A safe and effective protocol for postdilution hemofiltration with regional citrate anticoagulation.

BACKGROUND: Regional citrate anticoagulation (RCA) is recommended during continuous renal replacement therapy. Compared to systemic anticoagulation, RCA provides a longer filter lifespan with the risk of metabolic alkalosis and impaired calcium homeostasis. Surprisingly, most RCA protocols are designed for continuous veno-venous hemodialysis or hemodiafiltration. Effective protocols for continuous veno-venous hemofiltration (CVVH) are rare, although CVVH is a standard treatment for high-molecular-weight clearance. Therefore, we evaluated a new RCA protocol for postdilution CVVH. METHODS: This is a monocentric prospective interventional study to evaluate a new RCA protocol for postdilution CVVH. We recruited surgical patients with stage III acute kidney injury who needed renal replacement therapy. We recorded dialysis and RCA data and hemodynamic and laboratory parameters during treatment sessions of 72 h. The primary endpoint was filter patency at 72 h. The major safety parameters were metabolic alkalosis and severe hypocalcemia at any time. RESULTS: We included 38 patients who underwent 66 treatment sessions. The mean filter lifespan was 66 ± 12 h, and 44 of 66 (66%) filters were patent at 72 h. After censoring for non-CVVH-related cessation of treatment, 83% of all filters were patent at 72 h. The delivered dialysis dose was 28 ± 5 ml/kgBW/h. The serum levels of creatinine, urea and beta2-microglobulin decreased significantly from day 0 to day 3. Metabolic alkalosis occurred in one patient. An iCa++ below 1.0 mmol/L occurred in four patients. Citrate accumulation did not occur. CONCLUSIONS: We describe a safe, effective, and easy-to-use RCA protocol for postdilution CVVH. This protocol provides a long and sustained filter lifespan without serious adverse effects. The risk of metabolic alkalosis and hypocalcemia is low. Using this protocol, a recommended dialysis dose can be safely administered with effective clearance of low- and middle-molecular-weight molecules. TRIAL REGISTRATION: The study was approved by the medical ethics committee of Heinrich-Heine University Duesseldorf (No. 2018-82KFogU). The trial was registered in the local study register of the university (No: 2018044660) on 07/04/2018 and was retrospectively registered at ClinicalTrials.gov (ClinicalTrials.gov Identifier: NCT03969966) on 31/05/2019.

Epoprostenol (Prostacyclin Analog) as a Sole Anticoagulant in Continuous Renal Replacement Therapy for Critically Ill Children With Liver Disease: Single-Center Retrospective Study, 2010-2019.

OBJECTIVES: Despite deranged coagulation, children with liver disease undergoing continuous renal replacement therapy (CRRT) are prone to circuit clotting. Commonly used anticoagulants (i.e., heparin and citrate) can have side effects. The aim of this study was to describe our experience of using epoprostenol (a synthetic prostacyclin analog) as a sole anticoagulant during CRRT in children with liver disease. DESIGN: Single-center, retrospective study, 2010-2019. SETTING: Sixteen-bedded PICU within a United Kingdom supra-regional center for pediatric hepatology. PATIENTS: Children with liver disease admitted to PICU who underwent CRRT anticoagulation with epoprostenol. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Regarding CRRT, we assessed filter life duration, effective 60-hour filter survival, and effective solute clearance. We also assessed the frequency of major or minor bleeding episodes per 1,000 hours of CRRT, the use of platelet and RBC transfusions, and the frequency of hypotensive episodes per 1,000 hours of CRRT. In the 10 years 2010-2019, we used epoprostenol anticoagulation during 353 filter episodes of CRRT, lasting 18,508 hours, in 96 patients (over 108 admissions). Median (interquartile range [IQR]) filter life was 48 (IQR 32-72) hours, and 22.9% of filters clotted. Effective 60-hour filter survival was 60.5%.We identified that 5.9% of filters were complicated by major bleeding (1.13 episodes per 1,000 hr of CRRT), 5.1% (0.97 per 1,000 hr) by minor bleeding, and 11.6% (2.22 per 1,000 hr) by hypotension. There were no differences in filter life or clotting between patients with acute liver failure and other liver diseases; there were no differences in rates of bleeding, hypotension, or transfusion when comparing patients with initial platelets of ≤ 50 × 109 per liter to those with a higher initial count. CONCLUSIONS: Epoprostenol, or prostacyclin, as the sole anticoagulant for children with liver disease receiving CRRT in PICU, results in a good circuit life, and complications such as bleeding and hypotension are similar to reports using other anticoagulants, despite concerns about coagulopathy in this cohort.

