Continuous Renal Replacement Therapy Filter Research Articles

Evaluation of Clinical and Machine Data of Critically Ill Adult COVID Patients with Acute Kidney Injury Exposed to Enhanced Hemoadsorption during CRRT

Introduction: The FDA authorized the emergency use of enhanced hemoadsorption with oXiris in critically ill adult COVID patients with respiratory failure or severe disease to reduce inflammation. In this study, we evaluated critically ill adult COVID patients with acute kidney injury (AKI) who were exposed versus not exposed to enhanced hemoadsorption with oXiris during continuous renal replacement therapy (CRRT). Methods: Retrospective cohort study of critically ill adult COVID patients with AKI requiring CRRT. Exposure to oXiris was defined as receiving oXiris for >12 cumulative hours and more than one-third of the time within the first 72 h of CRRT. Study outcomes included filter-specific performance metrics and clinical outcomes such as ventilator requirement, mortality, and dialysis dependence. Inverse probability treatment weighting was used to balance potential confounders in weighted regression models. Results: 14,043 h of CRRT corresponding to 85 critically ill adult patients were analyzed. Among these, 2,736 h corresponded to oXiris exposure (n = 25 patients) and 11,307 h to a standard CRRT filter (n = 60 patients). Transmembrane pressures (TMPs) increased rapidly and were overall higher with oXiris versus standard filter, but filter life (median of 36.3 vs. 33.1 h, p = 0.913, respectively) and filter/clotting alarms remained similar in both groups. In adjusted models, oXiris exposure was not independently associated with the composite of hospital mortality and dialysis dependence at discharge (OR 2.13, 95% CI: 0.98–4.82, p = 0.06), but it was associated with fewer ventilator (β = −15.02, 95% CI: −29.23 to −0.82, p = 0.04) and intensive care unit days (β = −14.74, 95% CI: −28.54 to −0.95, p = 0.04) in survivors. Discussion/Conclusion: In critically ill adult COVID patients with AKI requiring CRRT, oXiris filters exhibited higher levels of TMP when compared to a standard CRRT filter, but no differences in filter life and filter/clotting alarm profiles were observed. The use of oXiris was not associated with improvement in clinical outcomes such as hospital mortality or dialysis dependence at discharge.

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.

PEDS8: Continuous Renal Replacement Therapy In Pediatric Extracorporeal Membrane Oxygenation: Life Span And Cost Of Filter Changes With Bivalirudin.

Background: The utilization of additional extracorporeal support devices utilized in conjunction with Extracorporeal Membrane Oxygenation (ECMO) has increased with more complex and sicker patients. The use of Continuous Renal Replacement Therapy (CRRT) has increased five-fold over the past 3 years at our institution after implementing Pediatric Nephrology Stewardship (PNS) on ECMO. Bivalirudin is the primary anticoagulant used for ECMO and CRRT at our institution which has resulted in increased ECMO circuit and CRRT filter life. The Prismalflex HF1000 and HF20 filter has a prime volume of 165 ml and 58 ml, respectively, with prime components which include packed red blood cells (pRBC) and albumin. Manufacturer recommendations for changing the CRRT filter is defined as every 72 hours (3 days). We sought to extend the filter length by augmenting the indication for the CRRT filter change from manufacturer recommendation. Filter changes were determined based on monitoring the filter pressure, transmembrane pressure, and pressure drop to diagnosis clotting/clogging. CRRT filter was also changed out if disconnection from ECMO was warranted due to ECMO circuit change or travel. Methods: Retrospective ECMO and CRRT data was collected for pediatric veno-arterial or veno-venous ECMO patients at a tertiary care hospital from January 2021-December 2022. Results: CRRT was performed on 16% (7/44) of ECMO patients. 100% of the patients received bivalirudin as the anticoagulant. 71% (5/7) were supported by VA ECMO. 43% (3/7) were neonates. Mean ECMO duration was 14 days (3-133). Of the 7 ECMO patients on CRRT, 80% (265/332) of their time on ECMO included CRRT support. There was a total of 41 CRRT filter changes performed during 265 days on CRRT with an average filter change occurring every 6.46 days (table 1). Utilizing cost of CRRT filter set ($358.00) and approximate cost of 1 unit of pRBC ($200.00), there was a savings of $26,226 to the hospital ($22,878 vs. $49,104). Discussion: Utilization of an alternative indication versus manufacturer recommendation for CRRT filter change out prolonged filter length from 3 days to 6.46 days (110% decrease in filter change out). By reducing the number of CRRT filters and blood usage for a filter change, cost to the hospital and patients was significantly reduced even without considering labor for CRRT set up and blood preparation. With careful attention to detail and collaboration with Nephrology and Hematology services, it appears CRRT filter length can be safely extended past manufacturers recommendations.

