Regional citrate anticoagulation

OVERVIEW

• 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)

CITRATE ANTICOAGLATION

• 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)

Levels

• 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

PROS AND CONS

Advantages

• 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

Disadvantages

• 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)

ALTERNATIVES IN  HITS

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

References and Links

LITFL

• CCC – Citrate toxicity

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.