Regional Citrate Anticoagulation for Intermittent Hemodialysis in Dogs.
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ABSTRACT: The traditional systemic heparinization used for anticoagulation in extracorporeal therapies may cause fatal complications in animals at risk of bleeding.To develop and validate a protocol of regional citrate anticoagulation (RCA) for intermittent hemodialysis in dogs.A total of 172 dogs treated with hemodialysis for acute kidney injury.In vitro titration was performed, adding trisodium citrate and calcium chloride to heparinized canine blood. A tentative protocol was used first in 66 treatments with additional heparinization and subsequently in 518 heparin-free treatments. Safety and adequacy of RCA were assessed based on clinical and laboratory monitoring, dialyzer pressure gradient, treatment completion, and visual scoring of the extracorporeal circuit.Addition of 1 mmol/L citrate to heparinized blood decreased the ionized calcium concentration by 0.23 mmol/L (95% confidence interval [CI], 0.16-0.30) and 1 mmol/L calcium increased it by 0.62 mmol/L (95% CI, 0.45-0.79). Heparin-free treatments were initiated with infusion of trisodium citrate (102 mmol/L) at 2.55 mmol/L blood and calcium chloride (340 mmol/L) at 0.85 mmol/L. Citrate and calcium administrations were adjusted in 27 and 34% of the treatments, respectively. Overall, anticoagulation was satisfactory in 92% of the treatments, with expected azotemia reduction in 95% (urea) and 86% (creatinine), stable dialyzer pressure gradient in 82%, and clean extracorporeal circuits in 92% of the treatments. Eighteen treatments (3.5%) were discontinued prematurely, 9 because of clotting and 9 for reasons unrelated to the RCA procedure.Regional citrate anticoagulation allows safe and efficient heparin-free hemodialysis in dogs at risk of bleeding.
Journal of veterinary internal medicine 20171124 1
<h4>Background</h4>The traditional systemic heparinization used for anticoagulation in extracorporeal therapies may cause fatal complications in animals at risk of bleeding.<h4>Hypothesis/objectives</h4>To develop and validate a protocol of regional citrate anticoagulation (RCA) for intermittent hemodialysis in dogs.<h4>Animals</h4>A total of 172 dogs treated with hemodialysis for acute kidney injury.<h4>Methods</h4>In vitro titration was performed, adding trisodium citrate and calcium chloride ...[more]
Project description:Regional citrate anticoagulation use in intermittent hemodialysis is limited by the increased risk of metabolic complications due to faster solute exchanges than with continuous renal replacement therapies. Several simplifications have been proposed. The objective of this study was to validate a mathematical model of hemodialysis anticoagulated with citrate that was then used to evaluate different prescription scenarios on anticoagulant effectiveness (free calcium concentration in dialysis filter) and calcium balance. A study was conducted in hemodialyzed patients with a citrate infusion into the arterial line and a 1.25 mmol/L calcium dialysate. Calcium and citrate concentrations were measured upstream and downstream of the citrate infusion site and in the venous line. The values measured in the venous lines were compared with those predicted by the model using Bland and Altman diagrams. The model was then used with 22 patients to make simulations. The model can predict the concentration of free calcium, bound to citrate or albumin, accurately. Irrespective of the prescription scenario a decrease in free calcium below 0.4 mmol/L was obtained only in a fraction of the dialysis filter. A zero or slightly negative calcium balance was observed, and should be taken into account in case of prolonged use.
Project description:BackgroundRegional citrate anticoagulation (RCA) is the gold standard of anticoagulation for continuous renal replacement therapy but is rarely used for intermittent hemodialysis (IHD) in ICU. Few studies assessed the safety and efficacy of RCA during IHD in ICU; however, no data are available comparing RCA to heparin anticoagulation, which are commonly used for IHD. The aim of this study was to assess the efficacy and safety of RCA compared to heparin anticoagulation during IHD.MethodsThis retrospective single-center cohort study included consecutive ICU patients treated with either heparin anticoagulation (unfractionated or low-molecular-weight heparin) or RCA for IHD from July to September in 2015 and 2017. RCA was performed with citrate infusion according to blood flow and calcium infusion by diffusive influx from dialysate. Using a propensity score analysis, as the primary endpoint we assessed whether RCA improved efficacy, quantified with Kt/V from the ionic dialysance, compared to heparin anticoagulation. The secondary endpoint was safety. Exploratory analyses were performed on the changes in efficacy and safety between the implementation period (2015) and at long term (2017).ResultsIn total, 208 IHD sessions were performed in 56 patients and were compared (124 RCA and 84 heparin coagulation). There was no difference in Kt/V between RCA and heparin (0.95 ± 0.38 vs. 0.89 ± 0.32; p = 0.98). A higher number of circuit clotting (12.9% vs. 2.4%; p = 0.02) and premature interruption resulting from acute high transmembrane pressure (21% vs. 7%; p = 0.02) occurred in the RCA sessions compared to the heparin sessions. In the propensity score-matching analysis, RCA was associated with an increased risk of circuit clotting (absolute differences = 0.10, 95% CI [0.03-0.18]; p = 0.008). There was no difference in efficacy and safety between the two time periods (2015 and 2017).ConclusionRCA with calcium infusion by diffusive influx from dialysate for IHD was easy to implement with stable long-term efficacy and safety but did not improve efficacy and could be associated with an increased risk of circuit clotting compared to heparin anticoagulation in non-selected ICU patients. Randomized trials to determine the best anticoagulation for IHD in ICU patients should be conducted in a variety of settings.