A practical design equation for accurate quantification of CRRT filter design factors and convection effects.

Considering the increasing clinical need for continuous renal replacement therapy (CRRT), further improvement in therapeutic efficacy has become an important focus for researchers. Here, we designed nine CRRT filters with various combinations of hollow fiber packing density (PD) and housing shape (effective hollow fiber length (L) and inner housing diameter (D) ratio (L/D ratio)) to evaluate the clearance of middle molecular uremic toxins (MMs) via simulation of an in vitro continuous veno-venous hemodialysis treatment model. We also used Doppler ultrasonography to measure the maximum internal filtration flow rate (QIF-Max) as an aid; this approach facilitated an exploration of the impacts of various design factors on convection effects, while revealing the mechanisms influencing MM removal performance. Furthermore, we constructed a multiple linear regression model of design factors and QIF-Max, then conducted experimental verification. Finally, we proposed an accurate and practical design equation to quantify the design factors influencing CRRT filters and convection effects: , where N/D2 and L/D affect QIF-Max by 15.0% and 85.0%, respectively. This design equation was able to effectively quantify the convection effects of CRRT filters with different design factors, thereby predicting MM removal performance; this convenient design equation can support the development of CRRT-related products.

Effects of hollow fiber packing density and housing shape on the albumin filtration performance of CRRT filters

Continuous renal replacement therapy (CRRT) has become the most commonly used acute blood purification therapy for critically ill patients. As a key point of extracorporeal blood circulation, the CRRT filter plays a decisive role in therapeutic efficacy. However, few in vitro studies have been conducted on CRRT filters, particularly concerning the effects of design factors on filter effectiveness and safety profile; no comprehensive evaluation system has been established. Here, we designed nine CRRT filters with various combinations of hollow fiber packing density (PD) and housing shape (effective hollow fiber length (L) and inner housing diameter (D) ratio (L/D ratio)) and introduced a high-frequency sampling pressure monitor to accurately monitor small changes in transmembrane pressure (TMP) and ultrafiltration rate (UFR) over time. We also used concentration polarization mass transfer resistance (Rc), change in sieving coefficient (S) of albumin over time, and amount of albumin removed (Mfld) to investigate the effects of two design factors on albumin filtration performance and analyze the mechanism of protein filtration performance over time, thereby establishing a comprehensive in vitro evaluation system to explore the safety profile of CRRT filters. Our results showed that the nine CRRT filters designed with different combinations of PD (50%, 55%, and 60%) and L/D ratio (2.9, 5.3, and 9.3) were able to maintain stability in terms of hemodynamics and water permeability; the lowest Mfld was PD = 60% and L/D ratio = 9.3, which indicates that design factor optimization can effectively control albumin filtration, thereby improving the safety profile of CRRT filters.

Is 10 min post heparin bolus ACT, alongside aPTT monitoring, predictive for CRRT filter survival?

When using heparin anticoagulation for continuous renal replacement therapy (CRRT), the main challenge is to tailor the dosage to patient response. This study aimed to determine if the first activated thromboplastin time (aPTT) (measured after 3 hours post heparin bolus) can be a predictor for CRRT filter survival and if the first activated clotting time-low range (ACT-LR) (10 min post heparin bolus) can be predictive for subtherapeutic or therapeutic first aPTT. An unfractionated heparin (UF) anticoagulation protocol was used in CRRT and heparin monitoring was performed by aPTT and ACT-LR. Extracorporeal therapy was analyzed and filter survival was assessed for general risk factors, especially coagulation tests. For statistical analysis, Logrank tests, ROC curve analysis, and the Kaplan-Meier chart for survival evaluations were utilized. Using the pLogrank test, the overall survival for the CRRT procedure was 47.8 hours (p=0.04), and no clotting events occurred during the first 12 hours for all examined therapies. Multivariate analysis for filter survival prediction to estimate 48 hours of CRRT revealed statistical relevance for Age (<60 years), BMI (<25.9), and INR (>1.3), with negative statistical significance for lipids, triglycerides, and fibrinogen. aPTT (180 min) values greater than 57 sec were shown to be predictive of 48-hour filter survival, and similar findings were obtained for aPTT measured at 6 hours. ACT-LR samplesassessed 10 minutes after the initial heparin bolus was shown to be predictive of 48-hour filter survival (cutoff > 218 sec; p=0.04). When ACT prediction potential for therapeutic aPTT values was evaluated, ACT-LR 10 min (cut off > 200 sec.), ACT-LR 60 min (cut off > 186 sec.), and ACT-LR 180 min (cut off > 182 sec.) were found to be predictive. Based on this study and its sample size, ACT-LR can be a complimentary assessment to aPTT for monitoring anticoagulation with heparin on CRRT.

