Safety Of Regional Citrate Anticoagulation Research Articles

Regional citrate anticoagulation vs systemic heparin anticoagulation for double-filtration plasmapheresis.

Double-filtration plasmapheresis (DFPP) has been utilized for immunomodulation in kidney transplantation. Anticoagulation is important to maintain circuit patency during DFPP. We aimed to compare the efficacy and safety of regional citrate anticoagulation (RCA) with systemic heparin anticoagulation during DFPP in kidney transplant recipients. A retrospective cohort study was conducted to compare the efficacy and safety of RCA (RCA-DFPP) to systemic heparin anticoagulation (Hep-DFPP) for DFPP among kidney transplant recipients in a single tertiary center. A total of 112 sessions of DFPP were performed for 23 subjects, of which 62 sessions were RCA-DFPP and 50 sessions were Hep-DFPP. There were 13 sessions (11.6%) of premature circuit clotting, 10 sessions (16.1%) for RCA-DFPP and 3 sessions (6.0%) for Hep-DFPP (P=.10). All premature circuit clotting episodes occurred in subjects who underwent DFPP through a vascular catheter. Premature circuit clotting was associated with the use of a vascular catheter (odds ratio [OR] 14.2, 95% confidence interval [CI] 2.7-73.7; P < .01) and high postfilter ionized calcium (OR 12.7, 95% CI 1.4-112.5; P < .01). There was no major bleeding event. Hep-DFPP was associated with higher occurrence of hypocalcemia (OR 1.1, 95% CI 1.0-1.2; P < .01) and metabolic acidosis (OR 1.4, 95% CI 1.2-2.0; P=.04), while hypomagnesemia was more common for RCA-DFPP (OR 2.9, 95% CI 1.1-7.4; P=.03). Amongst kidney transplant patients who receive DFPP therapy, RCA-DFPP may be comparable to Hep-DFPP for the maintenance of circuit patency. Functioning vascular access is vital in avoiding premature clotting of the circuit. Close monitoring of electrolyte imbalances and coagulopathy related to DFPP is recommended.

A mathematical estimation for quantified calcium supplementation during intermittent hemodialysis using regional citrate anticoagulation.

Regional citrate anticoagulation has been recommended as an alternative of anticoagulation for patients at high risk of bleeding undergoing intermittent hemodialysis. Precise calcium supplementation is important for the safety of regional citrate anticoagulation. In this study, we aimed to develop a possible method to optimize calcium supplementation for regional citrate anticoagulation in intermittent hemodialysis. The investigation consisted of a pilot study and a validation study. 18 patients undergoing intermittent hemodialysis anticoagulated by citrate, and six types of filters were included in the pilot study. The ionized calcium levels were monitored and maintained in the targeted range. Calcium-free dialysate was used in the study. After linear regression analysis of the clearance of non-protein bound calcium and calculating the ratio of the non-protein bound calcium concentration to total calcium concentration, we developed a mathematical model for estimation of extracorporeal circuit calcium removal. Another 8 maintenance hemodialysis patients (12 sessions) were enrolled in the validation study to validate the new version of the calcium supplementation approach. In the pilot study, positive correlations were found between the clearance of non-protein bound calcium and the hematocrit-adjusted clearance of creatinine and phosphate given in the dialyzer leaflet (R2 =0.31, p=0.0165). The ratio of the non-protein bound calcium concentration to total calcium concentration at the pre-filter point after infusion of citrate were constant about 0.75. In the validation study, we found that the systemic ionized calcium levels were stably maintained in the safe range and no filter clotting occurred during the hemodialysis when we used the new model of calcium supplementation. We developed a possible method to quantify calcium supplementation for intermittent hemodialysis anticoagulated by citrate which may help to avoid negative calcium balance and reduce the incidence of complications.

Optimized calcium supplementation approach in post-dilution CVVHDF using regional citrate anticoagulation.

