Regional Citrate Anticoagulation Protocol Research Articles

Safe and Effective Implementation of a Regional Citrate Anticoagulation Protocol in an Emergency Use Situation

Safe and Effective Implementation of a Regional Citrate Anticoagulation Protocol in an Emergency Use Situation

Safety of Citrate Anticoagulation in CKRT: Monocentric Experience of a Dynamic Protocol of Calcium Monitoring.

Regional Citrate Anticoagulation (RCA) is considered the first-line anticoagulation for Continuous Kidney Replacement Therapy (CKRT). The RCA requires strict protocols and trained staff to avoid unsafe use and ensure its benefit. We have analyzed all our CKRT prescriptions from December 2020 to April 2022 anonymously, collecting data on CKRT, lab tests, clinical conditions, and complications of RCA. In addition, in order to better detect citrate accumulation, we have performed an RCA protocol by reducing the CaTot/Ca2+ ratio cut-off from 2.50 to 2.40 and increasing the number of calcium checks according to its trend. Among the 374 patients in CKRT, 104 received RCA prescriptions, of which 11 (10.6%) were discontinued: 4 for the suspicion of citrate accumulation, 1 for the development of metabolic alkalosis, 1 for the shift to a different CKRT procedure due to the need for a higher bicarbonate dose, 4 for the elevation of hepatocytolysis indexes, and 1 due to a preemptive discontinuation following massive post-surgery bleeding. None of the patients have had citrate toxicity as indicated by a CaTot/Ca2+ greater than 2.50, and our protocol has allowed the early identification of patients who might develop clinical citrate toxicity.

Thromboelastography and Traditional Coagulation Testing in Non-ICU-Admitted Patients with Acute Kidney Injury: An Observational Cohort Study

Introduction: This study aimed to elucidate the coagulation disorders in non-ICU patients with acute kidney injury (AKI) and their contribution to clotting-related outcomes of intermittent kidney replacement therapy (KRT). Methods: We included non-ICU-admitted patients with AKI requiring intermittent KRT, clinically having a risk of bleeding and against systemic anticoagulant use during KRT between April and December 2018. The premature termination of treatment due to circuit clotting was considered a poor outcome. We analyzed the characteristics of thromboelastography (TEG)-derived and traditional coagulation parameters and explored the potential-affecting factors. Results: In total, 64 patients were enrolled. Hypocoagulability was detected in 4.7%–15.6% of patients by a combination of the traditional parameters, i.e., prothrombin time (PT)/international normalized ratio, activated partial PT, and fibrinogen. No patient had hypocoagulability observed on TEG-derived reaction time; only 2.1%, 3.1%, and 10.9% of patients had hypocoagulability on TEG-derived kinetic time (K-time), α-angle, and maximum amplitude (MA), respectively, which were also platelet-related coagulation parameters, despite 37.5% of the cohort having thrombocytopenia. In contrast, hypercoagulability was more prevalent, involving 12.5%, 43.8%, 21.9%, and 48.4% of patients on TEG K-time, α-angle, MA, and coagulation index (CI), respectively, although thrombocytosis was only in 1.5% of the cohort. Patients with thrombocytopenia showed lower fibrinogen level (2.6 vs. 4.0 g/L, p = 0.00), α-angle (63.5° vs. 73.3°, p = 0.00), MA (53.5 vs. 66.1 mm, p = 0.00), and CI (1.8 vs. 3.6, p = 0.00) but higher thrombin time (17.8 vs. 16.2 s, p = 0.00) and K-time (2.0 vs. 1.2 min, p = 0.00) than those with a platelet count over 100 × 10⁹/L. 41 patients were treated with heparin-free protocol, and 23 were treated with regional citrate anticoagulation (RCA). The premature termination rate was 41.5% on heparin-free patients, while 8.7% of patients underwent an RCA protocol (p = 0.006). Heparin-free protocol was the strongest adverse factor to poor outcomes. A heparin-free subgroup analysis found that the circuit clotting risk was increased by 61.7% with a 10 × 10⁹/L elevation in platelet count (odds ratio [OR] = 1.617, p = 0.049) and decreased by 67.5% following a second increase of PT (OR = 0.325, p = 0.041). No significant correlation was found between TEG parameters and premature circuit clotting. Conclusions: Most non-ICU-admitted patients with AKI had normal-to-enhanced hemostasis and activated platelet function based on TEG results, as well as a high rate of premature circuit clotting when receiving heparin-free protocol despite thrombocytopenia. Further studies are needed to better determine the use of TEG in respect to management of anticoagulation and bleeding complications in AKI patients with KRT.

