Further improvement of circuit survival in citrate based continuous renal replacement therapy.

Background: Continuous renal replacement therapy (CRRT) is the most frequently used modality of renal replacement therapy (RRT) in critical care patients with acute kidney injury (AKI). Adequate CRRT delivery can be challenging, due to problems with circuit patency. To improve circuit patency, we developed a new CRRT protocol using continuous veno-venous hemodiafiltration (CVVHDF) with 3.0 mmol/l regional citrate anticoagulation (CVVHDF/RCA3.0) as our first choice RRT modality. Methods: Retrospective comparison of efficacy and safety of a CVVHDF/RCA3.0 protocol with our former continuous veno-venous hemofiltration protocol with 2.2 regional citrate anticoagulation (CVVH/RCA2.2) in adult critically ill patients with AKI requiring CRRT between 25 April 2020 and 24 October 2021. Results: In total, 56 patients (257 circuits) and 66 patients (290 circuits) were included in the CVVH/RCA2.2 and CVVHDF/RCA3.0 groups, respectively. Median circuit survival was significantly higher in patients treated with CVVHDF/RCA3.0 (39.6 (IQR 19.5-67.3) hours) compared to patients treated with CVVH/RCA2.2 (22.9 (IQR 11.3-48.6) hours) (P < .001). Higher body weight and higher convective flow were associated with a lower circuit survival. Metabolic control was similar, except for metabolic alkalosis that occurred less frequently during CVVHDF/RCA3.0 (19% of patients) compared to CVVH/RCA2.2 (46% of patients) (P = .006). Conclusions: CRRT circuit survival was longer with CVVHDF/RCA3.0 compared to CVVH/RCA2.2. CRRT circuit survival was negatively associated with higher body weight and higher convective flow.

Regional citrate anticoagulation versus LMWH anticoagulation for CRRT in liver failure patients without increased bleeding risk.

BACKGROUND: The optimal anticoagulation regimen for continuous renal replacement therapy (CRRT) in liver failure (LF) patients without increased bleeding risk remains controversial. Therefore, we conducted a monocentric retrospective study to evaluate the efficacy and safety of the regional citrate anticoagulation (RCA) versus low molecular weight heparin (LMWH) anticoagulation for CRRT in LF without increased bleeding risk. METHOD: According to the anticoagulation strategy for CRRT, patients were divided into the RCA and LMWH-anticoagulation groups. The evaluated endpoints were patient survival, filter lifespan, bleeding, citrate accumulation, and totCa/ionCa ratio. RESULT: Totally 167 and 164 filters were used in the RCA and LMWH group, respectively. The median filter lifespan was significantly longer in the RCA group (34 h (IQR = 24-54) versus 24 h (IQR = 18-45.5) [95%CI, 24.5-33]; p < 0.001). The 4-week mortality rate was significantly higher in the LMWH-anticoagulation group (71 (57.72%) vs 53 (40.46%); p = 0.006). After adjusted the important parameters in the multivariate COX regression model, the mortality risk was significantly reduced in the RCA group (HR = 0.668 [95%CI, 0.468-0.955]; p = 0.027). In the LMWH group, 30 bleeding episodes (24,19%) were observed, whereas only 7 (5.34%) occurred in the RCA group (p < 0.001). Two patients (1.5%) in the RCA group occurred citrate accumulation. CONCLUSIONS: In LF patients without increased bleeding risk who underwent CRRT, RCA significantly extended the filter lifespan and improved patient survival rate. There was no significant difference in the rate of adverse events between the two groups.

Regional citrate anticoagulation with continuous renal replacement therapy as a cause of hypercalcemia.