Project description:IntroductionThe lack of individualized treatment protocols and complicated procedures are important factors limiting the use of regional citrate anticoagulation (RCA) technology in hemodialysis. This study aims to validate the safety and efficacy of a simplified individualized RCA protocol for hemodialysis.Materials and methodsFrom June 2019 to August 2019, 45 patients with active bleeding or bleeding tendency undergoing maintenance hemodialysis in the Nephrology Department of the First Affiliated Hospital of Nanchang University were randomly divided into a modified conventional RCA protocol group with a low-flux dialyzer, a simplified individualized RCA protocol group with a high-flux dialyzer, and a simplified individualized RCA protocol group with a low-flux dialyzer.ResultsA total of 45 patients were included in this study. The mean age of the patients was 57.38 ± 19.05 years, and 78% were men. Forty-three patients completed 4 hours of hemodialysis, and the median total clotting scores in the 3 groups were 11, 12, and 12. Compared with the modified conventional RCA protocol group with a low-flux dialyzer, the 2 simplified individualized RCA protocol groups had better clotting scores for the dialyzer, arterial bubble trap, and single-pool urea clearance index (spKt/VBUN) and lower costs. Moreover, these parameters did not differ between the 2 simplified individualized RCA protocol groups. No electrolyte or acid-base imbalances or citrate poisoning was observed in any of the 3 groups. Adverse events did not differ significantly among the 3 groups.ConclusionsThe simplified individualized RCA protocol is safe, effective, and easy to implement. Therefore, this protocol can be promoted for clinical practice.Trial registrationThis study was registered in the Chinese Clinical Study Registry under registration number ChiCTR1900023801.
Project description:BACKGROUND:Recommended regular saline flushing presents clinical ineffectiveness for hemodialysis (HD) patients at high risk of bleeding with heparin contraindication. Regional citrate anticoagulation (RCA) has previously been used with a Ca2+ containing dialysate with prefiltered citrate in one arm (RCA-one). However, anticoagulation is not always achievable and up to 40% results in serious clotting in the venous expansion chamber. In this study, we have transferred one-quarter of the TSC from the prefiltered to the post filter based on RCA-one, which we have called RCA-two. The objective of this study was to compare the efficacy and safety of RCA-two with either saline flushing or RCA-one in HD patients with a high bleeding risk. METHOD:In this investigator-initiated, multicenter, controlled, prospective, randomized clinical trial, 52 HD patients (77 sessions) were randomized to the RCA-2 and RCA-one group in part one of the trial, and 45 patients (64 sessions) were randomized to the RCA-2 and saline group in part two of the trial. Serious clotting events, adverse events and blood analyses were recorded. RESULTS:Serious clotting events in the RCA-two group were significantly lower compared with the RCA-one and saline group (7.89% vs. 30.77%, P?=?0.011; 3.03% vs. 54.84%, P?<?0.001, respectively). The median circuit survival time was 240?min (IQR 240 to 240) in the RCA-two group, was significantly longer than 230?min (IQR 155 to 240, P?<?0.001) in the RCA-one group and 210?min (IQR 135 to 240, P?=?0.003) in the saline group. The majority of the AEs were hypotension, hypoglycemia and chest tightness, most of which were mild in intensity. Eight patients (20.51%) in the RCA-one group, 4 patients (12.90%) in the saline group and 10 patients (26.31%) in the RCA-two group, P?>?0.05. CONCLUSIONS:Our data demonstrated that the modified anticoagulation protocol was more effective and feasible during hemodialysis therapy for patients at high risk of bleeding. TRIAL REGISTRATION:GDREC, GDREC2017250H. Registered February 2, 2018; retrospectively registered.
