis (CVVHD) (aOR 16.57, 95% CI: 3.54-77.49, p&amp;lt;0.001) was associated with higher likelihood of mortality among CRRT modalities. Conclusion Increased mortality was seen in patients who underwent CRRT especially CVVHD and was associated with age and number of vasopressors present during initiation of renal replacement therapy.

Predictors of renal function non-recovery in critically ill patients with acute kidney injury treated with continuous renal replacement therapy

Introduction/Objective. Acute kidney injury (AKI) is a highly prevalent complication among the critically ill individuals who are admitted to the intensive care unit (ICU). This study deals with identifying the frequency and predictors of the lack of renal function recovery in non-renal functions among critically ill patients requiring dialysis for AKI (AKI-D). Methods. The study included 440 ICU patients from the University Clinical Center of Vojvodina in the period from 2014 to 2018. The patients required Continuous Renal Replacement Therapy (CRRT). In this study, we analyzed various factors including demographic features, clinical characteristics, laboratory parameters, comorbidities, as well as the need for vasopressor therapy and mechanical ventilation on the day when AKI was confirmed. Additionally, we examined the different modalities of CRRT, which were used. Results. A retrospective analysis of the results included discovered that out of 440 patients with AKI-D, 242 (55%), average age 63.14, did not recover renal function. Significant predictors of renal function non-recovery in critically ill patients with AKI-D were: the patients age over 65 (p = 0.044), starting time of CRRT (p = 0.043), mechanical ventilation (p = 0.044) and previous kidney disease (p = 0.005). Significant predictors of renal function non-recovery in critically ill septic patients with AKI-D were: the patients age over 65 (p = 0.002), diabetes mellitus (p = 0.023), previous kidney disease (p = 0.045), CRP values &lt; 100 mg/l (p = 0.033) and procalcitonin (p = 0.010), while in non-septic patients, the significant predictors of renal function non-recovery includes previous kidney disease (p = 0.035). Conclusion. Out of all examined predictors, both in septic and non-septic patients, previous kidney damage presents the greatest risk for renal function non-recovery in critically ill patients with AKI-D.

Anakinra Removal by Continuous Renal Replacement Therapy: An Ex Vivo Analysis.

Patients with sepsis are at significant risk for multiple organ dysfunction, including the lungs and kidneys. To manage the morbidity associated with kidney impairment, continuous renal replacement therapy (CRRT) may be required. The extent of anakinra pharmacokinetics in CRRT remains unknown. The objectives of this study were to investigate the anakinra-circuit interaction and quantify the rate of removal from plasma. The anakinra-circuit interaction was evaluated using a closed-loop ex vivo CRRT circuit. CRRT was performed in three phases based on the method of solute removal: 1) hemofiltration, 2) hemodialysis, and 3) hemodiafiltration. Standard control samples of anakinra were included to assess drug degradation. University research laboratory. None. Anakinra was administered to the CRRT circuit and serial prefilter blood samples were collected along with time-matched control and hemofiltrate samples. Each circuit was run in triplicate to assess inter-run variability. Concentrations of anakinra in each reference fluid were measured by enzyme-linked immunosorbent assay. Transmembrane filter clearance was estimated by the product of the sieving coefficient/dialysate saturation constant and circuit flow rates. Removal of anakinra from plasma occurred within minutes for each CRRT modality. Average drug remaining (%) in plasma following anakinra administration was lowest with hemodiafiltration (34.9%). The average sieving coefficient was 0.34, 0.37, and 0.41 for hemodiafiltration, hemofiltration, and hemodialysis, respectively. Transmembrane clearance was fairly consistent across each modality with the highest during hemodialysis (5.53 mL/min), followed by hemodiafiltration (4.99 mL/min), and hemofiltration (3.94 mL/min). Percent drug remaining within the control samples (93.1%) remained consistent across each experiment, indicating negligible degradation within the blood. The results of this analysis are the first to demonstrate that large molecule therapeutic proteins such as anakinra, are removed from plasma with modern CRRT technology. Current dosing recommendations for patients with severe renal impairment may result in subtherapeutic anakinra concentrations in those receiving CRRT.

