Simplified citrate anticoagulation for continuous renal replacement therapy.

BACKGROUND: Regional anticoagulation with trisodium citrate is an effective form of anticoagulation for continuous renal replacement therapy (CRRT) for patients with contraindications to heparin. However, because of the metabolic complications of trisodium citrate, it is a complicated technique requiring specialized dialysis solutions. We have designed a simplified protocol for citrate regional anticoagulation for CRRT. METHODS: Two percent trisodium citrate was delivered at 250 mL/h via the prefilter port of a COBE PRISMA device, with the rate adjusted to maintain a postfilter ionized calcium (iCa++) <0.5 mmol/L. A central calcium gluconate infusion was used to maintain a systemic iCa++ at 1.1 mmol/L. A standard dialysate solution consisting of 0.9% saline, KCl 3 mmol/L, and MgSO4 1 mmol/L was delivered at 1000 mL/h. We retrospectively reviewed the outcomes and complications associated with this protoco1 in 29 patients treated from July 1999 to October 1999, evaluating the frequency of clotting of the dialyzer, bleeding complications, citrate toxicity, and patient mortality. RESULTS: The Kaplan-Meier curve for dialyzer survival demonstrated a 61% survival rate at 48 hours. There were no episodes of significant bleeding or citrate toxicity. Seventy-two percent of patients died for reasons unrelated to CRRT. CONCLUSIONS: A CRRT protocol using regional 2% trisodium citrate anticoagulation is not associated with significant bleeding complications or citrate toxicity, and represents a simplified approach compared with previous applications using 4% trisodium citrate.     

Regional citrate anticoagulation for continuous renal replacement therapy in newborns and infants: Focus on citrate accumulation

Continuous renal replacement therapy (CRRT) with regional citrate anticoagulation (RCA) in newborns and infants is challenging and accumulation of citrate can occur. There are only a few studies reporting the detailed data on RCA. We aimed to analyze RCA-CRRT at our institution with focus on citrate accumulation. Critically ill newborns and infants up to 11 kg of body weight (BW), treated with RCA-CRRT in the 2011-2016 period were included in this retrospective observational study. Prismaflex(R) and Multifiltrate-CiCa(R) dialysis monitors were used with either automated or manual RCA. Data was collected regarding the circuit lifetime, parameters of RCA, markers of citrate accumulation (total/ionized calcium ratio > 2.5), and metabolic complications. We included 10 children with mean age of 2.6 ± 3.8 months and BW of 4.6 ± 2.7 kg. In-hospital mortality was 60%. RCA-CRRT parameters were: blood flow 46 ± 9 mL/min (12 ± 5 mL/min/kg BW), citrate dose 2.8 ± 0.6 mmol/L of blood resulting in estimated citrate load to the patient of 1.7 ± 0.8 mmol/h/kg BW. In total, 57 dialysis circuits were used with mean filter lifetime of 39 ± 29 h. Citrate accumulation (total/ionized calcium ratio > 2.5) was observed in 7/10 patients and in 14/57 (25%) of circuits; those circuits were performed in children with lower age and BW, had higher relative blood flow and citrate load, while citrate dose was similar. When citrate load to the patient was used to predict citrate accumulation, AUC under the ROC curve was 0.78 and 1.7 mmol/h/kg BW was considered the optimal cutoff value (sensitivity 71% and specificity 72%). CRRT with RCA using equipment, developed for adult population, is feasible in newborns and infants. Signs of citrate accumulation developed relatively often. To prevent it, we suggest avoiding citrate loads above 1.7 mmol/h/kg BW, which can best be achieved by keeping the blood flow below 9 mL/min/kg BW.     

Acute renal failure - anticoagulation in continuous renal replacement therapy

Anticoagulation plays a pivotal role for the efficacy of continuous renal replacement therapy. The equilibrium between avoiding bleeding complications and keeping the system open considering patients} multiple diseases demands an individual and dynamic reasoned anticoagulation regime. For patients at risk of bleeding citrate anticoagulation has shown high efficacy and lesser bleeding complications than the standard heparin or other alternative anticoagulants such as regional protamin-heparin-, prostaglandin-heparin-anticoagulation or no anticoagulation.     

