Use Of Regional Citrate Anticoagulation Research Articles

Hypercitratemia is a mortality predictor among patients on continuous venovenous hemodiafiltration and regional citrate anticoagulation

The use of regional citrate anticoagulation (RCA) in liver failure (LF) patients can lead to citrate accumulation. We aimed to evaluate serum levels of citrate and correlate them with liver function markers and with the Cat/Cai in patients under intensive care and undergoing continuous venovenous hemodiafiltration with regional citrate anticoagulation (CVVHDF-RCA). A prospective cohort study in an intensive care unit was conducted. We compared survival, clinical, laboratorial and dialysis data between patients with and without LF. Citrate was measured daily. We evaluated 200 patients, 62 (31%) with LF. Citrate was significantly higher in the LF group. Dialysis dose, filter lifespan, systemic ionized calcium and Cat/Cai were similar between groups. There were weak to moderate positive correlations between Citrate and indicators of liver function and Cat/Cai. The LF group had higher mortality (70.5% vs. 51.8%, p = 0.014). Citrate was an independent risk factor for death, OR 11.3 (95% CI 2.74–46.8). In conclusion, hypercitratemia was an independent risk factor for death in individuals undergoing CVVHDF-ARC. The increase in citrate was limited in the LF group, without clinical significance. The correlation between citrate and liver function indicators was weak to moderate.

Clearance of Piperacillin-Tazobactam and Vancomycin During Continuous Renal Replacement With Regional Citrate Anticoagulation.

The use of regional citrate anticoagulation during continuous venovenous hemodiafiltration (CVVHDF) has increased worldwide. However, data on its effect on the pharmacokinetics of antibiotics are limited. In this study, the authors aimed to measure the clearance of piperacillin-tazobactam and vancomycin in patients receiving CVVHDF with regional citrate anticoagulation. This study measured piperacillin-tazobactam and vancomycin concentrations in patients receiving CVVHDF with regional citrate anticoagulation. Dosing regimens were independently selected by intensivists. Arterial blood and effluent fluid samples were obtained over a single dosing interval and analyzed using ultra-high-performance liquid chromatography with tandem mass spectrometry. Seventeen sampling intervals in 15 patients (9 receiving piperacillin-tazobactam only, 4 receiving vancomycin only, and 2 receiving both) were used. The median overall clearance for piperacillin was 35.2 mL/min [interquartile range (IQR): 32.2-38.6], 70 mL/min (IQR: 62.7-76.2) for tazobactam, and 29.5 mL/min (IQR: 26.2-32) for vancomycin. This is the first study to quantify the pharmacokinetics of vancomycin and piperacillin-tazobactam in patients receiving CVVHDF with regional citrate anticoagulation. These results indicate high clearance and provide key information to guide optimal dosing.

Artificial Intelligence in Continuous Kidney Replacement Therapy.

Artificial Intelligence in Continuous Kidney Replacement Therapy.

Use of regional citrate anticoagulation with medium cut-off membrane: pilot report