Lacosamide dosing in patients receiving continuous renal replacement therapy

BackgroundLacosamide is one of the anticonvulsants used in critically ill patients. This study aimed to suggest appropriate lacosamide dosing regimens in critically ill patients receiving continuous renal replacement therapy (CRRT) via Monte Carlo simulations.MethodsMathematical models were created using published demographic and pharmacokinetics in adult critically ill patients. CRRT modalities with different effluent rates were added into the models. Lacosamide regimens were evaluated on the probability of target attainment (PTA) using pharmacodynamic targets of trough concentrations and area under the curve within a range of 5–10 mg/L and 80.25–143 and 143–231 mg*h/L for the initial 72 h-therapy, respectively. Optimal regimens were defined from regimens that yielded the highest PTA. Each dosing regimen was tested in a group of different 10,000 virtual patients.ResultsOur results revealed the optimal lacosamide dosing regimen of 300–450 mg/day is recommended for adult patients receiving both CRRT modalities with 20–25 effluent rates. The dose of 600 mg/day was suggested in higher effluent rate of 35 mL/kg/h. Moreover, a patient with body weight > 100 kg was less likely to attain the targets.ConclusionsVolume of distribution, total clearance, CRRT clearance and body weight were significantly contributed to lacosamide dosing. Clinical validation of the finding is strongly indicated.

The Clearance of Midazolam and Metabolites during Continuous Renal Replacement Therapy in Critically Ill Patients with COVID-19

Introduction: Midazolam-based continuous intravenous sedation in patients admitted to the intensive care unit (ICU) was a necessity during the COVID-19 pandemic. However, benzodiazepine-based sedation is associated with a high incidence of benzodiazepine-related delirium and additional days on mechanical ventilation. Due to the requirement of high midazolam doses in combination with the impaired renal clearance (CL) of the pharmacological active metabolite 1-OH-midazolam-glucuronide (10% compared to midazolam), ICU patients with COVID-19 and continuous renal replacement therapy (CRRT) were at risk of unintended prolonged sedation. Several CRRT-related factors may have influenced the delivered CL of midazolam and its metabolites. Therefore, the aim of the study was to identify and describe these CRRT-related factors. Methods: Pre-filter blood samples and ultrafiltrate samples were collected simultaneously. Midazolam, 1-OH-midazolam, and 1-OH-midazolam-glucuronide plasma samples were analyzed using an UPLC-MS/MS method. The prescribed CRRT dose was corrected for downtime and filter integrity using the urea ratio (urea concentration in effluent/urea concentration plasma). CL of midazolam and its metabolites were calculated with the delivered CRRT dose (corrected for downtime and saturation coefficient [SD]). Results: Three patients on continuous venovenous hemodialysis (CVVHD) and 2 patients on continuous venovenous hemodiafiltration (CVVHDF) were included. Midazolam, 1-OH-midazolam, and 1-OH-midazolam-glucuronide concentrations were 2,849 (0–6,700) μg/L, 153 (0–295) μg/L, and 27,297 (1,727–39,000) μg/L, respectively. The SD was 0.03 (0.02–0.03) for midazolam, 0.05 (0.05–0.06) for 1-OH-midazolam, and 0.33 (0.23–0.43) for 1-OH-midazolam-glucuronide. The delivered CRRT CL was 1.4 (0–1.7) mL/min for midazolam, 2.7 (0–3.5) mL/min for 1-OH-midazolam, and 15.7 (4.0–27.7) mL/min for 1-OH-midazolam-glucuronide. Conclusions: Midazolam and 1-OH-midazolam were not removed during CVVHD and CVVHDF. However, 1-OH-midazolam-glucuronide was removed reasonably, approximately up to 43%. CRRT modality, filter integrity, and downtime affect this removal. These data imply a personalized titration of midazolam in critically ill patients with renal failure and awareness for the additional sedative effects of its active metabolites.

Transdermal Detection of MB-102 and Correlation to Meropenem Pharmacokinetics During Continuous Renal Replacement Therapy: In Vivo Results.