Effect of hollow fiber packing density and housing shape on the solute removal performance of CRRT filters for acute blood purification

Continuous renal replacement therapy (CRRT) has a good therapeutic effect in a variety of diseases, such as acute kidney injury. CRRT filters should feature small membrane surface area, excellent water permeability and solute removal performance for long-term use. Solute removal performance depends on the physicochemical structure of the dialysis membrane as well as on the housing design. On the basis of the same hollow fiber membrane, optimizing the housing design can maximize the performance of the dialysis membrane. In this article, we experimentally demonstrated the influence of hollow fiber packing density (PD) and housing shape (effective hollow fiber length (L) and inner housing diameter (D) ratio (L/D ratio)) on the performance of CRRT filters. In each continuous hemodialysis mode and post-diluted continuous hemodiafiltration mode, we tested nine CRRT filters with the same high-flux membrane but with different PDs (50%, 55%, and 60%) and L/D ratios (2.9, 5.3, and 9.3), and we evaluated the effect of different combinations of the two design factors on solute clearance. Our results showed that unlike with the clearance of small molecular weight solutes, the clearance of medium molecular weight solute was obviously affected by PD and L/D ratio, and the design providing the best removal of medium molecular solutes among the nine experiments was PD = 60% and L/D ratio = 9.3. This article will help address the lack of research on CRRT filter housing design as well as lead to the development of higher performance filters for acute blood purification.

Continuous renal replacement therapy in COVID-19\u2014associated AKI: adding heparin to citrate to extend filter life\u2014a retrospective cohort study

BackgroundCoronavirus disease 2019 (COVID-19) may predispose patients to thrombotic events. The best anticoagulation strategy for continuous renal replacement therapy (CRRT) in such patients is still under debate. The purpose of this study was to evaluate the impact that different anticoagulation protocols have on filter clotting risk.MethodsThis was a retrospective observational study comparing two different anticoagulation strategies (citrate only and citrate plus intravenous infusion of unfractionated heparin) in patients with acute kidney injury (AKI), associated or not with COVID-19 (COV + AKI and COV − AKI, respectively), who were submitted to CRRT. Filter clotting risks were compared among groups.ResultsBetween January 2019 and July 2020, 238 patients were evaluated: 188 in the COV + AKI group and 50 in the COV − AKI group. Filter clotting during the first filter use occurred in 111 patients (46.6%). Heparin use conferred protection against filter clotting (HR = 0.37, 95% CI 0.25–0.55), resulting in longer filter survival. Bleeding events and the need for blood transfusion were similar between the citrate only and citrate plus unfractionated heparin strategies. In-hospital mortality was higher among the COV + AKI patients than among the COV − AKI patients, although it was similar between the COV + AKI patients who received heparin and those who did not. Filter clotting was more common in patients with D-dimer levels above the median (5990 ng/ml). In the multivariate analysis, heparin was associated with a lower risk of filter clotting (HR = 0.28, 95% CI 0.18–0.43), whereas an elevated D-dimer level and high hemoglobin were found to be risk factors for circuit clotting. A diagnosis of COVID-19 was marginally associated with an increased risk of circuit clotting (HR = 2.15, 95% CI 0.99–4.68).ConclusionsIn COV + AKI patients, adding systemic heparin to standard regional citrate anticoagulation may prolong CRRT filter patency by reducing clotting risk with a low risk of complications.