Regional citrate anticoagulation has been recommended as first choice for anticoagulation of continuous renal replacement therapy. Precise calcium supplementation is important for the safety of regional citrate anticoagulation. In this study we aimed to provide an optimized calcium supplementation approach for regional citrate anticoagulation in post-dilution continuous venous-venous hemodiafiltration. Twenty-seven patients receiving post-dilution continuous venous-venous hemodiafiltration anticoagulated by citrate were included in this study. The ionized calcium levels were monitored and maintained in the targeted range. After linear regression analysis of the clearance of non-protein bound calcium and calculating the ratio of the non-protein bound calcium concentration to total calcium concentration, we concluded the mathematical model for calcium supplementation. Positive correlations were found between the clearance of non-protein bound calcium and both dialysate flow rates (r = 0.647, p < 0.001) and ultrafiltration plus substitution fluid flow rates (r = 0.525, p = 0.005). The ratio of the non-protein bound calcium concentration to total calcium concentration values at the pre-filter point after infusion of citrate were constant about 0.83. Based on the clearance and the calcium ratio, the amount of extracorporeal calcium removal can be estimated with a simplified equation. We provided an optimized calcium supplementation approach for post-dilution continuous venous-venous hemodiafiltration anticoagulated by citrate which may help to estimate the amount of extracorporeal circuit removal of calcium with regard to different dosages of regional citrate anticoagulation.

P1089REGIONAL CITRATE ANTICOAGULATION VERSUS LOW MOLECULAR WEIGHT HEPARIN ANTICOAGULATION FOR CONTINUS VENOVENOUS HEMOFILTRATION IN PATIENTS WITH SEVERE HYPERCALCEMIA: A RETROSPECTIVE CASE-CONTROL STUDY

Abstract Background and Aims Severe hypercalcemia, poor conservative treatment effect, or combined with renal dysfunction, heart failure, intermittent hemodialysis treatment is recommended. But calcium-free hemodialysis could cause rebound of serum calcium, hypovolemia and hypotension. Continuous renal replacement therapy (CRRT) is the most commonly used treatment in critically ill patients with severe AKI. Some case reports showed that CRRT successed control calcium with stable hemodynamics, no rebound hypercalcemia, but there was only one case used continuous venovenous hemofiltration (CVVH). During CVVH treatment, clotting in the extracorporeal circuit shortens the filter and catheter lifespan, causes blood loss, and decreases solute clearance, consequently, reduces the effectiveness of CVVH and increases the treatment cost and medical stuff’s workload. So how to safely decrease calcium level and how to choose appropriate anticoagulants during CVVH in esvere hypercalcemia patients is a challenging work. We conducted a retrospective study to evaluate the efficacy and safety of regional citrate anticoagulation (RCA) versus low molecular weight heparin (LMWH) anticoagulation for CVVH in severe hypercalcemia patients. Method Between January 2014 and May 2019, severe hypercalcemia patients requiring CVVH were screened and divided into the RCA and LMWH-anticoagulation group according to the CVVH anticoagulation strategy they accepted. Serum calcium reduction rate (RRSeCa), filter lifespan, bleeding, totCa/ionCa ratio, citrate accumulation, and catheter occlusion were evaluated as outcomes. Results Of the 33 included patients, RCA and LMWH-anticoagulation were employed for CVVH in 14 and 43 filters, respectively. The serum calcium reduction rate (RRSeCa) was not significantly different between the LMWH-anticoagulation and RCA group (P = 0.320). Compared to LMWH-anticoagulation, RCA significantly prolonged the filter lifespan (&amp;gt; 72 hours vs. 24.0 hours [IQR, 15.0-26.0], P = 0.012). The incidence of filter failure was 55.8% (24/43) in the LMWH -anticoagulation group and 21.4% (3/14) in the RCA group (P = 0.033), respectively. The adjusted results demonstrated that RCA could significantly reduce the risk of filter failure (P = 0.028, 95% CI 0.076-0.859, HR = 0.255). No citrate accumulation was observed in RCA-CVVH patients. Conclusion In patients with severe hypercalcemia who underwent CVVH, both RCA CVVH and LMWH-anticoagulation CVVH could effectively decrease calcium levels. RCA CVVH had better filter lifespan and no obvious adverse events, compared with the LMWH-anticoagulation CVVH. Further prospective, randomized, control studies are warranted to obtain robust evidences.

Regional citrate anticoagulation versus no-anticoagulation for continuous venovenous hemofiltration in patients with liver failure and increased bleeding risk: A retrospective case-control study.

