Continuous Renal Replacement Therapy Dose Research Articles

Successful Application of a Hemoperfusion Machine in Separated System CRRT: Evaluating Effectiveness and Safety in Critically Ill Patients With AKI in Resource-Limited Settings.

It is imperative to note that integrated system continuous renal replacement therapy (CRRT) necessitates a sophisticated and costly apparatus, potentially limiting its availability within resource-limited settings. The introduction of a separated system for continuous veno-venous hemofiltration (CVVH), characterized by uncomplicated setup procedures with a hemoperfusion machine, holds promise as a feasible alternative to CRRT for critically ill patients with acute kidney injury (AKI). We aimed to retrospectively analyze the effectiveness and safety of separated CRRT applied from a hemoperfusion machine in critically ill patients with AKI during the January 2015 to December 2021 period. We also examine the in-hospital mortality rate and multivariate logistic regression analysis to uncover the factors that affect mortality. We included a total of 129 critically ill patients who received separated system CRRT. The SOFA score at CRRT initiation was 12.6 ± 3.8. The fluid accumulation at the day of CRRT initiation was 3900 mL (622-8172 mL) All patients received pre- and postdilution CVVH. The mean prescribed CRRT dose was 22.4 ± 3.1 mL/kg/h. We found no serious complications including circuit explosion and air embolism. The in-hospital mortality rate was 68.9%. High SOFA score and positive fluid accumulation at CRRT initiation serve as predictors of survival. Separated system CRRT using a hemoperfusion machine provides a simplified system to operate and is proven to be effective and safe in real-life practice, especially in resource-limited areas.

Influence of utilizing hemodialysis membranes outside-in on solute clearance and filtration efficiency – One step towards a novel combined lung and kidney support device

Many membrane oxygenator patients suffer from renal disfunction. For these patients, a novel device integrating artificial lung and kidney support is being developed. Although outside-in blood flow is standard for membrane oxygenators, this is not typical for hemodialysis systems. The effect of outside-in blood flow on the efficiency of hemodialysis fibers for continuous hemodialysis and hemofiltration is yet unclear.This study evaluates the efficiency of commercial hemodialyzer membranes utilized outside-in compared to traditional inside-out mode regarding clearance of urea and creatinine, and ultrafiltration coefficient during in-vitro tests with porcine blood. Our results showed that dialyzers (1.2 m2, asymmetric hollow fibers) utilized outside-in had similar clearances of urea and creatinine compared to dialyzers used in the traditional mode (p > 0.7). However, outside-in dialyzers had an ultrafiltration coefficient four times lower than dialyzers applied in a conventional way, but adequate fluid removal could be achieved by controlling pressures in the system. This in-vitro study indicates that outside-in fibers could be sufficiently effective to maintain typical continuous renal replacement therapy doses. We regard this as one step towards a novel device with a mixed membrane fiber bundle utilizing blood flow outside both hemodialysis fibers and gas exchange fibers to provide simultaneous lung and kidney support.

Predictions of Serum Phosphate Concentration during Continuous Renal Replacement Therapy Using a Steady-State Mass Balance Model

Introduction: Hypophosphatemia is common during continuous renal replacement therapy (CRRT), but serum phosphate levels can potentially be maintained during treatment by either intravenous phosphate supplementation or addition of phosphate to renal replacement therapy (RRT) solutions. Methods: We developed a steady-state phosphate mass balance model to assess the effects of CRRT dose on serum phosphate concentration when using both phosphate-free and phosphate-containing RRT solutions, with emphasis on low CRRT doses. Results: The model predicted that measurements of serum phosphate concentration prior to (initial) and during CRRT (final) together with clinical data on CRRT dose, treatment duration, and phosphate supplementation can determine model patient parameters, that is, both the initial generation rate and clearance of phosphate prior to CRRT. Model parameters were then calculated from average patient data reported in several previous publications with a standard or high CRRT dose. Using representative model parameters for typical patients, predictions were then made of the effect of low CRRT dose on the change in serum phosphate levels after implementation of CRRT. The model predicted that CRRT at a low dose using phosphate-free RRT solutions will limit, but not eliminate, the incidence of hypophosphatemia. Further, the model predicted that CRRT at a low dose will have virtually no influence on the incidence of hyperphosphatemia when using phosphate-containing RRT solutions. Conclusions: This report identifies the clinical measurements to be used with the proposed model for individualizing the CRRT dose and RRT phosphate concentration to maintain serum phosphate concentrations in a desired range.