BackgroundRegional citrate anticoagulation during hemodialysis provides an immediate and complete anticoagulant effect, which is limited to the extracorporeal circuit. Citrate has become the standard anticoagulant in acute renal replacement therapy and is widely used in various intermittent hemodialysis modalities, especially for patients with contraindications for heparin. With the increased adoption of medium cut-off membranes, experience with regional citrate anticoagulation is needed. To our knowledge, this is the first report to assess the feasibility of regional citrate anticoagulation in expanded hemodialysis.MethodsWe prospectively analyzed 5 expanded hemodialysis procedures in 5 patients in which a medium cut-off membrane (Theranova®) was used. We followed our standard citrate protocol developed and tested for high-flux membrane. Anticoagulation was performed with a continuous infusion of 8% trisodium citrate into the arterial line and supplementation of 1 M calcium chloride into the venous line. We monitored ionized calcium and magnesium, sodium and blood gas analysis. Anticoagulation effectiveness was assessed by post-filter ionized calcium and by visual inspection of the anticoagulation in the circuit.ResultsThere were no prematurely terminated procedures due to anticoagulation-related complications. With a blood flow of 250 mL/min and a dialysate flow of 500 mL/min, we were able to maintain serum ionized calcium in the range of 0.89–1.29 mmol/L and serum sodium in the range of 136–144 mmol/L. The mean pre- and post-dialysis arterial circuit pH was 7.42 (± 0.04) and 7.53 (± 0.23), respectively. The mean pre- and post-dialysis serum ionized magnesium was 0.54 (± 0.04) mmol/L and 0.43 (± 0.03) mmol/L, respectively (measurements were done on a point-of-care ionometer with a lower normal range for ionized magnesium).ConclusionWe have shown that our standard citrate protocol for high-flux hemodialysis membrane could be successfully adopted for use in expanded hemodialysis with a medium cut-off membrane. Overall, electrolyte and acid-base balances were relatively well-controlled and anticoagulation effectiveness was excellent.Trial registrationThis is a pilot report with results taken from a larger ongoing trial (registered at ClinicalTrials.gov on October 25, 2019 under number NCT04139525) comparing citrate and heparin anticoagulation during expanded hemodialysis.

Effects of regional citrate anticoagulation in continuous veno-venous hemofiltration of severe burn patients

Objective: To investigate the effects of regional citrate anticoagulation in continuous veno-venous hemofiltration (CVVH) of severe burn patients. Methods: A retrospective non-randomized controlled study was conducted. From January 2017 to August 2020, sixty-eight severe burn patients who met the inclusion criteria were treated with CVVH in Affiliated Hospital of Nankai University. According to the different methods of blood anticoagulation in CVVH treatment, patients were divided into citrate group (n=40) and heparin group (n=28). In the citrate group, 32 males and 8 females were (40±18) years old with total burn area of (62±14)% total body surface area (TBSA); in the heparin group, 22 males and 6 females were (38±16) years old with total burn area of (57±20)%TBSA. Creatinine level, C-reactive protein (CRP) value, and urea nitrogen level in serum of patients were recorded at 0 (immediately), 48, and 96 h after CVVH treatment in 2 groups, urea clearance index was calculated based on urea nitrogen level at 0, 48, and 96 h after CVVH treatment in 2 groups, platelet count (PLT), prothrombin time (PT), and activated partial thromboplastin time (APTT) in total coagulation of patients were recorded. The frequency of forced hemofiltration termination caused by adverse reactions such as severe hypocalcemia, aggravated wound bleeding, and new bleeding on non-wound surface of patients was recorded within 96 h of CVVH treatment. The duration of daily CVVH use from the beginning to the end was recorded. Data were statistically analyzed with chi-square test, analysis of variance for repeated measurement, independent samples t test, and Bonferroni correction. Results: There were no significant differences in urea nitrogen level, creatinine level, and CRP value in serum of patients between 2 groups at 0 h after treatment (P>0.05). At 48 and 96 h after treatment, urea nitrogen level, creatinine level, and CRP value in serum of patients in citrate group were significantly lower than those in heparin group (t=3.366, -2.315, 2.942, -2.657, 2.011, -2.441, P<0.05), and urea clearance index of patients in citrate group was significantly higher than that in heparin group (t=1.017, 2.233, P<0.05). There were no statistically significant differences in PLT, PT, and APTT of patients between 2 groups at 0 h after treatment (P>0.05). At 48 and 96 h, PLT of patients in citrate group was significantly higher than that in heparin group (t=-3.417, -4.143, P<0.05 or P<0.01), PT of patients in citrate group was significantly shorter than that in heparin group (t=2.760, -3.655, P<0.01), APTT of patients in citrate group was significantly shorter than that in heparin group (t=3.719, 5.146, P<0.05 or P<0.01). Within 96 h of treatment, there was 1 case of hypocalcemia and 1 case of aggravated wound bleeding resulting in forced hemofiltration termination in citrate group, but there was no new bleeding on non-wound surface; in heparin group, there was no hypocalcemia, but 7 cases of aggravated wound bleeding and 2 cases of new bleeding on non-wound surface (both at the tracheotomy site) resulting in forced hemofiltration termination. The use time of blood purification filter of patients in citrate group was (11.7±4.8) h, obviously longer than (6.6±2.5) h in heparin group (t=3.310, P<0.01). Conclusions: The use of regional citrate anticoagulation in CVVH treatment of severe burn patients has the advantages including little effect on coagulation function and high safety, can effectively prolong the use time of filter and improve the therapeutic effect, but this conclusion still needs to be further verified in clinical application.