ObjectiveThere are controversial opinions on anticoagulation for continuous venovenous hemofiltration (CVVH) in patients with liver failure (LF) and increased bleeding risk. Therefore, we conducted a retrospective study to evaluate the efficacy and safety of regional citrate anticoagulation (RCA) versus no-anticoagulation for CVVH in these patients.MethodsThe included patients were divided into RCA and no-anticoagulation group according to the CVVH anticoagulation strategy they accepted for CVVH. Filter lifespan, bleeding, citrate accumulation, catheter occlusion, and totCa/ionCa ratio were evaluated as outcomes.ResultsIn the original cohort, the filter lifespan of the RCA group (41 patients, 79 filters) was significantly longer than the no-anticoagulation group (62 patients, 162 filters) (> 72 hours vs 39.5 hours (IQR 31.2–47.8), P = 0.002). The adjusted results demonstrated that RCA could significantly reduce the risk of filter failure (HR = 0.459, 95%CI 0.26–0.82, P = 0.008). Four episodes of totCa/ionCa > 2.5 were observed in the RCA group and continuously accepted RCA-CVVH after the reduction of citrate dose and blood flow. No obvious citrate accumulation was observed in these patients. In the matched cohort, the filter lifespan of the RCA group was significantly longer than the no-anticoagulation group (P = 0.013) as well. No significant difference in the episodes of totCa/ionCa > 2.5 was observed between the two matched groups (P = 0.074). Both in the original cohort and the matched cohort, the bleeding, acidosis, alkalosis, and catheter occlusion incidences were not significantly different between the two groups.ConclusionsIn LF patients with increased bleeding risk who underwent CVVH, RCA could prolong the filter lifespan and be safely used with careful blood gas monitoring and citrate dose adjusting. Further prospective, randomized, control studies are warranted to obtain robust evidences.

Regional citrate anticoagulation versus low molecular weight heparin anticoagulation for continuous venovenous hemofiltration in patients with severe hypercalcemia: a retrospective cohort study

Purpose We conducted a retrospective study to evaluate the efficacy and safety of regional citrate anticoagulation (RCA) versus those of low molecular weight heparin (LMWH) anticoagulation for CVVH in severe hypercalcemia patients. Methods Between January 2014 and May 2019, 33 severe hypercalcemia patients underwent CVVH. Patients were divided into the RCA and LMWH groups. Calcium-free replacement solution was used. Serum total calcium reduction rate (RRSeCa), filter lifespan, bleeding, totCa/ionCa ratio, citrate accumulation, and catheter occlusion were evaluated as outcomes. Results RCA and LMWH were employed for CVVH in 14 and 43 filters, respectively. RRSeCa was not significantly different between the LMWH and RCA groups (p = .320), but RCA-CVVH was more effective in reducing ionized calcium at half of the time points (p < .05). RCA significantly prolonged the median filter lifespan (>72 h vs. 24.0 h [IQR, 15.0–26.0], p = .012). The incidence of filter failure was 55.8% (24/43) in the LMWH group and 21.4% (3/14) in the RCA group (p = .033). The adjusted results demonstrated that RCA could significantly reduce the risk of filter failure (p = .043, 95% CI 0.059–0.957, HR = 0.238). No citrate accumulation or bleeding episodes were observed in the RCA-CVVH group. Seven bleeding episodes (7/43, 16.3%) occurred in the LMWH-CVVH group. Conclusions In patients with severe hypercalcemia who underwent CVVH, RCA more effectively decreased calcium levels and had a superior filter lifespan and no obvious adverse events compared with LMWH. Further prospective, randomized, controlled studies are warranted to obtain robust evidence.

Regional Citrate Anticoagulation versus No-Anticoagulation for Continuous Venovenous Hemofiltration in Acute Severe Hypernatremia Patients with Increased Bleeding Risk: A Retrospective Cohort Study

Purpose: This study was aimed at evaluating the efficacy and safety of regional citrate anticoagulation (RCA) versus no-anticoagulation continuous venovenous hemofiltration (CVVH) in acute severe hypernatremia patients with increased bleeding risk. Materials and Methods: Acute severe hypernatremia patients with high bleeding risk who underwent CVVH in our center between January 2011 and October 2017 were considered as candidates. Patients who were <18 years old, with hypovolemic hypernatremia, and had systemic anticoagulation were excluded. The included patients were divided into RCA and no-anticoagulation groups according to their anticoagulation strategy during CVVH and matched by age, sequential organ failure assessment scores, and vasopressor dependency. Results: Of the 64 included patients, no-anticoagulation and RCA were employed for CVVH in 23 and 41 patients, respectively. The serum sodium reduction rate (RRSeNa) was not significantly different between the no-anticoagulation and RCA groups (p = 0.729). Compared to no-anticoagulation, RCA significantly prolonged the circuit survival time (15 h [4.1–23.9] vs. 51 h [21.3–80.7], p = 0.001). The incidence of filter failure was 65.2% (15/23) in the no-anticoagulation group and 2.4% (1/41) in the RCA group (p < 0.001), respectively. In the matched cohort, the RRSeNas were not different between the 2 groups (p = 0.569), and the filter lifespan was significantly longer in the RCA group as well (p < 0.001). Conclusion: RCA might be safe and effective for acute severe hypernatremia patients who underwent CVVH treatment. Further prospective, randomized, control trials are warranted to obtain robust evidences.