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.

Continuous Renal Replacement Therapy and Mortality in Critically Ill Obese Adults.

The outcomes of critically ill adults with obesity on continuous renal replacement therapy (CRRT) are poorly characterized. The impact of CRRT dose on these outcomes is uncertain. This study aimed to determine if obesity conferred a survival advantage for critically ill adults with acute kidney injury (AKI) on CRRT. Secondarily, we evaluated whether the dose of CRRT predicted mortality in this population. A retrospective, observational cohort study performed at an academic medical center in Minnesota. The study population included critically ill adults with AKI managed with CRRT. The primary outcome of 30-day mortality was compared between obese (body mass index [BMI] ≥ 30 kg/m2) and nonobese (BMI < 30 kg/m2) patients. Multivariable regression assessed was used to assess CRRT dose as a predictor of outcomes. An analysis included dose indexed according to actual body weight (ABW), adjusted body weight (AdjBW), or ideal body weight (IBW). Among 1033 included patients, the median (interquartile range) BMI was 26 kg/m2 (23-28 kg/m2) in the nonobese group and 36 kg/m2 (32-41 kg/m2) in the obese group. Mortality was similar between groups at 30 days (54% vs. 48%; p = 0.06) but lower in the obese group at 90 days (62% vs. 55%; p = 0.02). CRRT dose predicted an increase in mortality when indexed according to ABW or AdjBW (hazard ratio [HR], 1.2-1.16) but not IBW (HR, 1.04). In critically ill adults with AKI requiring CRRT, short-term mortality appeared lower in obese patients compared with nonobese patients. Among weight calculations, IBW appears to be preferred to promote safe CRRT dosing in obese patients.

Dynamic dosing for continuous renal replacement therapy: Service evaluation of the safety and effectiveness of titrating dose to biochemistry

Introduction: Continuous renal replacement therapy (CRRT) dose is usually fixed and primarily weight-based. Whilst this is safe, theoretically, underdosing or overdosing may occur in those requiring acute versus maintenance CRRT respectively. We have developed a dynamic dosing protocol for CRRT which individualises and updates dosing according to biochemistry. Here we describe the protocol and compare it to a fixed dose protocol to evaluate its safety and effectiveness. Methods: We conducted a service evaluation of this novel protocol using data from consecutive non-COVID-19 admissions receiving CRRT within Barts Health NHS trust, United Kingdom (UK). Fifty admissions using the dynamic protocol were compared to historically collected data from 108 admissions who used the fixed protocol. Acute and maintenance CRRT subgroups were analysed. Results: For the dynamic protocol 49 patients were treated with 135 CRRT circuits. One patient had two admissions. Protocol compliance (compared in one ICU) was 76% (dynamic) vs 61% (fixed) ( p &lt; 0.05). For the dynamic versus fixed protocol, median CRRT lifespan censored for reasons other than clotting was: 56 h vs 58 h RCA (ns), 27 h versus 20 h heparin (ns) and 79 h versus 22 h no anticoagulation ( p &lt; 0.05). The dynamic vs fixed protocol average CRRT dose was: 30 ml/kg/h (14–57) vs 26 ml/kg/h (20–62) ( p &lt; 0.05). The dynamic protocol generated a similar rate of increase of bicarbonate in an acute phase (RCA: 0.2 mmol/l/h vs 0.21 mmol/l/h, ns) and maintained a more stable level in a maintenance phase (RCA: −0.01 mmol/l/h vs 0.07 mmol/l/h, p &lt; 0.05). Discussion: Dynamic dosing for CRRT in this institution was safe and may lead to more tailored maintenance of biochemical homoeostasis.

Dose in continuous renal replacement therapy.

Continuous renal replacement therapy (CRRT) is one of the most used types of renal replacement therapies for the treatment of critically ill patients with acute kidney injury (AKI). Recent practice clinical guidelines based on recent clinical trials recommend a prescribed dose of 20-25 mL/kg/h of effluent since these trials could not find differences between high-intensity versus low-intensity CRRT dose and different outcomes as mortality and recovery of renal function. Nevertheless, the results of these recent trials do not mean that CRRT dose is not important, and on the contrary, these trials inform us that dose needs to be continuously assessed and modified according to clinical, metabolic, and physiological needs of each patient. Dose prescription in CRRT needs to be a dynamic and precise process, in which evidence-based quality measures will be used to guide CRRT dose prescription that will match daily patients needs. Delivered dose should be routinely monitored to ensure that it will be achieved. Quality measures for monitoring delivered dose of CRRT have been proposed, but they still need validation, before be implemented into clinical practice.