Do anti-platelet drugs improve duration of continuous renal replacement therapy? A retrospective cohort study in cardiac ICU patients.

The objective of this study was to investigate the impact of anti-platelet drug/s on duration of continuous renal replacement therapy (CRRT) in those patients where anti-coagulants were not used due to certain contraindications and in cases where patients were on anti-platelet drugs and were given anti-coagulant during CRRT. This single-center, retrospective cohort study was conducted using the medical records patients treated with CRRT in the cardiac ICU of the inpatient urban facility, located in North India. Data was collected from only those patients who received CRRT for the duration of at least 12 h. Patient's in NAC group were not on any anti-platelet/s and did not receive anti-coagulant during CRRT. AC and AP group patients received anti-coagulant alone or were already on anti-platelet/s and did not receive anti-coagulant respectively while ACAP group patients were on anti-platelet drug/s and also received anti-coagulant during CRRT. Patients in AC, AP, or ACAP group showed significantly (p < 0.001) higher CRRT filter life compared to NAC group. The median CRRT filter life was significantly higher in the ACAP group compared to AC (p < 0.05) and AP (p < 0.001) groups. This study indicates that systemic anti-platelet therapy can provide additional support in critical patients undergoing CRRT even with or without anti-coagulant therapy. However, the increase in CRRT filter life was more profound in patients who were on anti-platelet/s and also received anti-coagulant drug/s during CRRT.

Decreased CRRT Filter Lifespan in COVID-19 ICU Patients.

(1) Background: Increased thromboembolic events and an increased need for continuous renal replacement therapy (CRRT) have been frequently reported in COVID-19 patients. Our aim was to investigate CRRT filter lifespan in intensive care unit (ICU) COVID-19 patients. (2) Methods: We compared CRRT adjusted circuit lifespan in COVID-19 patients admitted for SARS-CoV-2 infection to a control group of patients admitted for septic shock of pulmonary origin other than COVID-19. Both groups underwent at least one session of CRRT for AKI. (3) Results: Twenty-six patients (13 in each group) were included. We analysed 117 CRRT circuits (80 in the COVID-19 group and 37 in the control group). The adjusted filter lifespan was shorter in the COVID-19 group (17 vs. 39 h, p < 0.001). This trend persisted after adjustment for confounding factors (−14 h, p = 0.037). Before CRRT circuit clotting, the COVID-19 group had a more procoagulant profile despite higher heparin infusion rates. Furthermore, we reported a decreased relation between activated partial thromboplastin time (aPTT) and cumulative heparin dose in COVID-19 patients when compared to historical data of 23,058 patients, suggesting a heparin resistance. (4) Conclusion: COVID-19 patients displayed a shorter CRRT filter lifespan that could be related to a procoagulant profile and heparin resistance.