Safety and efficacy of regional citrate anticoagulation in continuous renal replacement therapy in the presence of acute kidney injury after hepatectomy

To evaluate the clinical effect and safety of regional citrate anticoagulation (RCA) in continuous renal replacement therapy (CRRT) for acute kidney injury (AKI) after hepatectomy. A retrospective analysis of the clinical data of all patients with AKI after hepatectomy for CRRT admitted to surgical intensive care unit (ICU) of the First Affiliated Hospital of Xi'an Jiaotong University from January 19th, 2013 to January 19th, 2018 was performed. According to the different anticoagulants, the patients were divided into no anticoagulant group (NA group), low molecular heparin anticoagulation (LMHA) group and RCA group. The general data of patients during the perioperative period; renal function, the internal environment, electrolyte and blood coagulation function before and after CRRT; the filter time, the number of filters and adverse events (bleeding, frequent filter blood coagulation, metabolic alkalosis, metabolic acidosis, hypocalcemia, citrate accumulation, etc.) during CRRT were collected. Kaplan-Meier survival curve was used to analyze the life span of the first filter during different anticoagulation. A total of 67 cases were included in this study, including 11 in the NA group, 25 in the LMHA group and 31 in the RCA group. There was no significant difference in gender, age, underlying disease, etiology (tumor), Child-Pugh stage (A or B), CT angiography (CTA), basic renal function [serum creatinine (SCr), cystatin C (Cys C)], the American Society of Anesthesiologists (ASA) stage; surgical approach; intraoperative bleeding volume, blood transfusion, blood pressure, time of duration of low blood pressure; and postoperative circulatory failure, hepatic insufficiency and sepsis among three groups. However, the length of ICU stay in RCA group was significantly less than the LMHA group and NA group (days: 8.16±2.24 vs. 10.48±5.11, 13.29±6.64, both P < 0.05). Compared with before CRRT, the levels of SCr, Cys C and Lac were significantly decreased in RCA group and LMHA group after CRRT [SCr (μmol/L): 89.02±21.90 vs. 248.30±55.32, 105.10±49.00 vs. 270.10±156.00; Cys C (mg/L): 2.18±0.95 vs. 2.94±1.26, 2.26±0.76 vs. 3.07±0.90; Lac (mmol/L): 2.21±1.46 vs. 3.62±1.73, 2.37±1.24 vs. 4.03±1.69, all P < 0.05]; in addition, LMHA group and NA group had significant effects on hemoglobin (Hb), platelet count (PLT) and activated partial thromboplastin time (APTT) after CRRT [Hb (g/L): 85.4±5.1 vs. 99.6±23.6, 80.0±7.6 vs. 101.4±7.8; PLT (×109/L): 27.60±8.22 vs. 62.04±16.49, 21.36±3.91 vs. 61.45±17.69; APTT (s): 63.07±10.25 vs. 41.52±3.65, 49.56±5.77 vs. 41.09±3.45, all P < 0.05]; at the same time, Cys C level and prothrombin time (PT) in the NA group after CRRT treatment were significantly increased compared with the others [Cys C (mg/L): 3.59±0.64 vs. 2.29±0.51, PT (s): 26.41±2.43 vs. 23.64±1.92 , both P < 0.05]. Finally, the time of filters (hours: 60.52±8.82, 31.04±7.03, 13.73±6.26, F = 183.412, P < 0.001) and the number of filter during treatment (number: 2.03±0.60, 3.12±0.73, 4.64±1.29, F = 45.933, P < 0.001) in the RCA group, LMHA group and NA group had statistically significant difference. Meanwhile, the incidence of adverse events such as bleeding (0 vs. 4, 7, χ 2 = 23.961, P < 0.001) and frequent filter coagulation (1 vs. 10, 11, χ 2 = 35.413, P < 0.001) in RCA group was significantly lower than that in LMHA group and NA group. Kaplan-Meier survival analysis showed that the life time of the first filter in RCA group was significantly longer than that in LMHA group and NA group (χ2 = 139.45, P < 0.05). The application of RCA in patients with AKI after hepatectomy during CRRT is safe and effective, which can significantly prolong the life of the filter and reduce the risk of bleeding.

