Continuous Renal Replacement Therapy System Research Articles

Incidence of Thrombocytopenia With Different Continuous Renal Replacement Systems and Modalities in a Cardiac Intensive Care Unit.

Background: Thrombocytopenia is due to multifactorial causes in critically ill patients. One etiology is continuous renal replacement therapy (CRRT); however, it is unknown if different modalities impact the incidence. Objectives: To compare the incidence of thrombocytopenia with the NxStage CRRT system using continuous venovenous hemodialysis (CVVHD) compared to the Prismaflex system using continuous venovenous hemodiafiltration (CVVHDF). Methods: This was a retrospective cohort study at a large academic medical center in the United States. Individuals aged 18 or older admitted to the cardiovascular ICU between June 1, 2016 and September 30, 2022, and received CRRT for at least 48hours were identified. Results: One hundred and forty-seven patients met inclusion criteria. Sixty-one patients received CVVHD with the NxStage system, while 86 received CVVHDF with the Prismaflex system. Thrombocytopenia occurred in 57.4% of patients treated with NxStage vs 19.8% treated with Prismaflex (OR 5.46; 95% confidence interval [CI], 2.62-11.39). These results were consistent in an adjusted model (OR 5.57; 95% CI, 2.34-13.28). There was no difference in the time to thrombocytopenia between groups. Patients treated with the NxStage system had lower platelet nadirs, more heparin-induced thrombocytopenia testing, more direct thrombin inhibitor use, and more blood transfusions. Conclusions: A greater incidence of thrombocytopenia occurred in cardiovascular ICU patients treated with CVVHD using the NxStage system vs CVVHDF with the Prismaflex system.

Modern CRRT systems are associated with lower risk of hypothermia.

One risk of continuous renal replacement therapy (CRRT) is inadvertent hypothermia (IH), which is defined as a non-therapeutic core temperature decrease below normal. In continuous renal replacement therapy, heat loss will always occur from blood pumped through the dialysis circuit to cooler environment, predisposing for hypothermia. Blood flow and effluent flows are the most important parameters causing heat loss. We investigated and compared the novel TherMax warmer to previous generation technologies during CRRT in a multicenter setting. This was a prospective observational multicenter study with historic single-center controls. The study group consisted of 100 patients in eight Swedish ICUs with clinical indication for CRRT, using the PrisMax platform and TherMax warmer. Both patient and set warmer temperatures were recorded hourly for the first 24h. The presence of treatment hours in hypothermia (< 36.0 Celsius) and the difference between set warmer temperature and measured patient temperature in the multi-center study cohort were compared to a matched single-center historic control cohort treated with the old Prismaflex platform and adjacent Barkey warmer. In the TherMax group 77/100 (77.0%) of patients, and for controls 26/86 (30.2%) of patients were free of hypothermia (Chi square, p < 0.001). The mean number of hours spent in hypothermia was (mean ± SD) 0.66 ± 1.60 and 6.92 ± 7.79h in the TherMax and control groups, respectively (Chi square p < 0.001).In the study group the patient temperature was higher than the set temperature on the warmer with a difference of Δ0.47 ± 0.80°C (minor difference), whereas in the control group the set temperature on the warmer was higher than the patient temperature with a difference of Δ4.55 ± 1.00°C (over-correction).The novel TherMax warmer technology protected against hypothermia and was significantly more accurate than the Barkey warmer.

Dialoxygenation: A Preclinical Trial for Transforming the Artificial Kidney Into an Oxygenator.