Critically ill patients undergoing continuous renal replacement therapy (CRRT) have medical conditions requiring extensive pharmacotherapy. Continuous renal replacement therapy impacts drug disposition. Few data exist regarding drug dosing requirements with contemporary CRRT modalities and effluent rates. The practical limitations of pharmacokinetic studies requiring numerous plasma and effluent samples, and lack of generalizability of observations from specific CRRT prescriptions, highlight gaps in bedside assessment of CRRT drug elimination and individualized dosing needs. We employed a porcine model using transdermal fluorescence detection of the glomerular filtration rate fluorescent tracer agent MB-102, with the aim to assess the relationship between systemic exposure of MB-102 and meropenem during CRRT. Animals underwent bilateral nephrectomies and received intravenous bolus doses of MB-102 and meropenem. Once MB-102 equilibrated in the animal, CRRT was initiated. Continuous renal replacement therapy prescriptions comprised four combinations of blood pump (low versus high) and effluent (low versus high) flow rates. Changes in transdermal detected MB-102 clearance occurred immediately with a change in CRRT rates. Blood side meropenem clearance mirrored transdermal MB-102 clearance (r2: 0.95-0.97, p value all <0.001). We suggest transdermal MB-102 clearance provides real-time personalized assessment of drug elimination and could optimize prescription of drugs for critically ill patients requiring CRRT.

#6306 SUSTAINED LOW-EFFICIENCY DIALYSIS VERSUS CONTINUOUS VENO-VENOUS HEMODIAFILTRATION OUTCOME IN CRITICALLY ILL PATIENTS

Abstract Background and Aims Acute kidney injury due to sepsis is the most common cause of AKI in critical care settings. Different modalities of renal replacement therapies (RRT) have been used to manage this condition including Continuous Renal Replacement Therapy (CRRT) and sustained low efficiency dialysis (SLED). The aim of this work was to compare the outcome of SLED and CRRT in the form of continuous veno-venous hemodiafiltration (CVVDHF) as methods of dialysis in sepsis induced AKI. Method We retrospectively analysed data from 120 patients; 20 patients received CVVHDF to manage AKI in the context of sepsis, 47 patients received SLED to manage AKI in the context of sepsis and the third group included 53 patients who have been treated with SLED to manage AKI not due to sepsis. Age was found to be significantly higher in sepsis induced AKI patients treated with SLED than patients treated with CVVHDF (65±10.1# 59.5±9.3 y, p = 0.03). Sex distribution or incidences of hypertension, diabetes mellitus, malignancy or liver disease were not statistically different between groups. Results Unadjusted 30 day mortality was 44.7% (21pt) in the SLED group Vs 50% (10pt) in the CVVHDF group, p = 0.07. Adjusted mortality was not statically significant between SLED and CVVHDF (OR 0.97, CI = 0.95-1.06). Hypotension occurred more frequently in patients treated with SLED (24 pt = 51.1% #5 pt = 25%, p &amp;lt; 0.001).Clotting occurred more frequently in the CVVHDF group as compared to SLED group (7 pt = 35% Vs 4pt = 8.5% p &amp;lt; 0.001). Conclusion Sustained low efficiency dialysis (SLED) and CVVHDF had comparable 30 day mortality as modalities of RRT in critically ill Patients with sepsis induced AKI. SLED still an attractive alternative to CRRT modalities due to lower cost and lower incidence of complications. Further larger studies are recommended.

Cefepime Dosing in a Critically Ill Neonate Receiving Continuous Renal Replacement Therapy With the Cardio-Renal Pediatric Dialysis Emergency Machine (CARPEDIEM).

We report on a former 27-week gestational age infant who was placed on the Cardio-Renal Pediatric Dialysis Emergency Machine (CARPEDIEM) at 4 months post-menstrual age while receiving cefepime treatment for an Enterobacter cloacae bacteremia and persistent peritonitis secondary to an infected peritoneal dialysis catheter. Using therapeutic drug monitoring while assessing the clearance of cefepime on continuous renal replacement therapy (CRRT), we were able to successfully treat this patient's infection while also minimizing the risk of side effects from this medication. Current literature supports dosing in adult patients on all modalities of CRRT with effluent flow rates of 20 to 25 mL/kg/hr; however, pharmacokinetic data on cefepime dosing in pediatric CRRT are scant. This case report describes the successful dosing strategy used for this patient while on various rates of continuous veno-venous hemodialysis with CARPEDIEM. Therapeutic drug monitoring of cefepime should be considered in critically ill pediatric patients on CARPEDIEM receiving CRRT.