CLINICAL RELEVANCE: Awareness of the causes of hypercalcemia is essential for timely diagnosis of calcium disorders and optimal treatment. Citrate is commonly used as an anticoagulant during continuous renal replacement therapy (CRRT). Accumulation of citrate in the systemic circulation during CRRT may induce several metabolic disturbances, including total hypercalcemia and ionized hypocalcemia. The aim of the present study is to increase awareness of citrate accumulation and toxicity as a cause of hypercalcemia by relating three cases and reviewing the pathophysiology and clinical implications. OBSERVATIONS: We utilized electronic health records to examine the clinical cases and outlined key studies to review the consequences of citrate toxicity and general approaches to management. CONCLUSIONS: Citrate toxicity is associated with high mortality. A safe threshold for tolerating hypercalcemia during citrate anticoagulation is not clearly defined, and whether citrate toxicity independently increases mortality has not been resolved. Greater attention to citrate toxicity as a cause of hypercalcemia may lead to earlier detection, help to optimize the management of systemic calcium levels, and foster interest in future clinical studies.

Construction of a coagulation prediction model of the extracorporeal circulation circuit during hemodialysis with regional citrate anticoagulant (RCA).

OBJECTIVE: To construct a prediction model of coagulation in the extracorporeal circulation circuit during hemodialysis with regional citrate anticoagulant(RCA) conditions. METHODS: This was a single-center, retrospective study. The clinical data of patients who received hemodialysis with RCA from February 2021 to March 2022 were collected. The risk predictors of coagulation in the extracorporeal circulation circuit were screened by LASSO regression. On this basis, we used multivariate logistic regression analysis to establish a nomogram prediction model. RESULTS: A total of 98 patients received RCA hemodialysis for 362 times. Among them, 155 treatments with complete data were included in the study. Among the 155 treatments, coagulation of the extracorporeal circulation circuit occurred 12 times. The use of arteriovenous fistulas(AVF), the venous pressure at 4 h after hemodialysis initiation, blood flow velocity, dialyzer manufacturer, Systemic iCa2+ at 1 h after hemodialysis initiation, plasma albumin level, and plasma d-dimer level were influencing factors of coagulation in the extracorporeal circuit during hemodialysis with RCA (p < 0.05). A nomogram model was made out of the above indicators. The area under the receiver operating characteristic (ROC) curve for predicting coagulation in the circuit was 0.967 (95% CI: 0.935-0.998). The internal validation result of the memory testing (bootstrap method) showed that the area under the ROC curve was 0.967 (95% CI: 0.918-0.991). CONCLUSION: The nomogram model has good discrimination and calibration and can intuitively and succinctly predict the risk of coagulation in the extracorporeal circulation circuit during hemodialysis with RCA.

Study on the application of a segmented sodium citrate solution anticoagulation strategy in critically ill patients receiving CRRT: a prospective, randomized controlled study.

BACKGROUND: To explore the feasibility and effectiveness of a segmented sodium citrate solution anticoagulation strategy in patients receiving CRRT. METHODS: A prospective, randomized controlled study was conducted. RESULTS: According to the inclusion and exclusion criteria, 80 patients were included and randomly divided into two groups. Moreover, coagulation indices, liver function indices, renal function indices, and SOFA and APACHE II scores did not significantly differ between the two groups (P > 0.05). The coagulation grade of the venous ports in the experimental group was lower than that in the control group and the two groups of filters, but the difference was not statistically significant (P = 0.337). Both sodium citrate solution infusion methods maintained a low blood calcium concentration (0.25-0.45 mmol/L) in the peripheral circulation pathway, and no patient developed hypocalcaemia (< 1.0 mmol/L). The lifespans of the extracorporeal circulation tube in the experimental group and the control group were 69.43 ± 1.49 h and 49.39 ± 2.44 h, respectively (t = 13.316, P = 0.001). CONCLUSION: The segmented citrate solution anticoagulation strategy could extend the lifespan of the extracorporeal circulation tube and improve CRRT efficacy. TRIAL REGISTRATION: The Chinese Clinical Trial Registry number is ChiCTR2200057272. Registered on March 5, 2022.

Factors influencing circuit lifetime in paediatric continuous kidney replacement therapies - results from the EurAKId registry.