Development of a Multivariable Prediction Model for Citrate Accumulation in Liver Transplant Patients Undergoing Continuous Renal Replacement Therapy with Regional Citrate Anticoagulation

Introduction: Patients with impaired citrate metabolism may experience citrate accumulation (CA), which causes life-threatening metabolic acidosis and hypocalcemia. CA poses a challenge for clinicians when deciding on the use of regional citrate anticoagulation (RCA) for patients with liver dysfunction. This study aimed to develop a prediction model integrating multiple clinical variables to assess the risk of CA in liver transplant patients. Methods: This single-center prospective cohort study included postoperative liver transplant patients who underwent continuous renal replacement therapy (CRRT) with RCA. The study end point was CA. A prediction model was developed using a generalized linear mixed-effect model based on the Akaike information criterion. The predictive values were assessed using the receiver operating characteristic curve and bootstrap resampling (times = 500) to estimate the area under the curve (AUC) and the corresponding 95% confidence interval (CI). A nomogram was used to visualize the model. Results: This study included 32 patients who underwent 133 CRRT sessions with RCA. CA occurred in 46 CRRT sessions. The model included lactate, norepinephrine >0.1 μg/kg/min, alanine aminotransferase, total bilirubin, and standard bicarbonate, which were tested before starting each CRRT session and body mass index, diabetes mellitus, and chronic kidney disease as predictors. The AUC of the model was 0.867 (95% CI 0.786–0.921), which was significantly higher than that of the single predictor (p < 0.05). A nomogram visualized the prediction model. Conclusions: The prediction model integrating multiple clinical variables showed a good predictive value for CA. A nomogram visualized the model for easy application in clinical practice.

Regional citrate anticoagulation versus low molecular weight heparin for CRRT in hyperlactatemia patients: A retrospective case-control study

There were controversial opinions on the use of regional citrate anticoagulation (RCA) versus low molecular weight heparin (LMWH) for continuous renal replacement therapy (CRRT) in hyperlactatemia patients, which was considered as one of the contraindications of citrate. The aim of our present study is to evaluate the efficacy and safety of RCA versus LMWH for CRRT in hyperlactatemia patients. Adult patients with hyperlactatemia who underwent RCA or LMWH CRRT in our center between January 2014 and March 2018 were retrospectively recruited. Filter lifespan, ultrafiltration, purification, bleeding, citrate accumulation, filter clot, and the infusion of blood production were evaluated as endpoints. Of the 127 patients included in the original cohort, 81 and 46 accepted RCA and LMWH CRRT, respectively. The filter lifespan was significantly prolonged in the RCA group compared to the LMWH group (44.25 h [2 -83] vs. 24 h [4 -67], p < 0.001). The accumulated filter survival proportions were significantly improved in the RCA group compared to the LMWH group in the original cohort (p < 0.001) as well as the matched group (p < 0.001). The filters clotted more frequently in the LMWH group than in the RCA group in both of the original (52.2% vs 26.8%, p = 0.001) and matched cohort (58.6% vs 19.4%, p = 0.001). The bleeding complication was significantly reduced in the RCA group than in the LMWH group in the matched cohort (28.6% vs 4.5%, p = 0.04). In critically ill patients with hyperlactatemia requiring CRRT, RCA is superior to LMWH in terms of filter lifespan and bleeding risk without significantly increased risk of citrate accumulation and citrate related metabolic complications. RCA most likely is a safe and effective anticoagulation method for CRRT in patients with hyperlactatemia.

