Regional citrate anticoagulation in cardiac surgery patients at high risk of bleeding: a continuous veno-venous hemofiltration protocol with a low concentration citrate solution

Abstract

IntroductionRegional citrate anticoagulation (RCA) is a valid option in patients at high risk of bleeding who are undergoing continuous renal replacement therapy (CRRT). The aim of this study was to evaluate, in critically ill patients with severe acute kidney injury following cardiac surgery, the efficacy and safety of RCA-continuous veno-venous hemofiltration (CVVH) using a low concentration citrate solution.MethodsIn high bleeding-risk cardiac surgery patients, we adopted, as an alternative to heparin or no anticoagulation, RCA-CVVH using a 12 mmol/l citrate solution. For RCA-CVVH settings, we developed a mathematical model to roughly estimate citrate load and calcium loss. In order to minimize calcium chloride supplementation, a calcium-containing solution was used as post-dilution replacement fluid.Statistical analysis was performed using the Student t-test or analysis of variance (ANOVA) with post-hoc tests, Wilcoxon or Kruskal-Wallis tests for non-parametric analysis, and Kaplan-Meier survival analysis with Log Rank test.ResultsThirty-three patients (age 70.8 ± 9.5, Sequential Organ Failure Assessment (SOFA) score 13.9 ± 2.5) were switched to RCA-CVVH from no anticoagulation CRRT. Among them, 16 patients had been previously switched from heparin to no anticoagulation because of bleeding or heparin-related complications. RCA-CVVH filter life (49.8 ± 35.4 hours, median 41, 152 circuits) was significantly longer (P < 0.0001) when compared with heparin (30.6 ± 24.3 hours, median 22, 73 circuits) or no anticoagulation (25.7 ± 21.2 hours, median 20, 77 circuits). Target circuit and systemic Ca++ were easily maintained (0.37 ± 0.09 and 1.18 ± 0.13 mmol/l), while the persistence of a mild metabolic acidosis required bicarbonate supplementation (5.8 ± 5.9 mmol/hours) in 27 patients. The probability of circuit running at 24, 48, 72 hours was higher during RCA-CVVH (P < 0.0001), with a lower discrepancy between delivered and prescribed CRRT dose (P < 0.0001). RCA was associated with a lower transfusion rate (P < 0.02). Platelet count (P = 0.012) and antithrombin III activity (P = 0.004) increased throughout RCA-CVVH, reducing the need for supplementation.ConclusionsRCA safely prolonged filter life while decreasing CRRT downtime, transfusion rates and supplementation needs for antithrombin III and platelets. In cardiac surgery patients with severe multiple organ dysfunction syndrome, the adoption of a 12 mmol/l citrate solution may provide a suboptimal buffers supply, easily overwhelmed by bicarbonate supplementation.

Regional Citrate Anticoagulation for RRTs in Critically Ill Patients with AKI

“…Several studies comparing citrate-based protocols with heparin-based protocols have reported better filter survival and/or fewer bleeding events during RCA (14)(15)(16)(17)(18)(19). Two separate meta-analyses, including six randomized trials comparing RCA with systemic anticoagulation with heparin, confirmed a significant decrease of bleeding events in the citrate arm (70,71); however, they provided slightly different results about filter survival.…”

“…The physiologic sodium content of isotonic solutions allows RCA CVVH or RCA CVVHDF without the need of a low-sodium replacement fluid and/ or dialysate (Table 1). In protocols using citrate-buffered replacement solutions, the buffer supply derives from citrate (predilution CVVH) or citrate and bicarbonate in various proportions (predilution and postdilution CVVH and CVVHDF) in relation to the composition and the combination of the solutions that are used (14,19,50,62,(64)(65)(66)(67). A simplification on the basis of the use of solutions with an appropriately low citrate concentration allows RCA CRRT as CVVH in the predilution-only modality (19,50).…”

“…Citrate accumulation represents the most common complication of RCA, with a reported incidence of 0%-12% of patients depending on the RCA protocol used and the patient case mix (14,16,18,19,(44)(45)(46)(47)(48)(49)(50)(51). Because hepatic clearance represents the main metabolic fate of endogenous and exogenous citrate, citrate metabolism may be significantly slowed in clinical conditions where liver function is impaired, with a higher risk of citrate accumulation and consequent acid-base and electrolyte complications.…”

“…A number of recent clinical studies has shown advantages of regional citrate anticoagulation (RCA) compared with heparin in terms of prolonged circuit life, reduced incidence of hemorrhagic complications, and lower transfusion needs (14)(15)(16)(17)(18)(19). On the basis of these data, the 2012 Kidney Disease Improving Global Outcomes (KDIGO) Clinical Practice Guidelines for Acute Kidney Injury recommend use of RCA as the preferred anticoagulation modality for continuous RRT (CRRT) in patients without contraindications for citrate, even in the absence of an increased bleeding risk or deranged coagulation (20).…”

“…Thus, the choice of the anticoagulant strategy, possibly limited to the extracorporeal circuit (i.e., regional anticoagulation), represents a key issue for safe and effective RRT in AKI. Although RRT can be performed without anticoagulation (8)(9)(10)(11), this approach increases the risk of delivering low RRT doses in up to 30% of patients (12) because of shorter circuit life, increased downtime, and reduced filter performance (12)(13)(14).…”