Critically ill patients sometimes require tandem application of extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT) which is easier and cheaper. We aimed to transform the kidney membrane into a lung membrane by adding hydrogen peroxide (H 2 O 2 ) to the dialysate as the oxygen source. A solution containing H 2 O 2 and a dialysate fluid mixture was used as the final dialysate. Starting with 100% H 2 O 2 solution and gradually reducing the volume of H 2 O 2 , respectively: 50%, 10%, 5%, 4%, 3%, 2%, and 1%. PRISMAFLEX system, Prismaflex M60 set and a bag of packed red blood cells (pRBCs) were the prototype. blood flow rate was about 40 ml/minute and the dialysis rate was about 200 ml/m 2 /minute/1.73 m 2 . blood sampling times were; at the beginning ( T0 ), at 15th ( T1 ), 30th ( T2 ), 60th ( T3 ) minutes. Amongst eight attempts H 2 O 2 concentration that increased the partial oxygen pressure (pO 2 ) level significantly in a reasonable period, without any bubbles, was 3%. Methemoglobinemia was not observed in any trial. After the test with 3%, H 2 O 2 in the dialysate fluid decreased progressively without any H 2 O 2 detection at post-membrane blood. Three percent H 2 O 2 solution is sufficient and safe for oxygenation in CRRT systems. With this new oxy-dialysate solution, both pulmonary and renal replacement can be possible viaa single membrane in a simpler manner.

Cytokine adsorption in patients with acute-on-chronic liver failure (CYTOHEP): A single center, open-label, three-arm, randomized, controlled intervention pilot trial.

To investigate the efficacy of bilirubin reduction by hemoadsorption with CytoSorb® in patients with acute-on-chronic liver failure (ACLF) receiving continuous renal replacement therapy (CRRT). A prospective, randomized, single-center, open-label, controlled pilot trial. Patients with ACLF, acute kidney injury, and serum bilirubin ≥5 mg/dL were assigned 1:1:1 to one of three study groups (CRRT with or without hemoadsorption, no CRRT). In the hemoadsorption group, the CytoSorb adsorber was incorporated into the CRRT system, replaced after 12, 24, and 48 h, and removed after 72 h. The primary endpoint was the serum bilirubin level after 72 h. CYTOHEP was terminated early due to difficulties in recruiting patients and ethical concerns. Three of 9 patients (33%) were treated in each group. Comparing the three groups, mean bilirubin levels after 72 h were lower by -8.0 mg/dL in the "CRRT with hemoadsorption" group compared to "CRRT without hemoadsorption" (95% CI, -21.3 to 5.3 mg/dL; p = 0.17). The corresponding mean difference between "CRRT without hemoadsorption" and "no CRRT" was -1.4 mg/dL (95% CI, -14.2 to 11.5 mg/dL; p = 0.78). Comparing "CRRT with hemoadsorption" and "no CRRT," it was -9.4 mg/dL (95% CI, -20.8 to 2.1 mg/dL; p = 0.0854). Only 1/9 patients (11%, "no CRRT" group) survived day 30 after study inclusion but died on day 89. IL-6, liver function parameters, and clinical scores were similar between the study groups. CYTOHEP failed to demonstrate that extracorporeal hemoadsorption combined with CRRT can reduce serum bilirubin in ACLF patients with acute kidney failure.

Hospital water environment and antibiotic use: key factors in a nosocomial outbreak of carbapenemase-producing Serratia marcescens

BackgroundThe healthcare water environment is a potential reservoir of carbapenem-resistant organisms (CROs). Here, we report the role of the water environment as a reservoir and the infection control measures applied to suppress a prolonged outbreak of Klebsiella pneumoniae carbapenemase-producing Serratia marcescens (KPC-SM) in two intensive care units (ICUs). MethodsThe outbreak occurred in the ICUs of a tertiary hospital from October 2020 to July 2021. Comprehensive patient contact tracing and environmental assessments were conducted, and a case–control study was performed to identify factors associated with the acquisition of KPC-SM. Associations among isolates were assessed via pulsed-field gel electrophoresis (PFGE). Antibiotic usage was analyzed. . ResultsThe outbreak consisted of two waves involving a total of 30 patients with KPC-SM. Multiple environmental cultures identified KPC-SM in a sink, a dirty utility room, and a communal bathroom shared by the ICUs, together with the waste bucket of a continuous renal replacement therapy (CRRT) system. The genetic similarity of the KPC-SM isolates from patients and the environment was confirmed by PFGE. A retrospective review of 30 cases identified that the use of CRRT and antibiotics were associated with acquisition of KPC-SM (p < 0.05). There was a continuous increase in the use of carbapenems; notably, the use of colistin has increased since 2019. ConclusionOur study demonstrates that CRRT systems, along with other hospital water environments, are significant potential sources of resistant microorganisms, underscoring the necessity of enhancing infection control practices in these areas.

