Citrate kinetics during regional citrate anticoagulation in extracorporeal organ replacement therapy
Regional citrate anticoagulation is an important alternative anticoagulation method for haemodialysis patients at high risk of bleeding. In order to better define the optimal dose of citrate and calcium infusion and to identify patients at risk for side effects, the kinetics of citrate and calcium were studied in vivo during and after 15 haemodialysis treatments and in vitro assessing the clearance of citrate-calcium complexes by F60S dialyzers. In addition, a mathematical model was developed to identify the parameters affecting calcium and citrate kinetics in order to predict citrate and calcium requirements in individual patients to avoid side effects. Citrate and calcium doses for effective anticoagulation Citrate dose should be adapted not only to blood flow (approx. 3 mmol per litre of blood) but also to hematocrit. Patients with low hematocrit need more citrate, because they have more plasma water per litre of blood. Sodium concentration in the dialysate of 138 mmol/l does not require any adaptation. Bicarbonate in the dialysate should be reduced by 4 mmol/l (e.g. from 32 to 28 mmol/l). Calcium supplementation should be at least as high as calcium removal by the dialyzer. Calcium removal is higher in patients with high initial total calcium, with use of effective high flux dialyzers, and with high blood flow. With use of high flux dialyzers previous recommendations of calcium supplementation in the literature may no longer be valid, because of the more efficient removal of calcium into the calcium free dialysate. Ionized calcium has to be monitored in the arterial line prior to citrate infusion for safety reasons, in order to detect any trend towards hypocalcemia. Risk assessment Citrate toxicity within the citrate concentration ranges that can be reached in intermittent haemodialysis is limited to the disturbances of ionized calcium concentration, mainly to the induction of hypocalcemia. Hypercalcemia rarely develops, probably due to calcium uptake e.g. by the bones. Hypocalcemia is potentially lethal and is the most important risk with use of citrate anticoagulation. During intermittent high-flux haemodialysis it is primarily due to calcium removal into the dialysate. Hypocalcemia develops rapidly (even within 15 minutes), if calcium substitution is interrupted and can reach life-threatening levels already after 1 hour in a small patient (45kg). All other possible causes for hypocalcemia are less important and less dangerous. Special patient groups and continuous dialysis Patients with liver failure have an increased risk to accumulate citrate, but removal by high-flux dialysis effectively limits accumulation. Slow continuous dialysis is more risky because of low citrate clearance. In this situation patients with liver failure may experience severe hypocalcemia. Patients with small body weight and thus smaller volume of distribution for citrate (e.g. children) can develop high citrate levels but can probably be managed safely with citrate anticoagulation if ionized calcium is closely monitored. The more precise estimation of the calcium requirements in these special patient groups needs further kinetic studies.
Calciumsalze, Calciumkomplexe, Calciumhomöostase, Calcium, dialysis, citrate, anticoagulation, pharmacokinetics
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