A novel method for regional citrate anticoagulation in continuous venovenous hemofiltration (CVVHF)

BACKGROUND: Continuous renal replacement therapy (CRRT) is increasingly used in managing acute renal failure (ARF) as it offers hemodynamic stability and significant solute clearance in this setting. However, it also requires anticoagulation. Traditionally, heparin has been the anticoagulant of choice but this increases hemorrhagic risk in already high-risk ARF patients. Regional citrate anticoagulation offsets this risk. However, it can be difficult to manipulate regional anticoagulation in CRRT. Moreover, citrate CRRT has been plagued by short optimal filter patency times. METHODS: We designed a novel citrate-based anticoagulation schema for continuous venovenous hemofiltration (CVVHF). We implemented this schema prospectively in caring for 24 individuals admitted to the intensive care unit with ARF requiring CRRT. Each individual had a contraindication to systemic anticoagulation. We evaluated filter patency using Kaplan-Meier methodology, comparing the effect of this citrate-CVVHF system to historical, saline-flush control CVVHF systems. RESULTS: 58 filters ran for a total of 2637.5 h. Average filter patency time was 45.4 +/- 25.5 h. At 48 h, 70% of the CVVHF-citrate system filters remained patent compared to only 16% of historical control saline-flush systems (p = 0.0001). The average filtered urea nitrogen/blood urea nitrogen ratio was 0.84 +/- 0.06 with an average urea clearance of 28.5 +/- 4.1 mL/min for CVVHF-citrate-treated individuals. Only three patients experienced transient complications related to CVVHF-citrate with resolution of these complications within 24 h. Ultimately, 58.3% of the CVVHF-citrate-treated patients survived to ICU discharge. CONCLUSIONS: This novel CVVHF-citrate system achieved excellent clearance and dramatically improved filter patency compared to saline-flush systems. Moreover, it did so with minimal toxicity.     

Citrate clearance in children receiving continuous venovenous renal replacement therapy

Anticoagulation is usually indicated in patients receiving continuous renal replacement therapy (CRRT) to prevent clotting of the extra-corporeal circuit. While heparin is the most frequently used anticoagulant, regional citrate anticoagulation is becoming the preferred choice in those patients at high risk for bleeding. However, it has been widely claimed that to avoid citrate toxicity, CRRT with citrate anticoagulation should utilize diffusive clearance (e.g., continuous venovenous hemodialysis). We studied citrate clearance in five children who received citrate anticoagulation during CRRT with a COBE PRISMA machine and an M-60 (AN-69) filter. The blood flow rate ranged from 50 to 150 ml/min (2.1-8.0 ml/kg per min). Citrate was infused in the circuit circulation as an acid citrate dextrose (ACD) solution at a rate of 1.6-3.7% of the blood flow rate to maintain the circuit ionized calcium (iCa) <0.5 mmol/l. Calcium-free replacement fluid with reduced alkali (NaHCO3 20 mEq/l) was infused in pre-filter mode at a rate of 1,800-2,000 ml/h per 1.73 m(2). In a separate central line, CaCl2 (0.8%) was infused (rate 25-50% of ACD infusion) to maintain systemic iCa between 1.0 and 1.3 mmol/l. Citrate concentration was measured using an enzymatic assay. Total CRRT duration was 1,224 h. Twenty-four filters were changed due to clotting, with a mean filter life of 51 h. Mean (range) citrate levels (mmol/l) were (1) before initiating CRRT ( n=2): patient baseline 0.13 (0.1-0.15), (2) during CRRT ( n=7): circuit 4.54 (3.95-6.25), effluent 4.31 (3.95-5.46), and patient 0.69 (0.30-1.13). Sieving coefficients for urea and citrate were 0.88-0.97 and 0.88-1.0, respectively. Citrate clearance (31-38 ml/min per 1.73 m(2)) was similar to that of urea (31-38 ml/min per 1.73 m(2)), and when evaluated in two patients, remained unchanged after substituting half of the convective clearance [continuous venovenous hemofiltration (CVVH)] by diffusive clearance [continuous venovenous hemodiafiltration (CVVHDF)]. The post-filter citrate load (mean+/-SD) delivered to the five patients during CRRT was 1.06+/-0.62 mmol/kg per hour. With the exception of alkalosis in one patient, no other complications were observed. Renal function recovered in all patients. We conclude that citrate anticoagulation in children is feasible, effective, and safe. Sufficient citrate clearance to prevent its toxic accumulation is achieved by convective clearance (CVVH) alone and diffusive clearance (CVVHDF) does not appear to be mandatory when utilizing citrate anticoagulation during CRRT.     