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.

An individualized regional citrate anticoagulation protocol for hemodialysis: a real-world retrospective study.

OBJECTIVE: To evaluate the safety and effectiveness of an individualized regional citrate anticoagulation (RCA) protocol for hemodialysis. METHODS: In this single-center, retrospective study, blood coagulation in the extracorporeal circulation, adverse reactions, in vivo ionized calcium (iCa2+) concentrations, and the infusion dose of citrate during RCA in hemodialysis were observed in 98 patients from February 2021 to March 2022. RESULTS: A total of 98 patients underwent RCA during hemodialysis 362 times, and blood coagulation occurred in the extracorporeal circulation 29 times. Among the 29 cases of coagulation, most of the patients exhibited hypercoagulability, and among approximately 80% of the treatments, the deviation between the actual infusion rate of citrate in the extracorporeal circulation and the theoretical value was ± 10%. After hemodialysis, pH values and bicarbonate ion (HCO3-) levels were clearly improved, and online conductivity monitoring (OCM) values and blood coagulation scores in the extracorporeal circulation were identical to those measured in similar studies. CONCLUSION: An individualized RCA protocol for hemodialysis is safe, effective, simple, and inexpensive and can meet the needs of individualized treatment; therefore, its application is worthy of promotion.

Cost-effectiveness of taurolidine-citrate in a cohort of patients with intestinal failure receiving home parenteral nutrition.

BACKGROUND: Catheter-related bloodstream infections (CRBSIs) in patients receiving home parenteral nutrition (HPN) for chronic intestinal failure (CIF) are associated with significant morbidity and financial costs. Taurolidine is associated with a reduction in bloodstream infections, with limited information on the cost-effectiveness as the primary prevention. This study aimed to determine the cost-effectiveness of using taurolidine-citrate for the primary prevention of CRBSIs within a quaternary hospital. METHODS: All patients with CIF receiving HPN were identified between January 2015 and November 2022. Data were retrospectively collected regarding patient demographics, HPN use, CRBSI diagnosis, and use of taurolidine-citrate. The direct costs associated with CRBSI-associated admissions and taurolidine-citrate use were obtained from the coding department using a bottom-up approach. An incremental cost-effective analysis was performed, with a time horizon of 4 years, to compare the costs associated with primary and secondary prevention against the outcome of cost per infection avoided. RESULTS: Forty-four patients received HPN within this period. The CRBSI rates were 3.25 infections per 1000 catheter days before the use of taurolidine-citrate and 0.35 infections per 1000 catheter days after taurolidine-citrate use. The incremental cost-effectiveness ratio indicates primary prevention is the weakly dominant intervention, with the base case value of $27.04 per CRBSI avoided. This held with one-way sensitivity analysis. CONCLUSION: Taurolidine-citrate in the primary prevention of CRBSIs in patients with CIF receiving HPN is associated with reduced hospital costs and infection rates.

Exploring clinical evaluation indicators for predicting coagulation in the extracorporeal circulation circuit in hemodialysis patients receiving individualized regional citrate anticoagulation-A single-center, retrospective clinical study.

