Citrate Anticoagulation In Patients Research Articles

Regional Citrate Anticoagulation versus No Anticoagulation for CKRT in Patients with Liver Failure with Increased Bleeding Risk.

The opinions on the efficacy and safety of no anticoagulation versus regional citrate anticoagulation for continuous KRT (CKRT) were controversial in patients with severe liver failure with a higher bleeding risk. We performed a randomized controlled trial to assess no anticoagulation versus regional citrate anticoagulation for CKRT in these patients. Adult patients with liver failure with a higher bleeding risk who required CKRT were considered candidates. The included participants were randomized to receive regional citrate anticoagulation or no-anticoagulation CKRT. The primary end point was filter failure. Of the included participants, 44 and 45 were randomized to receive regional citrate anticoagulation and no-anticoagulation CKRT, respectively. The no-anticoagulation group had a significantly higher filter failure rate (25 [56%] versus 12 [27%], P = 0.003), which was confirmed by cumulative incidence function analysis and sensitive analysis including only the first CKRT sessions. In the cumulative incidence function analysis, the cumulative filter failure rates at 24, 48, and 72 hours of the no-anticoagulation and regional citrate anticoagulation groups were 31%, 58%, and 76% and 11%, 23%, and 35%, respectively. Participants in the regional citrate anticoagulation group had significantly higher incidences of Ca 2+tot /Ca 2+ion >2.5 (7% versus 57%, P < 0.001), hypocalcemia (51% versus 82%, P = 0.002), and severe hypocalcemia (13% versus 77%, P < 0.001). However, most (73%) of the increased Ca 2+tot /Ca 2+ion ratios were normalized after the upregulation of the calcium substitution rate. In the regional citrate anticoagulation group, there was no significant additional increase in the systemic citrate concentration after 6 hours. For patients with liver failure with a higher bleeding risk who required CKRT, regional citrate anticoagulation resulted in significantly longer filter lifespan than no anticoagulation. However, regional citrate anticoagulation in patients with liver failure was associated with a significantly higher risk of hypocalcemia, severe hypocalcemia, and Ca 2+tot /Ca 2+ion >2.5. RCA for CRRT in Liver Failure and High Risk Bleeding Patients, NCT03791190 .

枸橼酸抗凝在肝衰竭患者进行人工肝血液净化治疗的安全性

枸橼酸抗凝在肝衰竭患者进行人工肝血液净化治疗的安全性

Application of regional citrate anticoagulation in patients at high risk of bleeding during intermittent hemodialysis: a prospective multicenter randomized controlled trial

Safe and effective anticoagulation is essential for hemodialysis patients who are at high risk of bleeding. The purpose of this trial is to evaluate the effectiveness and safety of two-stage regional citrate anticoagulation (RCA) combined with sequential anticoagulation and standard calcium-containing dialysate in intermittent hemodialysis (IHD) treatment. Patients at high risk of bleeding who underwent IHD from September 2019 to May 2021 were prospectively enrolled in 13 blood purification centers of nephrology departments, and were randomly divided into RCA group and saline flushing group. In the RCA group, 0.04 g/mL sodium citrate was infused from the start of the dialysis line during blood draining and at the venous expansion chamber. The sodium citrate was stopped after 3 h of dialysis, which was changed to sequential dialysis without anticoagulant. The hazard ratios for coagulation were according to baseline. A total of 159 patients and 208 sessions were enrolled, including RCA group (80 patients, 110 sessions) and saline flushing group (79 patients, 98 sessions). The incidence of severe coagulation events of extracorporeal circulation in the RCA group was significantly lower than that in the saline flushing group (3.64% vs. 20.41%, P<0.001). The survival time of the filter pipeline in the RCA group was significantly longer than that in the saline flushing group ((238.34±9.33) min vs. (221.73±34.10) min, P<0.001). The urea clearance index (Kt/V) in the RCA group was similar to that in the saline flushing group with no statistically significant difference (1.12±0.34 vs. 1.08±0.34, P=0.41). Compared with saline flushing, the two-stage RCA combined with a sequential anticoagulation strategy significantly reduced extracorporeal circulation clotting events and prolonged the dialysis time without serious adverse events.

Feasibility and safety of combined cytokine adsorption and continuous veno-venous hemodialysis with regional citrate anticoagulation in patients with septic shock.