Aminoglycoside Pharmacokinetics in Critically Ill Patients Undergoing Continuous Renal Replacement Therapy.

There are few studies describing aminoglycoside pharmacokinetics during continuous renal replacement therapy (CRRT). To characterize the effect of CRRT on aminoglycoside clearance and volume of distribution (Vd). Retrospective observational pharmacokinetic study of adult critically ill oncologic patients who received a first dose of amikacin or tobramycin during CRRT between February 2012 and May 2017. Study outcomes included aminoglycoside clearance, Vd, and attainment of the target peak: MIC (minimum inhibitory concentration) ratio as a surrogate for dosing appropriateness. In total, 80 patients were included, sustained low-efficiency dialysis (SLED), n = 49; continuous venovenous hemodialysis (CVVHD), n = 19; continuous venovenous hemofiltration (CVVH), n = 12. Fifty-one patients received amikacin at a median dose of 14.5 mg/kg per actual body weight and achieved a median peak level of 26.7 mg/L. Twenty-nine patients received tobramycin at a median dose of 6.5 mg/kg actual body weight and achieved a median peak level of 10.3 mg/L. The median aminoglycoside clearance was 63.1 mL/min and was similar between CRRT modality groups (P = 0.97). The median Vd was 0.47 L/kg and was different between the SLED and CVVH groups (P = 0.007). Attainment of target peak: MIC occurred in 29% in the total study population and 44% in the subgroup of 23 patients with isolates tested for aminoglycoside susceptibility. Critically ill oncology patients undergoing CRRT exhibited reduced clearance and expanded Vd that was not significantly different between CRRT modalities. Current dosing regimens led to low peak concentrations and poor attainment of pharmacokinetic targets.

MO298: Predictors of Renal Function Recovery in Critically ill Patients With Acute Kidney Injury

Abstract BACKGROUND AND AIMS Acute kidney injury (AKI) is a frequent and serious complication in critically ill patients admitted in intensive care unit (ICU). The development of acute kidney damage is associated with various adverse outcomes, such as prolonged stay in the ICU, the development of chronic kidney disease (CKD), increased mortality and increased treatment costs. The aim of this study was to determine the predictors of renal function recovery in critically ill patients with AKI who were treated with continuous renal replacement therapy (CRRT). METHOD We performed a single-centre retrospective study of 440 adult surgical and non-surgical patients with AKI or AKI episode in CKD who were admitted to the ICU between 2014 and 2018 and treated with CRRT. Demographic, clinical and laboratory parameters [urea, creatinine, C-reactive protein (CRP), procalcitonin (PCT), quick sequential organ failure assessment (qSOFA) score], comorbidities, the need for vasopressor therapy and mechanical lung ventilation on the day of confirmed AKI, as well as CRRT modalities were analysed. Renal recovery was defined by renal replacement therapy discontinuation within 90 days of its start. Patients with the Kidney Disease Improving Global Outcomes (KDIGO) stage 2 AKI and/or volume overload have had an ‘early’ start of CRRT within 24 h of the AKI diagnosis; patients with poor response to conservative treatment or evidence of clinical complications associated with AKI have had a ‘late’ start of CRRT. The patients were divided into two groups: patients with recovered renal function (RRF group) and patients who had not recovered renal function (NRRF group). RESULTS Out of a total of 440 patients, 242 (55%) recovered renal function. RRF versus NRRF group did not differ significantly by gender (males: 64.5% versus 69.7%) and age (mean age of 60.93 years versus 64.5 years). Cardiovascular diseases were the most common comorbidity in both groups of patients, and CKD was significantly more prevalent in the NRRF groups (88 versus 352, P &amp;lt; .001). There were no significant differences in examined laboratory parameters in the RRF and NRRF group (urea 27.28 versus 26.68 mmol/L; creatinine 401.43 versus 373.7 μmol/L; CRP 144.38 versus 143.52 mg/L; PCT 23.07 versus 22.44 ng/L). No significant difference was found in relation to mechanical lung ventilation (234 in the RRF group versus 206 in the NRRF group; P = .18) and vasopressor therapy (221 in the RRF group versus 219 in the NRRF group; P = 0.94). Values of the qSOFA score were significantly lower (P &amp;lt; .001) in patients with recovered renal function (Fig. 1). In the RRF group, the most commonly used CRRT modality was CVVHD (165; 37.6%), while in the NRRF group it was CVVHDF (181; 40.9%). Predictors of renal recovery in critically ill patients who were treated with CRRT were: age &amp;lt;65 years (P = .044), an ‘early’ start of RRT (P = .043), absence of mechanical ventilation (P = .044) and absence of earlier CKD (P = .005) (Table 1). Predictors of renal recovery in septic critically ill patients with AKI treated with CRRT were: age &amp;lt;65 years (P = .002), the absence of diabetes mellitus (P = .023) and previous CKD (P = .045) and CRP &amp;lt; 100 mg/L (P = .033), while in critically ill patients without sepsis, the predictor of renal function recovery was the absence of previous kidney disease (P = .035). CONCLUSION Previous kidney disease is the most significant factor for the prediction of renal function recovery in critically ill patients with AKI treated with CRRT. Individual consideration of potential predictors of renal recovery, as well as a timely decision to initiate continuous dialysis, will prevent complications and improve the outcome of critically ill patients with AKI.

