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.

Keywords: Anticoagulation; Calcium; Citrate; Dialysate; Hemodialysis; Modeling.

Fig. 1

(A) Free calcium measured in blood at H1 on the arterial line upstream of the citrate injection site (patient), on the arterial line downstream of the citrate injection site (prefilter) and on the venous line (postfilter). P-value of ANOVA for repeated measures. Values with different letters are significantly different with post-hoc Bonferroni test. (B). Patient free calcium measured at H0, H1 and H4. P-value of ANOVA for repeated measures. (C). Serum citrate concentration pre- and postfilter. P-value of paired T test. (D). Free calcium vs citrate concentration. Black line represents polynomial regression.

Fig. 2

Bland Altman diagram of postfilter values calculated with modeling, and measured values.

Fig. 3

Simulations of hemodialysis with blood citrate infusion and a dialysate containing calcium (1.25 mmol/L). Percentage of membrane length with free calcium concentration < 0.4 mmol/L (A). Postfilter free calcium (B) and total calcium concentration (C) values. Calcium balance (D). Values are calculated for different dialysate and blood flows (prefilter citrate concentration 5 mmol/L) or different prefilter citrate concentrations (dialysate and blood flows set at 500 and 300 mL/min, respectively).