Continuous Renal Replacement Therapy Prescription Research Articles

Managing the kidney – The role of continuous renal replacement therapy in neonatal and pediatric ECMO

Extracorporeal membrane oxygenation (ECMO) represents a lifesaving therapy utilized in in the most critically ill neonates and children with reversible cardiopulmonary failure. As a result of the severity of their critical illness these patients are among the highest risk populations for developing acute kidney injury (AKI) and disorders of fluid balance including the pathologic state of fluid overload (FO). In multiple studies AKI has been shown to occur commonly in 60-80% children treated with ECMO and is associated with adverse outcomes. In early studies evaluating ECMO in neonatal respiratory populations, the importance of fluid balance and the development of FO was recognized as an important contributor to adverse outcomes. Multiple single center studies and multicenter work have confirmed that FO occurs commonly across ECMO populations and is consistently associated with adverse outcomes. As a result of the high rates of AKI and the high rates of FO, continuous renal replacement therapy (CRRT) is increasingly utilized in neonatal and pediatric ECMO. In this state-of-the-art review, we cover the definitions, pathophysiology, incidence, and impact of AKI and FO in neonates and children supported with ECMO and summarize and appraise the evidence regarding the use of CRRT concurrently with ECMO. This review will cover the appropriate timing of this initiation, the options for providing CRRT with ECMO, overview of CRRT prescription, and the long-term implications of kidney support therapy in this population.

Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease (WE-ROCK)

Continuous renal replacement therapy (CRRT) is used for the symptomatic management of acute kidney injury (AKI) and fluid overload (FO). Contemporary reports on pediatric CRRT are small and single center in design. Large international studies evaluating CRRT practice and outcomes are lacking. Herein, we describe the design of a multinational collaborative. The Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease (WE-ROCK) is an international collaborative of pediatric specialists whose mission is to improve short- and long-term outcomes of children treated with CRRT. The aims of this multicenter retrospective study are to describe the epidemiology, liberation patterns, association of fluid balance and timing of CRRT initiation, and CRRT prescription with outcomes. We included children (n= 996, 0-25 years) admitted to an intensive care unit (ICU) and treated with CRRT for AKI or FO at 32 centers (in 7 countries) from 2018 to 2021. Demographics and clinical characteristics before CRRT initiation, during the first 7 days of both CRRT, and liberation were collected. Outcomes include the following: (i) major adverse kidney events at 90 days (mortality, dialysis dependence, and persistent kidney dysfunction), and (ii) functional outcomes (functional stats scale). The retrospective WE-ROCK study represents the largest international registry of children receiving CRRT for AKI or FO. It will serve as a broad and invaluable resource for the field of pediatric critical care nephrology that will improve our understanding of practice heterogeneity and the association of CRRT with clinical and patient-centered outcomes. This will generate preliminary data for future interventional trials in this area.

Safely correct hyponatremia with continuous renal replacement therapy: A flexible, all-purpose method based on the mixing paradigm.

Treating chronic hyponatremia by continuous renal replacement therapy (CRRT) is challenging because the gradient between a replacement fluid's [sodium] and a patient's serum sodium can be steep, risking too rapid of a correction rate with possible consequences. Besides CRRT, other gains and losses of sodium- and potassium-containing solutions, like intravenous fluid and urine output, affect the correction of serum sodium over time, known as osmotherapy. The way these fluids interact and contribute to the sodium/potassium/water balance can be parsed as a mixing problem. As Na/K/H2 O are added, mixed in the body, and drained via CRRT, the net balance of solutes must be related to the change in serum sodium, expressible as a differential equation. Its solution has many variables, one of which is the sodium correction rate, but all variables can be evaluated by a root-finding technique. The mixing paradigm is proved to replicate the established equations of osmotherapy, as in the special case of a steady volume. The flexibility to solve for any variable broadens our treatment options. If the pre-filter replacement fluid cannot be diluted, then we can compensate by calculating the CRRT blood flow rate needed. Or we can deduce the infusion rate of dextrose 5% water, post-filter, to appropriately slow the rise in serum sodium. In conclusion, the mixing model is a generalizable and practical tool to analyze patient scenarios of greater complexity than before, to help doctors customize a CRRT prescription to safely and effectively reach the serum sodium target.