An individualized regional citrate anticoagulation protocol for hemodialysis: a real-world retrospective study.

To evaluate the safety and effectiveness of an individualized regional citrate anticoagulation (RCA) protocol for hemodialysis. In this single-center, retrospective study, blood coagulation in the extracorporeal circulation, adverse reactions, in vivo ionized calcium (iCa2+) concentrations, and the infusion dose of citrate during RCA in hemodialysis were observed in 98 patients from February 2021 to March 2022. A total of 98 patients underwent RCA during hemodialysis 362 times, and blood coagulation occurred in the extracorporeal circulation 29 times. Among the 29 cases of coagulation, most of the patients exhibited hypercoagulability, and among approximately 80% of the treatments, the deviation between the actual infusion rate of citrate in the extracorporeal circulation and the theoretical value was ± 10%. After hemodialysis, pH values and bicarbonate ion (HCO3-) levels were clearly improved, and online conductivity monitoring (OCM) values and blood coagulation scores in the extracorporeal circulation were identical to those measured in similar studies. An individualized RCA protocol for hemodialysis is safe, effective, simple, and inexpensive and can meet the needs of individualized treatment; therefore, its application is worthy of promotion.

Non-anticoagulant factors affecting coagulation in the extracorporeal circulation circuit and the development of an individualized regional citrate anticoagulation protocol for hemodialysis: A real-world retrospective study.

To investigate non-anticoagulant factors that affect blood coagulation in the extracorporeal circulation (ECC) circuit of regional citrate anticoagulation (RCA) protocol for hemodialysis (HD). The clinical characteristics of patients undergoing an individualized RCA protocol for HD between February 2021 and March 2022 were collected; Coagulation scores, pressures in various parts of the ECC circuit, the incidence of coagulation, and citrate concentrations in the ECC circuit during treatment were determined, and non-anticoagulant factors affecting coagulation in the ECC circuit were analyzed. The lowest clotting rate was 2.8% in patients with arteriovenous fistula in various vascular access. Patients on Fresenius dialysis had a lower rate of clotting in the cardiopulmonary bypass line than patients on other brands of dialyzer. Low-throughput dialyzers are less likely to clot than high-throughput dialyzers. There are significant differences in the incidence of coagulation among different nurses during citrate anticoagulant hemodialysis. In the process of citrate anticoagulant hemodialysis, non-anticoagulant factors such as coagulation status, vascular access, dialyzer selection, and operator quality will affect the anticoagulant effect.

Simplified regional citrate anticoagulation protocol for CVVH, CVVHDF and SLED focused on the prevention of KRT-related hypophosphatemia while optimizing acid-base balance.

Hypophosphatemia 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. KRT was performed by the Prismax system (Baxter) and polyacrylonitrile AN69 filters (ST 150, 1.5 m2, Baxter), combining a 18mmol/L pre-dilution citrate solution (Regiocit 18/0, Baxter) with a phosphate-containing solution (HPO42- 1.0mmol/L, HCO3- 22.0mmol/L; Biphozyl, Baxter). When needed, phosphate loss was replaced with sodium glycerophosphate pentahydrate (Glycophos™ 20mmol/20mL, 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. Forty-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 <2.5mg/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. Our 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. NCT03976440 (registered 6 June 2019).

Circuit haemodynamics during non-citrate and regional citrate continuous renal replacement, and impact of blood flow on filter life.