Role of Fat-Free Mass Index on Amino Acid Loss during CRRT in Critically Ill Patients.

Background and objectives: Amino acid (AA) loss is a prevalent unwanted effect of continuous renal replacement therapy (CRRT) in critical care patients, determined both by the machine set-up and individual characteristics. The aim of this study was to evaluate the bioelectrical impedance analysis-derived fat-free mass index (FFMI) effect on amino acid loss. Materials and methods: This was a prospective, observational, single sample study of critical care patients upon initiation of CRRT. AA loss during a 24 h period was estimated. Conventional determinants of AA loss (type and dose of CRRT, concentration of AA) and FFMI were entered into the multivariate regression analysis to determine the individual predictive value. Results: Fifty-two patients were included in the study. The average age was 66.06 ± 13.60 years; most patients had a high mortality risk with APAHCE II values of 22.92 ± 8.15 and SOFA values of 12.11 ± 3.60. Mean AA loss in 24 h was 14.73 ± 9.83 g. There was a significant correlation between the lost AA and FFMI (R = 0.445, B = 0.445 CI95%: 0.541-1.793 p = 0.02). Multivariate regression analysis revealed the independent predictors of lost AA to be the systemic concentration of AA (B = 6.99 95% CI:4.96-9.04 p = 0.001), dose of CRRT (B = 0.48 95% CI:0.27-0.70 p < 0.001) and FFMI (B = 0.91 95% CI:0.42-1.41 p < 0.001). The type of CRRT was eliminated in the final model due to co-linearity with the dose of CRRT. Conclusions: A substantial amount of AA is lost during CRRT. The amount lost is increased by the conventional factors as well as by higher FFMI. Insights from our study highlight the FFMI as a novel research object during CRRT, both when prescribing the dosage and evaluating the nutritional support needed.

Continuous renal replacement therapy is a safe and effective modality for the initial management of dogs with acute kidney injury.

To describe the management of dogs with acute kidney injury (AKI) by continuous renal replacement therapy (CRRT), and to investigate the relationship between a prescribed CRRT dose, the hourly urea reduction ratio (URR), and the overall efficacy. 45 client-owned dogs diagnosed with severe AKI, receiving 48 CRRT treatments at a veterinary teaching hospital. Retrospective study. Search of medical records of dogs with AKI managed by CRRT. Median serum urea and creatinine at CRRT initiation were 252 mg/dL [Inter quartile range (IQR), 148 mg/dL; range, 64 to 603 mg/dL] and 9.0 mg/dL (IQR, 7 mg/dL; range, 4.3 to 42.2 mg/dL), respectively. Median treatment duration was 21 hours (IQR, 8.8 hours; range, 3 to 32 hours). Systemic heparinization and regional citrate anticoagulation were used in 24 treatments each (50%). The prescribed median CRRT dose for the entire treatment was 1 mL/kg/min (IQR, 0.4 mL/kg/min; range, 0.3 to 2.5 mL/kg/min). The median hourly URR was 4% (IQR, 1%; range, 2% to 12%), overall URR was 76% (IQR, 30%; range, 11% to 92%) and median Kt/V was 2.34 (IQR, 1.9; range, 0.24 to 7.02). The CRRT dose was increased gradually from 0.9 mL/kg/min to 1.4 mL/kg/min (P < .001) and the hourly URR decreased from 6.5% to 5.5% (P = .05). The main complication was clotting of the extra-corporeal circuit, occurring in 6/48 treatments (13%). Twenty-four dogs (53%) survived to discharge. CRRT is safe when the prescription is based on the current veterinary guidelines for gradual urea reduction. Treatment efficacy can be maximized by gradually increasing the dose according to the actual URR.

CRRT-associated ketoacidosis: Aseriesof5cases.

