CICM SAQ 2013.1 Q29

a) What is the mechanism by which citrate provides anticoagulation?

Forms a calcium – citrate complex which drops the serum ionized calcium level.
Calcium is necessary for IX Æ IXa, X Æ Xa and PT Æ thrombin.

b) What is the metabolic fate of the citrate?

Citrate complexed with calcium is partially removed by the filter, but some enters the circulation. Citrate is largely metabolized in the liver, entering the tricarboxylic acid pathway (Krebs cycle) generating NADH. Also generates bicarbonate (at a rate of 3 bicarb per 1 citrate).

c) What are the features of citrate toxicity?

2 sorts of problems:

• First (most commonly described), due to inadequate calcium replacement, are those of low ionized calcium, i.e. chilliness, anxiety, perioral paraesthesias, carpopedal spasm, tetany, QT prolongation and arrhythmias. Associated with metabolic alkalosis from citrate metabolism, and possibly with sodium overload from the hypertonic sodium citrate.
• Secondly (less common), due to citrate load in excess of hepatic ability to metabolise it, i.e. accumulation of citrate-calcium complex. Metabolic acidosis with high anion gap from citrate; raised ratio of total to ionized calcium from complexed calcium in circulation (normal total:ionized ratio 1.9-2.2:1, toxic ratio > 2.5:1.

d) What conditions may increase the risk of citrate toxicity?

• Hypocalcaemia
• Liver failure
• Low cardiac output (i.e. poor hepatic perfusion)

e) What alternative(s) to citrate could you use in a patient with severe HITS?

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