During continuous renal replacement therapy (CRRT) with regional citrate anticoagulation (RCA), blood flow (Qb) might affect vascular access dysfunction (AD) and, thereby, circuit life. Circuit life and circuit haemodynamics were studied in three intensive care units (ICUs) by analysing hemofilter device data (Prismaflex®, Baxter, Chicago, IL). The three sites shared similar RCA protocols but differed in Qb (120-130 vs 150-200 mL/h). Non-RCA circuits were compared with RCA circuits in which the impact of Qb was also assessed. About 3,981,906 min of circuit pressures were analysed in 2568 circuits in 567 patients. High-Qb RCA was associated with more extreme pressures, and greater AD (IRR 3.7 (1.93-7.08) as well as reduced filter life 21.1 (10.2-42.6) vs 27.0 (14.8-41.6) h). AD in high-Qb RCA circuits was associated with a 49% reduction in filter life, versus 24% reduction in low-Qb RCA, associated with a rise in the rate of increase in transfilter pressure. High-Qb RCA-CRRT was associated with greater access dysfunction, earlier filter loss and increased haemodynamic impacts of access dysfunction, suggesting low-Qb RCA-CRRT may improve circuit mechanics, function and longevity.

Comparison of two regional citrate anticoagulation modalities for continuous renal replacement therapy by a prospective analysis of safety, workload, effectiveness, and cost.

Currently, regional citrate anticoagulation (RCA) is the preferred approach for continuous renal replacement therapy (CRRT), and several RCA protocols are commercially available. This study was aimed at comparing two RCA modalities for CRRT in terms of safety, workload, effectiveness, and costs. We prospectively evaluated two different RCA approaches in patients admitted to our intensive care unit (ICU) who needed CRRT. Patients with acute liver failure were excluded. We compared a hypertonic sodium-citrate solution 136 mmol/L added before the filter as anticoagulant during bicarbonate continuous hemodialysis (RCA-CVVHD) versus citrate-buffered replacement fluid 13.3 mmol/L infused by predilution setting in continuous venovenous hemofiltration (RCA-CVVH). Alkalosis, calcium homeostasis, nursing workload, filter lifespan, urea-creatinine metabolic control, and costs were recorded. Forty-five and 31 patients who underwent RCA-CVVH and RCA-CVVHD, respectively, were included. Alkalosis-free time distributions were significantly different in favor of a higher alkalosis incidence in the RCA-CVVHD group (log-rank test χ2(1)=8.18, P=0.004). Multivariable analysis showed that RCA-CVVHD was associated with a longer filter lifespan (HR=0.47; 95% CI: 0.28-0.78), higher total cost (1362 CHF [782-1901] vs. 976 CHF [671-1353], P<0.001), and higher number of anticoagulation adjustments (9 [IQR, 4-14] vs. 2 [IQR, 1-4]). The mean urea and creatinine reduction ratios at the first 24 hours were significantly higher in the RCA-CVVHD group. Calcium homeostasis and filter downtime were similar in the two groups. Pre-filter hypertonic sodium-citrate solution (136 mmol/L) results in longer filter patency and improves depuration effectiveness. However, compared to RCA-CVVHF, it causes metabolic alkalosis and increases nursing interventions and cost.

Regional Citrate Anticoagulation during Double-Filtration Plasmapheresis in Kidney Transplant Recipients: A Single-Center Retrospective Cohort Study