A simplified protocol for individualized regional citrate anticoagulation for hemodialysis: A single-center, randomized clinical study.

The lack of individualized treatment protocols and complicated procedures are important factors limiting the use of regional citrate anticoagulation (RCA) technology in hemodialysis. This study aims to validate the safety and efficacy of a simplified individualized RCA protocol for hemodialysis. From June 2019 to August 2019, 45 patients with active bleeding or bleeding tendency undergoing maintenance hemodialysis in the Nephrology Department of the First Affiliated Hospital of Nanchang University were randomly divided into a modified conventional RCA protocol group with a low-flux dialyzer, a simplified individualized RCA protocol group with a high-flux dialyzer, and a simplified individualized RCA protocol group with a low-flux dialyzer. A total of 45 patients were included in this study. The mean age of the patients was 57.38 ± 19.05 years, and 78% were men. Forty-three patients completed 4 hours of hemodialysis, and the median total clotting scores in the 3 groups were 11, 12, and 12. Compared with the modified conventional RCA protocol group with a low-flux dialyzer, the 2 simplified individualized RCA protocol groups had better clotting scores for the dialyzer, arterial bubble trap, and single-pool urea clearance index (spKt/VBUN) and lower costs. Moreover, these parameters did not differ between the 2 simplified individualized RCA protocol groups. No electrolyte or acid-base imbalances or citrate poisoning was observed in any of the 3 groups. Adverse events did not differ significantly among the 3 groups. The simplified individualized RCA protocol is safe, effective, and easy to implement. Therefore, this protocol can be promoted for clinical practice. This study was registered in the Chinese Clinical Study Registry under registration number ChiCTR1900023801.

An Observational Cohort Study of the 2-Month Use of Regional Citrate Anticoagulation in Maintenance Hemodialysis Patients with Cerebral Hemorrhage.

BackgroundRegional citrate anticoagulation (RCA) is a recommended anticoagulation alternative for patients at high risk of bleeding while undergoing intermittent hemodialysis. Previous reports implied the risk of citrate application on bone metabolism. It is unclear whether long-term use of RCA is safe for maintenance hemodialysis patients in terms of bone metabolism.Material/MethodsSeven patients with cerebral hemorrhage were included in the study. Blood samples were collected at baseline and 4 and 8 weeks after treatment. Spent dialysate samples were collected during each mid-week dialysis session, using the partial dialysate collection method. All patients were treated with RCA for 4 to 8 weeks, according to their clinical condition. We assessed bone metabolism-associated parameters, bone turnover markers, and magnesium loss at each dialysis session.ResultsSerum magnesium levels were 1.24±0.13 mmol/L at baseline and significantly decreased to 1.16±0.14 mmol/L after 4 weeks of RCA treatment (P=0.025). Most patients had negative magnesium balance during citrate hemodialysis. Serum total calcium levels did not change significantly after treatment. One bone marker, N-terminal propeptide of type I procollagen (PINP), significantly decreased from 146.07±130.12 mmol/L to 92.42±79.01 mmol/L after citrate treatment (P=0.018). No significant changes were detected in other bone turnover markers.ConclusionsRelatively long-term RCA treatment may decrease serum magnesium levels due to negative magnesium balance. Bone formation marker PINP seemed to decrease after treatment, while other bone turnover markers did not change significantly. Further investigation is needed to verify the effect of RCA on bone remodeling.

How To Prescribe And Troubleshoot Continuous Renal Replacement Therapy: A Case-Based Review.