Improving the delivery of continuous renal replacement therapy using regional citrate anticoagulation

AIMS: Regional citrate anticoagulation during acute renal replacement therapy (RRT) effectively prevents extracorporeal thrombosis and avoids bleeding risk. There have been a number of citrate anticoagulation protocols published; but a simple and predictable scheme with standardized components and procedures, as well as clearly defined citrate pharmacokinetics, is needed for continuous RRT (CRRT) that is now used frequently in the critical care setting. The present study sets forth methodology with standardized blood flow and dialysate composition, and with citrate and calcium infusions that are quantitatively linked to extracorporeal blood flow rate--a predictable and easily replicated CRRT paradigm. MATERIALS AND METHODS: CRRT using continuous venovenous hemofiltration with dialysis (CVVHD) was standardized using 150-200 ml/min blood flow, calcium-free dialysate with only moderate sodium (135 mEq/l) and bicarbonate (28 mEq/l) concentrations, and ultrafiltration limited to that needed for overall fluid balance in the intensive care unit. Citrate infusion (ACD-A solution) into the extracorporeal blood and calcium repletion in blood returned to the patient were proportional to blood flow. Anticoagulation was accomplished by keeping extracorporeal ionized calcium below 0.4 mM/l. Filter performance, citrate removal and changes in calcium, sodium and alkali were evaluated longitudinally. RESULTS: CVVHD using this protocol delivered urea clearance exceeding 2 l/h (48 l/d) when filter function was sustained. Filter longevity was markedly improved using citrate when compared with standard heparin anticoagulation, and nursing time spent on initiating and troubleshooting CRRT was approximately halved using this protocol. Sieving coefficients for urea, creatinine and citrate were approximately 0.9 and were sustained through nearly 3 days of filter use. Citrate clearance and removal were quantitatively linked to dialysate and ultrafiltration flow, resulting in 35-50% direct removal of the citrate-calcium chelate and reduced systemic citrate load. Serum tonicity and acid-base status were not problematic. The only notable side effect was modest calcium accumulation that necessitated reduction in calcium repletion rate. CONCLUSIONS: CVVHD is well suited to regional citrate anticoagulation. The present protocol is straightforward and predictable, with minor metabolic consequences that can be anticipated and adjusted. These results commend regional citrate anticoagulation to wider application.     