Continuous renal replacement therapy (CRRT) is a dialysis modality used in critically ill patients with acute kidney injury (AKI). Although most dialysate and replacement fluids are dextrose-containing, CRRT-associated hypophosphatemia sometimes warrants the use of phosphorus-containing solutions which are dextrose free. The other less commonly used dextrose-free dialysate solutions are certain formulations of Prismasol and Prismasate. As glucose is a small molecule, which is readily cleared with dialysis, use of these solutions can result in increased caloric loss, net glucose deficit, and shifting of the metabolic pathway towards gluconeogenesis and ketogenesis. Starvation ketosis is usually a benign entity, however when combined with factors such as stress of critical illness, can produce metabolic acidosis which at times can be severe. We describe five patients who developed worsening metabolic acidosis despite adequate clearance from CRRT and were diagnosed with CRRT-associated ketoacidosis. Administration of dextrose-containing fluids or tube feeds promptly resulted in resolution of ketonemia and acidosis. Recognition of this entity is of great importance as the reflexive reaction to increase the prescribed dose of CRRT to improve the acidosis, in fact worsens the problem.

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.

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.

The importance of anticoagulation in COVID-19-related acute kidney injury requiring continuous renal replacement therapy

Introduction/Objective. In Serbia, the coronavirus disease 2019 (COVID-19) pandemic began in early March 2020. The aim of this study is to summarize clinical experience in the treatment of COVID-19-associated acute kidney injury by methods of continuous renal replacement therapy (CRRT) with the focus on the amount of the administered dose of unfractionated heparin. Methods. The study covers 12 patients treated with CRRT at the Clinic for Infectious Diseases at the Clinical Center of Vojvodina from March 6 to May 20, 2020. Antithrombotic prophylaxis, risk of venous thromboembolism (VTE), applied therapy, biochemical parameters before and after CRRT, anticoagulation and other CRRT parameters were analyzed. Results. The mean age of the patients was 61.54 ? 10.37 years and seven (58.3%) were men. All the patients received standard thromboprophylaxis. Nine (75%) patients had Padua Prediction Score for Risk of VTE ? 4, but none developed a thrombotic event. Seven critically ill patients with multi-organic dysfunction developed acute kidney injury dependent on CRRT. The mean CRRT dose was 36.6 ml/kg/h, the mean bolus dose of unfractionated heparin was 3250 ? 1138.18 IU, and the continuous dose was 1112.5 ? 334.48 IU/kg/h. Discontinuation of CRRT due to the clotting circuit was necessary in only one patient. The values of leukocytes, AST, ALT, GGT, aPTT, PT were significantly higher after CRRT compared to urea, creatinine, potassium, chlorine and magnesium, whose values were significantly lower. Conclusion. In our COVID-19 patients who had high inflammatory parameters and D-dimer and an estimated risk of developing deep vein thrombosis, the implementation pre-dilution continuous venovenous hemodiafiltration with antithrombotic membrane and 1/? to 1/? higher unfractionated heparin doses than the recommended one, the filter life lasted longer with no complications.

Methods for dose quantification in continuous renal replacement therapy: Toward a more precise approach

Periodic dose assessment is quintessential for dynamic dose adjustment and quality control of continuous renal replacement therapy (CRRT) in critically ill patients with acute kidney injury (AKI). The flows‐based methods to estimate dose are easy and reproducible methods to quantify (estimate) CRRT dose at the bedside. In particular, quantification of effluent flow and, mainly, the current dose (adjusted for dialysate, replacement, blood flows, and net ultrafiltration) is routinely used in clinical practice. Unfortunately, these methods are critically influenced by several external unpredictable factors; the estimated dose often overestimates the real biological delivered dose quantified through the measurement of urea clearance (the current effective delivered dose). Although the current effective delivered dose is undoubtedly more precise than the flows‐based dose estimation in quantifying CRRT efficacy, some limitations are reported for the urea‐based measurement of dose. This article aims to describe the standard of practice for dose quantification in critically ill patients with AKI undergoing CRRT in the intensive care unit. Pitfalls of current methods will be underlined, along with solutions potentially applicable to obtain more precise results in terms of (a) adequate marker solutes that should be used in accordance with the clinical scenario, (b) correct sampling procedures depending on the chosen indicator of transmembrane removal, (c) formulas for calculations, and (d) quality controls and benchmark indicators.

Clinical outcomes and prognostic factors of mortality in liver cirrhosis patients on continuous renal replacement therapy in two tertiary hospitals in Korea.