Septic shock is characterized by severe metabolic and hemodynamic alterations. It is often accompanied by acute kidney injury. A new adjunct treatment is hemoadsorption using a cytokine adsorber in line with continuous veno-venous renal replacement therapy. We studied the feasibility, efficacy, and safety of cytokine adsorption with citrate-anticoagulated continuous veno-venous hemodialysis (regional citrate anticoagulation-continuous veno-venous hemodialysis). In 11 patients with septic shock and acute kidney injury stage 3, we studied 12 cycles of cytokine adsorption and regional citrate anticoagulation-continuous veno-venous hemodialysis. We monitored parameters of citrate anticoagulation, circuit lifetime, laboratory parameters, hemodynamics, and vasopressor demand. Ten out of 12 adsorber/continuous veno-venous hemodialysis circuits reached the target lifetime of 24 h for the adsorber. One system clotted and one was stopped for non-device-related reasons. Nine of the remaining continuous renal replacement therapy circuits reached 72 h lifetime. With default settings for regional citrate anticoagulation, serum ionized calcium and pH were in the normal range. Urea and creatinine were reduced significantly, and norepinephrine dose decreased from 0.47 (±0.09) to 0.16 (±0.04) µg/kg/min (p = 0.016) after 24 h. We show that combined cytokine adsorption/continuous veno-venous hemodialysis is effective to control pH, to reduce urea and creatinine, and to improve hemodynamics by reducing norepinephrine doses in patients with septic shock. It can be applied safely with standard settings of regional citrate anticoagulation rendering sufficiently long filter lifetimes for the adsorber and the continuous veno-venous hemodialysis circuit. Further studies are on the way to investigate whether these effects translate into improved outcomes in septic shock patients.

CRRT Regional Anticoagulation Using Citrate in the Liver Failure and Liver Transplant Population.

Regional citrate for continuous renal replacement therapy (CRRT) use in patients with liver failure or post-liver transplant has been considered a contraindication because of the risk of citrate toxicity development. Regional citrate has the benefit of decreased bleeding risks over systemic anticoagulation; therefore, it is of great benefit to the coagulopathic and surgical populations. This article analyzes current empiric data and compares with a case study specifically related to liver failure, liver transplant, and CRRT use. We found that the use of a total serum to ionized calcium ratio was much more reliable in measuring liver function than liver enzyme figures. This when paired with a citrate-reduction guideline based on serum to ionized calcium ratios provided effective, early management of citrate toxicity. Using new measurements to calculate liver metabolism of citrate and using a new citrate-reducing guideline allow the bedside practitioner to use regional citrate anticoagulation in patients with liver failure and liver transplant who require CRRT.

Regional citrate anticoagulation in patients with liver failure - time for a rethink?

Regional citrate anticoagulation (RCA) for continuous renal replacement therapy (CRRT) has become increasingly attractive in recent years due to its favourable low bleeding risk profile. Its use in liver failure, however, has been limited due to the risk of citrate accumulation and toxicity. In the previous issue of Critical Care, Schultheiss and colleagues look at CRRT using RCA in liver failure patients. They demonstrate that citrate accumulation can be predicted using the total calcium (Catot) to ionised calcium (Caion) ratio (Catot/Caion), and determine that despite the occurrence of significant citrate accumulation, the effects of citrate accumulation are not as severe as might have been expected. This study raises interesting prospects with regard to RCA use in liver failure, and we postulate that citrate may have a role as a prognostic marker of metabolic capacity much as in the way of lactate and methacetin. However, further studies are warranted, in particular examining its application in subgroups of liver failure (chronic, acute, hyperacute and subacute), before its use becomes commonplace.