Acute Sodium Chlorite Poisoning Associated with Renal Failure

Background and Objectives: Different techniques of continuous renal replacement therapy (CRRT) might have different effects on azotemic control. Accordingly, we tested whether continuous veno-venous hemodiafiltration (CVVHDF) or continuous veno-venous hemofiltration (CVVH) would achieve better control of serum creatinine and plasma urea levels. Design: Retrospective controlled study. Setting: Two tertiary Intensive Care Units. Patients: Critically ill patients with acute renal failure (ARF) treated with CVVHDF (n = 49) or CVVH (n = 50). Interventions: Retrieval of daily morning urea and creatinine values before and after the initiation of CRRT for up to 2 weeks of treatment. Measurements and Results: Before treatment, serum urea and creatinine concentrations were significantly lower in the CVVH group than in CVVHDF group (urea: 31.0 ± 15.0 mmol/L for CVVHDF and 24.7 ± 16.1 mmol/L for CVVH, p = 0.01, creatinine: 547 ± 308 µmol/L vs. 326 ± 250 µmol/L, p < 0.0001). These differences were still significant after 48 h of treatment (urea: 20.1 ± 8.3 mmol/L vs. 14.1 ± 6.1 mmol/L; p = 0.0003, creatinine: 360 ± 189 µmol/L vs. 215 ± 118 µmol/L; p < 0.0001). Throughout the duration of therapy, mean urea levels (22.3 ± 9.0 mmol/L for CVVHDF vs. 16.7 ± 7.8 mmol/L for CVVH, p < 0.0001) and mean creatinine levels (302 ± 167 vs. 211 ± 103 µmol/L, p < 0.0001) were better controlled in the CVVH group. Conclusions: CRRT strategies based on different techniques might have a significantly different impact on azotemic control.     

Regional citrate anticoagulation in continuous venovenous hemofiltration in critically ill patients with a high risk of bleeding

BACKGROUND: Systemic heparinization is associated with a high rate of bleeding when used to maintain patency of the extracorporeal circuit during continuous renal replacement therapy (CRRT) in critically ill patients. Regional anticoagulation can be achieved with citrate, but previously described techniques are cumbersome and associated with metabolic complications. METHODS: We designed a simplified system for delivering regional citrate anticoagulation during continuous venovenous hemofiltration (CVVH). We evaluated filter life and hemorrhagic complications in the first 17 consecutive patients who received this therapy at our institution. Blood flow rate was set at 180 ml/min. Ultrafiltration rate was maintained at 2.0 liters/hr and citrate-based replacement fluid (trisodium citrate 13.3 mM, sodium chloride 100 mM, magnesium chloride 0.75 mM, dextrose 0.2%) was infused proximal to the filter to maintain the desired fluid balance. Calcium gluconate was infused through a separate line to maintain a serum-ionized calcium level of 1.0 to 1.1 mM. RESULTS: All patients were critically ill and required mechanical ventilation and vasopressor therapy. Systemic heparin anticoagulation was judged to be contraindicated in all of the patients. A total of 85 filters were used, of which 64 were lost because of clotting, with a mean life span of 29.5 +/- 17.9 hours. The remaining 21 filters were discontinued for other reasons. Control of fluid and electrolyte balance and azotemia was excellent (mean serum creatinine after 48 to 72 hr of treatment was 2.4 +/- 1.2 mg/dl). No bleeding episodes occurred. Two patients, one with septic shock and the other with fulminant hepatic failure, developed evidence for citrate toxicity without a significant alteration in clinical status. Nine patients survived (52.9%). CONCLUSION: Our simplified technique of regional anticoagulation with citrate is an effective and safe form of anticoagulation for CVVH in critically ill patients with a high risk of bleeding.     

Citrate anticoagulation in pediatric continuous venovenous hemofiltration

Regional citrate anticoagulation has become a common alternative to systemic heparinization in adult continuous venovenous hemofiltration (CVVH) practice. We report our experience with the technique in critically ill children. We carried out a retrospective chart review of a 22-bed pediatric intensive care unit. CVVH with pre-filter citrate and systemic calcium replacement infusions was performed according to a strict protocol in nine consecutive critically ill children. All charts were reviewed for patient characteristics and CVVH circuit parameters, including filter survival. All complications were noted. Nurse specialists were interviewed about the practical management of citrate anticoagulation. All patient measurements of blood urea nitrogen, creatinine, sodium, ionized calcium (iCa), potassium, and bicarbonate were collected over the CVVH period. In seven patients, 12 simultaneous citrate measurements were taken from patient blood, pre-filter blood, and hemofiltrate fluid. Nine patients (mean age 8.8±6.8 years) were treated with CVVH and regional citrate anticoagulation for 1–14 days (mean 5.2±4.0 days). Of 19 filters used, 15 were replaced non-electively (mean filter survival 55.6±22.0 h). Control of azotemia and hyperkalemia was good. Sodium and iCa levels were well maintained. Bicarbonate levels were elevated in four patients without adverse effects. The mean systemic citrate level at equilibrium was 1.6±0.23 mmol/l. No systemic bleeding complications were observed. In children, regional citrate anticoagulation provides equivalent filter survival to heparin without bleeding complications. With good staff preparation, it is simple to perform and safe with respect to metabolic side effects.     