BACKGROUND: Continuous kidney replacement therapy (CKRT) has recently become the preferred kidney replacement modality for children with acute kidney injury (AKI). We hypothesise that CKRT technical parameters and treatment settings in addition to the clinical characteristics of patients may influence the circuit lifetime in children. METHODS: The study involved children included in the EurAKId registry (NCT02960867), who underwent CKRT treatment. We analysed patient characteristics and CKRT parameters. The primary end point was mean circuit lifetime (MCL). Secondary end points were number of elective circuit changes and occurrence of dialysis-related complications. RESULTS: The analysis was composed of 247 children who underwent 37,562 h of CKRT (median 78, IQR 37-165 h per patient). A total of 1357 circuits were utilised (3, IQR 2-6 per patient). MCL was longer in regional citrate anticoagulation (RCA), compared to heparin (HA) and no anticoagulation (NA) (42, IQR 32-58 h; 24, IQR 14-34 h; 18, IQR 12-24 h, respectively, p < 0.001). RCA was associated with longer MCL regardless of the patient's age or dialyser surface. In multivariate analysis, MCL correlated with dialyser surface area (beta = 0.14, p = 0.016), left internal jugular vein vascular access site (beta = -0.37, p = 0.027), and the use of HA (beta = -0.14, p = 0.038) or NA (beta = -0.37, p < 0.001) vs. RCA. RCA was associated with the highest ratio of elective circuit changes and the lowest incidence of complications. CONCLUSION: Anticoagulation modality, dialyser surface, and vascular access site influence MCL. RCA should be considered when choosing first-line anticoagulation for CKRT in children. Further efforts should focus on developing guidelines and clinical practice recommendations for paediatric CKRT.

Citrate and low-dose heparin combined anticoagulation in pediatric continuous renal replacement therapy.

There remains no optimal anticoagulation protocol for continuous renal replacement therapy (CRRT) with regional citrate anticoagulation (RCA) in pediatric patients with elevated D-dimer levels. We aimed to assess the effects of different anticoagulation strategies on the risk of CRRT filter clotting in these patients. Pediatric patients undergoing CRRT were retrospectively grouped based on pre-CRRT D-dimer levels and anticoagulant: D-RCA group (normal D-dimer, RCA only, n = 22), D+ RCA group (elevated D-dimer, RCA only, n = 50), and D+ RCA+ systemic heparin anticoagulation (SHA) group (elevated D-dimer, RCA combined with SHA, n = 55). The risk of filter clotting and incidence of bleeding were compared among the groups. Among the groups, the D+ RCA+ SHA group had the longest filter lifespan; further, the incidence of bleeding was not increased by concurrent use of low-dose heparin for anticoagulation. Moreover, concurrent heparin anticoagulation was associated with a decreased risk of filter clotting. Contrastingly, high pre-CRRT hemoglobin and D-dimer levels and post-filter ionized calcium level > 0.4 mmol/L were associated with an increased risk of filter clotting. RCA combined with low-dose heparin anticoagulation could reduce the risk of filter clotting and prolong filter lifespan without increasing the risk of bleeding in patients with elevated D-dimer levels undergoing CRRT.

Safety and Feasibility of Regional Citrate Anticoagulation for Continuous Renal Replacement Therapy With Calcium-Containing Solutions: A Randomized Controlled Trial.

BACKGROUND: Calcium-free (Ca-free) solutions are theoretically the most ideal for regional citrate anticoagulation (RCA) in continuous renal replacement therapy (CRRT). However, the majority of medical centers in China had to make a compromise of using commercially available calcium-containing (Ca-containing) solutions instead of Ca-free ones due to their scarcity. This study was designed to probe into the potential of Ca-containing solution as a secure and efficient substitution for Ca-free solutions. METHODS: In this prospective, randomized single-center trial, 99 patients scheduled for CRRT were randomly assigned in a 1:1:1 ratio to one of three treatment groups: continuous veno-venous hemodialysis Ca-free dialysate (CVVHD Ca-free) group, continuous veno-venous hemodiafiltration calcium-free dialysate (CVVHDF Ca-free) group, and continuous veno-venous hemodiafiltration Ca-containing dialysate (CVVHDF Ca-containing) group at cardiac intensive care unit (CICU). The primary endpoint was the incidence of metabolic complications. The secondary endpoints included premature termination of treatment, thrombus of filter, and bubble trap after the process. RESULTS: The incidence of citrate accumulation (18.2% vs. 12.1% vs. 21.2%) and metabolic alkalosis (12.1% vs. 0% vs. 9.1%) did not significantly differ among three groups (p > 0.05 for both). The incidence of premature termination was comparable among the groups (18.2% vs. 9.1% vs. 9.1%, p = 0.582). The thrombus level of the filter and bubble trap was similar in the three groups (p > 0.05 for all). CONCLUSIONS: In RCA-CRRT for CICU population, RCA-CVVHDF with Ca-containing solutions and traditional RCA with Ca-free solutions had a comparable safety and feasibility. TRIAL REGISTRATION: ChiCTR2100048238 in the Chinese Clinical Trial Registry.