Continuous Renal Replacement Therapy in Critically Ill Children in the Pediatric Intensive Care Unit: A Retrospective Analysis of Real-Life Prescriptions, Complications, and Outcomes.

Introduction: Severe acute kidney injury is a common finding in the Pediatric Intensive Care Unit (PICU), however, Continuous Renal Replacement Therapy (CRRT) is rarely applied in this setting. This study aims to describe our experience in the rate of application of CRRT, patients' clinical characteristics at admission and CRRT initiation, CRRT prescription, predictors of circuit clotting, short- and long-term outcomes.Methods: A 6-year single center retrospective study in a tertiary PICU.Results: Twenty-eight critically ill patients aged 0 to 18 years received CRRT between January 2012 and December 2017 (1.4% of all patients admitted to PICU). Complete clinical and CRRT technical information were available for 23/28 patients for a total of 101 CRRT sessions. CRRT was started, on average, 40 h (20–160) after PICU admission, mostly because of fluid overload. Continuous veno-venous hemodiafiltration and systemic heparinization were applied in 83.2 and 71.3% of sessions, respectively. Fifty-nine sessions (58.4%) were complicated by circuit clotting. At multivariate Cox-regression analysis, vascular access caliber larger than 8 Fr [HR 0.37 (0.19–0.72), p = 0.004] and regional citrate anticoagulation strategy [HR 0.14 (0.03–0.60), p = 0.008] were independent protective factors for clotting. PICU mortality rate was 42.8%, and six survivors developed chronic kidney disease (CKD), within an average follow up of 3.5 years.Conclusions: CRRT is uncommonly applied in our PICU, mostly within 2 days after admission and because of fluid overload. Larger vascular access and citrate anticoagulation are independent protective factors for circuit clotting. Patients' PICU mortality rate is high and survival often complicated by CKD development.

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.

The future of continuous renal replacement therapy.

Over the last 40years, acute renal replacement therapy (RRT) in the intensive care units (ICUs) of high-income countries has transitioned from the predominant use of intermittent hemodialysis (and the much less common use of peritoneal dialysis) to the almost exclusive use of continuous renal replacement therapy (CRRT). Accordingly, CRRT has become the most common form of vital organ support delivered to critically ill patients. A series of clinical and technical advances has enabled the transformation of basic CRRT machines into highly sophisticated and customized devices. Recent work has focused on using evidence from clinical trials to enhance the application of CRRT with regard to timing of initiation, choice of modality, dose, and anticoagulation. However, many questions remain unanswered. Uncertainty surrounding volume control and the utility of strategies to minimize circulatory stress are key areas for future development. Advances in membrane technology, combination with other extracorporeal therapies, and personalization of CRRT delivery may provide additional benefit to certain subgroups. Development of quality metrics and use of data analytics to audit and benchmark could provide important insight into practice, while biofeedback and automated CRRT prescription could increase safety. In this review, we summarize the evolution of CRRT and highlight several future areas for development.

Variation of High-Sensitivity Troponin T Results in Patients Undergoing Continuous Renal Replacement Therapy.