Continuous RRT (CRRT) is the preferred dialysis modality for solute management, acid-base stability, and volume control in patients who are critically ill with AKI in the intensive care unit (ICU). CRRT offers multiple advantages over conventional hemodialysis in the critically ill population, such as greater hemodynamic stability, better fluid management, greater solute control, lower bleeding risk, and a more continuous (physiologic) approach of kidney support. Despite its frequent use, several aspects of CRRT delivery are still not fully standardized, or do not have solid evidence-based foundations. In this study, we provide a case-based review and recommendations of common scenarios and interventions encountered during the provision of CRRT to patients who are critically ill. Specific focus is on initial prescription, CRRT dosing, and adjustments related to severe hyponatremia management, concomitant extracorporeal membrane oxygenation support, dialysis catheter placement, use of regional citrate anticoagulation, and antibiotic dosing. This case-driven simulation is made as the clinical status of the patient evolves, and is on the basis of step-wise decisions made during the care of this patient, according to the specific patient's needs and the logistics available at the corresponding institution.

Effect of Regional Citrate Anticoagulation vs Systemic Heparin Anticoagulation During Continuous Kidney Replacement Therapy on Dialysis Filter Life Span and Mortality Among Critically Ill Patients With Acute Kidney Injury

Although current guidelines suggest the use of regional citrate anticoagulation (which involves the addition of a citrate solution to the blood before the filter of the extracorporeal dialysis circuit) as first-line treatment for continuous kidney replacement therapy in critically ill patients, the evidence for this recommendation is based on few clinical trials and meta-analyses. To determine the effect of regional citrate anticoagulation, compared with systemic heparin anticoagulation, on filter life span and mortality. A parallel-group, randomized multicenter clinical trial in 26 centers across Germany was conducted between March 2016 and December 2018 (final date of follow-up, January 21, 2020). The trial was terminated early after 596 critically ill patients with severe acute kidney injury or clinical indications for initiation of kidney replacement therapy had been enrolled. Patients were randomized to receive either regional citrate anticoagulation (n = 300), which consisted of a target ionized calcium level of 1.0 to 1.40 mg/dL, or systemic heparin anticoagulation (n = 296), which consisted of a target activated partial thromboplastin time of 45 to 60 seconds, for continuous kidney replacement therapy. Coprimary outcomes were filter life span and 90-day mortality. Secondary end points included bleeding complications and new infections. Among 638 patients randomized, 596 (93.4%) (mean age, 67.5 years; 183 [30.7%] women) completed the trial. In the regional citrate group vs systemic heparin group, median filter life span was 47 hours (interquartile range [IQR], 19-70 hours) vs 26 hours (IQR, 12-51 hours) (difference, 15 hours [95% CI, 11 to 20 hours]; P < .001). Ninety-day all-cause mortality occurred in 150 of 300 patients vs 156 of 296 patients (Kaplan-Meier estimator percentages, 51.2% vs 53.6%; unadjusted difference, -2.4% [95% CI, -10.5% to 5.8%]; unadjusted hazard ratio, 0.91 [95% CI, 0.72 to 1.13]; unadjusted P = .38; adjusted difference, -6.1% [95% CI, -12.6% to 0.4%]; primary adjusted hazard ratio, 0.79 [95% CI, 0.63 to 1.004]; primary adjusted P = .054). Of 38 prespecified secondary end points, 34 showed no significant difference. Compared with the systemic heparin group, the regional citrate group had significantly fewer bleeding complications (15/300 [5.1%] vs 49/296 [16.9%]; difference, -11.8% [95% CI, -16.8% to -6.8%]; P < .001) and significantly more new infections (204/300 [68.0%] vs 164/296 [55.4%]; difference, 12.6% [95% CI, 4.9% to 20.3%]; P = .002). Among critically ill patients with acute kidney injury receiving continuous kidney replacement therapy, anticoagulation with regional citrate, compared with systemic heparin anticoagulation, resulted in significantly longer filter life span. The trial was terminated early and was therefore underpowered to reach conclusions about the effect of anticoagulation strategy on mortality. ClinicalTrials.gov Identifier: NCT02669589.