Nafamostat mesylate versus regional citrate anticoagulation for continuous renal replacement therapy in patients at high risk of bleeding: a retrospective single-center study.

PURPOSE: The choice of continuous renal replacement therapy (CRRT) anticoagulation program for patients at high risk of bleeding has always been a complex problem in clinical practice. Clinical regimens include regional citrate anticoagulation (RCA) and nafamostat mesylate (NM). This study aimed to evaluate the efficacy and safety of these two anticoagulants for CRRT in patients at high risk of bleeding to guide their clinical use better. PATIENTS AND METHODS: Between January 2021 and December 2022, 307 patients were screened for this study. Forty-six patients were finally enrolled: 22 in the regional citrate anticoagulation group and 24 in the nafamostat mesylate group. We collected patients' baseline characteristics, laboratory indicators before CRRT, and CRRT-related data. We then performed a statistical analysis of the data from both groups of patients. RESULTS: In our study, the baseline characteristics did not differ significantly between the two groups; the baseline laboratory indicators before CRRT of patients in the two groups were not significantly different. The duration of CRRT was 600 min in the regional citrate anticoagulation (RCA) group, 615 min in the nafamostat mesylate (NM) group; the success rate was 90.7% in the RCA group, and 85.6% in the NM group, the anticoagulant efficacy between the two groups was comparable. There was no significant difference in the safety of anticoagulation between the two groups. We used Generalized Estimating Equations (GEE) to test whether different anticoagulation methods significantly affected the success rate of CRRT and found no statistical difference between RCA and NM. CONCLUSION: Our study suggests that nafamostat mesylate's anticoagulant efficacy and safety are not inferior to regional citrate anticoagulation for continuous renal replacement therapy in patients at high risk of bleeding.

Clinical application of regional citrate anticoagulation for membrane-based therapeutic plasma exchange in children with liver failure.

Background: Regional citrate anticoagulation (RCA) is being used more commonly in children for continuous renal replacement therapy. Few reports describe the application of membrane-based therapeutic plasma exchange (mTPE) with RCA in children with liver failure (LF). Aims: To explore the application of RCA-mTPE in children with LF. Methods: We retrospectively analyzed data from children with LF who underwent RCA-mTPE in the Children's Hospital of Chongqing Medical University's pediatric intensive care unit. We used the total to ionized calcium ratio (T/iCa) > 2.5 as the diagnostic criteria for citrate accumulation (CA). The patients were divided into two groups according to the occureence of CA at the end of RCA-mTPE (CA group: T/iCa > 2.5; NCA group: T/iCa ≤ 2.5). To evaluate the clinical safety and efficacy of RCA-mTPE, the following data from medical records were assessed and compared between groups: clinical characteristics, reasons for LF, RCA-mTPE parameters and duration, laboratory findings, and complications. Results: In total, 92 RCA-mTPE treatments were administered to 21 children with LF over 3.8 ± 0.9 h. The following mean values were determined: blood flow rate (QB) = 2.8 ml/kg/min, 4% sodium citrate dose/blood flow rate ratio (QCi/QB) = 1.1(QCi,ml/kg/h); plasma dose/body weight ratio(QP/BW) = 18.5 (QP, ml/kg/h); 10% calcium gluconate dose/blood flow rate ratio (QCa/QB) = 0.2(QCa, ml/kg/h). The mean concentration of iCa in vitro was 0.38 ± 0.07 mmol/L. Citrate accumulation was recorded after 34 (37%) treatments. Hypocalcemia occurred in 11 (12%) and 7 (7.6%) treatments, during and after mTPE, respectively. Three hypotensive and one convulsive events, related to hypocalcemia, and two clotting events occurred during RCA-mTPE. After RCA-mTPE, the patients' pH, HCO3- and Na+ levels, and T/iCa were significantly increased and the total bilirubin (TB), conjugated bilirubin (DB), prothrombin time (PT), activated partial thromboplastin time (APTT), alanine aminotransferase (ALT), aspartate aminotransferase (AST),and ammonia levels were significantly decreased. The TB, DB, and lactic acid levels, before RCA-mTPE, were significantly higher in the CA group than in the NCA group, but there were no significance between the two groups in QB/BW, QCi/QB, and QP/BW, mTPE duration, and estimated amount of citrate metabolized. Conclusions: Children with LF undergoing RCA-mTPE are at risk of hypocalcemia. With proper protocol adjustment, however, RCA-mTPE can be used safely and effectively in these patients.