Project description:BACKGROUND:Flexitrate, an innovative regional citrate anticoagulation (RCA) protocol, was compared to traditional RCA (tRCA) and Heparin anticoagulation protocols in intensive care patients treated with continuous renal replacement therapy (CRRT). METHODS:A single-center, retrospective, cohort study, was done in a 26-bed intensive care unit in a large community hospital. Eighty dialysis sessions (Flexitrate?=?2852?h, tRCA?=?3580?h and Heparin?=?2026?h), performed in 53 patients, were evaluated for filter life, RCA control, and metabolic control. RESULTS:In the Flexitrate cohort, 3.8% of filters clotted, compared to 16.9% with tRCA and 28.3% with Heparin (p <?0.001 for Flexitrate compared to either tRCA or Heparin). Filter survival was significantly improved with Flexitrate compared to tRCA (HR 0.24, p =?0.018) or Heparin (HR 0.14, p =?0.004). Anticoagulation control was superior with Flexitrate with Patient Ionized Calcium out of target a median of 16% of the time, compared to 27% for tRCA (p <?0.001). Filter Ionized Calcium was out of target a median of 6.8% of the time, compared to 23% for tRCA (p =?0.03). Flexitrate produced significantly less alkalosis, hypernatremia, and hypocalcemia than tRCA, and overall metabolic control was comparable to Heparin anticoagulation. The only adverse metabolic outcome with Flexitrate was increased hypomagnesemia. CONCLUSIONS:The Flexitrate protocol extended filter life, delivered more consistent anticoagulation, and provided superior metabolic control compared to a tRCA protocol. Filter life was superior to Heparin anticoagulation, with similar metabolic control. A randomized control trial comparing these protocols is recommended.
Project description:ABSTRACT Background Current ways to diagnose citrate accumulation (CA) in patients receiving regional citrate anticoagulation (RCA) continuous renal replacement therapy (CRRT) are confounded by various clinical factors. Serum citrate measurement emerges as a more direct way to diagnose CA, but its clinical utility and optimal cut-off values remain undefined. This study examined serum citrate kinetics and its diagnostic performance for CA in patients receiving RCA CRRT. Methods A multicentre prospective study was carried out in two tertiary referral centre intensive care units in Hong Kong with serum citrate levels measured at baseline and 2, 6, 12, 24, 36, 48 and 72 h after initiation of RCA CRRT and their relationships with the development of CA. Results Among the 133 patients analysed, 18 patients (13.5%) developed CA. The serum citrate levels at baseline and 2, 6 and 12 h after initiation of RCA CRRT in patients who had CA were significantly higher than the non-CA group (P < .001 for all). The CA group also had higher serum citrate levels than the non-CA group {median 0.93 mmol/L [interquartile range (IQR) 0.81–1.16) versus 0.37 mmol/L (IQR 0.26–0.57), P < .001}. Using a cut-off of 0.85 mmol/L, the serum citrate level had a sensitivity of 0.77 and a specificity 0.96 for the diagnosis of CA [area under the receiver operating characteristics curve (AUROC) 0.90, P < .001]. The 2-h and 6-h serum citrate levels had good discriminatory abilities for predicting subsequent development of CA (AUROC 0.86 and 0.83 for 2-h and 6-h citrate levels using cut-off values of 0.34 and 0.63 mmol/L, respectively; P < .001). Conclusion Serum citrate levels were significantly higher in patients with CA compared with patients without CA. Serum citrate levels showed good performance in diagnosing and predicting the development of CA. Graphical Abstract Graphical Abstract
Project description:BackgroundClotting is a major drawback of continuous renal replacement therapy (CRRT) performed on critically ill pediatric patients. Although anticoagulation is recommended to prevent clotting, limited results are available on the effect of each pharmacological strategy in reducing filter clotting in pediatric CRRT. This study defines which anticoagulation strategy, between regional citrate anticoagulation (RCA) and systemic anticoagulation with heparin, is safer and more efficient in reducing clotting, patient mortality, and treatment complications during pediatric CRRT.MethodsA systematic literature review was run considering papers published in English until December 2021 and describing patients' and treatments' complications in CRRT performed with heparin and RCA on patients aged less than 18 years.ResultsEleven studies were considered, cumulatively comprising 1.706 CRRT sessions (62% with systemic anticoagulation and 38% with RCA). Studies have consistently identified RCA's superiority over systemic anticoagulation with heparin in prolonging circuit life. The pooled estimate (95% CI) of filter clotting risk showed that RCA is a protective factor for clotting risk (RR = 0.204).ConclusionsRCA has a potential role in prolonging circuit life and seems superior to systemic anticoagulation with heparin in decreasing the risk of circuit clotting during CRRT performed in critically ill pediatric patients.