Introduction: Double-filtration plasmapheresis (DFPP) may be used for immunomodulation in kidney transplant (KTx). While DFPP reduces plasma product exposure, risk of circuit clotting merits adequate anticoagulation. Regional citrate anticoagulation (RCA) avoids the risks of systemic anticoagulation, but a protocol for RCA-DFPP is not previously widely described. Methods: We conducted a single-center retrospective cohort study involving adult (≥21 years old) KTx recipients who underwent RCA-DFPP from 2018 to 2020 to investigate efficacy and safety for an RCA protocol during DFPP in KTx recipients. Results: Fifty-one (85%) of 60 RCA-DFPP sessions in 17 patients completed without circuit clotting. Circuit clotting was associated with high post-filter ionized calcium (28 vs. 3.7%, odds ratio 10.1, 95% CI 1.1–89.4, p = 0.037). Hypo- and hypercalcemia developed in 5 (8.3%) and 8 (13.3%) sessions, respectively, but no adverse effects were noted despite severe hypocalcemia in one. There was no significant change in pre- and post-RCA-DFPP sodium, bicarbonate, albumin, and platelet levels. With regards DFPP procedure, prolongation of prothrombin time (PT) and activated partial thromboplastin time (aPTT) was observed following 38 (64.4%) and 12 (20.3%) sessions, respectively. Severely prolonged (>1.5 × upper limit normal) PT and aPTT were recorded in 2 sessions each. Expectedly, hypofibrinogenemia developed after 31 (51.7%) sessions: including 4 (6.7%) severe hypofibrinogenemia (<0.5 g/L). Two patients developed bleeding requiring blood product transfusion. The median total volume of fluids administered per session was 1.495 (1.373–1.612) L; post-RCA-DFPP significant weight gain of 0.5 (0–1.25) kg was noted. Diuretic was commenced or dose increased following 20 (33.3%) sessions for fluid balance management. Discussion/Conclusion: Protocol-based RCA for DFPP is feasible and safe in KTx recipients. However, DFPP-related coagulopathy can develop consequent to treatment; caution should be exercised for patients with bleeding risk. Close monitoring and management of the patients’ electrolytes, especially hypocalcemia and hypomagnesemia, and fluid status is recommended.

Continuous Renal-Replacement Therapy in Critically Ill Children: Practice Changes and Association With Outcome.

This study was designed to evaluate practice changes and outcomes over a 10-year period in a large single-center PICU cohort that received continuous renal-replacement therapy. Retrospective study design. A multidisciplinary tertiary PICU of a university-affiliated hospital in Guangzhou, China. All critically ill children who were admitted to our PICU from January 2010 to December 2019 and received continuous renal-replacement therapy were included in this study. A total of 289 patients were included in the study. Of the two study periods, 2010-2014 and 2015-2019, the proportion of continuous renal-replacement therapy initiation time greater than 24 hours was significantly reduced ([73/223] 32.73% vs. [40/66] 60.60%, p < 0.001), the percentage of fluid overload at continuous renal-replacement therapy initiation was lower (3.8% [1.6-7.2%] vs. 12.1% [6.6-23.3%], p < 0.001), the percentage of regional citrate anticoagulation protocol was increased ([223/223] 100% vs. [15/66] 22.7%, p < 0.001), and the ICU survival rate was significantly improved ([24/66] 36.4% vs. [131/223] 58.7%, p = 0.001) in the latter period compared with the former. In addition, subgroup analysis found that survival were higher in patients with continuous renal-replacement therapy initiation time less than 24 hours, regional citrate anticoagulation protocol, and fluid overload less than 10%. The survival rate of patients received continuous renal-replacement therapy treatment in our center has improved over past 10 years, and some changes have taken place during these periods. Among them, early initiation of continuous renal-replacement therapy, lower fluid overload, and regional citrate anticoagulation method seems to be related to the improvement of outcome. Ongoing evaluation of the practice changes and quality improvement of continuous renal-replacement therapy for critically ill pediatric patients still need attention.

Regional citrate anticoagulation protocol suitable for intermittent hemodialysis and post-dilution hemodiafiltration.