Intermittent hirudin versus continuous heparin for anticoagulation in continuous renal replacement therapy

BACKGROUND: Besides possible bleeding complications a further problem in anticoagulation during continuous renal replacement therapy (CRRT) is the development of heparin-induced thrombocytopenia type II (HIT II) where further anticoagulation with heparin is contraindicated. The application of continuous hirudin as alternative for heparin caused bleeding complications by comparable filter efficacy. Aim of this prospective-controlled pilot study was to compare the efficacy and safety of intermittent hirudin and continuous heparin for anticoagulation during CRRT in critically ill patients. METHODS: 26 patients receiving CRRT were randomly allocated to two groups: Heparin group (14 patients): continuous administration of 250 IU/h heparin, dose was adjusted in 125 IU/h steps with a targeted activated clotting time (ACT) of 180-210 s. Hirudin group (12 patients): initial bolus application of 2-2-5 microg/kg hirudin, dose was adjusted in 2 microg/kg bolus steps with a targeted ecarin clotting time (ECT) >80 s. Observation time was 96 hours. RESULTS: Measured filter run time was virtually longer for heparin. No bleeding complications were observed in the hirudin group, two bleeding complications in the heparin group. CONCLUSIONS: Intermittent hirudin can be used safely for anticoagulation in CRRT. However, the in tendency better filter survival for heparin elucidates the need for further investigations to find the right dosage equilibrium between filter clotting and bleeding complications.     

Citrate anticoagulation for continuous renal replacement therapy in small children

Background

Regional citrate anticoagulation (RCA) is one of the methods used to prevent clotting in continuous renal replacement therapy (CRRT). The aim of this study was to describe the outcomes and complications of RCA-CRRT in comparison to heparin anticoagulation (HA)-CRRT in critically ill children.

Methods

This study was a retrospective review of 30 critically ill children (16 on RCA- and 14 on HA-CRRT) who underwent at least 24 h of CRRT. The mean body weight of the children was 8.69?±?5.63 kg. RCA-CRRT was performed with a commercially available pre-dilution citrate solution (Prismocitrate 18/0).

Results

The mean time on RCA-CRRT and HA-CRRT was 148.73?±?131.58 and 110.24?±?105.38 h, respectively. Circuit lifetime was significantly higher in RCA-CRRT than in HA-CRRT (58.04?±?51.18 h vs. 37.64?±?32.51 h, respectively; p?=?0.030). Circuit clotting was observed in 11.63 % of children receiving RCA-CRRT and 34.15 % of those receiving HA-CRRT. Episodic electrolyte and metabolic disturbances were more common in children receiving RCA-CRRT. The survival at discharge from the hospital was 37.5 and 14.3 % among children receiving RCA-CRRT and HA-CRRT, respectively.

Conclusions

In critically ill children with a low body weight, RCA appeared to be safe and easy to used. Among our patient cohort, RCA was more effective in preventing circuit clotting and provided a better circuit lifetime than HA.     

Effects of dermatan sulfate for anticoagulation in continuous renal replacement therapy

BACKGROUND: Dermatan sulfate (DS) is a natural glycosaminoglycan with a unique mechanism of action on the coagulation system. Unlike unfractionated heparin (UFH), DS selectively inhibits thrombin, does not inhibit factor Xa, is effective on both free and fibrin-bound thrombin and does not interfere with platelets. This study represents the first experience using DS as anticoagulant in patients on continuous renal replacement therapy (CRRT). METHODS: A total of 147 patients in our intensive care unit who developed acute renal failure after cardiovascular surgery were on CRRT according to the same protocol: machine, Gambro Prisma; filter, AN69, 0.9 m2; QB, 150 ml/min; QD, 2,000 ml/hour; and Q(Infusate), 500 ml/hour. In a retrospective cohort of 100 patients, anticoagulation was performed with UFH (UFH-CRRT): initial bolus of 530 +/- 363 IU, then i.v. infusion of 598 +/- 261 IU/hour. A prospective cohort of 47 patients received DS (DS-CRRT) as a 150-mg bolus followed by a 13.5 +/- 3 mg/hour infusion. Hematology tests were performed at baseline and during CRRT; filter lifetime was measured from the start to filter clotting. RESULTS: Median filter lifetime was 58 hours in DS-CRRT vs. 47 hours in UFH-CRRT (p<0.001). No differences emerged in basal hematology and hemostasis tests between groups. During CRRT, DS produced a smaller activated partial thromboplastin time increase than UFH (p<0.01). Platelet count exhibited a comparable small decline in both DS-CRRT and UFH-CRRT (p<0.01). No significant bleeding episodes occurred during DS-CRRT. In-hospital mortality was similar in the 2 cohorts. CONCLUSIONS: DS can be suggested as an anticoagulant for CRRT in patients who develop acute renal failure following major cardiovascular surgery.     

