Regional citrate anticoagulation


  • Regional Citrate Anticoagulation is the infusion of citrate into the blood circuit during renal replacement therapy (RRT) to chelate ionized Ca2+ forming calcium-citrate complexes, thus preventing coagulation of blood
  • calcium is required for the generation of thrombin (involved in the activation of factors II, IX and X)


  • target circuit ionized calcium level to prevent clotting = 0.25-0.4mmol/L

No systemic anticoagulation due to:

  1. citrate-Ca2+ complexes cross membrane in haemofilter -> ultrafiltrate
  2. citrate or citrate-Ca2+ complexes that remain in venous line and is delivered to patient -> diluted in blood and rapidly metabolized by liver, kidney and muscles to form bicarbonate (1 citrate = 3 bicarbonate ions)
  3. during metabolism Ca2+ liberated -> helps to normalize Ca2+ levels
  4. Ca2+ infused systemically to restore normal levels (ionized 1.1-1.3mmol/L)


  • total Ca2+ range = 2.2-2.5mmol/L
  • ionized Ca2+ range (50%) = 1.1-1.3mmol/L
  • protein bound Ca2+ range (40%) = 0.95-1.2mmol/L
  • complex Ca2+ (10% – calcium phosphate, salts) = 0.05mmol/L

Types of citrate

  1. 4% trisodium citrate
  2. acid citrate dextrose solution
  3. citrate-containing replacement solution



  • reduces haemorrhagic risk and need for blood transfusion
  • can use in HITS
  • a longer or similar circuit life
  • possibly less inflammatory response to the circuit
  • possibly better patient and kidney survival (needs to be confirmed in a large RCT)
  • provides additional energy source (citrate is a fuel)
  •  feasible and safe


  • metabolic alkalosis -> 1mmol of citrate becomes 3 mmol of HCO3 (can be an advantage)
  • amount of citrate loss proportional to ultrafiltration and fluid removal rate
  • when trisodium citrate used -> increased sodium load to patient (hypernatraemia)
  • citrate can accumulate if there is liver or skeletal muscle dysfunction -> metabolic acidosis (HAGMA)
  • hypocalcaemia
  • hypomagnesaemia (from binding to citrate-Ca2+ complex)


  • Prostacyclin (PGI2)
  • Argatroban
  • Danaparoid
  • Bivalirudin
  • Fondaparinux
  • Lepirudin

References and Links


Journal articles

  • Lee G, Arepally GM. Anticoagulation techniques in apheresis: from heparin to citrate and beyond. J Clin Apher. 2012;27(3):117-25. doi: 10.1002/jca.21222. Epub 2012 Apr 24. Review. PubMed PMID: 22532037; PubMed Central PMCID: PMC3366026.
  • Oudemans-van Straaten HM, Ostermann M. Bench-to-bedside review: Citrate for continuous renal replacement therapy, from science to practice. Crit Care. 2012 Dec 7;16(6):249. [Epub ahead of print] PubMed PMID: 23216871; PubMed Central PMCID: PMC3672558.
  • Oudemans-van Straaten HM, Kellum JA, Bellomo R. Clinical review: anticoagulation for continuous renal replacement therapy–heparin or citrate? Crit Care. 2011 Jan 24;15(1):202. doi: 10.1186/cc9358. Review. PubMed PMID: 21345279; PubMed Central PMCID: PMC3222015.
  • Zheng Y, Xu Z, Zhu Q, Liu J, Qian J, You H, Gu Y, Hao C, Jiao Z, Ding F. Citrate Pharmacokinetics in Critically Ill Patients with Acute Kidney Injury. PLoS One. 2013 Jun 18;8(6):e65992. Print 2013. PubMed PMID: 23824037; PubMed Central PMCID: PMC3688847.

CCC 700 6

Critical Care


Chris is an Intensivist and ECMO specialist at the Alfred ICU in Melbourne. He is also a Clinical Adjunct Associate Professor at Monash University. He is a co-founder of the Australia and New Zealand Clinician Educator Network (ANZCEN) and is the Lead for the ANZCEN Clinician Educator Incubator programme. He is on the Board of Directors for the Intensive Care Foundation and is a First Part Examiner for the College of Intensive Care Medicine. He is an internationally recognised Clinician Educator with a passion for helping clinicians learn and for improving the clinical performance of individuals and collectives.

After finishing his medical degree at the University of Auckland, he continued post-graduate training in New Zealand as well as Australia’s Northern Territory, Perth and Melbourne. He has completed fellowship training in both intensive care medicine and emergency medicine, as well as post-graduate training in biochemistry, clinical toxicology, clinical epidemiology, and health professional education.

He is actively involved in in using translational simulation to improve patient care and the design of processes and systems at Alfred Health. He coordinates the Alfred ICU’s education and simulation programmes and runs the unit’s education website, INTENSIVE.  He created the ‘Critically Ill Airway’ course and teaches on numerous courses around the world. He is one of the founders of the FOAM movement (Free Open-Access Medical education) and is co-creator of litfl.com, the RAGE podcast, the Resuscitology course, and the SMACC conference.

His one great achievement is being the father of three amazing children.

On Twitter, he is @precordialthump.

| INTENSIVE | RAGE | Resuscitology | SMACC

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