0391-3988/418-07 $25.00/0
The International Journal of Artificial Organs / Vol. 31 / no. 5, 2008 / pp. 418-424
Regional citrate anticoagulation for hemodialysis:
calcium-free vs. calcium containing dialysate -
A randomized trial
J. BUTUROVIC-PONIKVAR, S. CERNE, J. GUBENSEK, R. PONIKVAR
Center for Dialysis, Department of Nephrology, University Medical Center Ljubljana, Ljubljana - Slovenia
©
Wichtig Editore, 2008
ABSTRACT: Background: The majority of citrate protocols for hemodialysis (HD) use calcium (Ca)-
free dialysate, a limited number use dialysate with Ca, aiming to simplify the procedure. This ran-
domized clinical study sought to compare the anticoagulant effect of citrate using Ca-free dialysate
and dialysate with Ca 1.25 mmol/L.
Methods: Fifty HD procedures (in 5 chronic HD patients treated by chronic citrate anticoagulation)
were randomly assigned to Ca-free dialysate (25 procedures) or Ca-1.25 dialysate (25 procedures),
both with Mg 0.5 mmol/L, Na 138 mmol/L, and bicarbonate 28 mmol/L. Ca-free HD: 15% Na
3
citrate
80 ml/hour was infused into the arterial line, and 1 M CaCl
2
, 14 ml/hour into the venous line. Ca-1.25
group: 15% Na
3
citrate 100 ml/hour, 1 M CaCl2 2-4 ml/hour. Polyflux H dialyzers were used. An-
tithrombotic effect was assessed visually after HD at 3 points: dialyzer, arterial, and venous bubble
traps, using a score of 5 (no clotting) to 1 (total clotting).
Results: Ca-free group: arterial bubble trap score 4.7 ± 0.5, dialyzer 4.5 ± 0.6, venous bubble trap
4.8 ± 0.6. Ionized calcium (iCa) at dialyzer inlet 0.34 ± 0.17, outlet 0.21 ± 0.06 mmol/L. All HDs were
completed successfully. Ca-1.25 group: arterial bubble trap score 4.7 ± 0.5 (NS), dialyzer 2.6 ± 1.04
(p<0.01), venous bubble trap 2.4 ± 0.9 (p<0.01). Volume of clot in venous bubble trap was 1.9 ± 1.8
mL (range 0.5-6 mL). iCa at dialyzer inlet 0.24 ± 0.05 mmol/L (p<0.05), outlet 0.63 ± 0.11 mmol/L
(p<0.01). Four of 25 HD procedures (16%) were prematurely terminated due to threatening dialyzer
clotting, in 6/25 HD procedures (24%), the venous line was changed (p<0.01).
Conclusion: Citrate anticoagulation with Ca-1.25 dialysate resulted in significantly worse anticoagu-
lation of dialyzer and venous bubble trap compared with Ca-free dialysate, despite higher citrate
dose. (Int J Artif Organs 2008; 31: 418-24)
KEY WORDS: Anticoagulation, Citrate, Hemodialysis, Metabolic alkalosis, Regional citrate anti-
coagulation
INTRODUCTION
Citrate has many characteristics of the ideal anticoagu-
lant for hemodialysis. Its anticoagulant effect is excellent
and is limited to the dialysis circuit, without causing sys-
temic anticoagulation. In addition to inhibiting coagula-
tion, it reduces platelet deposition on the dialyzer mem-
brane (1). By the decreased activation of platelets and
coagulation, citrate anticoagulation may also increase the
dialysis dose delivered. By chelating calcium (Ca) and
magnesium, citrate reduces some of the effects of blood
interaction with the dialyzer membrane (2-4), which are
Ca- and magnesium-dependent, thus improving biocom-
patibility of dialysis circuit. Using citrate, we avoid he-
parin-induced thrombocytopenia, the condition that is in-
creasingly recognized especially in intensive care units.
Citrate is easily dialyzable (molecular weight of trisodium
citrate is 294 Da), with an extraction coefficient of 70% or
Artificial Kidney and Dialysis