Filter Clotting with Continuous Renal Replacement Therapy in COVID-19

Background: Coronavirus disease 2019 (COVID-19) appears to be associated with increased arterial and venous thromboembolic disease. These presumed abnormalities in hemostasis have been associated with filter clotting during continuous renal replacement therapy (CRRT). The incidence, clinical features, and treatment strategies to address severe filter clotting in patients with COVID-19 is unknown.Aim: We aimed to characterize the burden of CRRT filter clotting in patients with COVID-19 infection and to describe a CRRT anticoagulation protocol that used anti-factor Xa levels for systemic heparin dosing.Methods: Consecutive patients with confirmed COVID-19 infection admitted between March 16, 2020 and April 27, 2020 who required CRRT were included in this multi-center retrospective study. Severe clotting was defined as >2 filter losses in 48 hours or one filter loss <8 hours into CRRT. Primary outcome was time to CRRT filter loss. Due to the unreliability of PTT levels in patients with COVID-19, a COVID-specific CRRT anticoagulation protocol (referred to as protocol henceforth) which dosed systemic unfractionated heparin (UFH) by anti-factor Xa levels was piloted at one center starting April 13, 2020.Given that there was no difference in the treatment plan from CRRT initiation to first filter loss between the two anticoagulation approaches, this period served as a run-in period. Time from first to second filter loss (where protocol patients were exposed to low systemic UFH dosing) and time from second to third filter loss (where protocol patients were exposed to high systemic UFH dosing) were analyzed with a log-rank test.Results: Sixty-five patients were analyzed, with 17 using the anti-factor Xa protocol to guide systemic heparin dosing whereas 48 were treated with standard of care anticoagulation dosed by PTT . There were no major differences between groups in age, sex, race, ethnicity, body mass index, or baseline medications. Fifty-seven out of 65 patients (88%) initiated CRRT for AKI, whereas 8/65 patients (12%) had end stage renal disease. At the time of CRRT initiation, 64/65 patients (98%) were mechanically ventilated, 22/65 patients (34%) required prone ventilation, and 59/65 patients (91%) were on intravenous vasopressors. Patients spent a median of 6 [2, 13] days on CRRT.Fifty-four out of 65 patients (83%) lost at least one filter. Median first filter survival time was 6.5 [2.5, 33.5] hours. There was no difference between groups in percentage who lost their first filter (88% vs. 81%), or second filter (73% vs. 72%). However, fewer patients in the protocol group lost their third filter (55% vs. 93%) resulting in a longer median third filter survival time (24 [15.1, 54.2] vs. 17.3 [9.5, 35.1] hours, p = 0.04), Figure 1.Conclusions: The rate of CRRT filter loss is high in COVID-19 infection. An anticoagulation protocol using systemic unfractionated heparin, dosed by anti-factor Xa levels is a reasonable approach to anticoagulation in this population.DisclosuresRosovsky:Bristol-Myers Squibb: Consultancy, Research Funding; Portola: Consultancy; Janssen: Consultancy, Research Funding; Dova: Consultancy. Sise:EMD-Serono: Research Funding; Abbvie: Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Research Funding; Bioporto: Consultancy. Steele:HealthReveal: Consultancy; Blackstone Life Sciences: Consultancy. Czarnecki:Alexion: Consultancy; Reata: Consultancy. Allegretti:Mallinckrodt Pharmaceuticals: Consultancy.

Filter clotting with continuous renal replacement therapy in COVID-19.

Coronavirus disease 2019 (COVID-19) appears to be associated with increased arterial and venous thromboembolic disease. These presumed abnormalities in hemostasis have been associated with filter clotting during continuous renal replacement therapy (CRRT). We aimed to characterize the burden of CRRT filter clotting in COVID-19 infection and to describe a CRRT anticoagulation protocol that used anti-factor Xa levels for systemic heparin dosing. Multi-center study of consecutive patients with COVID-19 receiving CRRT. Primary outcome was CRRT filter loss. Sixty-five patients were analyzed, including 17 using an anti-factor Xa protocol to guide systemic heparin dosing. Fifty-four out of 65 patients (83%) lost at least one filter. Median first filter survival time was 6.5 [2.5, 33.5] h. There was no difference in first or second filter loss between the anti-Xa protocol and standard of care anticoagulation groups, however fewer patients lost their third filter in the protocolized group (55% vs. 93%) resulting in a longer median third filter survival time (24 [15.1, 54.2] vs. 17.3 [9.5, 35.1] h, p = 0.04). The rate of CRRT filter loss is high in COVID-19 infection. An anticoagulation protocol using systemic unfractionated heparin, dosed by anti-factor Xa levels is reasonable approach to anticoagulation in this population.Electronic supplementary materialThe online version of this article (10.1007/s11239-020-02301-6) contains supplementary material, which is available to authorized users.

Walking While Dialyzing: A Retrospective Observation of Early Mobility and Ambulation for Patients on Continuous Renal Replacement Therapy.