Development and Use of an Ex-Vivo In-Vivo Correlation to Predict Antiepileptic Drug Clearance in Patients Undergoing Continuous Renal Replacement Therapy.

Results from previous ex-vivo continuous renal replacement therapy (CRRT) models have successfully demonstrated similar extraction coefficients (EC) identified from in-vivo clinical trials. The objectives of this study are to develop an ex-vivo in-vivo correlation (EVIVC) model to predict drug clearance for commonly used antiepileptics and to evaluate similarity in drug extraction across different CRRT modalities to extrapolate dosing recommendations. Levetiracetam, lacosamide, and phenytoin CRRT clearance was evaluated using the Prismaflex CRRT system and M150 hemodiafilters using an albumin containing normal saline (ALB-NS) vehicle with 3 different albumin concentrations (2g/dL, 3g/dL, and 4g/dL) and a human plasma vehicle at 3 different effluent flow rates (1 L/hr, 2 L/hr, and 3 L/hr). Blood and effluent/dialysate concentrations were collected after circuit priming. ECs were calculated for each drug, modality, vehicle, and experimental arm combination. The calculated average EC for levetiracetam and lacosamide was approximated to the fraction unbound from plasma protein. Human plasma and ALB-NS vehicles demonstrated adequate prediction of in-vivo CRRT clearance. Geometric mean ratios indicated similarity in extraction coefficients when comparing between hemofiltration and hemodiafiltration modalities and between filtration and dialysis modalities at effluent flow rates ≤ 2L/hr. Evaluation of phenytoin provided inconsistent findings with regards to extraction coefficient similarity across different CRRT modalities. The findings indicate that an ex-vivo study can be used as a surrogate to predict in-vivo levetiracetam and lacosamide clearance in patients receiving CRRT.

Optimizing Antimicrobial Dosing for Critically Ill Patients with MRSA Infections: A New Paradigm for Improving Efficacy during Continuous Renal Replacement Therapy.