The safety of regional citrate anticoagulation in renal replacement therapy.

The safety of regional citrate anticoagulation in renal replacement therapy.

Clinical research on regional citrate anticoagulation for continuous veno-venous hemofiltration in children

Objective To study the reasonable doses, efficacy and safety of regional citrate anticoagulation(RCA) for continuous veno-venous hemofiltration(CVVH) in children. Methods There were 66 patients hospita-lized in Pediatric Intensive Care Unit of Zhujiang Hospital, Southern Medical University treated with RCA-CVVH that were recruited in the study from October 2012 to July 2014.The patients were divided into 4 groups according to their weight: ≤10 kg(group Ⅰ), 20 kg≥weight>10 kg(group Ⅱ), 30 kg≥weight>20 kg(group Ⅲ), >30 kg(group Ⅳ), and each group randomly received 2 different doses of anticoagulant acid citrate dextrose formula A(ACD-A): ACD-A(mL/h)=0.75×blood flow rate(BFR)(mL/min)(A dose) and ACD-A=1.5×BFR(B dose). Data of hemofilter duration, activated partial thromboplastin time(APTT)(systemic and circuit), ionized calcium(Ca2+) (systemic and circuit), blood urea nitrogen(BUN), serum creatinine(Cr), alanine aminotransferase(ALT), aspartate aminotransferase(AST), blood pH, sodium ion(Na+), bicarbonate ion(HCO3-) were collected and analyzed. Results There was no significant difference in BUN, Cr, ALT, AST and APTT of 2 different doses of ACD-A among the groups(all P>0.05); pH of B dose of ACD-A in group Ⅰwas significantly higher than that in A dose(F=7.384, P=0.015); pH of B dose of ACD-A in group Ⅱ was significantly higher than that in A dose(F=4.492, P=0.046), HCO3- of B dose of ACD-A in group Ⅰ was significantly higher than that in A dose(F=7.735, P=0.013); HCO3- of B dose of ACD-A in group Ⅱwas significantly higher than that in A dose(F=4.644, P=0.042); hemofilter duration of B dose of ACD-A in group Ⅲ was significantly higher than that in A dose(t=-3.147, P=0.016); hemofilter duration of B dose of ACD-A in group Ⅳ was significantly higher than that in A dose(t=-6.342, P=0.000). Conclusions RCA-CVVH is effective and safe for critical children, and different doses of ACD-A for children with different weight can reduce metabolic alkalosis and enhance regional anticoagulation. Key words: Continuous veno-venous hemofiltration; Child; Citrate; Anticoagulation

Randomized Controlled Trial to Evaluate Regional Citrate Anticoagulation Plus Low-Dose of Dalteparin in Continuous Veno-Venous Hemofiltration

Background/Aims: To evaluate the efficacy and safety of regional citrate anticoagulation (RCA) plus low-dose dalteparin in patients receiving continuous veno-venous hemofiltration (CVVH). Methods: Patients requiring pre-dilution CVVH at 4 l/h were randomly assigned to group A (RCA only), group B (normal-dose dalteparin anticoagulation only) or group C (RCA plus low-dose dalteparin). The primary endpoint was filter runtime and the secondary endpoints were premature clotting of the filter and anticoagulation-related side effects. Results: Fifty-three patients completed the study. The mean filter runtime was significantly longer in group C (40.4 ± 30.9 h) than those in group A (21.2 ± 13.5 h, p = 0.006) and group B (25.1 ± 24.0 h, p = 0.040). The rate of premature clotting, new onset of bleeding, hypocalcemia and metabolic acidosis did not differ significantly in three groups. Conclusions: RCA plus low-dose dalteparin prolonged filter runtime compared with RCA only or normal-dose dalteparin only without increasing the incidence of anticoagulation-related complications.