POSSIBLE STRATEGIES TO PROLONG CIRCUIT LIFE DURING HEMOFILTRATION: THREE CONTROLLED STUDIES

Background and Aims: The prevention of filter clotting is an important goal in the management of continuous renal replacement therapy (CRRT). Anticoagulation is the mainstay of such prevention. However, other strategies might prolong filter life without increasing the risk of bleeding. We tested the effectiveness of three strategies (use of flat plate configuration, heparin administration into the air chamber and use of a larger membrane surface) aimed at prolonging circuit life without increasing the dose of anticoagulation. Methods: Thirty-one critically ill patients with acute renal failure (ARF) managed with continuous venovenous hemofiltration (CVVH) were studied. Filters were randomized in a crossover design to three consecutive studies: (1) filtration with either hollow-fiber or flat-plate hemofilters, (2) administration of heparin dose pre-filter or divided into pre-filter and directly into the bubble trap chamber and (3) use of two different surface areas with Filtral 8 (surface area 0.75 m²) vs. Filtral 12 (surface area 1.30 m²) hemofilters. Results: Mean circuit life for flat-plate and hollow-fiber hemofilters (cohort 1) was 14.7 ± 4.7 h and 17.1 ± 2.8 h respectively (NS). Mean circuit life for single heparin administration site vs. double site administration (cohort 2) was 17 ± 3.2 h and 18 ± 3.1 h respectively (NS). Mean circuit lifespan for 0.75 m² and 1.30 m² hemofilters was 16 ± 12.2 h and 15.7 ± 14.3 h respectively (NS) (cohort 3). Visible clot formation in the bubble trap chamber was a frequent cause of circuit failure. Conclusion: Neither flat plate membrane configuration nor increasing membrane surface area, nor heparin administration in the air chamber prolong circuit life during CVVH. The bubble trap chamber is a frequent site of circuit clotting.     

Safety and Efficacy of Citrate Anticoagulation for Continuous Renal Replacement Therapy for Acute Kidney Injury After Liver Transplantation: A Single-Center Experience

Background

Acute kidney injury (AKI) after liver transplantation (LT) is a frequent and serious complication. The incidence of AKI requiring continuous renal replacement therapy (CRRT) ranges from 10% to 30%. Kidney Disease: Improving Global Outcomes guidelines indicate the use of citrate as a locoregional anticoagulant drug for CRRT regardless of the patient's hemorrhagic risk. Despite this indication, however, the use of citrate is still under debate in patients with liver failure and/or LT owing to the potential risk of plasmatic citrate accumulation due to reduced liver clearance. The aim of this study was to evaluate the safety and efficacy of citrate as a locoregional anticoagulation drug in CRRT for AKI after LT.

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.     