The dosage regimen of vancomycin, teicoplanin and daptomycin remains controversial for critically ill patients undergoing continuous renal replacement therapy (CRRT). Monte Carlo simulation was applied to identify the optimal regimens of antimicrobial agents in patients with methicillin-resistant Staphylococcus aureus (MRSA) infections based on the mechanisms of different CRRT modalities on drug clearance. The optimal vancomycin dosage for patients received a CRRT doses ≤ 30 mL/kg/h was 20 mg/kg loading dose followed by 500 mg every 8 h, while 1 g every 12 h was appropriate when 35 mL/kg/h was prescribed. The optimal teicoplanin dosage under a CRRT dose ≤ 25 mL/kg/h was four loading doses of 10 mg/kg every 12 h followed by 10 mg/kg every 48 h, 8 mg/kg every 24 h and 6 mg/kg every 24 h for continuous veno-venous hemofiltration, continuous veno-venous hemodialysis and continuous veno-venous hemodiafiltration, respectively. When the CRRT dose increased to 30–35 mL/kg/h, the teicoplanin dosage should be increased by 30%. The recommended regimen for daptomycin was 6–8 mg/kg every 24 h under a CRRT dose ≤ 25 mL/kg/h, while 8–10 mg/kg every 24 h was optimal under 30–35 mg/kg/h. The CRRT dose has an impact on probability of target attainment and CRRT modality only influences teicoplanin.

Comparison of the Treatment Efficacy of Continuous Renal Replacement Therapy and Intermittent Hemodialysis in Patients With Acute Kidney İnjury Admitted to the Intensive Care Unit.

Introduction and aimAcute kidney injury (AKI) is part of the multiple organ dysfunction syndrome in critically ill patients and is a common condition in intensive care units (ICUs). Renal replacement therapy (RRT) is the cornerstone of treatment for AKI in critically ill patients. This patient population has a high mortality rate despite RRT. There are two methods of RRT for patients in ICUs: intermittent hemodialysis (IHD) and continuous renal replacement therapy (CRRT). Both CRRT and IHD similarly provide adequate metabolic control. We aimed to compare these two RRT modalities in terms of ICU stay, mortality, and laboratory recovery in these patients with high mortality.Materials and methodsA total of 120 patients with AKI who needed RRT in the ICU were included in the study (CRRT, n:40; IHD, n:80). Acute Physiology and Chronic Health Evaluation (APACHE) II, Sepsis-related Organ Failure Assessment (SOFA), and Simplified Acute Physiology Score (SAPS)-II scores at the time of admission to the ICU were calculated. Mean arterial pressure, urea, creatinine, sodium, potassium, calcium, pH, lactate, and bicarbonate levels were measured before and after dialysis. Patients were classified as living and deceased. Factors affecting the length of stay in the intensive care unit and 30-day mortality were evaluated. The variability in laboratory parameters between groups before and after dialysis was examined. The groups were compared with these parameters.ResultsSixty-one point seven percent (61.7%, n:74) of the patients were female. The mean age was 62.90±13.64 years. At the time of admission to the ICU, the patients' SAPS II score was 45.05±12.76, APACHE II score was 22.05±6.32, and SOFA score was 8.26±2.48. 66.7% (n:80) of the patients included in the study died, and the length of stay of these patients in the ICU was 12.85±10.23 days. When the groups were compared, SAPS II, APACHE II scores, and SOFA scores were significantly higher in the CRRT group than in the IHD group (p:0.038, p:0.015, p:0.027, respectively). Although the length of stay in the ICU was shorter in the CRRT group, it was not statistically significant (p:0.075). There was no statistically significant difference between the groups in terms of mortality (p: 0.891). SAPS-II, APACHE II, and SOFA score affected 30-day mortality while age, gender, and RRT modalities were not associated with mortality. The improvement in laboratory parameters between the pre and post-RRT groups was statistically more significant in the IHD group (p<0.001). It was determined that there was a statistically greater decrease in mean arterial pressure in the IHD group (p<0.001).ConclusionsIt was determined that there was no difference between the CRRT and IHD modalities applied in patients with AKI admitted to the ICU in terms of mortality and length of stay in the ICU. It was observed that both modalities improved on laboratory parameters, but the improvement was greater in the IHD group. However, it was determined that there was a statistically greater decrease in mean arterial pressure in the IHD group.

Population Pharmacokinetics and Dosing Optimization of Gentamicin in Critically Ill Patients Undergoing Continuous Renal Replacement Therapy.