Objectives:To describe the practice of physical therapy for patients requiring continuous renal replacement therapy and assess data related to the safety and feasibility of physical therapy interventions.Design:A retrospective observational cohort study.Patients:Surgical and cardiovascular patients receiving continuous renal replacement therapy during a 2-year period from December 2016 to November 2018.Setting:Two ICUs at a single academic medical center.Intervention:Physical mobility and ambulation while on continuous renal replacement therapy.Measurements and Main Results:Therapy data including ICU Mobility Scale score, number of physical therapy sessions with and without ambulation and gait distance, along with safety data including filter life, safety events, and mortality were analyzed. The cohort of patients receiving continuous renal replacement therapy during the 2-year period was 206. Of these, 172 (83.49%) received simultaneous physical therapy. The median ICU Mobility Scale was 5 (interquartile range, 4–7) over a total of 1,517 physical therapy sessions. Ambulation with concomitant continuous renal replacement therapy connected was achieved in 78 patients (37.86%). There were 377 ambulation sessions (24.85% of all sessions) with a mean of 4.83 (sds 4.94) ambulation sessions per ambulatory patient. Patients walked an average of 888.53 feet (sd 1,365.50) while on continuous renal replacement therapy and a daily average of 150.61 feet (sd 133.50). In-hospital mortality was lowest for patients who ambulated (17.95%) and highest for patients who received no therapy (73.53%). Continuous renal replacement therapy filter life was longest for patients who ambulated (2,047.20 min [sd 1,086.50 min]), and shortest in patients who received no therapy (1,682.20 min [sd 1,343.80 min]). One safety event was reported during this time (0.0007% of all physical therapy sessions).Conclusions:Ambulation while on continuous renal replacement therapy was not associated with an increased risk of safety events and was feasible with the use of nonfemoral catheters and dialysis equipment with internal batteries.

Continuous Renal Replacement Therapy Without Anticoagulation: Top Ten Tips to Prevent Clotting

Continuous renal replacement therapy (CRRT) is intended to function continuously and is prescribed for this outcome. Anticoagulants may not always be used. Clotting and clogging within the CRRT filter stopping therapy occurs with a variability in the total elapsed time associated. This is commonly known as the circuit or filter “life”. It is very useful and important to record this time at the bedside and refer to this as a measure of success and quality. Filter life (i.e., hours) is reported in many reports investigating CRRT but is not well understood or clear for when this is considered inadequate and clinical review strategies should be considered. Failure before 8 h could be associated with inadequate renal support and “therapy”. Anticoagulation is the key intervention to prolong filter function; however, the extracorporeal circuit design and set up, access catheter profile and insertion site, CRRT machine settings, and the human interface operating CRRT are always important and the only consideration to prevent failure when no anticoagulation is mandated for CRRT.

Anemia, Blood Transfusion, and Filter Life Span in Critically Ill Patients Requiring Continuous Renal Replacement Therapy for Acute Kidney Injury: A Case-Control Study.

Background Filter clotting is frequent during continuous renal replacement therapy (CRRT), which increases anemia risk. We studied anemia and blood transfusion in critically ill patients requiring CRRT for acute kidney injury and assessed the relationship between CRRT filter life span and PRBC transfusion. Methods A case-control study was conducted at a tertiary-care intensive care unit (ICU) where CRRT cases were matched with controls for age, gender, admission category, and severity of illness. Daily hemoglobin levels, blood transfusions, and life span of CRRT filter were noted. CCRT patients were categorized according to the median of the filter life span (20 hours). Results Ninety-five cases and 102 controls were enrolled. The hemoglobin level on admission was similar in the two groups, yet cases had significantly lower hemoglobin levels than controls (72.8 ± 15.3 versus 82.5 ± 20.7 g/L, p < 0.001) during ICU stay. Anemia <70 g/L occurred in 50% of cases and 19% of controls (p < 0.001). Most (56.3%) cases were transfused compared with 29.9% for controls (p < 0.001) with higher number of transfused packed red blood cell (PRBC) units in cases (2.6 ± 4.0 versus 1.5 ± 3.2 units per patient, p=0.03). Patients with shorter versus longer filter life had similar hemoglobin level in the first 7 days of CRRT with no difference in PRBC transfusion requirement. Prefilter heparin use and hemodialysis access location were not associated with longer filter life span. The mortality was similar in patients with shorter versus longer filter life. Conclusions CRRT in ICU was associated with larger drop in hemoglobin and more PRBC transfusion. Shorter (<20 hours) versus longer CCRT filter life was not associated with increased PRBC transfusion.