Background:Cardiac troponins are the preferred biomarker to diagnose myocardial injury. Complicating the interpretation of serial troponins in patients with end-stage renal disease, it has been shown that the hemodialysis procedure results in a small but significant decline in high-sensitivity cardiac troponins (hs-cTnT). This raises the possibility that continuous renal replacement therapy (CRRT) might similarly alter cardiac troponin levels and affect their interpretation when cardiac ischemia is being considered.Objective:We sought to determine the effect of CRRT on hs-cTnT levels over time in a group of patients without active myocardial injury.Design:Prospective, observational studySetting:Single tertiary care hospital, Montreal, QuebecPatients:Ten critically ill patients with acute kidney injury (AKI) undergoing CRRT. Cardiac ICU (intensive care unit) patients and acute coronary syndrome patients were excluded from the study. The CRRT prescription was at the discretion of the treating intensivist and relatively high doses were used in this study.Measurements:The hs-cTnT levels were drawn pre-CRRT, within 6 hours of initiation, and approximately every 6 hours thereafter along with routine CRRT blood work.Methods:Changes in hs-cTnT, creatinine, and albumin levels were recorded over the course of CRRT. Mean change in serum analyte concentration and 95% confidence interval was determined for specified time intervals relative to baseline, with paired t tests used to determine statistical significance.Results:Among the 10 patients included in the study, the cause of AKI was primarily acute tubular necrosis from septic shock or hemorrhagic shock. Compared with baseline hs-cTnT levels prior to CRRT initiation, mean hs-cTnT level fell by 42% at 5 to 10 hours post-CRRT initiation, followed by a plateauing of levels for the duration of time on CRRT.Limitations:Single-center study only applicable to hs-cTnT assay.Conclusions:This study demonstrates a significant decrease in hs-cTnT within 5 to 10 hours of CRRT initiation. This suggests that interpretation of cardiac troponin changes during CRRT must take into consideration the timing of dialysis initiation relative to the time of sample collection.

Continuous renal replacement therapy: individualization of the prescription.

Continuous renal replacement therapy (CRRT) is now the mainstay of renal organ support in the critically ill. As our understanding of CRRT delivery and its impact on patient outcomes improves there is a focus on researching the potential benefits of tailored, patient-specific treatments to meet dynamic needs. The most up-to-date studies investigating aspects of CRRT prescription that can be individualized: CRRT dose, timing, fluid management, membrane selection, anticoagulation and vascular access are reviewed. The use of different doses of CRRT lack conventional high-quality evidence and importantly studies reveal variation in assessment of dose delivery. Research reveals conflicting evidence for clinicians in distinguishing which patients will benefit from 'watchful waiting' vs. early initiation of CRRT. Both dynamic CRRT dosing and precision fluid management using CRRT are difficult to investigate and currently only observational data supports individualization of prescriptions. Similarly, individualization of membrane choice is largely experimental. Clinicians have limited evidence to individualize the prescription of CRRT. To develop this, we need to understand the requirements for renal support for individual patients, such as electrolyte imbalance, fluid overload or clearance of systemic inflammatory mediators to allow us to target these abnormalities in appropriately designed randomized trials.

Abstract P-059: INTER-PROFESSIONAL EDUCATION IN PEDIATRIC CRRT SIMULATION

Aims & Objectives: Continuous renal replacement therapy (CRRT) is an advanced treatment frequently required to support the critically ill children. Healthcare professionals usually encounter some difficulties and disharmony to deliver an effective and safe care to the children in PICU. The aim of this work was the assessment of the effectiveness and safety of multidisciplinary team work and determination of the problems of the pediatric CRRT collaborative practice through the inter-professional education (IPE) simulation sessions. Methods Different pediatric CRRT simulation scenarios were conducted within a full day workshop as well as in-site in pediatric ICU in our center without prior notification to our candidates every few weeks. The candidates of those simulation sessions were pediatric nephrology physicians, intensivists, nurses, CRRT technicians and clinical pharmacists. The participants’ performance and the Inter-professional education (IPE) core competencies were assessed. Two forms were filled one by the participants after the sessions and the other by the facilitators from their direct observation of the team performance during the sessions. Results We conducted three parallel simulation sessions during the workshop and two in-site simulation sessions. Two major themes were emerged from this study. First theme was the prolonged time taken to transmit the CRRT prescription from the protocol to the machine. Second theme was the good harmony among the different professionals to deliver the treatment. Conclusions The author concluded that PCRRT simulation is an effective training method to enhance the quality of children care among the IPE. Team members involved in the simulation became more confident and comfortable to deliver the CRRT.

Ensuring Quality of Care through Monitoring of Continuous Renal Replacement Therapies.