BACKGROUND: Citrate anticoagulation is an important anticoagulation method in hemodialysis (HD) but cannot completely prevent the occurrence of coagulation in the extracorporeal circulation (ECC) circuit, and the clinical coagulation status can significantly affect the effect of citrate anticoagulation. In this study, the relationships between clinical coagulation status indicators and coagulation in the ECC circuit in HD patients receiving individualized citrate anticoagulant were studied to explore indicators that may predict coagulation in the ECC circuit. METHODS: This study was a single-center, retrospective clinical study, and clinical data and laboratory tests related to the coagulation status of HD patients receiving individualized regional citrate anticoagulation (RCA) were collected. The relationships between indicators commonly used in clinical practice to evaluate clinical coagulation status and coagulation in the ECC circuit were statistically analyzed to find indicators that can predict the occurrence of coagulation in the ECC circuit. RESULTS: The individualized RCA had a good anticoagulation effect, and the actual citrate infusion rate in nearly 80% of the patients was within ±10% of the theoretical infusion rate. The combined diseases or conditions that affect the coagulation status in vivo may increase the incidence of coagulation in the ECC circuit. The clinical D-dimer level is an independent risk factor that affects and can predict coagulation in the ECC circuit, with a cutoff value of 2.03 mg/L, sensitivity of 59%, and specificity of 78%. CONCLUSION: Individualized RCA can meet the needs of most HD treatments. Abnormal coagulation status in HD patients may increase the incidence of coagulation in the ECC circuit during individualized RCA for HD, and the D-dimer level can predict the occurrence of coagulation in the ECC circuit during this treatment.

Anticoagulation in renal replacement therapies: Why heparin should be abandoned in critical ill patients?

Extracorporeal circuits used in renal replacement therapy (RRT) can develop thrombosis, leading to downtimes and reduced therapy efficiency. To prevent this, anticoagulation is used, but the optimal anticoagulant has not yet been identified. Heparin is the most widely used anticoagulant in RRT, but it has limitations, such as unpredictable pharmacokinetics, nonspecific binding to plasma proteins and cells, and the possibility of suboptimal anticoagulation or bleeding complications, specifically in critically ill patients with acute renal failure who are already at high risk of bleeding. Citrate anticoagulation is a better alternative, being considered a standard for continuous renal replacement therapy, since it is associated with a lower risk of bleeding complications and better efficacy, even in patients with acute renal failure or liver disease. The aim of this article is to provide an updated review of the different strategies of anticoagulation in renal replacement therapies that can be implemented in critical scenarios, focusing on the advantages and disadvantages of each one and the beneficial aspects of using citrate over heparin in critical ill patients.

Comparison of Class-Specific Side Effects Across Preventative Pharmacologic Therapies for Kidney Stone Disease.

INTRODUCTION: Clinical guidelines recommend monitoring for metabolic derangements while on preventive pharmacologic therapy for kidney stone disease. The study objective was to compare the frequency of side effects among patients receiving alkali citrate, thiazides, and allopurinol. METHODS: Using claims data from working-age adults with kidney stone disease (2008-2019), we identified those with a new prescription for alkali citrate, thiazide, or allopurinol within 12 months after their index stone-related diagnosis or procedure. We fit multivariable logistic regression models, adjusting for cohort characteristics like comorbid illness and medication adherence, to estimate 2-year measured frequencies of claims-based outcomes of acute kidney injury, falls/hip fracture, gastritis, abnormal liver function tests/hepatitis, hypercalcemia, hyperglycemia/diabetes, hyperkalemia, hypokalemia, hyponatremia, and hypotension. RESULTS: Our cohort consisted of 1776 (34%), 2767 (53%), and 677 (13%) patients prescribed alkali citrate, thiazides, or allopurinol, respectively. Comparing unadjusted rates of incident diagnoses, thiazides compared to alkali citrate and allopurinol were associated with the highest rates of hypercalcemia (2.3% vs 1.5% and 1.0%, respectively, P = .04), hypokalemia (6% vs 3% and 2%, respectively, P < .01), and hyperglycemia/diabetes (17% vs 11% and 16%, respectively, P < .01). No other differences with the other outcomes were significant. In adjusted analyses, compared to alkali citrate, thiazides were associated with a higher odds of hypokalemia (OR=2.01, 95% CI 1.44-2.81) and hyperglycemia/diabetes (OR=1.52, 95% CI 1.26-1.83), while allopurinol was associated with a higher odds of hyperglycemia/diabetes (OR=1.34, 95% CI 1.02-1.75). CONCLUSIONS: These data provide evidence to support clinical guidelines that recommend periodic serum testing to assess for adverse effects from preventive pharmacologic therapy.