连续性肾脏替代治疗时枸橼酸药物代谢动力学数学模型的构建

目的 构建连续性肾脏替代治疗（CRRT）时枸橼酸药物代谢动力学数学模型,并运用该模型预测肝功能异常患者进行局部枸橼酸抗凝（RCA）-CRRT时发生枸橼酸蓄积的风险。 方法 将体外枸橼酸输注速度、体内枸橼酸药物动力学、体外枸橼酸透析清除动力学等影响血浆枸橼酸浓度的参数综合,构建一个服从一室模型、一级消除动力学的枸橼酸药物代谢动力学数学模型。运用模型采用文献报道的肝硬化和非肝硬化危重患者体内枸橼酸药物代谢动力学参数,预测枸橼酸代谢正常、肝功能损害及肝衰竭的患者在实施不同CRRT治疗方案时发生枸橼酸蓄积的风险。 结果 枸橼酸药物代谢动力学数学模型： 。由模型得到的血浆枸橼酸浓度预测值与文献报道的实测浓度拟合理想。根据模型推算,体内枸橼酸清除正常的患者在接受RCA-CRRT时,血浆枸橼酸浓度始终﹤1 mmol/L;当CRRT抽提分数高于66%时,肝功能异常患者体内枸橼酸稳态浓度将低于中毒浓度。 结论 枸橼酸药物代谢动力学模型可预测危重患者在实施RCA-CRRT时发生枸橼酸蓄积的风险,并为体内枸橼酸代谢清除障碍的患者选择合适安全的RCA-CRRT方案提供理论依据。     

Sustained low-efficiency dialysis in the ICU: cost, anticoagulation, and solute removal

Hemodialysis (HD) for critically ill patients with acute renal failure has been provided as intermittent hemodialysis (IHD) or continuous renal replacement therapy (CRRT). IHD is often complicated by hypotension and inadequate fluid removal, and CRRT by high cost of solutions and problems with anticoagulation. Sustained low-efficiency daily dialysis (SLED) has been suggested as an alternative treatment. This is an observational, prospective pilot study describing the introduction of SLED at our institution. We compared SLED (23 patients, 165 treatments) with CRRT (11 patients, 209 days), focusing on cost, anticoagulation, and small solute removal. SLED consisted of 8 h of HD 6 days a week, with blood flow of 200 ml/min, dialysate flows of 350 ml/min, and hemofiltration with 1 l of saline/h. CRRT patients were anticoagulated with either heparin or citrate, and SLED patients with either heparin or saline flushes. The weekly costs to the hospital were $1431 for SLED, $2607 for CRRT with heparin, and $3089 for CRRT with citrate. Sixty-five percent of SLED treatments were heparin-free; filter clotting occurred in 18% of heparin treatments and 29% of heparin-free treatments (NS). Weekly Kt/V was significantly higher for SLED (8.4+/-1.8) and time-averaged serum creatinine was lower; equivalent renal clearance (EKRjc) was 29+/-6 ml/min for SLED, similar to that for CRRT. In summary, SLED may be routinely performed without anticoagulation; it provides solute removal equivalent to CRRT at significantly lower cost.     

Continuous renal replacement therapies: anticoagulation in the critically ill at high risk of bleeding

BACKGROUND: The ongoing necessity for systemic heparinization is a well-known disadvantage of continuous renal replacement therapies (CRRT), and alternative methods of anticoagulation may be required. Our aim was to evaluate, in patients with a high risk of bleeding, the possibility of an acceptable filter life with non-anticoagulation CRRT and, in case of early filter failure, the efficacy and safety of bedside monitored regional anticoagulation with heparin and protamine. METHODS: Fifty-nine patients underwent CRRT for acute renal failure (ARF) following cardiac surgery. Patients who fulfilled one of the following criteria were selected for non-anticoagulation CRRT: spontaneous bleeding, aPTT > 45 sec, thrombocytopenia and recent surgery (< 48 hr). Filter life < 24 hr without anticoagulation was the cut-off point for starting the regional anticoagulation CRRT. Heparin was infused pre-filter and protamine post-filter at an initial ratio of 1 mg protamine:100 IU heparin. The ratio was adjusted to achieve a patient aPTT < 45 sec and a circuit > 55 sec. RESULTS: Twenty-two (37.3%) patients had been selected for non-anticoagulation. Of them, 12 patients continued to receive non-anticoagulation (filter life: 38.3 +/- 30.5 hr) while 10 switched to regional anticoagulation (filter life: 38.6 +/- 25 hr). During regional anticoagulation no statistical difference was found between baseline aPTT (36.7 +/- 6.4 sec) and patient aPTT (41.5 +/- 12.6 sec) while circuit aPTT (77.7 +/- 43.3 sec) was significantly higher than patient aPTT (p < 0.0001). The probabilities of the circuits remaining free from clotting after 24, 48 and 72 hr were: a) non-anticoagulation: 55.5%, 30.1% and 16.6%, b) regional anticoagulation: 76.2%, 39.6% and 19.8%. There was no rebound anticoagulation observed after regional anticoagulation CRRT ended. CONCLUSIONS: Non-anticoagulation CRRT allowed an adequate filter life in most patients with a high risk of bleeding for prolonged aPTT and/or thrombocytopenia. Despite concerns regarding the need for careful monitoring, regional anticoagulation with heparin and protamine can be considered as a safe and valid alternative when non-anticoagulation is unsuitable because of early filter failure.     