BackgroundData on liver cirrhosis (LC) patients undergoing continuous renal replacement therapy (CRRT) are lacking despite of the dismal prognosis. We therefore evaluated clinical characteristics and predictive factors related to mortality in LC patients undergoing CRRT.MethodsWe performed a retrospective observational study at two tertiary hospitals in Korea. A total of 229 LC patients who underwent CRRT were analyzed. Patients were classified into survivor and non-survivor groups. We used multivariable Cox regression analyses to identify predictive factors of in-hospital mortality.ResultsDuring a median follow-up of 5 days (interquartile range, 1–19 days), in-hospital mortality rate was 66.4%. In multivariable analysis, the Acute Physiology and Chronic Health Evaluation II (APACHE II) score (hazard ratio [HR], 1.03; 95% confidence interval [CI], 1.01–1.06; p = 0.02), Model for End-Stage Liver Disease (MELD) score (HR, 1.08; 95% CI, 1.04–1.11; p < 0.001), and delivered CRRT dose (HR, 0.95; 95% CI, 0.92–0.98; p = 0.002) were significant risk factors for in-hospital mortality. Patients with a CRRT delivered dose < 25 mL/kg/hr had a higher mortality rate than those with a delivered dose > 35 mL/kg/hr (HR, 3.13; 95% CI, 1.62–6.05; p = 0.001). Subgroup analysis revealed that a CRRT delivered dose < 25 mL/kg/hr was a significant risk factor for in-hospital mortality among LC patients with a MELD score ≥ 30.ConclusionHigh APACHE II score, high MELD score, and low delivered CRRT dose were significant risk factors for in-hospital mortality. CRRT delivered dose impacted mortality significantly, especially in patients with a MELD score ≥ 30.

CRRT prescription and delivery of dose.

Continuous renal replacement therapy (CRRT) is the preferred modality of extracorporeal renal support for critically ill patients with acute kidney injury (AKI). The dose of CRRT is reported as effluent flow in ml/kg body weight per hour (ml/kg/h). Solid evidence supports that the delivered CRRT effluent dose for critically ill patients with AKI should be 20-25ml/kg/h on average. To account for treatment interruptions and the natural decline in filter efficiency over time, it is recommended to prescribe 25-30ml/kg/h of effluent dose. However, transient higher doses of CRRT in specific clinical scenarios may be needed to accommodate specific solute control needs of a particular patient at a given time. Consequently, there should be consideration of the potential adverse consequences of non-selective clearance such as undesired antimicrobials and nutrients removal. In this manuscript, we provide a summary of evidence related to CRRT dose, practical aspects for its calculation at the time of prescribing CRRT, and considerations for addressing the expected gap between prescribed and delivered CRRT dose. We also provide a framework for monitoring and implementation of CRRT dose as a quality indicator of CRRT delivery.

Regional citrate anti-coagulation dose titration: impact on dose of continuous renal replacement therapy

Regional citrate anti-coagulation (RCA) is the recommended anti-coagulation for continuous renal replacement therapy (CRRT). Citrated replacement fluids provide convenience but may compromise effluent delivery when adjusted to maintain circuit ionised calcium levels (circuit-iCa). This study aims to evaluate the effect of RCA titration on the delivered CRRT effluent dose. This prospective observational study evaluated patients on RCA-CRRT in continuous veno-venous hemodiafiltration mode. Citrated replacement fluid was titrated to target circuit-iCa 0.26-0.40mmol/L. Patients were then stratified into 'reduced-dose' who required citrate down-titration and 'stable-dose' who did not. Data from 200 RCA-CRRT sessions were collected. The reduced-dose RCA group (n = 114) had higher median initial citrate dose (3.00 vs 2.50; P < 0.001) but lower time-averaged dose (2.49 vs 2.60; P < 0.001). In addition, median prescribed effluent dose was 33.3mL/kg/h (28.6-39.2) but median delivered effluent dose was significantly lower at 29.9mL/kg/h (25.4-36.9; P < 0.001). Mortality was higher in the reduced-dose RCA group (39.5% vs 25.6%; P = 0.022) and in patients with delivered-to-prescribed effluent dose ratio of < 0.9 vs ≥ 0.9 (51.3% vs 29.2%; P = 0.014). RCA titration can significantly impact delivered CRRT effluent dose. Measures should be taken to address the CRRT dose deficit and prevent poor outcomes due to inadequate dialysis.

Continuous renal replacement therapy principles.