The continuous renal replacement therapy (CRRT) has offered life-saving treatment for kidney failure. Technological advances coupled with findings from clinical trials have allowed for refinements both in the therapy and in the way it is applied to patients. However, outcomes for patients requiring CRRT remain suboptimal. The use of information technology coupled with structured quality improvement programs offers a methodology for studying the delivery of CRRT with an eye toward improving outcomes. Furthermore, integration of information from the CRRT treatment can be combined with real-time data from other patient-monitoring sources to create "feedback" loops where more timely changes in the CRRT prescription can occur. It is hoped that these advances may lead to further improvements in patient outcomes.

Acute kidney injury in cancer patients and impedance cardiography-assisted renal replacement therapy: Experience from the onconephrology unit of a Chinese tertiary hospital.

Acute kidney injury (AKI) in cancer patients may disrupt anticarcinogenic treatment and greatly increase associated mortality rates. The present study reported on the management of cancer patients with AKI and, from the nephrologic viewpoint, on the significance of fine volume control during the continuous renal replacement therapy (CRRT). The records of 117 cancer patients with AKI treated over three years were reviewed and their data were compared with those of 120 healthy controls. AKI was defined according to the Kidney Disease: Improving Global Outcomes criteria with serum creatinine levels determined on initial admission and for the diagnosis of AKI. CRRT with concomitant impedance cardiography (ICG) monitoring was performed in 79 patients. On average, AKI manifested as a 1.68±0.38-fold increase in serum creatinine within 10.2±5.7 days. The causes of AKI were diverse, with the major ones being nephrotoxic agents, hypotension and obstructive nephropathy. Renal biopsy confirmed two cases of thrombotic microangiopathy, due to the use of interfon-α and sunitinib malate, respectively, and a third case of cast nephropathy caused by immunoglobulin D multiple myeloma. The patients were generally marantic and had compromised cardiac function compared with the healthy controls. The CRRT prescription was discriminatingly optimized by the ICG parameters effecting discreet fluid balance, as the thoracic fluid content was significantly correlated with the ultrafiltration rate. By considering the causative mechanisms and applying subtle ICG-assisted volume control, the present study may thus help to improve the safety and efficacy of CRRT in cancer patients with AKI. In addition, it provided information to bring advances in onconephrology, a novel nephrological subspecialty field.

Serum sodium shift in hyponatremic patients undergoing liver transplantation: a retrospective cohort study

Introduction: We aimed to describe the pre-operative incidence of hyponatremia in patients undergoing liver transplantation (LTx), as well as the rate and consequences of rapid peri-operative sodium rises in these patients. Methods: This was a retrospective before and after observational study performed at a University-affiliated LTx center between January 2007 and June 2013. The primary exposure was pre-operative hyponatremia, defined as a serum sodium (SNa) <133 mmol/L. The primary outcome was occurrence of a rapid SNa shift, defined as ≥10 mmol/L in the first 24 h following LTx. The rates of rapid peri-operative SNa shift were compared before and after a focused quality assurance (QA) initiative performed in July 2009. Results: Of 366 LTx, 69 (18.9%) had pre-operative hyponatremia, 6 (8.7%) of whom had a rapid rise in serum sodium (SNa). Rapid rise was associated with a greater intra-operative positive fluid balance (p < 0.001) and use of intra-operative continuous renal replacement therapy (CRRT) (p = 0.017). A rapid rise in SNa was associated with more neurological investigations in the post-transplant period (brain computed tomography, electroencephalogram, swallow studies), increased neurological deficits (p = 0.006), more abnormal swallowing assessments (p = 0.003), a tendency for more neurology consultations (p = 0.058), increased discharge to a rehabilitation or long-term care facility (p < 0.001), and increased 6-month mortality (p < 0.001). Following a QA initiative, rapid peri-operative rises in SNa among hyponatremic patients was significantly reduced (20% vs. 0%, p < 0.003). Conclusion: Pre-operative hyponatremia and rapid peri-operative SNa shifts are associated with a more complicated post-operative course and worse outcomes following LTx. Increased education and awareness, along with process changes, such as standardizing CRRT prescription, can reduce iatrogenic rapid peri-operative shifts in SNa.