Regional citrate anticoagulation vs no-anticoagulation for CRRT in hyperlactatemia patients with increased bleeding risk: A retrospective cohort study.

There are controversial opinions on the use of regional citrate anticoagulation (RCA) continuous renal replacement therapy (CRRT) in hyperlactatemia patients with increased bleeding risk. Patients with hyperlactatemia and increased bleeding risk who accepted RCA or no-anticoagulation CRRT in our center were retrospectively included. Eighty patients who underwent RCA-CRRT and 47 patients received no-anticoagulation CRRT were included. Filter lifespan was significantly longer in the RCA group than the no-anticoagulation group (44.5hours [2-89] vs 24.5hours [1.5-70], P<.001). The adjusted results demonstrated that patients in the no-anticoagulant group had significantly higher risk of filter failure (HR=4.765, 95% CI 2.703-8.4, P<.001). Bleeding episodes occurred in 19 (24.1%) and 22 (46.8%) patients in the RCA and no-anticoagulation group, respectively (P=.012). The overall citrate accumulation (CA) rate was 5% in the RCA group. Patient mortality was associated with the comorbidity of hypertension, increased serum lactate level, and increased SOFA score. After matching, the filter lifespan was significantly longer in the RCA group than the no-anticoagulation group. With careful monitoring and timely adjustment, RCA most likely was safe and effective for CRRT in hyperlactatemia patients with increased bleeding risk.

Attenuation of Circuit Longevity in COVID-19 Critical Illness with AKI on Continuous Venovenous Hemodiafiltration Despite the Use of Regional Citrate Anticoagulation (RCA) and Heparin-Bonded AN 69 (Oxiris®) Filter

Attenuation of Circuit Longevity in COVID-19 Critical Illness with AKI on Continuous Venovenous Hemodiafiltration Despite the Use of Regional Citrate Anticoagulation (RCA) and Heparin-Bonded AN 69 (Oxiris®) Filter

Use of regional citrate anticoagulation for continuous venovenous hemodialysis in critically ill cancer patients with acute kidney injury

PurposeThis study aimed to evaluate the safety and efficacy of a regional citrate anticoagulation (RCA) protocol for continuous venovenous hemodialysis (CVVHD) in cancer patients with acute kidney injury (AKI) in the intensive care unit (ICU) setting. Material and methodsOne hundred twenty two consecutive ICU cancer patients with AKI treated with citrate-based CVVHD were prospectively evaluated in this prospective observational study. ResultsA total of 7198 h of CVVHD therapy (250 filters) were performed. Patients were 61.3 ± 15.7 years old, 78% had solid cancer and the main AKI cause was sepsis (50%). The in-hospital mortality was 78.7%. Systemic ionized calcium (SCai) was 4.35 (4.10–4.60) mg/dL, severe hypocalcemia (SCai <3.6 mg/dL) was observed in 4.3% of procedures and post-filter ionized calcium was 1.60 (1.40–1.80) mg/dL. Median filter patency was 24.8 (11–43) hours. Factors related to filter clotting were: no tumor evidence (OR 0.44, CI 0.18–0.99); genitourinary tumor (OR 1.83, CI 1.18–2.81); platelets number (each 10,000/mm3) (OR 1.02, CI 1.00–1.04); International Normatized Ratio (INR) (OR 0.59, CI 0.41–0.85) and citrate dose (each 10 mL/h) (OR 0.88, CI 0.82–0.95). ConclusionFilter patency was relatively short and clotting was associated with active cancer disease, genitourinary tumor, lower citrate dose and lower INR.

Clinical Complications of Continuous Renal Replacement Therapy.

