Regarding regional citrate anticoagulation for continuous renal replacement therapy (CRRT):
- a) What is the mechanism by which citrate provides anticoagulation?
- b) What is the metabolic fate of the citrate?
- c) What are the features of citrate toxicity?
- d) What conditions may increase the risk of citrate toxicity?
- e) What alternative(s) to citrate could you use in a patient with severe HITS?
Answer and interpretation
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?
- 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)
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.