PurposeAppropriate gentamicin dosing in continuous renal replacement therapy (CRRT) patients remains undefined. This study aimed to develop a population pharmacokinetic (PK) model of gentamicin in CRRT patients and to infer the optimal dosing regimen for gentamicin.MethodsFourteen CRRT patients dosed with gentamicin were included to establish a population PK model to characterize the variabilities and influential covariates of gentamicin. The pharmacokinetic/pharmacodynamic (PK/PD) target attainment and risk of toxicity for different combinations of gentamicin regimens (3–7 mg/kg q24h) and CRRT effluent doses (30–50 mL/h/kg) were evaluated by Monte Carlo simulation. The probability of target attainment (PTA) was determined for the PK/PD indices of the ratio of drug peak concentration/minimum inhibitory concentration (Cmax/MIC > 10) and the ratio of area under the drug concentration–time curve/MIC over 24 h (AUC0-24h/MIC > 100), and the risk of toxicity was estimated by drug trough concentration thresholds (1 and 2 mg/L).ResultsA one-compartment model adequately described the PK characteristics of gentamicin. Covariates including body weight, age, gender, and CRRT modality did not influence the PK parameters of gentamicin based on our dataset. All studied gentamicin regimens failed to achieve satisfactory PTAs for pathogens with an MIC ≥2 mg/L. A good balance of PK/PD target attainment and risk of toxicity (>2 mg/L) was achieved under 7 mg/kg gentamicin q24h and 40 mL/kg/h CRRT dose for an MIC ≤1 mg/L. CRRT dose intensity had a significant impact on the target attainment of AUC0-24h/MIC >100 and risk of toxicity.ConclusionA combination of 7 mg/kg gentamicin q24h and 40 mL/kg/h CRRT dose might be considered as a starting treatment option for CRRT patients, and drug monitoring is required to manage toxicity.

A Loading Micafungin Dose in Critically Ill Patients Undergoing Continuous Venovenous Hemofiltration or Continuous Venovenous Hemodiafiltration: A Population Pharmacokinetic Analysis.

In this study, the authors aimed to compare the pharmacokinetics (PK) of micafungin in critically ill patients receiving continuous venovenous hemofiltration (CVVH, 30 mL·kg-1·h-1) with those of patients receiving equidoses of hemodiafiltration (CVVHDF, 15 mL·kg-1·h-1 + 15 mL·kg-1·h-1) and determine the optimal dosing regimen using the developed model. Patients with septic shock undergoing continuous renal replacement therapy and receiving a conventional dose of 100 mg micafungin once daily were eligible for inclusion. Total micafungin plasma concentrations from 8 CVVH sessions and 8 CVVHDF sessions were subjected to a population PK analysis using Pmetrics. Validation of the model performance was reinforced by external validation. Monte Carlo simulations were performed considering the total ratio of free drug area under the curve (AUC) over 24 hours to the minimum inhibitory concentration (MIC) (AUC0-24/MIC) in plasma. The median total body weight (min-max) was 94.8 (66-138) kg. Micafungin concentrations were best described by a 2-compartmental PK model. No covariates, including continuous renal replacement therapy modality (CVVH or CVVHDF), were retained in the final model. The mean parameter estimates (SD) were 0.96 (0.32) L/h for clearance and 14.8 (5.3) L for the central compartment volume. External validation confirmed the performance of the developed PK model. Dosing simulations did not support the use of standard 100 mg daily dosing, except for Candida albicans on the second day of therapy. A loading dose of 150 mg followed by 100 mg daily reached the probability of target attainment for all C. albicans and C. glabrata, but not for C. krusei and C. parapsilosis. No difference was observed in micafungin PK between equidoses of CVVH and CVVHDF. A loading dose of 150 mg is required to achieve the PK/PD target for less susceptible Candida species from the first day of therapy.

Pharmacokinetics of Commonly Used Medications in Children Receiving Continuous Renal Replacement Therapy: A Systematic Review of Current Literature.

