Heparin-Free Regional Anticoagulation: There Are Significant Differences Between Citrate-Containing Dialysate and Regional Citrate Anticoagulation

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Faguer et al (1), in a recent issue of Critical Care Medicine, described a new method of heparin-free regional anticoagulation during intermittent hemodialysis using calcium-free and citrate-containing dialysate. Since citrate-containing dialysates are gaining popularity and are often claimed to have anticoagulant properties, we would like to stress some important differences with regional citrate anticoagulation (RCA).
Although the authors correctly named the new technique a “heparin-free regional anticoagulation” and not RCA, they nevertheless postulate in discussion that “... mean postfilter iCa was kept below 0.45 mmol/L, confirming that the amount of free citrate in the dialysate was sufficient to decrease iCa in the filter to below the coagulation threshold” (1). The low citrate concentration used in the dialysate (0.8 mmol/L) cannot achieve efficient anticoagulation. It was shown that a citrate concentration of above approximately 2 mmol/L is required to lower ionized calcium below 0.4 mmol/L and sufficiently prolong clotting (2). Therefore, also commercially available protocols (Prismaflex, Gambro and MultiFiltrate, Fresenius) use this range (2–6 mmol/L of blood) of citrate concentrations for RCA in continuous dialysis methods. On the other hand, it is well known that in RCA, the majority of the need for calcium replacement derives from loss of calcium in the dialyzer against a calcium-free dialysate and only a minority due to citrate chelation. This is illustrated by the fact that RCA can be performed with little (below 4 mmol/hr [3]) or even no calcium replacement (in continuous methods with low blood flow [4]), when calcium-containing dialysate is used. Therefore, also with the new protocol, it is the calcium-free dialysate that achieved low postfilter ionized calcium and efficient anticoagulation and not the low concentration of citrate in dialysate.
Furthermore, excellent biocompatibility is a major advantage of RCA and one of the reasons it is proposed as the first-line anticoagulation in critically ill. As acknowledged by the authors, the proposed protocol achieves good anticoagulation only from mid-dialyzer to the venous return, but not at the arterial side. Although this is enough to provide good anticoagulation, it cannot be expected to provide the same excellent biocompatibility as true RCA, where ionized calcium is lowered almost at the first contact of blood with artificial surfaces.
Regarding protocol safety and the possibility of severe hypocalcemia, the authors claim that the new protocol “allows prolonged hemodialysis sessions... without the need to systemically monitor ionized calcium”, while RCA with “TSC and ACD-A... could potentially cause life-threatening systemic calcium disorders” (1). It is indeed true that uncontrolled infusion of (especially concentrated) citrate can cause severe hypocalcemia and even cardiac arrest secondary to hypocalcemia, but the use of calcium-free dialysate is also potentially dangerous (5), due to significant removal of calcium as discussed above. Although the new protocol includes a more precise calcium replacement using ionic dialysance, a severe hypocalcemia can still develop due to technical or human error, for example, calcium pump malfunction or mistaken use of a solution not containing calcium. Therefore, at least occasional ionized calcium measurement would be advised, especially in the critically ill population.

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