Regional citrate versus systemic heparin anticoagulation for continuous renal replacement in critically ill patients

BACKGROUND: We determined the effect of regional citrate versus systemic heparin anticoagulation for continuous renal replacement therapy in critically ill subjects suffering from acute renal failure who were not at high risk for hemorrhagic complications. METHODS: Between April 1999 and June 2002, 30 critically ill subjects requiring continuous renal replacement therapy and using 79 hemofilters were randomly assigned to receive regional citrate or systemic heparin anticoagulation. RESULTS: The median hemofilter survival time was 124.5 hours (95% CI 95.3 to 157.4) in the citrate group, which was significantly longer than the 38.3 hours (95% CI 24.8 to 61.9) in the heparin group (P < 0.001). Increasing illness severity score, male gender, and decreasing antithrombin-III levels were independent predictors of an increased relative hazard of hemofilter failure. After adjustment for illness severity, antithrombin-III levels increased significantly more over the period of study in the citrate as compared to the heparin group (P= 0.038). Moreover, after adjustment for antithrombin-III levels and illness severity score, the relative risk of hemorrhage with citrate anticoagulation was significantly lower than that with heparin (relative risk of 0.14; 95% CI 0.02 to 0.96, P= 0.05). CONCLUSION: Compared with systemic heparin anticoagulation, regional citrate anticoagulation significantly increases hemofilter survival time, and significantly decreases bleeding risk in critically ill patients suffering from acute renal failure and requiring continuous renal replacement therapy.     

Unexpected severe hypocalcemia during continuous venovenous hemodialysis with regional citrate anticoagulation

Citrate is known to induce acute hypocalcemia in patients undergoing liver transplantation during the anhepatic phase. We describe the case of a 71-year-old woman with fulminant hepatic failure secondary to hepatitis A, who was started on continuous venovenous hemodialysis (CVVHD) for acute renal failure. Because anticoagulation with heparin was untenable, regional anticoagulation was accomplished by trisodium citrate (46.7%) infusion. Unfortunately, severe hypocalcemia developed when citrate accumulated because of impaired hepatic metabolism. Because of chelation by citrate, the ionized calcium concentration declined to values as low as 2.72 mg/dL (normal, 4.5 to 5.6 mg/dL), whereas the total calcium concentration remained in the normal range. With an unusually high calcium chloride infusion rate via a central line (up to 140 mL/h of 10 mEq/dL CaCl₂ ) and additional boli of CaCl₂ (for a total of 190 mEq), the ionized calcium concentration could be maintained at target levels. Nevertheless, the ionized calcium concentration was maintained in the normal range, and the total calcium concentration increased to a value as high as 15 mg/dL. Thus, the total to ionized calcium ratio was 3.5:1. After 24 hours of treatment, trisodium citrate infusion was gradually reduced from 15 mL/h to 7 mL/h, and the calcium chloride infusion was decreased to 50 mL/h. Nevertheless, persistence of the elevated total to ionized calcium ratio (3:1) indicated citrate accumulation likely secondary to decreased hepatic metabolism. Using this approach, the patient was successfully maintained on CVVHD with regional citrate anticoagulation for a total of 11 days without any additional complications. We conclude that CVVHD with regional citrate anticoagulation can be used in patients with acute hepatic failure if increased CaCl₂ requirements are anticipated and if citrate is infused at a lower rate compatible with decreased citrate metabolism. Citrate accumulation should be suspected in patients with an elevated total to ionized Ca⁺⁺ ratio during CVVHD with citrate anticoagulation.     

