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Deciphering simplified regional anticoagulation with citrate in intermittent hemodialysis: a clinical and computational study.

ABSTRACT: 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.

SUBMITTER: Aniort J

PROVIDER: S-EPMC11347690 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

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Deciphering simplified regional anticoagulation with citrate in intermittent hemodialysis: a clinical and computational study.

Aniort Julien J Richard Felix F Thouy François F Le Guen Louis L Philipponnet Carole C Garrouste Cyril C Heng Anne Elisabeth AE Dupuis Claire C Adda Mireille M Julie Durif D Elodie Lebredonchel L Chupin Laurent L Bouvier Damien D Souweine Bertrand B Cindea Nicolae N

Scientific reports 20240826 1

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 filte ...[more]

PMID: 39187537

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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:BackgroundRecommended 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.MethodIn 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.ResultsSerious 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.ConclusionsOur data demonstrated that the modified anticoagulation protocol was more effective and feasible during hemodialysis therapy for patients at high risk of bleeding.Trial registrationGDREC, GDREC2017250H. Registered February 2, 2018; retrospectively registered.

Project description:BackgroundHypophosphatemia is a common electrolyte disorder in critically ill patients undergoing prolonged kidney replacement therapy (KRT). We evaluated the efficacy and safety of a simplified regional citrate anticoagulation (RCA) protocol for continuous venovenous hemofiltration (CVVH), continuous venovenous hemodiafiltration (CVVHDF) and sustained low-efficiency dialysis filtration (SLED-f). We aimed at preventing KRT-related hypophosphatemia while optimizing acid-base equilibrium.MethodsKRT was performed by the Prismax system (Baxter) and polyacrylonitrile AN69 filters (ST 150, 1.5 m2, Baxter), combining a 18 mmol/L pre-dilution citrate solution (Regiocit 18/0, Baxter) with a phosphate-containing solution (HPO42- 1.0 mmol/L, HCO3- 22.0 mmol/L; Biphozyl, Baxter). When needed, phosphate loss was replaced with sodium glycerophosphate pentahydrate (Glycophos™ 20 mmol/20 mL, Fresenius Kabi Norge AS, Halden, Norway). Serum citrate measurements were scheduled during each treatment. We analyzed data from three consecutive daily 8-h SLED-f sessions, as well as single 72-h CVVH or 72-h CVVHDF sessions. We used analysis of variance (ANOVA) for repeated measures to evaluate differences in variables means (i.e. serum phosphate, citrate). Because some patients received phosphate supplementation, we performed analysis of covariance (ANCOVA) for repeated measures modelling phosphate supplementation as a covariate.ResultsForty-seven patients with acute kidney injury (AKI) or end stage kidney disease (ESKD) requiring KRT were included [11 CVVH, 11 CVVHDF and 25 SLED-f sessions; mean Acute Physiology and Chronic Health Evaluation II (APACHE II) score 25 ± 7.0]. Interruptions for irreversible filter clotting were negligible. The overall incidence of hypophosphatemia (s-P levels <2.5 mg/dL) was 6.6%, and s-P levels were kept in the normality range irrespective of baseline values and the KRT modality. The acid-base balance was preserved, with no episode of citrate accumulation.ConclusionsOur data obtained with a new simplified RCA protocol suggest that it is effective and safe for CVVH, CVVHDF and SLED, allowing to prevent KRT-related hypophosphatemia and maintain the acid-base balance without citrate accumulation.Trial registrationNCT03976440 (registered 6 June 2019).

Dataset Information

Deciphering simplified regional anticoagulation with citrate in intermittent hemodialysis: a clinical and computational study.

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Deciphering simplified regional anticoagulation with citrate in intermittent hemodialysis: a clinical and computational study.

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