Cost-utility analysis of separated continuous renal replacement therapy systems versus intermittent hemodialysis in critically ill patients with acute kidney injury in a low-resource setting.

The aim of this study is to perform a cost-utility analysis of separated continuous renal replacement therapy (CRRT) compared with intermittent hemodialysis (IHD) in critically ill patients with acute kidney injury (AKI). Cost and clinical data were gathered from adult patients with AKI who received separated CRRT or IHD at a tertiary hospital in Thailand. We applied a Markov model in this study. Our primary outcome was the incremental cost-effectiveness ratio (ICER). We performed sensitivity analysis to assess the influence of parameter uncertainty. We enrolled 199 critically ill patients with AKI. Of these patients, 129 underwent separated CRRT, and the rest underwent IHD. The mortality rate and dialysis dependence status were not significantly different between the groups. The total costs of separated CRRT were lower than IHD ($73 042.20 vs. $89 244.37). We estimated that separated CRRT increased quality-adjusted life years (QALYs) by 0.21 compared with IHD. The ICER of -74 035.16 USD/QALY gained in the case-based analysis indicated that separated CRRT is superior to IHD due to the lower cost and more cumulative QALYs. After performing sensitivity analysis by varying parameter ranges, separated CRRT remained a cost-saving approach. Separated CRRT is a cost-saving modality compared with IHD in critically ill patients with AKI. This approach can be applied in resource-limited settings.

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.

Heparin versus citrate anticoagulation for continuous renal replacement therapy in intensive care: the RRAM observational study.