The various complications of continuous renal replacement therapy (CRRT) are mostly preventable. Hemodynamic disturbances are dominated by hypotension due to the modification of volume status, myocardial dysfunction, cardiac arrhythmia, or modification of systemic vascular resistances, which are correlated with body temperature changes. Metabolic complications remain at the forefront and have profoundly changed with the use of regional citrate anticoagulation (RCA). RCA may lead to two distinct situations: citrate overload and citrate accumulation, respectively, responsible for metabolic alkalosis and metabolic acidosis. Electrolyte imbalance is also a classic occurrence with RCA. The chelation of cations by citrate results in hypocalcemia and hypomagnesemia in case of inappropriate substitution. Hemorrhagic complications have been drastically reduced mostly for two reasons: the use of systematic ultrasound guidance for the insertion of dialysis catheters and the use of RCA instead of systemic heparin anticoagulation. Hypothermia induced by CRRT and complications associated with prolonged bed rest are also better controlled today. Finally, the removal of undesired substances remains a major issue, especially when it comes to antibiotics, vitamins and micronutrients, molecules for which the intake should be adapted in case of CRRT.

Regional citrate anticoagulation for RRTs in critically ill patients with AKI.

Hemorrhagic complications have been reported in up to 30% of critically ill patients with AKI undergoing RRT with systemic anticoagulation. Because bleeding is associated with significantly increased mortality risk, strategies aimed at reducing hemorrhagic complications while maintaining extracorporeal circulation should be implemented. Among the alternatives to systemic anticoagulation, regional citrate anticoagulation has been shown to prolong circuit life while reducing the incidence of hemorrhagic complications and lowering transfusion needs. For these reasons, the recently published Kidney Disease Improving Global Outcomes Clinical Practice Guidelines for Acute Kidney Injury have recommended regional citrate anticoagulation as the preferred anticoagulation modality for continuous RRT in critically ill patients in whom it is not contraindicated. However, the use of regional citrate anticoagulation is still limited because of concerns related to the risk of metabolic complications, the complexity of the proposed protocols, and the need for customized solutions. The introduction of simplified anticoagulation protocols based on citrate and the development of dialysis monitors with integrated infusion systems and dedicated software could lead to the wider use of regional citrate anticoagulation in upcoming years.

Citrate anticoagulation during continuous renal replacement therapy in pediatric critical care.

To provide the pediatric intensivist an in-depth understanding of citrate as regional anticoagulant during continuous renal replacement therapy. We searched the PubMed.gov database using the initial key words: citrate anticoagulation [title] AND continuous; citrate [title] AND pediatric AND continuous; prospective pediatric renal replacement AND citrate; and regional citrate anticoagulation. Additional searchers were performed using EMBASE, CINAHL, and SCOPUS with similar keywords and limits. Further articles were gathered from bibliographic references of relevant studies and reviews. Only articles published in English were reviewed. In the pediatric population, there are no prospective interventional or randomized studies comparing regional versus systemic anticoagulation. However, there are 11 (retrospective and prospective observational studies) in the pediatric population using citrate anticoagulation. These studies have shown that regional citrate anticoagulation in the pediatric population can be effective, provide equivalent circuit survival, and decrease bleeding compared with heparin anticoagulation. In the adult population, there are six prospective randomized controlled trials comparing the efficacy of regional citrate anticoagulation versus heparin. Two systematic reviews with meta-analysis of these six trials have been performed. The adult data on the use of regional citrate anticoagulation during continuous renal replacement therapy show a decreased risk of bleeding and at the least equivalent circuit survival as compared to heparin. Current pediatric and adult studies support regional citrate anticoagulation as an effective alternative to systemic heparin anticoagulation in most patient populations. Continuous renal replacement therapy is the most common modality of renal replacement in the critical care setting. Regional anticoagulation is an ideal option in a critically ill child after recent surgery or with coagulopathy. Therefore, regional citrate anticoagulation in the pediatric critical care population requiring renal replacement therapy is commonly employed. Complications of citrate anticoagulation can be avoided with a greater understanding of the properties and clearance of citrate. Continued reporting of observational data and the development of prospective multicenter trials using citrate anticoagulation are needed to ensure safe and standardized care in the pediatric population.