Meropenem in children receiving continuous renal replacement therapy: clinical trial simulations using realistic covariates.

Meropenem is frequently prescribed in children receiving continuous renal replacement therapy (CRRT). Fluid overload is often present in critically ill children and affects drug disposition. The purpose of this study was to develop a pharmacokinetic model to (1) evaluate target attainment of meropenem dosing regimens against P. aeruginosa in children receiving CRRT and (2) estimate the effect of fluid overload on target attainment. Clinical trial simulations were employed to evaluate target attainment of meropenem in various age groups and degrees of fluid overload in children receiving CRRT. Pharmacokinetic parameters were extracted from published literature, and 287 patients from the prospective pediatric CRRT registry database provided realistic clinical covariates including patient weight, fluid overload, and CRRT prescription characteristics. Target attainment at 40% and 75% time above the minimum inhibitory concentration was evaluated. Clinical trial simulations demonstrated that children greater than 5 years of age achieved acceptable target attainment with a dosing regimen of 20 mg/kg every 12 hours. In children less than 5, however, increased dosing of 20 mg/kg every 8 hours was needed to optimize target attainment. Fluid overload did not affect target attainment. These in silico model predictions will need to be verified in vivo in children receiving meropenem and CRRT.

In Vitro Glucose Kinetics during Continuous Renal Replacement Therapy: Implications for Caloric Balance in Critically Ill Patients

To examine the impact of continuous renal replacement therapy (CRRT) on glucose kinetics and therefore caloric balance. In vitro experiments were conducted to characterize glucose kinetics in a variety of CRRT modalities and prescriptions. Additional experiments evaluated the impact of citrate anticoagulation using anti-coagulant dextrose solution A (ACD-A) on CRRT glucose movement. A formula was developed to predict the glucose delivery to/from the patient per day of CRRT, and this data was extrapolated to determine the net caloric impact of CRRT. A total of 104 experiments were conducted with an overall glucose extraction coefficient of 1.04 (95% CI 1.03-1.05). CRRT-related glucose removal was directly related to effluent (dialysate and/or hemofiltration) rate and pre-filter blood glucose concentration, and inversely related to dialysis solution glucose concentration. In all modalities tested, CRRT resulted in a net negative glucose balance, with estimated caloric losses ranging between 20 kcal and 550 kcal depending on the conditions tested. The addition of ACD-A resulted in net glucose delivery in some conditions and a positive caloric balance of up to 470 kcal per day. CRRT can have a significant effect on glucose balance and result in either significant daily caloric gains or losses, and this effect can be predicted based on CRRT prescription and patient characteristics. Clinicians should be aware of this potential impact when prescribing nutritional therapy to patients undergoing CRRT, as an imbalance in caloric feeding can adversely affect outcomes in critically ill patients.

Continuous Renal Replacement Therapy for Children ≤10 kg: A Report from the Prospective Pediatric Continuous Renal Replacement Therapy Registry

To report circuit characteristics and survival analysis in children weighing ≤10 kg enrolled in the Prospective Pediatric Continuous Renal Replacement Therapy (ppCRRT) Registry. We conducted prospective cohort analysis of the ppCRRT Registry to: (1) evaluate survival differences in children ≤10 kg compared with other children; (2) determine demographic and clinical differences between surviving and non-surviving children ≤10 kg; and (3) describe continuous renal replacement therapy (CRRT) circuit characteristics differences in children ≤5 kg versus 5-10 kg. The ppCRRT enrolled 84 children ≤10 kg between January 2001 and August 2005 from 13 US tertiary centers. Children ≤10 kg had lower survival rates than children >10 kg (36/84 [43%] versus 166/260 [64%]; P<.001). In children ≤10 kg, survivors were more likely to have fewer days in intensive care unit prior to CRRT, lower Pediatric Risk of Mortality 2 scores at intensive care unit admission and lower mean airway pressure (P(aw)), higher urine output, and lower percent fluid overload (FO) at CRRT initiation. Adjusted regression analysis revealed that Pediatric Risk of Mortality 2 scores, FO, and decreased urine output were associated with mortality. Compared with circuits from children 5-10 kg at CRRT initiation, circuits from children ≤5 kg more commonly used blood priming for initiation, heparin anticoagulation, and higher blood flows/effluent flows for body weight. Mortality is more common in children who are ≤10 kg at the time of CRRT initiation. Like other CRRT populations, urine output and FO at CRRT initiation are independently associated with mortality. CRRT prescription differs in small children.