Quality indicators in prolonged hemodialysis with regional citrate anticoagulation with the genius system: retrospective cohort of critical patients with acute kidney injury.

BACKGROUND: Prolonged hemodialysis (HD) is performed from 6 to 12 h and can last up to 24 h. To prevent system clotting some studies suggest that Regional Citrate Anticoagulation (RCA) use reduces bleeding rates relative to systemic heparin. However, there may be difficulties in the patient's clinical management and completing the prescribed HD with Genius system using RCA. OBJECTIVE: To analyze safety Quality Indicators (IQs) and follow up on prolonged HD with 4% sodium citrate solution in a Genius® hybrid system. METHODS: This is a retrospective cohort conducted in an intensive care unit. RESULTS: 53 random sessions of prolonged HD with 4% sodium citrate solution of critically ill patients with AKI assessed. Evaluated safety indicators were dysnatremia and metabolic alkalosis, observed in 15% and 9.4% of the sessions, respectively. Indicators of effectiveness were system clotting which occurred in 17.3%, and the minimum completion of the prescribed HD time, which was 75.5%. CONCLUSION: The assessment of the indicators showed that the use of RCA with a 4% sodium citrate solution in prolonged HD with the Genius system in critically ill patients with AKI can be performed in a simple, safe, and effective way.

Treatment of dabigatran intoxication in critically ill patients with Acute Kidney Injury: The role of Sustained Low-Efficiency Dialysis.

The use of dabigatran in patients with non-valvular atrial fibrillation (AF) has widely increased in the last decades, due to its positive effects in terms of safety/efficacy. However, because of the risk of major bleeding, a great degree of attention has been suggested in elderly patients with multiple comorbidities. Notably, dabigatran mainly undergoes renal elimination and dose adjustment is recommended in patients with Chronic Kidney Disease (CKD). In this regard, the onset of an abrupt decrease of kidney function may further affect dabigatran pharmacokinetic profile, increasing the risk of acute intoxication. Idarucizumab is the approved antagonist in the case of dabigatran-associated major bleeding or concomitant need of urgent surgery, but its clinical use is limited by the lack of data in patients with Acute Kidney Injury (AKI). Thus, the early start of Extracorporeal Kidney Replacement Therapy (EKRT) could be indicated to remove the drug and to reverse the associated excess anticoagulation. Sustained Low-Efficiency Dialysis (SLED) could represent an effective therapeutic option to reduce the dabigatran plasma levels rapidly while avoiding post-treatment rebound. We present here a case series of three AKI patients with acute dabigatran intoxication, effectively and safely resolved with a single SLED session.

Safety and Metabolic Tolerance of Citrate Anticoagulation in Critically Ill Polytrauma Patients with Acute Kidney Injury Requiring an Early Continuous Kidney Replacement Therapy.