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.

Calcium-Citrate Anticoagulation during Continuous Renal Replacement Therapy in Patients with Metformin Intoxication: A Case Series, Mathematical Estimation of Citrate Accumulation, and Literature Review.

INTRODUCTION: Metformin intoxication causes lactic acidosis by inhibiting Krebs' cycle and oxidative phosphorylation. Continuous renal replacement therapy (CRRT) is recommended for metformin removal in critically ill patients. According to current guidelines, regional citrate anticoagulation (RCA) is the first-line strategy. However, since metformin also inhibits citrate metabolism, a risk of citrate accumulation could be hypothesized. In the present study, we monitored the potential citrate accumulation in metformin-associated lactic acidosis (MALA) patients treated with CRRT and RCA using the physical-chemical approach to acid-base interpretation. METHODS: We collected a case series of 3 patients with MALA. Patients were treated with continuous venovenous hemofiltration (CVVH), and RCA was performed with diluted citrate solution. Citrate accumulation was monitored through two methods: the ratio between total and ionized plasma calcium concentrations (T/I calcium ratio) above 2.5 and the strong ion gap (SIG) to identify an increased concentration of unmeasured anions. Lastly, a mathematical model was developed to estimate the expected citrate accumulation during CVVH and RCA. RESULTS: All 3 patients showed a resolution of MALA after the treatment with CVVH. The T/I calcium ratio was consistently below 2.5, and SIG decreased, reaching values lower than 6 mEq/L after 48 h of CVVH treatment. According to the mathematical model, the estimated SIG without citrate metabolism should have been around 21 mEq/L due to citrate accumulation. CONCLUSIONS: In our clinical management, no signs of citrate accumulation were recorded in MALA patients during treatment with CVVH and RCA. Our data support the safe use of diluted citrate to perform RCA during metformin intoxication.

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.

Effectiveness of salvage catheters in home parenteral nutrition: A single-center study and systematic literature review.

BACKGROUND & AIMS: There are sparse data regarding the rate of catheter salvage and long-term effectiveness of antibiotic lock treatment outcome after central line-associated bloodstream infections (CLABSI). Objectives were to analyze the effectiveness of central venous catheter (CVC) rescue strategy and its impact on catheter lifespan. Secondary objective included effectiveness of taurolidine+4% citrate in primary prevention, compared to a secondary prevention strategy, by analyzing infection incidence during two successive periods. METHOD: Real-life 5-year observational study assessing CLABSI occurrence and CVC salvage outcomes in adult patients requiring Home Parenteral Nutrition (HPN) managed in a single-center Intestinal Failure Unit. RESULTS: Over the 5-year period, there were 106 confirmed infections (63/143 patients (44%)). Infection incidence was 0.92/1000 catheter-days. Incidence was 1.02/1000 catheter-days during the taurolidine+4% citrate period while lower at 0.84/1000 catheter-days (p = 0.034) during the systematic taurolidine lock period. Of the total number of infections, 89 CVCs were immediately removed and 17 were salvaged. The success rate of catheter salvage with antibiotic lock was 82.4%, with 53% remaining CLABSI-free at one year. The salvage strategy extended catheter lifespan by a median 165 days (IQR 50-214). However, the rate of new infection was significantly higher in instances of salvage (71.4%) vs. removal (36%). Parenteral Nutrition (PN) ≥12 months (p = 0.002), PN (vs. hydroelectrolytic support) (p = 0.028) and self-management by patients (p = 0.049) were independent risk factors of CLABSI. CONCLUSION: Catheter salvage appears to be an effective long-term strategy with >50% of CVCs remaining CLABSI-free at one year and a prolonged catheter life, although may expose to a more frequent and earlier infection recurrence. CLINICAL TRIAL REGISTRATION: Cohort approved by the French CNIL (National Committee for Data Protection, authorization number CNIL 2015-25). referred to as "observational research", "non-interventional", or « non-RIPH ¼.