Regional citrate anticoagulation (RCA) during intermittent hemodialysis (iHD) effectively prevents circuit clotting without systemic anticoagulation and is especially beneficial for patients at increased bleeding risk. The performance of RCA under different iHD modes is not well documented. We retrospectively studied all consecutive iHD sessions with our RCA protocol during a 3-year period. We compared low-flux iHD, high-flux iHD, and online post-dilution hemodiafiltration (oHDF) with regard to flow rates, calcium changes, metabolic outcomes, and complications. We used a calcium-free dialysate, concentrated sodium citrate (0.5M), and calcium chloride substitution (0.5M). Several safety measures were implemented to prevent human errors. We performed 111 RCA treatments in 66 cases. Seven sessions were prematurely stopped due to malfunctioning vascular access or pre-existing severe hypotension. The other 104 treatments (94%) consisting of 28 low-flux iHD, 31 high-flux iHD, and 45 oHDF were completed without clotting or complications. The protocol settings were used without adaptations in 75% of low-flux iHD, 93% of high-flux iHD, and 84% of oHDF sessions. Minor adjustments of the calcium flow rate were made within the first 2 hours. We did not observe any clinically relevant differences between the three modes regarding flow rates, systemic iCa, post-filter iCa, pH, or bicarbonate levels. Our protocol was similarly suitable for low-flux iHD, high-flux iHD, and oHDF, with only minor adaptations. Clotting, relevant calcium changes, metabolic or other complications were not observed. Our protocol could serve as a template for a commercial RCA solution in iHD.

A simplified protocol for individualized regional citrate anticoagulation for hemodialysis: A single-center, randomized clinical study.

The 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. From 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. A 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. The simplified individualized RCA protocol is safe, effective, and easy to implement. Therefore, this protocol can be promoted for clinical practice. This study was registered in the Chinese Clinical Study Registry under registration number ChiCTR1900023801.

Sustained low-efficiency dialysis with regional citrate anticoagulation in critically ill patients with COVID-19 associated AKI: A pilot study.

Acute Kidney Injury (AKI) is a frequent complication in critically ill patients with Coronavirus disease 2019 (COVID-19), and it has been associated with worse clinical outcomes, especially when Kidney Replacement Therapy (KRT) is required. A condition of hypercoagulability has been frequently reported in COVID-19 patients, and this very fact may complicate KRT management. Sustained Low Efficiency Dialysis (SLED) is a hybrid dialysis modality increasingly used in critically ill patients since it allows to maintain acceptable hemodynamic stability and to overcome the increased clotting risk of the extracorporeal circuit, especially when Regional Citrate Anticoagulation (RCA) protocols are applied. Notably, given the mainly diffusive mechanism of solute transport, SLED is associated with lower stress on both hemofilter and blood cells as compared to convective KRT modalities. Finally, RCA, as compared with heparin-based protocols, does not further increase the already high hemorrhagic risk of patients with AKI. Based on these premises, we performed a pilot study on the clinical management of critically ill patients with COVID-19 associated AKI who underwent SLED with a simplified RCA protocol. Low circuit clotting rates were observed, as well as adequate KRT duration was achieved in most cases, without any relevant metabolic complication nor worsening of hemodynamic status.

Regional Citrate Anticoagulation Protocol for Patients with Presumed Absent Citrate Metabolism.

Regional citrate anticoagulation (RCA) is not recommended in patients with shock or severe liver failure. We designed a protocol with personalized precalculated flow settings for patients with absent citrate metabolism that abrogates risk of citrate toxicity, and maintains neutral continuous KRT (CKRT) circuit calcium mass balance and normal systemic ionized calcium levels. A single-center prospective cohort study of patients in five adult intensive care units triaged to the CVVHDF-RCA "Shock" protocol. Of 31 patients included in the study, 30 (97%) had AKI, 16 (52%) had acute liver failure, and five (16%) had cirrhosis at the start of CKRT. The median lactate was 5 mmol/L (interquartile range [IQR], 3.2-10.7), AST 822 U/L (IQR, 122-2950), ALT 352 U/L (IQR, 41-2238), total bilirubin 2.7 mg/dl (IQR, 1.0-5.1), and INR two (IQR, 1.5-2.6). The median first hemofilter life censored for causes other than clotting exceeded 70 hours. The cumulative incidence of hypernatremia (Na >148 mM), metabolic alkalosis (HCO3- >30 mM), and hypophosphatemia (P<2 mg/dl) were one out of 26 (4%), zero out of 30 (0%), and one out of 30 (3%), respectively, and were not clinically significant. Mild hypocalcemia occurred in the first 4 hours in two out of 31 patients, and corrected by hour 6 with no additional Ca supplementation beyond the per-protocol administered Ca infusion. The maximum systemic total Ca (tCa; mM)/ionized Ca (iCa; mM) ratio never exceeded 2.5. The Shock protocol can be used without contraindications and is effective in maintaining circuit patency with a high, fixed ACDA infusion rate to blood flow ratio. Keeping single-pass citrate extraction on the dialyzer >0.75 minimizes the risk of citrate toxicity even in patients with absent citrate metabolism. Precalculated, personalized dosing of the initial Ca-infusion rate from a table on the basis of the patient's albumin level and the filter effluent flow rate maintains neutral CKRT circuit calcium mass balance and a normal systemic iCa level.