Regional citrate anticoagulation for continuous renal replacement therapy in severe burns—A retrospective analysis of a protocol-guided approach

IntroductionFor critically ill patients, the use of regional citrate anticoagulation as part of continuous renal replacement therapy (CRRT) has become increasingly common in recent years. However, there are scarce data on the use of this technique in patients with burns. The aim of this study was to examine the effectiveness, feasibility and complications of regional citrate anticoagulation for CRRT in burn patients, as well as the effects on coagulation and the electrolyte and acid–base balance. MethodsThis retrospective study included all patients who received renal replacement therapy with citrate anticoagulation to treat acute kidney injury (AKI) between January 1, 2004 and December 31, 2009 at the burn unit of St. Georg Hospital GmbH in Leipzig. ResultsDuring the examination period, 18 patients were treated using CRRT with regional citrate anticoagulation (CVVHDF in the pre-dilution mode). The median patient age was 64 years (49.5; 71), with a median TBSA of 42.5% (33.25; 52.5) and a median ABSI score of 10 (9; 10). The CRRT was initiated on a median of 6 days (4; 8.75) after admission to the hospital and continued for a median duration of 7 days (5; 8). The median dialysis dose was 38.2mlkgBW−1h−1 (31.8; 42.1). The median effective filter operation time was 67h (46; 72). No relevant disorders associated with acid–base balance, electrolytes or coagulation occurred, and there were no bleeding complications. ConclusionIn terms of bleeding risk and electrolyte and acid–base balance, regional citrate anticoagulation may be considered to be an effective, safe and user-friendly procedure for patients with severe burns and AKI.

Efficacy and Safety of Regional Citrate Anticoagulation in Critically Ill Patients Undergoing Continuous Renal Replacement Therapy

A meta-analysis of randomised controlled trials comparing regional citrate anticoagulation (RCA) to control anticoagulation for haemofiltration revealed that citrate anticoagulation is effective at maintaining circuit patency and reducing the risk of bleeding during haemofiltration. The use of regional citrate anticoagulation also prolongs the haemofiltration circuit life, but this result is not significant when compared to the use of heparin. There was however, marked heterogeneity between trials reported. Level of evidence: 1- (Meta-analysis with a high risk of bias)

A Retrospective Review of the Use of Regional Citrate Anticoagulation in Continuous Venovenous Hemofiltration for Critically Ill Patients

Background. The emergence of a commercially prepared citrate solution has revolutionized the use of RCA in the intensive care unit (ICU). The aim of this study was to evaluate the safety profile of a commercially prepared citrate solution. Method. Predilution continuous venovenous hemofiltration (CVVH) was performed using Prismocitrate 10/2 at 2500 mL/h and a blood flow rate of 150 mL/min. Calcium chloride solution was infused to maintain ionized calcium within 1.0–1.2 mmol/L. An 8.4% sodium bicarbonate solution was infused separately. Treatment was stopped when the predefined clinical target was reached or the filter clotted. Result. 58 sessions of citrate RCA were analyzed. The median circuit lifetime was 26.0 h (interquartile range IQR 21.2–44.3). The percentage of circuits lasting more than 12 h, 24 h, and 48 h was 94.6%, 58.9%, and 16.1%, respectively. There was no incidence of hypernatremia and median pH was <7.5. Hypomagnesemia and hypophosphatemia were detected in 41.6% and 17.6% of blood samples taken, respectively. Although 16 episodes had a total calcium/ionized calcium (total Ca/iCa) >2.5, only four patients had evidence of citrate accumulation. Conclusion. The commercially prepared citrate solution could be used safely in critically ill patients who required CVVH with no major adverse events.