A prospective randomized open-label crossover trial of regional citrate anticoagulation vs. anticoagulation free liver dialysis by the Molecular Adsorbents Recirculating System

IntroductionThe Molecular Adsorbent Recycling System (MARS) is used to treat patients with liver failure. Observational data suggest that citrate anticoagulation during MARS is feasible. Comparative studies on the optimal anticoagulation regimen during MARS are lacking. The aim of the current study was to evaluate two heparin-free anticoagulation regimens.MethodsWe performed a prospective randomized open-label crossover study of regional citrate anticoagulation against no anticoagulation. Ten patients (age 55 ± 11 years) with liver failure undergoing MARS treatment were included. The primary endpoint was completion of MARS sessions. Secondary endpoints included treatment efficacy and safety. Longevity of MARS treatment was plotted as a Kaplan-Meier estimate. Fisher's exact test was used for contingency table analysis.ResultsOf a total of 27 6-hour sessions, four sessions had to be terminated prematurely, three due to occlusive clotting of the extracorporeal circuit and one due to uncontrollable bleeding from the vascular access site. All four events occurred in the group without anticoagulation. Between group comparison demonstrated citrate anticoagulation to significantly increase the likelihood of completed MARS treatment (Fisher's exact test, P 0.04). This translates into higher bilirubin reduction ratios when citrate was applied (reduction ratio 0.25 vs. 0.15, P 0.02). Systemic ionized calcium concentrations were significantly reduced during citrate anticoagulation (P < 0.001) but remained within a safe range. We observed no major adverse events.ConclusionsRegional citrate anticoagulation in patients with liver failure is feasible. Citrate anticoagulation provides superior patency of the extracorporeal circuit. Avoidance of anticoagulation during MARS results in significant loss of treatment efficacy, due to treatment downtime. Additional studies are required to identify the optimal anticoagulation regimen for extracorporeal circulation in patients with liver failure.

Continuous venovenous hemodialysis with regional citrate anticoagulation in patients with liver failure: a prospective observational study

IntroductionLiver failure patients might be at risk for citrate accumulation during continuous venovenous hemodialysis (CVVHD) with regional citrate anticoagulation. The aim of this study was to investigate the predictive capability of baseline liver function parameters regarding citrate accumulation, expressed as an increase in the calcium total/calcium ionized (Catot/Caion) ratio ≥2.5, and to describe the feasibility of citrate CVVHD in liver failure patients.MethodsWe conducted a prospective observational study in medical ICU patients treated in a German university hospital. We performed 43 CVVHD runs using citrate for regional anticoagulation in 28 critically ill patients with decompensated liver cirrhosis or acute liver failure (maximum of two CVVHD runs per patient). Liver function was characterized before CVVHD using laboratory parameters, calculation of Child-Pugh and Model of End-stage Liver Disease scores, and determination of the plasma disappearance rate of indocyanine green. In addition to blood gas analysis, we measured total calcium and citrate in serum at baseline and after definitive time points for each CVVHD run.ResultsAccumulation of citrate in serum correlated with an increase in the Catot/Caion ratio. Although the critical upper threshold of Catot/Caion ratio ≥2.5 was exceeded 10 times in seven different CVVHD runs, equalization of initial metabolic acidosis was possible without major disturbances of acid-base and electrolyte status. Standard laboratory liver function parameters showed poor predictive capabilities regarding citrate accumulation in terms of an elevated Catot/Caion ratio ≥2.5. In contrast, serum lactate ≥3.4 mmol/l and prothrombin time ≤26% predicted an increase in the Catot/Caion ratio ≥2.5 with high sensitivity (86% for both lactate and prothrombin time) and specificity (86% for lactate, 92% for prothrombin time).ConclusionsDespite substantial accumulation of citrate in serum, CVVHD with regional citrate anticoagulation seems feasible in patients with severely impaired liver function. Citrate accumulation in serum is reflected by an increase in the Catot/Caion ratio. To identify patients at risk for citrate accumulation in terms of a Catot/Caion ratio ≥2.5, baseline serum lactate (threshold ≥3.4 mmol/l) and prothrombin time (threshold ≤26%) may be useful for risk prediction in daily clinical practice. Careful monitoring of electrolytes and acid-base status is mandatory to ensure patient safety.