Hemostasis in patients with acute kidney injury secondary to acute liver failure

Acute kidney injury (AKI) occurs in over half of patients with acute liver failure. Despite prolonged prothrombin times and thrombocytopenia, continuous renal replacement therapy circuits frequently develop clots during patient treatment. Here we assessed factors contributing to this by measuring coagulation parameters (standard coagulation tests, pro- and anticoagulant factors, thromboelastography, and thrombin generation) in 20 consecutive patients with acute liver failure; mean age 42 years. Within 48 h, 10 had developed stage 3 AKI and 9 required continuous renal replacement therapy, of whom 2 had frequent circuit clots. The patients with stage 3 AKI were found to have significantly lower platelet counts and levels of factor V and the natural anticoagulants antithrombin, Protein C and Protein S, but increased extrinsic pathway activation and von Willebrand factor levels. Tissue factor levels were greater in those with stage 3 AKI, as was microparticle activity. Although patients with acute liver failure and advanced AKI requiring continuous renal replacement therapy have an even more marked thrombocytopenia and more prolonged extrinsic pathway activation, this was not associated with increased bleeding. Thus, more frequent circuit clots during continuous renal replacement therapy appear to be due to a combination of increased tissue factor and microparticle release, endothelial activation, and reduction in natural anticoagulants.

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)

Efficacy and safety of regional citrate anticoagulation in critically ill patients undergoing continuous renal replacement therapy

Regional citrate anticoagulation (RCA) is an attractive anticoagulation mode in continuous renal replacement therapy (CRRT) because it restricts the anticoagulatory effect to the extracorporeal circuit. In recent years, several randomized controlled trials have been conducted to investigate its superiority over other anticoagulation modes. Thus, we performed a systematic review of available evidence on the efficacy and safety of RCA. A systematic review of randomized controlled trials investigating the efficacy and safety of RCA was performed. PubMed, Current Contents, CINAHL, and EMBASE databases were searched to identify relevance articles. Data on circuit life span, bleeding events, metabolic derangement, and mortality were abstracted. Mean difference was used for continuous variables, and risk ratio was used for binomial variables. The random effects or fixed effect model was used to combine these data according to heterogeneity. The software Review Manager 5.1 was used for the meta-analysis. Six studies met our inclusion criteria, which involved a total of 658 circuits. In these six studies patients with liver failure or a high risk of bleeding were excluded. The circuit life span in the RCA group was significantly longer than that in the control group, with a mean difference of 23.03 h (95% CI 0.45-45.61 h). RCA was able to reduce the risk of bleeding, with a risk ratio of 0.28 (95% CI 0.15-0.50). Metabolic stability (electrolyte and acid-base stabilities) in performing RCA was comparable to that in other anticoagulation modes, and metabolic derangements (hypernatremia, metabolic alkalosis, and hypocalcemia) could be easily controlled without significant clinical consequences. Two studies compared mortality rate between RCA and control groups, with one reported similar mortality rate and the other reported superiority of RCA over the control group (hazards ratio 0.7). RCA is effective in maintaining circuit patency and reducing the risk of bleeding, and thus can be recommended for CRRT if and when metabolic monitoring is adequate and the protocol is followed. However, the safety of citrate in patients with liver failure cannot be concluded from current analysis. The metabolic stability can be easily controlled during RCA. Survival benefit from RCA is still controversial due to limited evidence.

Efficacy and safety of regional citrate anticoagulation in liver transplant patients requiring post-operative renal replacement therapy

Liver transplant patients with acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT) early post-operatively are at high risk for bleeding. Using heparin for anticoagulation during CRRT may contribute to the increased bleeding risk. Regional anticoagulation with citrate may decrease the risk of bleeding. However, citrate anticoagulation may be associated with metabolic complications in patients with liver impairment. The aim of the study was to evaluate the safety and efficacy of citrate anticoagulation in liver transplant patients. All liver transplant recipients transplanted between November 2004 and August 2007, requiring CRRT and using citrate as the anticoagulant were included in this retrospective study. Demographic data, CRRT specific and metabolic data were collected and analysed. Sixty-eight patients (40 male/28 female) with a mean age of 47.1±11.8 years and a Model of End-stage Liver Disease score of 23±9 developed post-operative AKI requiring CRRT using citrate as the anticoagulant. The median duration on CRRT was 8 days (range 1-39 days) with a mean circuit life of 22.7±14.6 h. There was no relevant time trend of serum sodium, potassium, calcium, bicarbonate and pH values during CRRT. Bleeding occurred in 8 of 68 (11.7%) patients during CRRT. Regional citrate anticoagulation for CRRT in the early post-operative period after liver transplantation is effective and safe. Therefore, the general exclusion of citrate anticoagulation during CRRT in patients after liver transplantation is not justified.