Should Nicorandil Infusion Be Adapted in Dialysis‐Dependent Patients Undergoing Continuous Renal Replacement Therapy After Cardiac Surgery?

In this report, we studied whether plasma concentration of nicorandil is maintained effectively and safely in dialysis‐dependent patients with stage 5 chronic kidney disease (CKD5D) undergoing continuous renal replacement therapy (CRRT). Participants consisted of 10 patients undergoing CRRT after cardiac surgery. CRRT was performed with an effluent flow rate of either 600 mL/h (low‐flow group; n = 5) or 1800 mL/h (high‐flow group; n = 5). Nicorandil was infused intravenously at 0.1 mg/kg/h for more than 15 h starting 8 h before and 7 h after the start of CRRT. Plasma nicorandil concentrations were measured from arterial blood lines 1 h before and 7 h after CRRT initiation. Nicorandil clearance by CRRT was also calculated 1 h after CRRT initiation. Nicorandil plasma concentrations before and 7 h after CRRT initiation were 68.0 ng/mL and 74.6 ng/mL, respectively. Nicorandil clearance 1 h after CRRT initiation was 20.2 mL/min. Increasing the effluent flow rate from 600 mL/h to 1800 mL/h tended to increase nicorandil clearance. When nicorandil was infused intravenously during CRRT at 0.1 mg/kg/h in patients with CKD5D, plasma nicorandil concentrations were maintained within an effective concentration range.     

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.     

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.     

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 38.2 ml kg BW⁻¹ h⁻¹ (31.8; 42.1). The median effective filter operation time was 67 h (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.     

A systematic review of continuous renal replacement therapy and intermittent haemodialysis in management of patients with acute renal failure

Background: Acute renal failure (ARF) still bears a poor prognosis with mortality rates up to 70% and the ideal form of renal replacement therapy (RRT) remains controversial. The purpose of this study was to conduct a systematic review and meta-analysis of all randomized controlled trials (RCT) to examine the effect of dialysis modality (IHD: Intermittent haemodialysis; CRRT: continuous renal replacement therapy) on survival of patients with ARF and to also study the effect of each modality on dialysis dependence (DD). Methods: Using and combining two comprehensive search themes (ARF and RRT), we searched electronic databases from 1969 through September of 2007, supplemented by a manual review of abstracts from nephrology meetings and reference lists of review articles. All RCT comparing IHD with CRRT in adult patients with ARF and with explicit reporting of mortality were included. The primary outcome was the pooled estimate of the odds ratio (OR) of mortality for patients with ARF treated with CRRT versus IHD. The secondary outcome was OR of DD at time of discharge for surviving patients. Results: A total of 587 studies were identified, 554 of which were excluded on initial screening. Analysis of the nine RCT (1635 patients) showed an OR of 0.89 (0.63–1.24) for survival in patients on CRRT. Limiting the analysis to the seven RCT published after the year 2000, revealed an OR of 0.72 (0.58–0.90). The OR of all the studies before 2000 was 1.06 (95% CI 0.67–1.68), as compared with OR of 0.61 (95% CI 0.50–0.74) for studies post-2000. Four studies showed a significantly lower risk of DD among the CRRT group and none showed higher OR for DD. When analysis was limited to the RCT, the OR for DD was 1.07 (0.47–2.39), suggesting no difference in DD between the modalities. Conclusions: Similar to previously reported meta-analyses, we did not find a significant effect of CRRT on the OR of survival. The progressive reduction in the OR of survival with CRRT relative to IHD might reflect progressive improvements in IHD. The OR of DD was not affected by mode of RRT. In conclusion, compared with IHD, CRRT does not offer an advantage with regards to survival or DD in ARF. Considering its cost and potential disadvantages, it is imperative to identify the subset of patients with ARF that would potentially derive maximum benefit from CRRT. This will require large, adequately powered studies with sufficient follow-up.     