Distinction between induction and maintenance dosing in continuous renal replacement therapy

In their excellent review of dosing continuous renal replacement therapy (CRRT), Dr Prowle and colleagues concluded that patients should be prescribed 20 to 25 ml/kg/h [1]. However, by averaging CRRT dose over time, studies in this area obfuscate the benefits of appropriately higher dose therapy early in the course of illness, potentially misguiding clinicians into blindly adopting a 'one-size-fits-all' approach and consequently prescribing inadequate doses in life-threatening emergencies. To take a crude example, it would be inappropriate to prescribe 20 ml/kg/h CRRT in a patient with serum potassium 9 mmol/L. Rather, the highest possible dose of CRRT should be initially prescribed to maximize solute clearance. This depends on the maximum circuit flow permitted by the access catheter, which in turn determines the maximum dose, assuming that the countercurrent flow to blood flow ratio should be <0.3 with diffusive CRRT, or a filtration fraction with convective therapy <0.2 [2]. As the potassium level falls, the dose can be lowered to more conventional levels. Parallels could be drawn to general anaesthesia, where induction and maintenance are two distinct phases with different requirements. CRRT prescription could similarly be conceptualized as 'induction', where life-threatening abnormalities are corrected quickly with high-dose therapy, then 'maintenance' where solute clearance is achieved with more temperate doses (for example, 20 to 25 ml/kg/h) to avoid complications such as hypophosphataemia. It seems unlikely that this issue will be the subject of prospective research. Yet the principle that faster correction of life-threatening abnormalities leads to better patient outcomes seems both practical and intuitive.

Middle-Molecule Clearance at 20 and 35 ml/kg/h in Continuous Venovenous Hemodiafiltration

Background: Of 5 clinical trials testing dose response of continuous renal replacement therapy (CRRT) in acute kidney injury, 2 showed a benefit, 2 showed none, and 1 appeared equivocal. However, blood-membrane interactions may dominate macromolecule transport in continuous venovenous hemodiafiltration, reducing the impact of dose adjustment. The dosing arms in the Acute Renal Failure Trial Network (ATN) study may have delivered similar clearances for middle molecules. Methods: We simulated the 2 CRRT doses in the ATN study using a synthetic polydisperse macromolecular probe in bovine blood. Clearance of tracers between 10 and 100 kDa molecular weight was measured during 6 h of therapy. Results: Middle-molecule clearance differed by less than 2 ml/min between the 2 dosing arms. Conclusion: The CRRT prescription used in the ATN study appears to have achieved dose separation for small molecules while holding middle-molecule clearance nearly constant. This may explain the outcome difference between the ATN study and earlier studies, and suggests subsequent trial designs.

Circuit lifespan during continuous renal replacement therapy: children and adults are not equal

In the field of continuous renal replacement therapy (CRRT), session length, downtime and dose require detailed research, which will provide information important in relation to prescription, anticoagulation and circuit material choice (membrane type and size, vascular access site and size). In particular, it appears that many of the data currently existing in the literature and accepted regarding CRRT prescription and delivery in critically ill adult patients are not strictly applicable to the paediatric setting. Furthermore, many of the available paediatric studies are small, retrospective or underpowered. In paediatric CRRT, epidemiological investigations and prospective trials to investigate practical aspects of extracorporeal therapies are welcome and urgently needed.