Regional citrate anticoagulation in patients with liver failure supported by a molecular adsorbent recirculating system*

Regional citrate anticoagulation has emerged as a promising method in critically ill patients at high risk of bleeding. However, in patients with liver failure, citrate accumulation may lead to acid-base and electrolyte imbalances, notably of calcium. The aim of this study was to evaluate the feasibility and safety of regional citrate anticoagulation during liver support using a molecular adsorbent recirculating system as well as its effects on electrolyte and acid-base balance in patients with liver failure. Prospective observational study. University hospital. Twenty critically ill patients supported by molecular adsorbent recirculating system resulting from liver failure between January 2007 and May 2009. The median duration of molecular adsorbent recirculating system treatment was 20 hrs (interquartile range, 18-22 hrs). Two of 77 molecular adsorbent recirculating system treatments (2%) were prematurely discontinued as a result of filter clotting and bleeding, respectively. The median citrate infusion rate, necessary to maintain the postfilter ionized calcium between 0.2 and 0.4 mmol/L, was 3.1 mmol/L (interquartile range, 2.3-4 mmol/L) blood flow. The median calcium chloride substitution rate was 0.9 mmol/L (0.3-1.7 mmol/L) dialysate. Total serum calcium remained stable during molecular adsorbent recirculating system treatments. There was a statistically significant increase of the ratio of total calcium to systemic ionized calcium (2.04 ± 0.32 mmol/L to 2.17 ± 0.35; p = .01), which reflected citrate accumulation resulting from liver failure. Under close monitoring, no clinically relevant electrolytes or acid-base disorders were observed. Our results suggest that regional citrate anticoagulation is a safe and feasible method to maintain adequate circuit lifespan without increasing the risk of hemorrhagic complications while maintaining a normal acid-base as well as electrolyte balance in patients with liver failure supported by molecular adsorbent recirculating system.

Comparison of the efficacy and safety of two regional citrate anticoagulation protocols using acid citrate dextrose A or Prismocitrate 10/2, in patients with acute renal failure undergoing continuous venovenous haemodiafiltration

Continuous renal replacement therapy (CRRT) is the treatment of choice for acute renal failure in critically ill patients. Our study compared the efficacy and safety of regional citrate anticoagulation (RCA) with acid citrate dextrose A (ACD-A) against Prismocitrate 10/2 (Gambro). Use of Prismocitrate 10/2 eliminates the need for a separate infusion pump for ACD-A as it doubles as replacement fluid and anticoagulant. This removes a source of error in the calculation of fluid balance. The combination of tri-sodium citrate and citric acid in Prismocitrate 10/2 avoids the metabolic alkalosis associated with ACD-A [1,2].

Crush Syndrome after the Wenchuan Earthquake: New Experience with Regional Citrate Anticoagulation Continuous Veno-Venous Hemofiltration

Acute renal failure (ARF) related to crush syndrome is usually treated with hemodialysis. Continuous veno-venous hemofiltration (CVVH) has seldom been adopted in this situation due to the main drawback of continuous anticoagulation. The purpose of this study was to evaluate the effectiveness and safety of regional citrate anticoagulation (RCA)-CVVH in two crush syndrome patients following the Wenchaun earthquake. Two victims from the Wenchuan earthquake in Southwest China were admitted to our hospital on May 23, 2008, 11 days after their injury. The total entrapment time under the rubble was 5.5 and 22.5 hrs respectively. They remained oliguric on admission, in spite of vigorous treatment in the local hospital including aggressive fluid infusion, fasciotomy and intermittent hemodialysis. On admission, their serum myoglobin levels were 765 and 829 ng/mL, respectively. Further debridement and drainage were performed. RCA-CVVH was conducted; the citrate containing substitution fluid was infused in a pre-dilution manner at a rate of 4 l/h; calcium was infused through a separate access to the venous inlet of the double lumen catheter. The infusion rate was adjusted according to the serum ionized calcium and whole blood activated clotting time (WBACT). A low dose of low molecular weight heparin (LMWH) was infused at the rate of 150 approximately 300 U/h simultaneously for anticoagulation after anemia had been corrected and their wounds were stable. RCA-CVVH was substituted by conventional CVVH and LMWH anticoagulation when case 2 complicated with hypoxia. RCA-CVVH was well tolerated, hemodynamic status was stable, and no complications related with RCA-CVVH were noted. The body temperature and WBC decreased to normal range, while anemia and hypoalbuminia were corrected. The levels of serum myoglobin and creatine phosphokinase were also decreased to normal range. Their urine volume increased after 20 and 22 days of oliguria and the tubular function of the patients recovered well. Although the second case encountered acute cholecystitis and acute lung injury in the hospital, both the patients recuperated and neither of them underwent amputation. The present two crush patients have been successfully treated, but due to the limits of the small sample, it is difficult to generalize whether RCA-CVVH is safe enough for crush syndrome with a high risk of bleeding diathesis. Additional investigation with a larger number of patients is required. Fluid equilibrium, nutritional support, prevention of bleeding and infection are fundamental in this situation.