Non anti-coagulant factors associated with filter life in continuous renal replacement therapy (CRRT): a systematic review and meta-analysis

BackgroundOptimising filter life and performance efficiency in continuous renal replacement therapy has been a focus of considerable recent research. Larger high quality studies have predominantly focussed on optimal anticoagulation however CRRT is complex and filter life is also affected by vascular access, circuit and management factors. We performed a systematic search of the literature to identify and quantify the effect of vascular access, circuit and patient factors that affect filter life and presented the results as a meta-analysis.MethodsA systematic review and meta-analysis was performed by searching Pubmed (MEDLINE) and Ovid EMBASE libraries from inception to 29th February 2016 for all studies with a comparator or independent variable relating to CRRT circuits and reporting filter life. Included studies documented filter life in hours with a comparator other than anti-coagulation intervention. All studies comparing anticoagulation interventions were searched for regression or hazard models pertaining to other sources of variation in filter life.ResultsEight hundred nineteen abstracts were identified of which 364 were selected for full text analysis. 24 presented data on patient modifiers of circuit life, 14 on vascular access modifiers and 34 on circuit related factors. Risk of bias was high and findings are hypothesis generating.Ranking of vascular access site by filter longevity favours: tunnelled semi-permanent catheters, femoral, internal jugular and subclavian last. There is inconsistency in the difference reported between femoral and jugular catheters.Amongst published literature, modality of CRRT consistently favoured continuous veno-venous haemodiafiltration (CVVHD-F) with an associated 44% lower failure rate compared to CVVH. There was a trend favouring higher blood flow rates. There is insufficient data to determine advantages of haemofilter membranes.Patient factors associated with a statistically significant worsening of filter life included mechanical ventilation, elevated SOFA or LOD score, elevations in ionized calcium, elevated platelet count, red cell transfusion, platelet factor 4 (PF-4) antibodies, and elevated fibrinogen.Majority of studies are observational or report circuit factors in sub-analysis. Risk of bias is high and findings require targeted investigations to confirm.ConclusionThe interaction of patient, pathology, anticoagulation, vascular access, circuit and staff factors contribute to CRRT filter life. There remains an ambiguity from published data as to which site and side should be the first choice for vascular access placement and what interaction this has with patient factors and timing. Early consideration of tunnelled semi-permanent access may provide optimal filter life if longer periods of CRRT are anticipated. There remains an absence of robust evidence outside of anti-coagulation strategies despite over 20 years of therapy delivery however trends favour CVVHD-F over CVVH.

Survey of continuous renal replacement therapy application status

Objective: To investigate the condition of implementation of continuous renal replacement therapy (CRRT) in quality control center of critical care medicine. Methods: Questionnaire mails were issued to all of the quality control respondents to survey the application of CRRT in June 2015 from Jiangsu quality control center of critical care medicine. Results: Among the 69 quality control respondents, 62 were equipped with CRRT devices, and in 58 of which patients were treated with CRRT. There were 195 doctors and 253 nurses in 62 quality control respondents attended CRRT training at or above the provincial level; the proportions of hospitals in southern, central and northern regions of Jiangsu were 63%, 79% and 86% respectively with trained doctors (more than 2), and 34%, 38% and 43% respectively with trained nurses (more than 3). The preferred material for CRRT filter were AN69 and acrylic, accounting for 48% and 45% respectively. The average life span was less than 12 h for 21% filters, 12-24 h for 34% filters, and more than 72 h for only 2% filters. Manual displacement liquids were currently mainly used in our province, accounting for 75%. Heparin is the most frequently used anticoagulants, accounting for 48%. Citrate and low molecular weight heparin used for anticoagulation accounted for 31% and 21% respectively. Bleeding was the most common clinical complication (43%) in patients with CRRT, followed by low temperature (22%). The average hospitalization expenses for patients with CRRT amounted to 69 643 yuan RMB per person, in which the cost for CRRT accounted for 19 525 yuan RMB per person. Conclusion: The application of CRRT varies in filter materials, anticoagulants, replacement frequencies and dilution mode. Bleeding is the most common clinical complication in patients with CRRT. Besides, the proportion of trained doctors and nurses at the provincial level is still very low. It will be improved with intensive training and reasonable implementation for us to prolong the lifespan of the filters and reduce the cost for patients with CRRT.