Continuous renal replacement therapy (CRRT) is an extracorporeal blood purification therapy that aims to support kidney function over an extended period of time. One of the main objectives of CRRT is the removal of excess fluid and solutes retained as a consequence of acute kidney injury. Because prescription of CRRT requires goals to be set with regard to the rate and extent of solute and fluid removal, a comprehensive understanding of the mechanism by which solute and fluid removal occurs during CRRT is essential. Basic mechanisms of fluid transport and solute removal (ultrafiltration, diffusion, convection, and adsorption) and the factors influencing these processes in CRRT are described. From the combination of the different transport mechanisms, a number of CRRT modalities are identified and described. Finally, these principles are applied to provide a brief overview of the concept of effluent-based CRRT dose.

Renal replacement therapy in intensive care units in KwaZulu-Natal Province, South Africa.

Background Renal replacement therapy (RRT) is a scarce resource in southern Africa. Critically ill patients are at risk of developing acute kidney injury (AKI), which may require RRT. There are few data on the utilisation of RRT in southern African intensive care units (ICUs). Objectives To determine the indications for initiating RRT in critically ill patients in ICUs in KwaZulu-Natal, South Africa (SA) and to describe the methods and dosing of RRT. Methods A prospective observational study was performed to investigate the indications for initiating, methods and dosing of RRT among patients admitted to four ICUs in KwaZulu-Natal Province, SA. All adult patients were eligible for inclusion. Results A total of 108 patients who received RRT were included in the study. The most common reasons for initiation of RRT were a high/rising creatinine, high/rising urea, acidosis and fluid balance. The majority of the patients (79.6%; n=86) had three or more indications for RRT. A total of 353 intermittent haemodialysis/slow low-efficiency dialysis (IHD/SLED) sessions and 84 continuous renal replacement therapy (CRRT) sessions were recorded. The median (interquartile range (IQR)) CRRT dose was 25.8 (19.1 - 28.8) mL/kg/h. The median (IQR) urea reduction ratio for IHD/SLED was 32.4% (15.0 - 49.8). Conclusion Patients in this study had multiple indications for initiating RRT. The dosing of RRT was not optimal, with a wide range shown in CRRT, and the majority of patients did not achieve a urea reduction ratio (URR) >65%. Contributions of the study Renal replacement therapy is a scarce resource in Africa. Little is known about the current types and dosing of RRT in critical care units in South Africa. We showed that critically ill patients had multiple indications for RRT and the dosing was not optimal.

Optimizing ceftaroline dosing in critically ill patients undergoing continuous renal replacement therapy.

Currently, no dosing information exists for ceftaroline fosamil in patients undergoing continuous renal replacement therapy (CRRT). The objectives of this study are to characterize the pharmacokinetics of ceftaroline in critically ill patients undergoing CRRT modalities and to derive individualized dosing recommendations. This pharmacokinetic study aimed to enroll critically ill patients receiving ceftaroline fosamil and any CRRT modality from adult intensive care units. Selection of the specific CRRT modality and dosing regimen was based on clinical discretion. Pre-filter, post-filter, and ultrafiltrate samples were obtained before the administration of the fourth dose, after the completion of the infusion, and up to five additional time points post-infusion. Plasma concentrations were measured using a validated ultra-high performance liquid chromatography assay. Individual pharmacokinetic parameters were calculated using non-compartmental analysis. Four patients were enrolled to investigate the need for dosing adjustments. The average sieving coefficient for ceftaroline was 0.81±0.1, indicating high filter efficiency. The average volume of distribution was 41.8 L (0.48 L/kg) and is within the previously reported range in patients with normal renal function. Non-renal clearance accounted for more than 50% of the total clearance observed in patients. The observed pharmacokinetic profiles suggest that the pharmacodynamic target for 2-log10 CFU reduction from baseline (%fT >1mg/L of 50%) was met for each patient. Due to the impact of CRRT and non-renal clearance, dosing recommendations were derived for different ranges of effluent flow rates and adjusted body weights. For a patient with an adjusted body weight of 70kg and receiving CRRT at an effluent flow rate of 3 L/h, a ceftaroline fosamil dosing regimen of 400mg every 12 h is proposed. Ceftaroline is cleared extensively in critically ill patients receiving CRRT and may impact pharmacodynamic target achievement. Dose adjustments should be based on the intensity of the CRRT regimen, patient weight, and the clinical status of the patient.