Safety of Regional Citrate Anticoagulation for Continuous Sustained Low Efficiency Dialysis (C-SLED) in Critically Ill Patients

Background. Sustained low efficiency dialysis (SLED) is a hybrid therapy that uses a conventional hemodialysis machine to deliver lower solute clearance over prolonged periods of time, typically 8 to 12 hours per treatment, and utilizes the same sodium and bicarbonate concentrations as intermittent hemodialysis. The therapy has been shown to be an effective dialysis mode for the critically ill patient with acute renal failure and hemodynamic instability. At our institution, critically ill patients requiring renal replacement therapy receive SLED on a continuous, 24-hour schedule (C-SLED). The higher dialysis dose with C-SLED compared to continuous venovenous hemodiafiltration (CVVHDF) or traditional SLED would likely alter the prescription needed to provide regional citrate anticoagulation and the incidence of hypernatremia and metabolic alkalosis. Objective. To evaluate the safety of utilizing regional citrate anticoagulation with continuous SLED in critically ill patients who frequently clot the hemofilter and have contraindications to systemic anticoagulation with heparin. We hypothesized that the higher dialysis dose with C-SLED would affect the prescription of citrate anticoagulation and the development of hypernatremia and metabolic alkalosis. Design. We prospectively followed the first 20 patients who received regional citrate anticoagulation on C-SLED for acute renal failure in the intensive care unit. Important outcomes measured included serum sodium, bicarbonate, ionized calcium concentration, serum pH, and PCO2. The number of clotting episodes for each patient while on regional citrate anticoagulation was recorded. Setting. Surgical and medical intensive care units at The University of Texas MD Anderson Cancer Center. Results. In over 2200 hours of continuous dialysis with citrate anticoagulation none of the 20 patients had derangements in the serum sodium or acid base status requiring cessation of regional citrate anticoagulation. In 14 patients, no clotting occurred during 1500 hours of SLED with the citrate infusion. There were eight episodes of hemofilter clotting in six patients during 750 hours of C-SLED. Conclusion. Regional citrate anticoagulation is a safe method of anticoagulation in critically ill patients on continuous SLED.

Regional Citrate Anticoagulation in Critically Ill Patients Treated with Plasma Filtration and Adsorption

Background: In high-risk bleeding conditions conventional systemic anticoagulation with heparin is a contraindication to renal replacement therapy. We evaluate the feasibility and safety of regional citrate anticoagulation in high-risk bleeding conditions during coupled plasma filtration adsorption (CPFA). Methods: Thirteen critically ill patients (9 severely burned, 4 polytraumas) with septic shock and acute renal failure treated with CPFA-CVVHD by using bicarbonate-based solutions (heparin-CPFA group, 58 sessions) or with CPFA-CVVHF using citrate (citrate-CPFA group, 36 sessions). Results: Plasma flow and used cartridges showed no differences between the citrate-CPFA and heparin-CPFA groups, while lost clotted cartridges were significantly lower in the citrate-CPFA group. Blood ionized calcium (iCa²⁺), Ca²⁺ infusion, pH and bicarbonates remained constant during citrate-CPFA, with no difference between pre- and post-cartridge plasma citrate. A significant positive correlation between iCa²⁺ in blood and ultrafiltrate was present. Conclusions: These results demonstrate the feasibility and safety of regional citrate anticoagulation in severely burned and polytrauma septic patients treated by CPFA.