Anticoagulation options for continuous renal replacement therapy in critically ill patients: a systematic review and network meta-analysis of randomized controlled trials.

BACKGROUND: Continuous renal replacement therapy (CRRT) is a widely used standard therapy for critically ill patients with acute kidney injury (AKI). Despite its effectiveness, treatment is often interrupted due to clot formation in the extracorporeal circuits. Anticoagulation is a crucial strategy for preventing extracorporeal circuit clotting during CRRT. While various anticoagulation options are available, there were still no studies synthetically comparing the efficacy and safety of these anticoagulation options. METHODS: Electronic databases (PubMed, Embase, Web of Science, and the Cochrane database) were searched from inception to October 31, 2022. All randomized controlled trials (RCTs) that examined the following outcomes were included: filter lifespan, all-cause mortality, length of stay, duration of CRRT, recovery of kidney function, adverse events and costs. RESULTS: Thirty-seven RCTs from 38 articles, comprising 2648 participants with 14 comparisons, were included in this network meta-analysis (NMA). Unfractionated heparin (UFH) and regional citrate anticoagulation (RCA) are the most frequently used anticoagulants. Compared to UFH, RCA was found to be more effective in prolonging filter lifespan (MD 12.0, 95% CI 3.8 to 20.2) and reducing the risk of bleeding. Regional-UFH plus Prostaglandin I2 (Regional-UFH + PGI2) appeared to outperform RCA (MD 37.0, 95% CI 12.0 to 62.0), LMWH (MD 41.3, 95% CI 15.6 to 67.0), and other evaluated anticoagulation options in prolonging filter lifespan. However, only a single included RCT with 46 participants had evaluated Regional-UFH + PGI2. No statistically significant difference was observed in terms of length of ICU stay, all-cause mortality, duration of CRRT, recovery of kidney function, and adverse events among most evaluated anticoagulation options. CONCLUSIONS: Compared to UFH, RCA is the preferred anticoagulant for critically ill patients requiring CRRT. The SUCRA analysis and forest plot of Regional-UFH + PGI2 are limited, as only a single study was included. Additional high-quality studies are necessary before any recommendation of Regional-UFH + PGI2. Further larger high-quality RCTs are desirable to strengthen the evidence on the best choice of anticoagulation options to reduce all-cause mortality and adverse events and promote the recovery of kidney function. Trial registration The protocol of this network meta-analysis was registered on PROSPERO ( CRD42022360263 ). Registered 26 September 2022.

Non-anticoagulant factors affecting coagulation in the extracorporeal circulation circuit and the development of an individualized regional citrate anticoagulation protocol for hemodialysis: A real-world retrospective study.

OBJECTIVE: To investigate non-anticoagulant factors that affect blood coagulation in the extracorporeal circulation (ECC) circuit of regional citrate anticoagulation (RCA) protocol for hemodialysis (HD). METHOD: The clinical characteristics of patients undergoing an individualized RCA protocol for HD between February 2021 and March 2022 were collected; Coagulation scores, pressures in various parts of the ECC circuit, the incidence of coagulation, and citrate concentrations in the ECC circuit during treatment were determined, and non-anticoagulant factors affecting coagulation in the ECC circuit were analyzed. RESULT: The lowest clotting rate was 2.8% in patients with arteriovenous fistula in various vascular access. Patients on Fresenius dialysis had a lower rate of clotting in the cardiopulmonary bypass line than patients on other brands of dialyzer. Low-throughput dialyzers are less likely to clot than high-throughput dialyzers. There are significant differences in the incidence of coagulation among different nurses during citrate anticoagulant hemodialysis. CONCLUSION: In the process of citrate anticoagulant hemodialysis, non-anticoagulant factors such as coagulation status, vascular access, dialyzer selection, and operator quality will affect the anticoagulant effect.