Project description:Background: To investigate pro- and anticoagulant alterations in uremic critically ill patients prior to and during continuous renal replacement therapy. In addition to the conventional thrombin generation assay (TGA), we performed a thrombomodulin-modified variant to better elucidate procoagulant imbalances. Platelet function was determined via multiple electrode aggregometry (MEA) to round off hemostatic analysis. Methods: We prospectively enrolled patients at surgical intensive care units (ICU) with acute kidney injury undergoing continuous veno-venous hemodialysis using regional citrate anticoagulation. TGA and platelet function testing were performed at baseline (≤ 12 h prior to continuous renal replacement therapy) and on 3 consecutive days (day A-C) of extracorporeal therapy. Results: We did not observe significant changes in thrombin generation after start or during renal replacement therapy. Ratios of endogenous thrombin potential in patients were significantly increased (p < 0.001) compared to standardized plasma of healthy donors confirming the assumed procoagulant alterations in ICU patients. Test results of the conventional TGA differed significantly (p < 0.05) from those of the thrombomodulin-modified assay. The area under the curve remained below MEA reference values during the entire observation period, indicating a persistent reduction in platelet function. Conclusion: In summary, in-depth analysis using standard and modified TGA, as well as calculation of endogenous thrombin potential (ETP) ratios, revealed no further aggravation of the procoagulatory shift in the critically ill patient during CVVHD using regional citrate anticoagulation. MEA ruled out the potential impact of platelets. Clinical Trial Registration: German Clinical Trials Register (DRKS00004336), 29 August 2012; www.drks.de.
Project description:BackgroundThere is an unmet need to develop safe and successful heparin-free regional anticoagulation modalities in haemodialysed patients at risk of bleeding. Whether the addition of citrate as a prefilter injection or in the dialysate itself is required to reach anticoagulation objectives when calcium-free dialysate is used as regional anticoagulation remains unclear.MethodsIn this monocentric retrospective study, we report our experience of 908 dialysis sessions performed with a calcium-free citrate-containing dialysate and calcium reinjection according to the ionic dialysance, without additional heparin.ResultsPremature termination for filter clotting occurred in 20 sessions (2.2%) and duration of session was >4.5 h in 135 (15%; maximum duration 6 h). In addition, we could investigate the citrate, calcium and acid-basis status during haemodialysis sessions performed with (citrate group, n = 20 sessions) or without (citrate-free group, n = 19 sessions) citrate in the dialysate. In 20 sessions performed in patients with underlying liver disorders and using calcium-free citrate-containing dialysate, patients' ionized calcium (iCa) and serum citrate levels were stable and remained within the normal range, respectively. Post-filter iCa was below 0.4 mmol/L in 19/20 sessions and citrate was 0.304 mmol/L (range: 0.011; 0.548). In 19 sessions that used calcium and citrate-free dialysate, post-filter iCa was 0.41 mmol/L (0.34; 0.5) and all sessions extended to 4 h or beyond.ConclusionsRegional anticoagulation of haemodialysis with a calcium-free dialysate and calcium reinjection according to the ionic dialysance is safe. Adding citrate to the dialysate is not mandatory to prevent dialysis circuit clotting in most patients.
Project description:BackgroundRegional anticoagulation with citrate during renal replacement therapy (RRT) reduces the risk of bleeding, extends dialyzer lifespan and is cost-effective. Therefore, current guidelines recommend its use if patients are not anticoagulated for another reason and if there are no contraindications against citrate. RRT with regional citrate anticoagulation has been established in critically ill patients as continuous veno-venous hemodialysis (CVVHD) to reduce citrate load. However, CVVHD is inferior regarding middle molecule clearance compared to continuous veno-venous hemofiltration (CVVH). The use of a high cut-off dialyzer in CVVHD may thus present an option for middle molecule clearance similar to CVVH. This may allow combining the advantages of both techniques.MethodsIn this prospective, randomized, single-blinded single-center-trial, sixty patients with acute renal failure and established indication for renal replacement therapy were randomized 1:1 into two groups. The control group was put on CVVHD using regional citrate anticoagulation and a high-flux dialyzer, while the intervention group was on CVVHD using regional citrate anticoagulation and a high-cut-off dialyzer. The concentrations of urea, creatinine, β2-microglobulin, myoglobin, interleukin 6 and albumin were measured pre- and post-dialyzer 1, 6, 12, 24 and 48 hours after initiating CVVHD.ResultsMean plasma clearance for β2-microglobulin was 19.6±5.8 ml/min in the intervention group vs. 12.2±3.6 ml/min in the control group (p<0.001). For myoglobin (8.0±4.5 ml/min vs. 0.2±3.6 ml/min, p<0.001) and IL-6 (1.5±4.3 vs. -2.5±3.5 ml/min, p = 0.002) a higher mean plasma clearance using high-cut-off dialyzer could be detected too, but no difference for urea, creatinine and albumin could be observed concerning this parameter between the two groups.ConclusionCVVHD using a high cut-off dialyzer results in more effective middle molecule clearance than that with high-flux dialyzer.Trial registrationGerman Clinical Trials Register (DRKS00005254, registered 26th November 2013).