For severe polytrauma patients with an early AKI requiring renal replacement therapy, anticoagulation remains a great challenge. Due to a high bleeding risk, hemodynamic instability, and increased lactate levels, continuous modality (CKRT) and citrate anticoagulation seem to be the most appropriate. However, their safety with regard to the potential risk of impaired citrate metabolism is not documented. A retrospective study of 60 severe polytrauma patients admitted to the emergency department between January 2000 and December 2021 was conducted; the patients requiring CKRT during the first 72 h were treated with citrate (n. 46, group Citrate) or with heparin (n. 14, group Heparin). Out of 60 patients, 31 survived (51.7%). According to logistic regression analysis, age and SOFA score were significant predictors of mortality. The incidence of rhabdomyolysis was more common in the survivors (77.4 vs. 51.7%), and Kaplan-Meyer analysis showed a better trend towards survival at 90 days for the group Citrate than the group Heparin (p 0.0956). In the group Citrate, hemorrhagic episodes were significantly less common (0.045 vs. 0.273 episodes/day, p < 0.001); the effective duration (h/day) of CKRT was longer; and the effective net ultrafiltration rate (mL/kg/h) and blood flow rate were lower. For severe polytrauma patients, early, soft CKRT with citrate anticoagulation at a low blood flow rate and circuit citratemia showed a better safety and hemodynamic stability, suggesting that citrate should be the first choice anticoagulant in this subset of patients.

Feasibility, Efficacy, and Safety of Peripheral Venous Access for Chronic Double-Filtration Plasmapheresis with Regional Citrate Anticoagulation.

INTRODUCTION: Peripheral venous access (PVA) is recommended as a first-line vascular approach for therapeutic plasmapheresis with centrifugation methods but not filtration, which usually requires high blood flow. We evaluated the feasibility, efficacy, and safety of double-filtration plasmapheresis (DFPP) with PVA, using ultrasound guidance and regional citrate anticoagulation (RCA), i.e., PVA-RCA-DFPP in patients undergoing chronic DFPP. Secondly, we assessed the number of central venous catheters (CVCs) avoided. METHODS: A single-center retrospective study evaluated 22 adult patients on chronic DFPP to perform PVA-RCA-DFPP. They were classified into 3 groups: successful (i.e., completion of sessions with PVA), primary failure (i.e., no sessions completed), secondary failure (i.e., ≥1 session with PVA completed but secondary return with CVC or arteriovenous fistula). RESULTS: Among the 22 patients included (64% men), 7 patients (32%) were classified as primary failures (2 patient refusals, 5 inadequate PVAs), 1 patient (5%) as a secondary failure (due to uncomfortable venipunctures), and 14 patients (64%) as successful. In the successful group including 12 patients treated for chronic inflammatory demyelinating polyneuropathy (CIDP) and 2 patients for familial hypercholesterolemia (FH) (2 patients), 116 sessions were performed, with a median treated plasma volume of 4.3 L [IQR 3.6-4.6] (45 mL/kg) for a median duration of 134 min [IQR 122-144], and a median blood flow of 94 mL/min [IQR 87-103]. For the CIDP group, 90% of sessions achieved a plasma volume >1 TPV, and for the FH group 91% of sessions achieved an LDLc reduction >60%. Eleven sessions out of 116 (9%) were interrupted, mostly due to PVA dysfunction (5/11) and circuit clotting (4/11). Session interruptions decreased significantly between each patient's first and following sessions (29% to 7%, p = 0.009). CONCLUSION: Chronic PVA-RCA-DFPP can be performed safely and efficiently, avoiding the use of CVCs.

Safety of Citrate Anticoagulation in CKRT: Monocentric Experience of a Dynamic Protocol of Calcium Monitoring.

Regional Citrate Anticoagulation (RCA) is considered the first-line anticoagulation for Continuous Kidney Replacement Therapy (CKRT). The RCA requires strict protocols and trained staff to avoid unsafe use and ensure its benefit. We have analyzed all our CKRT prescriptions from December 2020 to April 2022 anonymously, collecting data on CKRT, lab tests, clinical conditions, and complications of RCA. In addition, in order to better detect citrate accumulation, we have performed an RCA protocol by reducing the CaTot/Ca2+ ratio cut-off from 2.50 to 2.40 and increasing the number of calcium checks according to its trend. Among the 374 patients in CKRT, 104 received RCA prescriptions, of which 11 (10.6%) were discontinued: 4 for the suspicion of citrate accumulation, 1 for the development of metabolic alkalosis, 1 for the shift to a different CKRT procedure due to the need for a higher bicarbonate dose, 4 for the elevation of hepatocytolysis indexes, and 1 due to a preemptive discontinuation following massive post-surgery bleeding. None of the patients have had citrate toxicity as indicated by a CaTot/Ca2+ greater than 2.50, and our protocol has allowed the early identification of patients who might develop clinical citrate toxicity.