Hirudin versus citrate as an anticoagulant for ROTEM platelet whole blood impedance aggregometry in thrombocytopenic patients.

Citrate is widely used as an anticoagulant for platelet function tests (PFTs). Due to an intrinsic inhibitory effect of citrate on platelet function, hirudin is used as an alternative. However, studies comparing the effect of these anticoagulants on rotational thromboelastometry (ROTEM) platelet whole blood impedance aggregometry in thrombocytopenic patients are scant. Cross-sectional study was done in 105 patients who entered the critical phase of Dengue hemorrhagic fever with plasma leakage and severe thrombocytopenia (<100 × 109/L). Samples were collected on two consecutive days and considered as a combined data set for analysis, out of which 200 have been included in the data analysis. Platelet count was used from routine full blood count. ROTEM platelet used TRAPTEM assay, which was performed with 3.2% sodium citrate and 525 ATU/ml hirudin anticoagulated blood. Means of all the TRAPTEM parameters were significantly higher in hirudin, compared to citrate samples (p < .05). Significantly higher overall platelet aggregation was observed in hirudinized samples with a significant mean difference (p < .05) compared to citrate in each quartile of platelet count. Higher platelet aggregation was observed with hirudin compared to citrate in ROTEM platelet whole blood impedance aggregometry in thrombocytopenic patients elaborating the importance of using hirudin anticoagulation in PFTs, particularly in patients with severe thrombocytopenia.

Citrate is the most commonly used anticoagulant for coagulation studies including rotational thromboelastometry (ROTEM).Hirudin is an alternative option to be used as an anticoagulant for PFTs because of the inhibitory effect of citrate on platelet function.One study (Nissen et al. (2020)) reported higher precision and platelet aggregation with hirudinized blood of healthy individuals, over citrate using ROTEM platelet.However, none of the studies were performed in patients in actual clinical context.We evaluated the potential benefit of using hirudin anticoagulated blood over citrate in thrombocytopenic patients due to Dengue hemorrhagic fever using ROTEM platelet.We observed higher platelet aggregation with hirudin compared to citrate suggesting the importance of using hirudin anticoagulation in PFTs, particularly in patients with severe thrombocytopenia.

Regional Citrate Anticoagulation or Heparin Anticoagulation for Renal Replacement Therapy in Patients With Liver Failure: A Systematic Review and Meta-Analysis.

In patients with liver failure complicated by acute kidney injury, renal replacement therapy (RRT) is often required to improve the internal environment. The use of anticoagulants for RRT in patients with liver failure remains controversial. We searched the PubMed, Embase, Cochrane Library, and Web of Science databases for studies. The methodological quality of the included studies was assessed using the Methodological Index for Nonrandomized Studies. A meta-analysis was performed using R software (version 3.5.1) and Review Manager (version 5.3.5). During RRT, 348 patients from 9 studies received regional citrate anticoagulation (RCA), and 127 patients from 5 studies received heparin anticoagulation (including heparin and LMWH). Among patients who received RCA, the incidence of citrate accumulation, metabolic acidosis, and metabolic alkalosis were 5.3% (95% confidence interval [CI]: 0%-25.3%), 26.4% (95% CI: 0-76.9), and 1.8% (95% CI: 0-6.8), respectively. The potassium, phosphorus, total bilirubin (TBIL), and creatinine levels were lower, whereas the serum pH, bicarbonate, base excess levels, and total calcium/ionized calcium ratio were higher after treatment than before treatment. Among patients who received heparin anticoagulation, the TBIL levels were lower, whereas the activated partial thromboplastin clotting time and D-dimer levels were higher after treatment than before treatment. The mortality rates in the RCA and heparin anticoagulation groups were 58.9% (95% CI: 39.2-77.3) and 47.4% (95% CI: 31.1-63.7), respectively. No statistical difference in mortality was observed between the 2 groups. For patients with liver failure, the administration of RCA or heparin for anticoagulation during RRT under strict monitoring may be safe and effective.