A target-oriented algorithm for maintaining serum calcium stability automatically in regional citrate anticoagulation.

Regional citrate anticoagulation (RCA) for renal replacement therapy is widely practiced in critically ill patients. However, concern exists regarding its labor-intensiveness for monitoring and the associated hypocalcemia. In this study, we provided an algorithm for prescribing RCA and evaluated its safety in patients. During 18 hemofiltration treatments with calcium-free replacement solution, participants were randomized to receive algorithm-based or trial-and-error RCA protocol. The effluent volume, post-filter and in vivo ionized calcium (iCa), and calcium in the sera and effluents were periodically measured at an interval of 1 to 2 h. For patients received algorithm-based RCA protocol, no one had a serum iCa less than 0.9 mmol/L, and none needed calcium supplement adjustment to maintain serum calcium stability. For patients accepted trial-and-error protocol, all patients had a serum iCa below 0.9 mmol/L, their serum iCa and calcium levels fluctuated dramatically, and all patients need additional calcium supplement adjustment during RCA. None of the participants showed a post-filter iCa > 0.4 mmol/L. We provided a safe algorithm for calculating calcium supplementation doses that could maintain serum calcium stability without additional adjustment during RCA.

Dialysis Filter Life, Anticoagulation, and Inflammation in COVID-19 and Acute Kidney Injury.

In recent studies, 5%–20% of hospitalized patients with coronavirus disease 2019 (COVID-19) developed AKI requiring RRT (CoV-AKI-RRT) (1,2) (L. Chan et al., unpublished observations). Hypercoagulability has been recognized as a salient feature of COVID-19 in the critically ill (3,4) and there have been anecdotal accounts of unexpectedly frequent dialysis filter clotting. However, there are limited data describing the magnitude of the problem. A recent report described clotting events in 28 of 29 patients with CoV-AKI-RRT and shorter filter lifespan compared with a historical control, but no details were provided regarding anticoagulation (4). Our objective was to examine the delivery of RRT and circuit interruptions in patients with CoV-AKI-RRT in comparison with those in the pre-COVID-19 era. With approval of the Institutional Review Board, waiver of informed consent, and in accordance with the Declaration of Helsinki, we conducted a retrospective single-center study, ancillary from our previously reported cohort (2). We identified hospitalized patients with COVID-19 (positive severe acute respiratory syndrome coronavirus 2 RNA PCR by nasopharyngeal swab) and AKI, who underwent RRT by sustained low-efficiency dialysis (SLED) for ≥8 hours in an intensive care unit between March and April of 2020 (study period: 4 weeks) by either prolonged intermittent or continuous RRT modality (5,6) using Fresenius 2008K/K2 (Bad Homburg, Germany) machines. At our hospital, continuous venovenous hemodiafiltration (CVVHDF) with PrismaFlex (Deerfield, IL) machines was restricted to the neurointensive care unit and was not expanded during the pandemic due to logistics. As pre-COVID-19 control, we included consecutive patients (reverse chronological order) with AKI without COVID-19 who underwent SLED in December of 2019. Electronic medical records were accessed and RRT flowsheets were manually reviewed to extract timing of initiation and interruption, blood flow rate (BFR), dialysate flow rate, and filter transmembrane pressure (TMP). Standard BFR was 200 …