The use of continuous renal replacement therapy (CRRT) for renal support has increased substantially in critically ill children compared with intermittent modalities owing to its preferential effects on hemodynamic stability. With the expanding role of CRRT, the quantification of extracorporeal clearance and the effect on primary pharmacokinetic parameters is of the utmost importance. Within this review, we aimed to summarize the current state of the literature and compare published pharmacokinetic analyses of commonly used medications in children receiving CRRT to those who are not. A systematic search of the literature within electronic databases PubMed, EMBASE, Cochrane Library, and Web of Science was conducted. Published studies that were included contained relevant information on the use of commonly administered medications to children, from neonates to adolescents, receiving CRRT. Pharmacokinetic parameters that were analyzed included volume of distribution, total clearance, extracorporeal clearance, area under the curve, and elimination half-life. Information regarding CRRT circuit, flow rates, and membrane components was analyzed to investigate differences in pharmacokinetics between each modality. Forty-five studies met the final inclusion criteria within this systematic review, totaling 833 pediatric patients, with 586 receiving CRRT. Antimicrobials were the most common pharmacological class represented within the literature, representing 81% (35/43) of studies analyzed. Children receiving CRRT largely had similar volume of distribution and total clearance to critically ill children not receiving CRRT, suggesting reno-protective dose adjustments may lead to subtherapeutic dosing regimens in these patients. Overall, there was a tendency for hydrophilic agents, with a low protein binding to undergo elevated total clearance in these children. However, results should be interpreted with caution because of the large variability amongst patient populations and heterogeneity with CRRT modalities, flow rates, and use of extracorporeal membrane oxygenation within studies. This review was able to identify that variation in solute removal, or CRRT modalities, properties (i.e., flow rates), and membrane composition, may have differing effects on the pharmacokinetics of commonly administered medications. The current state of the literature regarding medications administered to children receiving CRRT largely focuses on antimicrobials. Significant gaps remain with other commonly used medications such as sedatives and analgesics. Overall reporting of patient clinical characteristics, CRRT settings, and circuit composition was poor, with only 10% of articles including all relevant information to assess the impact of CRRT on total clearance. Changes in pharmacokinetics because of CRRT often required higher than labeled doses, suggesting renally adjusted or reno-protective doses may lead to subtherapeutic dosing regimens. A thorough understanding of the interplay between patient, drug, and CRRT-circuit factors are required to ensure adequate delivery of dosing regimens to this vulnerable population.

Efficacy of Three Renal Replacement Therapy Modalities for the Treatment of Acute Kidney Injury Caused by Wasp Sting

Background/Aim: This study mainly aimed to explore the therapeutic effects of 3 renal replacement therapy (RRT) modalities on acute kidney injury (AKI) caused by wasp stings. Methods: A retrospective study from September 2016 to December 2019 was conducted. Thirty-one patients with AKIs caused by wasp sting were selected and divided into 3 groups according to the initial RRT modality received, namely, (1) the intermittent hemodialysis combined with hemoperfusion (IHD + HP) group, (2) the continuous veno-venous hemodiafiltration (CVVHDF) group, and (3) the CVVHDF combined with HP (CVVHDF + HP) group. The laboratory results were measured and analyzed before treatment on the 3rd, 7th, and 14th days of treatment. The renal function outcomes and survival of the patients were investigated at 3 months follow-up. Results: The laboratory results of enzyme measures and inflammatory indicators in wasp sting patients increased significantly in the early stage and 3 RRT modalities were effective in reducing these indicators. In addition, continuous RRT modality (CVVHDF and CVVHDF + HP) showed better clearance of myoglobin than IHD + HP. The serum creatinine levels of patients in the 3 groups did not recover to baseline within 14 days after beginning treatment. Nevertheless, the CVVHDF + HP group was better than the CVVHDF group, and CVVHDF was better than the IHD + HP group on the 3rd day. The interleukin (IL)-6 and IL-10 levels in CVVHDF + HP and IHD + HP groups were obviously lower than those in the CVVHDF group on the 3rd day. In the follow-up study, the recovery rate of renal function in CVVHDF and CVVHDF + HP groups was significantly better than that in the IHD + HP group. Conclusion: Early RRT was effective in the treatment of patients with A KI caused by wasp sting. CVVHDF + HP and CVVHDF modalities were better than the IHD + HP group in venom clearance and renal function recovery.