Impact d’un programme d’amélioration de la stabilité de l’épuration extrarénale continue

ObjectivesDuring continuous renal replacement therapy (CRRT), circuit clotting increases nursing workload, cost of the therapy and blood loss. The aim of this study was to assess the impact of a program designed to improve CRRT stability on unexpected circuit clotting.Study designRetrospective and observational study.Patients and methodsIn January 2011, several changes have been adopted regarding CRRT management. Regional citrate anticoagulation, continuous hemodialysis using super high-flux membranes and a specific training for intensive care unit nurses were implemented. CRRT sessions before (year 2009 and 2010, “Before group”) and after (year 2011 and 2012, “After group”) were analyzed. The primary endpoint was the incidence of unexpected CRRT session end.ResultsDuring the study period, 401 sessions performed in 152 patients were analyzed. Sixty-three unexpected session's end (40%) occurred before and 43 (17%) after the implementation of the program (P < 0.0001). Median filter life time was 33 (13–48) hours before and 55 (27–67) hours after (P < 0.0001).ConclusionOur program designed to improve CRRT stability reduced filter losses by reducing unexpected circuit clotting.     

局部枸橼酸抗凝在重症患者连续性肾脏替代治疗中的应用

目的 探讨在连续性肾脏替代治疗（continuous renal replacement therapy,CRRT）过程中应用局部枸橼酸抗凝（regional citrate anticoagulation,RCA）对凝血功能及治疗效果的影响.方法 前瞻性观察我院2010年1月至2013年9月期间进行CRRT的重症患者21例,治疗时间为连续72 h及（或）日间间断治疗8～16 h,4％枸橼酸钠以180～200 ml/h由体外循环的动脉端泵入,血流量150 ml/min;通过监测血气分析中血钙水平,使体外循环局部游离血钙维持在0.25～0.35 mmol/L之间,达到局部抗凝效果,并以调整外源钙的补充,增加（或减少）枸橼酸输入、血流量或透析液量等,达到安全有效的抗凝效果.监测治疗前及治疗后24 h的血浆凝血酶原时间（prothrombin time,PT）,活化部分凝血酶时间（actived partial thrombolastin time,APTT）,国际标准化比值（International normalized ratio,INR）,血小板（platelet,PLT）,pH值,血钙,血肌酐（SCr）,尿素氮（BUN）,C反应蛋白（C-reaction protein,CRP）,丙氨酸氨基转移酶（alanine aminotransferase,ALT）的变化,观察体外循环凝血情况、滤器使用寿命及临床出血事件.结果 ①监测患者凝血指标PT、APTT、INR及PLT无明显变化,差异无统计学意义（P＞0.05）;②在进行CRRT治疗过程中平均滤器使用寿命为21.34 h;③治疗过程中未引起凝血功能紊乱,未增加患者活动性出血的风险;④治疗后监测患者血气分析和血生化指标中pH值、SCr、BUN、CRP、ALT明显好转,差异有统计学意义（P＜0.05）.结论 RCA在重症患者行CRRT过程中是较理想的抗凝方式,安全又有效,对患者凝血指标无影响,能明显延长滤器使用寿命,无临床出血事件发生,可改善患者预后.