Evaluation of the efficacy and associated complications of regional citrate anticoagulation in neonates: experience from a fourth level neonatal intensive care unit.

Continuous kidney replacement therapy (CKRT) use has increased in recent years, but anticoagulation is a challenge for neonates. Regional citrate anticoagulation (RCA) is rarely preferred in neonates because of citrate accumulation (CA) and metabolic complications. We aimed to demonstrate the efficacy and safety of RCA in neonates. We retrospectively analyzed the medical records of 11 neonates treated with RCA-CKRT between 2018 and 2023. The initial dose of RCA was 2.1-3 mmol/l, and then, its dose was increased according to the level of ionized calcium (iCa+2) in the circuit and patients. The total/iCa+2 ratio after-treatment > 2.5 was indicated as CA. We evaluated to citrate dose, CA, circuit lifespan, and dialysis effectivity. The median gestational age was 39 (36.4-41.5) weeks, the median body weight (BW) was 3200 (2400-4000) grams, and the mean postnatal age was 4 (2-24) days. The most common indication for CKRT was hyperammonemia (73%). All neonates had metabolic acidosis and hypocalcemia during CKRT. Other common metabolic complications were hypophosphatemia (90%), hypokalemia (81%), and hypomagnesemia (63%). High dialysate rates with a median of 5765 ml/h/1.73 m2 allowed for a rapid decrease in ammonia levels to normal. Four patients (36.3%) had CA, and seven (63.7%) did not (non-citrate accumulation, NCA). Mean BW, median postnatal age, biochemical parameters, coagulation tests, and ammonia levels were similar between the CA and NCA groups. Low pH, low HCO3, high lactate, and SNAPPE-II scores could be associated with a higher T/iCa ratio. CONCLUSION:  RCA was an efficient and safe anticoagulation for neonates requiring CKRT. Metabolic complications may occur, but they could be managed with adequate supplementation. WHAT IS KNOWN: • Continuous kidney replacement therapy (CKRT) has become popular in recent years due to its successful treatment of fluid overload, electrolyte imbalance, metabolic acidosis, multi-organ failure, and hyperleucinemia/hyperammonemia associated with inborn errors of metabolism. • The need for anticoagulation is the major difficulty in neonatal CKRT. In adult and pediatric patients, regional citrate anticoagulation has been shown to be effective. WHAT IS NEW: • RCA is an effective and safe anticoagulation method for neonates who require CKRT. • Electrolyte imbalances and metabolic acidosis could be managed with adequate supplementation and appropriate treatment parameters such as citrate dose, blood flow rate, and dialysate flow rate.

Novel blood product transfusion regimen to prevent clotting and citrate accumulation during continuous renal replacement therapy with regional citrate anticoagulation in children.