Ability of Nafamostat Mesilate to Prolong Filter Patency during Continuous Renal Replacement Therapy in Patients at High Risk of Bleeding: A Randomized Controlled Study

Continuous renal replacement therapy (CRRT) is considered as an effective modality for renal replacement therapy in hemodynamically unstable patients within intensive care units (ICUs). However, the role of heparin anticoagulation, which is used to maintain circuit patency, is equivocal due to the risk of bleeding and morbidity. Among various alternative anticoagulants, nafamostat mesilate has been shown to be an effective anticoagulant in patients prone to bleeding. Hence, we conducted a prospective, randomized controlled study investigating the effect of nafamostat mesilate on mortality, CRRT filter life span and adverse events in patients with bleeding tendency. Seventy-three Patients were randomized into either the futhan or no-anticoagulation group. Thirty-six subjects in the futhan group received nafamostat mesilate, while thirty seven subjects in the no-anticoagulation group received no anticoagulants. Baseline characteristics and appropriate laboratory tests were taken from each group. The mortality between the two groups was not significantly different. Nevertheless, between the futhan group and the no-anticoagulation group, the overall number of filters used during CRRT (2.71±2.12 vs. 4.50±3.25; p = 0.042) and the number of filters changed due to clots per 24 hours (1.15±0.81 vs. 1.74±1.62; p = 0.040) were significantly different. When filter life span was subdivided into below and over 12 hours, the number of filters functioning over 12 hours was significantly higher in the futhan group than in the no-anticoagulation group (p = 0.037, odds ratio 1.84). There were no significant differences in transfusion, mortality, or survival between the two groups, and no adverse events related to nafamostat mesilate were noted. Hence, nafamostat mesilate may be used as an effective and safe anticoagulant, without increasing the risk of major bleeding complications, in patients prone to bleeding.Trial RegistrationClinicaltrials.gov NCT01761994

THE CLINICAL APPLICATION OF CRRT—CURRENT STATUS: Anticoagulation for Continuous Renal Replacement Therapy

Continuous renal replacement therapy (CRRT) has emerged as the preferred dialysis modality for critically ill patients with acute kidney injury, particularly those with hemodynamic instability. Anticoagulation is necessary for effective delivery of CRRT, but this requirement can also present challenges, as many critically ill patients with sepsis and inflammation already have a higher risk of bleeding as well as clotting. Without anticoagulation, CRRT filter and circuit survival are diminished, and therapy becomes less helpful. Heparins are presently the most commonly used anticoagulants worldwide for CRRT. They are widely available and can be easily monitored, but disadvantages include risks of hemorrhage, heparin resistance, and heparin-induced thrombocytopenia (HIT). Because of the potential side effects of heparin, alternative methods of anticoagulation have been investigated, including regional heparin/protamine, low molecular weight heparins, heparinoids, thrombin antagonists (hirudin and argatroban), regional citrate, and platelet inhibiting agents (prostacyclin and nafamostat). Each of these techniques has unique advantages and disadvantages, and anticoagulation for CRRT should be adapted to the patient's characteristics and institution's experience. Of the alternative methods, citrate anticoagulation is gaining wider acceptance with the development of simplified and safer protocols.

Multi-centre evaluation of anticoagulation in patients receiving continuous renal replacement therapy (CRRT)

Heparin (hepACG) and regional citrate anticoagulation (citACG) remain the most commonly reported continuous renal replacement therapy (CRRT) ACG methods employed. No prospective multi-centre published data exist that compare different ACG methods with respect to CRRT filter life span or patient complications. A total of 138 patients from seven US centres receiving 18 208 h of CRRT comprising a total of 442 CRRT circuits were utilized to assess filter life span and ACG-related complications in patients receiving CRRT with hepACG, citACG or no ACG (noACG). Mean circuit life was 41.2+/-30.8 h. Mean circuit survival was no different for circuits receiving hepACG (42.1+/-27.1 h) and citACG (44.7+/-35.9 h), but was significantly lower for circuits with noACG (27.2+/-21.5 h, P<0.005). Kaplan-Meier analyses revealed no survival difference between hepACG and citACG circuits, but significantly lower survival for noACG circuits (P<0.001). Log-rank analysis showed that 69% of hepACG and citACG circuits whereas only 28% of noACG were functional at 60 h. Clotting rates were similar for hepACG circuits (58 out of 230, 25%) and citACG circuits (43 out of 158, 27%), but were significantly higher for noACG circuits (27 out of 54, 50%, P < 0.001). Life-threatening bleeding complications attributable to ACG were noted in the hepACG group but were absent in the citACG group. The current analysis represents the largest evaluation of CRRT ACG methods to date. While the standard hepACG and citACG methods studied in the prospective paediatric CRRT registry led to similar filter life spans and were superior to noACG, our data suggest that citACG may result in less life-threatening complications.