Safety and Efficacy of a New Simplified Regional Citrate Anticoagulation Protocol for Continuous Venovenous Hemodiafiltration and Sustained Low-Efficiency Dialysis Focused on Acid-Base Balance Optimization and Prevention of Kidney Replacement Therapy-Induced Hypophosphatemia

Safety and Efficacy of a New Simplified Regional Citrate Anticoagulation Protocol for Continuous Venovenous Hemodiafiltration and Sustained Low-Efficiency Dialysis Focused on Acid-Base Balance Optimization and Prevention of Kidney Replacement Therapy-Induced Hypophosphatemia

Precision renal replacement therapy.

This article reviews the current evidence supporting the use of precision medicine in the delivery of acute renal replacement therapy (RRT) to critically ill patients, focusing on timing, solute control, anticoagulation and technologic innovation. Precision medicine is most applicable to the timing of RRT in critically ill patients. As recent randomized controlled trials have failed to provide consensus on when to initiate acute RRT, the decision to start acute RRT should be based on individual patient clinical characteristics (e.g. severity of the disease, evolution of clinical parameters) and logistic considerations (e.g. organizational issues, availability of machines and disposables). The delivery of a dynamic dialytic dose is another application of precision medicine, as patients may require different and varying dialysis doses depending on individual patient factors and clinical course. Although regional citrate anticoagulation (RCA) is recommended as first-line anticoagulation for continuous RRT, modifications to RCA protocols and consideration of other anticoagulants should be individualized to the patient's clinical condition. Finally, the evolution of RRT technology has improved precision in dialysis delivery through increased machine accuracy, connectivity to the electronic medical record and automated reduction of downtime. RRT has become a complex treatment for critically ill patients, which allows for the prescription to be precisely tailored to the different clinical requirements.

P1096SAFETY AND EFFICACY OF A NEW SIMPLIFIED REGIONAL CITRATE ANTICOAGULATION PROTOCOL FOR SUSTAINED LOW EFFICIENCY DIALYSIS FOCUSED ON PREVENTION OF RRT-INDUCED HYPOPHOSPHATEMIA IN CRITICALLY ILL RENAL PATIENTS