Objective: Introduce a novel protocol to prevent clotting and citrate accumulation (CA) from blood product transfusion (BPT) during continuous renal replacement therapy (CRRT) with regional citrate anticoagulation (RCA) in children. Methods: We prospectively compared fresh frozen plasma (FFP) and platelet transfusions between the two BPT protocols, direct transfusion protocol (DTP) and partial replacement of citrate transfusion protocol (PRCTP), in terms of the risks of clotting, citric accumulation (CA), and hypocalcemia. For DTP, blood products were directly transfused without any adjustment to the original RCA-CRRT regimen. For PRCTP, the blood products were infused into the CRRT circulation near the sodium citrate infusion point, and the dosage of 4% sodium citrate was reduced depending on the dosage of sodium citrate in the blood products. Basic information and clinical data were recorded for all children. Heart rate, blood pressure, ionized calcium (iCa) and various pressure parameters were recorded before, during and after BPT, as well as coagulation indicators, electrolytes, and blood cell counts before and after BPT. Results: Twenty-six children received 44 PRCTPs and 15 children received 20 DTPs. The two groups had similar in vitro ionized calcium (iCa) concentrations (PRCTP: 0.33 ± 0.06 mmol/L, DTP: 0.31 ± 0.04 mmol/L), total filter lifespan (PRCTP: 49.33 ± 18.58, DTP: 50.65 ± 13.57 h), and filter lifespan after BPT (PRCTP: 25.31 ± 13.87, DTP: 23.39 ± 11.34 h). There was no visible filter clotting during BPT in any of the two groups. The two groups had no significant differences in arterial pressure, venous pressure, and transmembrane pressure before, during, or after BPT. Neither treatment led to significant decreases in WBC, RBC, or hemoglobin. The platelet transfusion group and the FFP group each had no significant decrease in platelets, and no significant increases in PT, APTT, and D-dimer. The most clinically significant changes were in the DTP group, in which the ratio of total calcium to ionized calcium (T/iCa) increased from 2.06 ± 0.19 to 2.52 ± 0.35, the percentage of patients with T/iCa above 2.5 increased from 5.0% to 45%, and the level of in vivo iCa increased from 1.02 ± 0.11 to 1.06 ± 0.09 mmol/L (all p < 0.05). Changes in these three indicators were not significant in the PRCTP group. Conclusion: Neither protocol was associated with filter clotting during RCA-CRRT. However, PRCTP was superior to DTP because it did not increase the risk of CA and hypocalcemia.

Regional citrate anticoagulation (RCA) in critically ill patients undergoing renal replacement therapy (RRT): expert opinion from the SIAARTI-SIN joint commission.

Renal replacement therapies (RRT) are essential to support critically ill patients with severe acute kidney injury (AKI), providing control of solutes, fluid balance and acid-base status. To maintain the patency of the extracorporeal circuit, minimizing downtime periods and blood losses due to filter clotting, an effective anticoagulation strategy is required.Regional citrate anticoagulation (RCA) has been introduced in clinical practice for continuous RRT (CRRT) in the early 1990s and has had a progressively wider acceptance in parallel to the development of simplified systems and safe protocols. Main guidelines on AKI support the use of RCA as the first line anticoagulation strategy during CRRT in patients without contraindications to citrate and regardless of the patient's bleeding risk.Experts from the SIAARTI-SIN joint commission have prepared this position statement which discusses the use of RCA in different RRT modalities also in combination with other extracorporeal organ support systems. Furthermore, advise is provided on potential limitations to the use of RCA in high-risk patients with particular attention to the need for a rigorous monitoring in complex clinical settings. Finally, the main findings about the prospective of optimization of RRT solutions aimed at preventing electrolyte derangements during RCA are discussed in detail.

Impact of increasing post-filter ionized calcium target on filter lifespan in renal replacement therapy with regional citrate anticoagulation: A before-and-after study.

INTRODUCTION: Regional citrate anticoagulation (RCA) is the recommended method for anticoagulation in continuous renal replacement therapy (CRRT). However, the optimal post-filter ionized calcium (iCa) target level remains unclear. This study aims to assess the effect of increasing the post-filter iCa target level from 0.25-0.35 mmol/L to 0.30-0.40 mmol/L on filter lifespan until clotting during RCA-CRRT. METHODS: This before-and-after single-center study included patients who underwent RCA-CRRT sessions without systemic anticoagulation during two periods. The first period included patients with a post-filter iCa target between 0.25 and 0.35 mmol/L, while the second period included those with a target between 0.30 and 0.40 mmol/L. The primary outcome was filter lifespan until clotting. RESULTS: A total of 1037 CRRT sessions were analyzed, with 610 sessions in the first period and 427 sessions in the second period. After adjusting for confounding factors, there was no significant difference in filter lifespan until clotting between the two groups (hazard ratio, 1.020 [0.703; 1.481]; p = 0.92). CONCLUSION: Increasing the post-filter iCa target level from 0.25-0.35 mmol/L to 0.30-0.40 mmol/L during RCA-CRRT does not reduce filter lifespan until clotting and may decrease unnecessary citrate exposure. However, the optimal post-filter iCa target should be individualized according to the patient's clinical and biological status.