In the UK, 10% of admissions to intensive care units receive continuous renal replacement therapy with regional citrate anticoagulation replacing systemic heparin anticoagulation over the last decade. Regional citrate anticoagulation is now used in > 50% of intensive care units, despite little evidence of safety or effectiveness. The aim of the Renal Replacement Anticoagulant Management study was to evaluate the clinical and health economic impacts of intensive care units moving from systemic heparin anticoagulation to regional citrate anticoagulation for continuous renal replacement therapy. This was an observational comparative effectiveness study. The setting was NHS adult general intensive care units in England and Wales. Participants were adults receiving continuous renal replacement therapy in an intensive care unit participating in the Intensive Care National Audit & Research Centre Case Mix Programme national clinical audit between 1 April 2009 and 31 March 2017. Exposure - continuous renal replacement therapy in an intensive care unit after completion of transition to regional citrate anticoagulation. Comparator - continuous renal replacement therapy in an intensive care unit before starting transition to regional citrate anticoagulation or had not transitioned. Primary effectiveness - all-cause mortality at 90 days. Primary economic - incremental net monetary benefit at 1 year. Secondary outcomes - mortality at hospital discharge, 30 days and 1 year; days of renal, cardiovascular and advanced respiratory support in intensive care unit; length of stay in intensive care unit and hospital; bleeding and thromboembolic events; prevalence of end-stage renal disease at 1 year; and estimated lifetime incremental net monetary benefit. Individual patient data from the Intensive Care National Audit & Research Centre Case Mix Programme were linked with the UK Renal Registry, Hospital Episode Statistics (for England), Patient Episodes Data for Wales and Civil Registrations (Deaths) data sets, and combined with identified periods of systemic heparin anticoagulation and regional citrate anticoagulation (survey of intensive care units). Staff time and consumables were obtained from micro-costing. Continuous renal replacement therapy system failures were estimated from the Post-Intensive Care Risk-adjusted Alerting and Monitoring data set. EuroQol-3 Dimensions, three-level version, health-related quality of life was obtained from the Intensive Care Outcomes Network study. Out of the 188 (94.9%) units that responded to the survey, 182 (96.8%) use continuous renal replacement therapy. After linkage, data were available from 69,001 patients across 181 intensive care units (60,416 during periods of systemic heparin anticoagulation use and 8585 during regional citrate anticoagulation use). The change to regional citrate anticoagulation was not associated with a step change in 90-day mortality (odds ratio 0.98, 95% confidence interval 0.89 to 1.08). Secondary outcomes showed step increases in days of renal support (difference in means 0.53 days, 95% confidence interval 0.28 to 0.79 days), advanced cardiovascular support (difference in means 0.23 days, 95% confidence interval 0.09 to 0.38 days) and advanced respiratory support (difference in means, 0.53 days, 95% CI 0.03 to 1.03 days) with a trend toward fewer bleeding episodes (odds ratio 0.90, 95% confidence interval 0.76 to 1.06) with transition to regional citrate anticoagulation. The micro-costing study indicated that regional citrate anticoagulation was more expensive and was associated with an estimated incremental net monetary loss (step change) of -£2376 (95% confidence interval -£3841 to -£911). The estimated likelihood of cost-effectiveness at 1 year was less than 0.1%. Lack of patient-level treatment data means that the results represent average effects of changing to regional citrate anticoagulation in intensive care units. Administrative data are subject to variation in data quality over time, which may contribute to observed trends. The introduction of regional citrate anticoagulation has not improved outcomes for patients and is likely to have substantially increased costs. This study demonstrates the feasibility of evaluating effects of changes in practice using routinely collected data. (1) Prioritise other changes in clinical practice for evaluation and (2) methodological research to understand potential implications of trends in data quality. This trial is registered as ClinicalTrials.gov NCT03545750. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 13. See the NIHR Journals Library website for further project information.

Comparison of the Accuracy of the Novel PrisMax Continuous Renal Replacement Therapy System to the Classic Prismaflex System

Background/Aims: We assessed how the novel PrisMax continuous renal replacement therapy (CRRT) system performed in an international multicentre setting. The system has multiple novel tools aiming to increase accuracy and dose delivery. Methods: Data was prospectively collected from 7 intensive care units in 6 countries. The PrisMax device data logs constituted the raw material and last generation Prismaflex data was used as comparison. Clinical parameters like treatment time, filter life span, downtime as well as prescribed and delivered dose were recorded. Results: PrisMax delivered/prescribed effluent ratios (mean ± SD) 0.92 ± 0.15 vs. Prismaflex ratios 0.85 ± 0.21, p < 0.001; delivered effluent dose (mL/kg/h) was 18.16 ± 12.93 vs. 10.95 ± 10.96, p < 0.0001; and (Kt/V) 0.76 ± 0.52 vs. 0.44 ± 0.44, p < 0.0001. Moreover, downtime was 27 minutes less for the newer device. Conclusion: The PrisMax CRRT device outperforms its predecessor with regard to dose delivery and accuracy.

Considerations for Medication Management and Anticoagulation During Continuous Renal Replacement Therapy.

Providing safe and high-quality care to critically ill patients receiving continuous renal replacement therapy (CRRT) includes adequate drug dosing and evaluation of patients' response to medications during therapy. Pharmacokinetic drug studies in acute kidney injury and CRRT are limited, considering the number of medications used in critical care. Therefore, it is important to understand the basic principles of drug clearance during CRRT by evaluating drug properties, CRRT modalities, and how they affect medication clearance. Few published studies have addressed drug disposition and clinical response during CRRT. Additionally, clotting in the CRRT circuit is a concern, so a few options for anticoagulation strategies are presented. This article reviews (1) the CRRT system and drug property factors that affect medication management, (2) the evidence available to guide drug dosing, and (3) anticoagulation strategies for critically ill patients receiving CRRT.