Abstract Background and Aims Sustained-Low Efficiency Dialysis (SLED) is a hybrid Renal Replacement Therapy (RRT) increasingly used in critically ill patients with Acute Kidney Injury (AKI). Usually lasting 8-12 hours, this modality combines several advantages of both intermittent and continuous RRT (CRRT). Regional citrate anticoagulation (RCA) represents the most adequate anticoagulation strategy to avoid the extracorporeal circuit clotting. Hypophosphatemia (serum phosphorus, s-P, levels ≤ 2.5 mg/dl) is a common electrolyte disorder in critically ills, with an increased incidence in course of prolonged RRTs, especially when standard dialysis/replacement solutions and highly intensive modalities are employed. Given the potentially negative impact of hypophosphatemia on patients’ outcomes, strategies aimed at preventing its onset should be appropriately implemented. This pilot study is aimed at evaluation of safety and efficacy of a simplified RCA protocol for SLED, based on the combination of a low-concentrated citrate solution with a phosphate-containing solution. Methods a prospective observational study was conducted on critically ill patients with AKI requiring RRT or End Stage Renal Disease (ESRD) previously on RRT admitted to our renal Intensive Care Unit (ICU). SLED was performed by the Prismax system (Baxter) and polyacrylonitrile AN69 haemofilters (ST 150, 1.5 m2, Baxter). 8-hours SLED sessions were prescribed, in the SLED-f variant, by using a 18 mmol/l pre-dilution trisodium citrate solution (Regiocit 18/0, Baxter) combined with a phosphate-containing solution acting as dialysate (Ca2+ 0, HPO42- 1, Mg2+ 0.75, HCO3- 22 mmol/l; Biphozyl, Baxter) and a standard RRT solution acting as post-dilution replacement fluid (Prismasol 4, Baxter). Calcium chloride (CaCl 10%) was infused in a separate central venous line to maintain the systemic Ca2+ (s-Ca2+) within a normal range. Each patient underwent three consecutive daily SLED sessions. The activated coagulation time (ACT), acid–base parameters, s-Ca2+ and potassium were measured at SLED start and every 2 h. Phosphorus and magnesium losses with RRT were replaced, when needed, with sodium glycerophosphate pentahydrate (GlycophosTM 20 mmol/20 ml, Fresenius Kabi Norge AS, Halden, Norvegia) and magnesium sulphate. Results a total of 60 SLED-f sessions were performed in 20 ICU patients. At ICU admission, the average APACHE II score was 21.8 and half of patients were mechanically ventilated. Many of them showed hemodynamic instability and AKI was oliguric in 90% of cases. No premature interruptions for irreversible filter clotting occurred and the prescribed dialysis dose was delivered in 95% of cases. No statistically significant differences were observed between systemic ACT at SLED start and during RRT sessions, and no major hemorrhagic events were observed. Regarding RCA, no clinically relevant episode of hypo or hypercalcemia was observed, and calcium infusion rate remained constant in course of treatments. Acid-base status was effectively maintained during the entire period of treatment and no episodes of clinically relevant metabolic acidosis or alkalosis were registered. The analysis of the main laboratory variables at SLED start, in course and after 24 h of treatment did not show statistically significant differences. Regardless of starting values, s-P and s-Mg were progressively corrected and maintained within the normality range, limiting the need for exogenous supplementations. Conclusions These preliminary data suggest that our simplified RCA protocol for SLED, combining a low-citrate solution with a phosphate-containing solution, is safe and efficacious allowing to optimizing acid-base balance and to preventing RRT-related hypophosphatemia.

Complications of Regional Citrate Anticoagulation for Continuous Renal Replacement Therapy: An Observational Study

Introduction: Regional citrate anticoagulation (RCA) is the recommended anticoagulation modality for continuous renal replacement therapy (CRRT). RCA was associated with a low rate of complications in randomized controlled trials. However, little is known about the type and rate of complications in real life. We sought to describe complications associated with RCA in comparison with those associated with heparin anticoagulation. Methods: In our institution, RCA has been the default anticoagulation modality for CRRT in all patients without contraindications since 2013. We have retrospectively reviewed all consecutive patients who received CRRT between January and December 2016 in our institution. For each CRRT session, we have assessed circuit duration, administered dose, as well as therapy-associated complications. Those parameters were compared according to whether the circuit was run in continuous veno-venous hemodialysis (CVVHD) mode with RCA or continuous veno-venous hemofiltration (CVVH) mode with heparin anticoagulation. Results: We analyzed 691 CRRT sessions in 121 patients. Of those 400 (57.9%) were performed in CVVHD-RCA mode and 291 (42.1%) in CVVH-Heparin Mode. Compared with ­CVVH-Heparin mode, CVVHD-RCA mode was associated with a longer circuit lifespan (median duration 54.9 interquartile range [IQR 44.6] vs. 15.3 h [IQR 22.4], p < 0.0001). It was associated with a higher rate of metabolic acidosis 77 (20.2%) vs. 18 (7.2%), (p < 0.0001), alkalosis 186 (48.7%) vs. 43 (17.1%), (p= 0.0001), and hypocalcemia 96 (25.07%) vs. 26 events (10.79%), p < 0.0001. However, the majority of these alterations were of benign or moderate severity. Only one possible citrate intoxication was observed. Conclusions: CVVHD-RCA was associated with a much longer circuit life but an increased rate of minor metabolic complications, in particular acid-base derangements. Some of these complications might have been prevented by therapy adaptation. Medical and nursing staff education is of major importance in the implementation of an RCA protocol.