Evaluation of the registry DIALYREG for the assessment of continuous renal replacement techniques in the critically ill patient.

Continuous renal replacement techniques (CRRT) can induce complications and monitoring is crucial to ensure patient safety. We designed a prospective multicenter observational and descriptive study using the DIALYREG registry, an online database located on a REDCap web-based platform that allows real-time data analysis. Our main objective was to identify CRRT-related complications in our intensive care units (ICUs) and implement security measures accordingly. From January 2019 to December 2020, we included 323 patients with admission diagnoses of medical illness (54%), sepsis (24%), postoperative care (20%), and trauma (2%). CRRT indications were homeostasis (42%), oliguria (26%), fluid overload (15%), and hemodynamic optimization (13%). The median initial therapy dose was 30 ml/kg/h (IQR 25-40), and dynamic adjustment was performed in 61% of the treatments. Sets were anticoagulated with heparin (40%), citrate (38%) or no anticoagulation (22%). Citrate anticoagulation had several advantages: more frequent dynamic CRRT dose adjustment (77% vs. 58% with heparin and 56% without anticoagulation, p < 0.05), longer duration of set (median of 55 h, IQR 24-72 vs. 23 h, IQR 12-48 with heparin and 12 h, IQR 12-31 without anticoagulation, p < 0.05), less clotting of the set (26% vs. 46.7% with heparin, p < 0.05), and lower incidence of hypophosphatemia (1% citrate vs. 6% with heparin and 5% without anticoagulation). It was also safe and effective in subgroup analysis of patients with liver disease or sepsis. The main global complications were hypothermia (16%), hypophosphatemia (13%) and metabolic acidosis (10%). Weaning of the therapy was achieved through early discontinuation (56%), nocturnal therapy transition (26%) and progressive SLED (18%). 52% of the patients were discharged from the hospital, while 43% died in the ICU and 5% died during hospitalization. We can conclude that the DIALYREG registry is a feasible tool for real-time control of CRRT in our ICU.

Customized Citrate Anticoagulation versus No Anticoagulant in Continuous Venovenous Hemofiltration in Critically Ill Patients with Acute Kidney Injury: A Prospective Randomized Controlled Trial.

INTRODUCTION: The use of anticoagulants during continuous renal replacement therapy (CRRT) is essential. Regional citrate anticoagulation (RCA) is recommended rather than systemic heparinization to prolong the filter's lifespan in patients at high risk of bleeding. However, commercial citrate is expensive and may not be available in resource-limited areas. The objective of this study is comparing filter life between our locally made customized RCA and no anticoagulation. The primary outcomes were the first circuit life in hours and the number of filters used within the first 72 h of therapy. METHODS: We conducted a single-center prospective randomized controlled trial in critically ill patients requiring CRRT. The participants were randomized to receive continuous venovenous hemofiltration (CVVH) with either customized RCA or no anticoagulant. RESULTS: Of 76 patients, 38 were randomized to receive customized RCA and 38 to receive CVVH without anticoagulant. There was no significant difference in baseline characteristics between the two groups. Compared to anticoagulant-free group, the median circuit life of customized RCA group was significantly longer [44.9 (20.0, 72.0) vs. 14.3 (7.0, 22.0) hours; p < 0.001]. The number of filters used within 72 h was significant lower [2.0 (1.0, 2.0) vs. 2.5 (1.0, 3.0); p < 0.015]. RCA was prematurely discontinued in 5 patients due to citrate accumulation (2 cases) and severe metabolic acidosis requiring higher dose of CVVH (3 cases). No differences in bleeding complications were observed (p = 0.99). CONCLUSION: Customized citrate-based replacement solution improved filter survival in CVVH compared to anticoagulant-free strategy. This regimen is safe, feasible, and suitable for low- to middle-income countries.