Online Hemoglobin and Oxygen Saturation Sensing During Continuous Renal Replacement Therapy with Regional Citrate Anticoagulation

Optical hemoglobin and oxygen saturation sensor (OHOS) monitor when used in combination with other hemodynamic tools may be useful for continuous hemodynamic monitoring during ultrafiltration. The stand-alone OHOS monitor can easily be deployed predialyzer into the extracorporeal circuit of continuous renal replacement therapy (CRRT) systems. To maximize the accuracy of the OHOS in 24 hr CRRT systems, clotting in the optical blood chamber and the presensor dilution incurred by replacement fluid should be minimized. Sustained low-efficiency dialysis (SLED) with regional citrate anticoagulation is a therapy that incorporates an OHOS and maintains the overall reliability of hemoglobin (Hb) and saturation sensing. The system operates at a blood flow rate of 60 ml/min and a fixed acid citrate infusion rate of 150 ml/hr. The presensor dilution incurred by concentrated citrate infusion would result in a minimal Hb dilution (<0.7 g/dl) while minimizing optical blood chamber clotting during 24 hr SLED.

Dosing patterns for continuous renal replacement therapy at a large academic medical center in the United States

We sought to retrospectively review the dosing patterns of continuous renal replacement therapy (CRRT) in patients with acute renal failure (ARF) and determine their actual delivered dosage of CRRT. Computerized records of patients (n = 115) who received CRRT for ARF at a single, large, academic, tertiary care hospital from September 1, 1999 through August 31, 2000 were reviewed. The delivered dose of CRRT for each patient/day was calculated from the hourly effluent flow rate, the patient's weight, and the duration (in hours) of CRRT for that day. A mean effluent flow rate (in L/h) for each patient was then calculated. The average number of hours/day on CRRT was 16.1 +/- 3.53 (mean +/- SD), with a mean flow rate (averaged over 24 h) of 1.36 +/- 0.31 L/h. The mean CRRT dose prescribed for these patients was 24.46 +/- 6.73 mL/Kg/h, but the mean dose delivered was only 16.55 +/- 5.41 mL/Kg/h (68% of the prescribed dose, P <.000001). Many patients are prescribed low doses of CRRT. Furthermore, the dose delivered is considerably lower than that prescribed. Methods and procedures to extend CRRT system life may improve the dose delivery.

The Acute Dialysis Quality Initiative--part V: operational characteristics of CRRT.

This report represents the consensus statement of the ADQI workgroup addressing the operational characteristics of continuous renal replacement therapy (CRRT). Issues addressed included the specific operational characteristics of continuous hemofiltration (HF), continuous hemodialysis (HD), and continuous hemodiafiltration (HDF) and the impact of these different modalities on solute removal. The relative roles of arteriovenous (AV) and venovenous (VV) modalities of therapy were also evaluated. The workgroup also addressed the optimal components of a CRRT system from an operational standpoint.

Continuous Arteriovenous Renal Replacement Therapy

As urea and creatinine clearances achieved by continuous arteriovenous hemofiltration tend to be low, efforts were made to increase urea and creatinine elimination by modifying the original continuous arteriovenous hemofiltration system. We investigated the urea and creatinine clearances of different continuous renal replacement therapy systems. Urea clearance achieved by spontaneous arteriovenous hemofiltration was 9.1 ml/min, suction-supported arteriovenous hemofiltration 15.3 ml/min, arteriovenous hemodiafiltration 15.4 to 19.3 ml/min, arteriovenous hemodialysis 18.9 to 22.1 ml/min. Creatinine clearances ranged between 11.1 (spontaneous arteriovenous hemofiltration) and 25.1 ml/min (arteriovenous hemodialysis). Continuous arteriovenous hemodialysis seems at present to be the ideal renal replacement therapy system to compensate azotemia in hypercatabolic patients. Its urea and creatinine clearances are high, its clinical tolerance good and it is simple and safe.