Citrate anticoagulation using ACD solution A during long‐term haemodialysis

Haemodialysis with regional citrate anticoagulation in patients with contraindications for heparin is increasingly performed in the USA and Europe. Most published protocols use trisodium citrate, which is not readily available nor is it licensed in Australia. We established a protocol for citrate-anticoagulation in haemodialysis using acid citrate dextrose solution A (ACDA), which is approved for apheresis procedures in Australia. The aim of the present study was to assess the safety and efficacy of this protocol for routine use in haemodialysis patients. Systemic and post-filter blood ionized calcium, serum sodium and bicarbonate and dialyzer clotting score were analyzed prospectively in 14 patients undergoing 150 consecutive haemodialysis treatments with citrate anticoagulation using calcium-free dialysate. A simple algorithm allowed the attending nurse to adjust citrate infusion (to maintain post-filter ionized calcium at 0.2-0.3 mmol/L) and i.v. calcium substitution. Scheduled dialysis time was 4 h, and point-of-care monitoring of blood ionized calcium during dialysis was done at 0, 15, 60, 120 and 240 min. ACDA infusion rates of 300 mL/h were used in the first 52 treatments, but resulted in high dialyzer clotting score and 6% of treatments were discontinued due to complete clotting. Thereafter, ACDA infusion rate was increased to 350 mL/h, with all 98 subsequent treatments completed successfully. Ionized calcium levels were stable during all procedures with post-dialysis serum sodium averaging 135 ± 3 mmol/L and bicarbonate 23.8 ± 2 mmol/L. Routine use of citrate anticoagulation in the setting of a long-term haemodialysis unit is safe and efficient. Point-of-care measurements of ionized calcium levels are critical to safely and successfully perform citrate anticoagulation.

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.

33 Citrate Anticoagulation during Plasma Exchange in Patients with Thrombotic Thrombocytopenic Purpura – Short Heparin‐Free Hemodialysis Helps to Remove Citrate Load

Background Treatment of thrombotic thrombocytopenic purpura (TTP) requires daily or even twice daily plasma exchanges (PE) with fresh frozen plasma as a replacement solution. If citrate anticoagulation is needed, citrate load (both from fresh frozen plasma and citrate as an anticoagulant) can be significant, causing severe alkalosis. Citrate as a small molecule is easily dialyzable, so short heparin‐free hemodialyses performed periodically after or between PE procedures can help to remove citrate load. The aim of our report is to present our experience with citrate anticoagulation in patients with TTP treated with daily PEs.Methods Fifteen protocols of plasma exchange procedures performed in a 46‐year‐old female with TTP were analyzed. Blood flow in all procedures was 100 mL/min, 4% trisodium citrate was used as anticoagulant, infused into the arterial line at rate 130 mL/h. 1 m CaCl2 was infused into the venous line in a dose adjusted to maintain ionized calcium (iCa) within normal limits (mean dose of 11.5 ± 1.5 mL/h). Fresh frozen plasma was used as a replacement solution, 3258 ± 548 mL per procedure.Results Ionized calcium before PE ranged from 1.10–1.45 mmol/L (mean 1.27 ± 0.12). The initial iCa level gradually increased after several procedures, as a consequence of citrate‐calcium complex metabolism between the procedures. Levels of iCa during PE were: 1.15 ± 0.09 mmol/L after 1 hour, 1.18 ± 0.06 after 2 hours and 1.16 ± 0.09 after 3 hours. Significant alkalosis occurred after several PEs with plasma pH 7.51 and bicarbonate 40.7 mmol/L. It was corrected by a 2‐hour heparin‐free hemodialysis with dialysate: K 4.0 mmol/L, calcium 1.5 mmol/L, sodium 140 mmol/L and bicarbonate set to 24 mmol/L. After dialysis pH was 7.38 and bicarbonate 28.5 mmol/L. Such hemodialysis was repeated during PE treatment.Conclusion Citrate anticoagulation can be safely performed in patients treated with PE by daily plasma exchanges. Periodically performed short heparin‐free hemodialysis can remove excess citrate and help to correct and avoid severe metabolic alkalosis.

Regional sodium citrate anticoagulation in patients with active bleeding undergoing hemodialysis.

Sodium citrate was used as a regional anticoagulant in the dialysis system in four patients with acute renal failure and active bleeding of various sources during a total of 38 dialysis treatments. All four patients had exacerbation of existing hemorrhage with low-dose heparin dialysis. A special circuit was used through which sodium citrate was infused into the arterial sleeve of the dialysis blood line; dialysis was achieved against calcium-free bath and calcium was infused into the venous sleeve of the dialysis blood line. When data was compared to low-dose heparin dialysis, citrate anticoagulation is as effective, carries no risk of exacerbation of bleeding, and had negligible adverse effects.