Regional citrate versus systemic heparin for anticoagulation in critically ill patients on continuous venovenous haemofiltration: a prospective randomized multicentre trial

Nephrol Dial Transplant. 2011 Jan;26(1):232-9. doi: 10.1093/ndt/gfq575. Epub 2010 Sep 27.


Background: Continuous venovenous haemofiltration (CVVH) in the intensive care setting requires anticoagulation to prevent clotting of the extracorporeal circuit. Several protocols avoiding heparin and using regional citrate anticoagulation have been developed to diminish bleeding risks. However, data from randomized trials comparing citrate anticoagulation with systemic heparinization are very limited.

Methods: One hundred and seventy-four patients on mechanical ventilation, requiring renal replacement therapy for acute renal failure, were included in this prospective randomized multicentre trial comparing regional citrate with systemic heparin. The study was performed at nine different intensive care units at university or academic teaching hospitals. The participants were randomized to either CVVH using regional citrate anticoagulation or CVVH using systemic anticoagulation with unfractionated heparin. The primary outcome was to compare treatment efficacy represented by the patients' acid base status on Day 3 and on each consecutive day. Several parameters of safety and efficacy were analysed as secondary outcomes.

Results: Comparison of standard bicarbonate from Day 3 to Day 11 revealed no difference between both treatment modalities. Use of citrate resulted in less systemic anticoagulation, a lower risk of bleeding and a longer haemofilter patency. Episodes of hypercalcaemia, hypocalcaemia and the need for additional bicarbonate infusions occurred more often under citrate. The patients' high mortality was not influenced by the mode of anticoagulation.

Conclusions: Citrate may be used as a regional anticoagulant and the only buffering agent in CVVH with adequate treatment efficacy and safety. However, neither citrate nor heparin anticoagulation should be regarded as a therapeutic standard, since there is no advantage of one of these substances with regard to patient mortality.

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / therapy*
  • Aged
  • Anticoagulants / therapeutic use*
  • Bicarbonates / therapeutic use
  • Buffers
  • Citrates / therapeutic use*
  • Critical Illness*
  • Female
  • Hemofiltration*
  • Hemorrhage / etiology
  • Hemorrhage / prevention & control
  • Heparin / therapeutic use*
  • Humans
  • Male
  • Middle Aged
  • Prospective Studies
  • Renal Dialysis
  • Survival Rate
  • Treatment Outcome


  • Anticoagulants
  • Bicarbonates
  • Buffers
  • Citrates
  • Heparin