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

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

Regional citrate anti-coagulation dose titration: impact on dose of continuous renal replacement therapy

Clinical and Experimental Nephrology - Regional citrate anti-coagulation (RCA) is the recommended anti-coagulation for continuous renal replacement therapy (CRRT). Citrated replacement fluids...     

Profound hypocalcaemia in a patient being anticoagulated with citrate for continuous renal replacement therapy

Citrate, as an anticoagulant for continuous renal replacement therapy in critically ill patients, has some potential advantages over heparin, including a prolonged dialysis filter life and reduced risk of bleeding. The key parameter involved in monitoring the adequacy and safety of citrate anticoagulation during continuous renal replacement therapy pertains to the ionised and total plasma calcium levels. We report a case of severe systemic hypocalcaemia during continuous renal replacement therapy with citrate anticoagulation resulting from relentless sequestration of calcium due to undiagnosed evolving rhabdomyolysis. Although excessive systemic citrate accumulation can also cause hypocalcaemia, this complication was not observed in our patient. While an acceptable lower limit of ionised calcium remains unknown, severe rhabdomyolysis needs to be considered when a patient's ionised calcium levels are not responsive to standard calcium replacement therapy during continuous renal replacement therapy using citrate anticoagulation in critically ill patients.     

Anticoagulation in continuous renal replacement therapy

Continuous renal replacement therapies (CRRTs) allow for gradual solute and fluid removal. In very sick patients with acute renal failure, they may be better tolerated than hemodialysis. The major drawback to CRRTs is the need for anticoagulation to maintain filter patency. The patients who are likely to benefit from CRRTs are also at higher risk for bleeding from systemic anticoagulation. The most commonly used form of anticoagulation for CRRTs, low-dose heparin, causes bleeding in 10-50% of patients. Regional anticoagulation using protamine may reduce the risk of bleeding, but it is difficult to use. Low molecular weight heparin and prostacyclin both may partially reduce bleeding, but are difficult to dose. Regional anticoagulation with citrate is easy to use and has been shown to prolong filter life without systemic anticoagulation. It is the anticoagulant of choice for most patients on CRRT.     

无抗凝连续性肾脏替代治疗体外循环装置使用时间影响因素的研究

目的探讨影响无抗凝连续性肾脏替代治疗(CRRT)体外循环装置使用时间的主要影响因素,为合理的无抗凝CRRT护理风险评估提供依据。方法对2015年7月至2018年7月首次行无抗凝CRRT合并高危出血风险的257例急慢性肾衰竭患者进行回顾性分析。结果无抗凝CRRT治疗中体外循环装置发生衰竭125例(48.64%),CRRT体外循环装置使用时间为(248.51±87.56)min。多因素Cox比例风险回归模型分析显示,4个独立影响因素与体外循环装置使用时间显著相关,分别为:治疗中血流量不畅停泵次数(HR=1.572,95%CI=1.373～1.801),静脉壶栓塞容积比(HR=1.022,95%CI=1.014～1.030),红细胞压积(HR=1.037,95%CI=1.007～1.068),CRRT治疗剂量(HR=1.336,95%CI=1.007～1.772)。结论治疗中血流量不畅停泵次数、高静脉壶栓塞容积比、高红细胞压积、高CRRT剂量是影响无抗凝CRRT体外循环装置使用时间的独立危险因素;治疗中施行周期性生理盐水冲洗并不能有效延长体外循环装置的使用时间。临床工作者应针对相关危险因素有针对性地制定干预措施,进而最大限度地降低体外循环装置衰竭的发生率,延长装置使用时间,保障医疗护理安全。     

Anticoagulation and continuous renal replacement therapy

More than half of patients with acute renal failure in the intensive care unit require dialysis, and the majority of them have significant hemodynamic instability. Continuous renal replacement therapy (CRRT) is often the preferred dialysis modality in these patients. One requirement for CRRT is anticoagulation, which can expose patients to the risk of bleeding. However, absence of effective anticoagulation may result in clotting of the CRRT circuit and subsequently less effective treatment. While heparins are widely used for anticoagulation, because of potential side effects such as bleeding and heparin-induced thrombocytopenia, alternative anticoagulation protocols should be considered. Citrate anticoagulation, regional heparin/protamine, predilution, r-hirudin, prostacyclin, and nafamostat are among these methods.