Citrate Toxicity


Citrate toxicity is primarily a result of hypocalcaemia and metabolic effects of excess citrate


  • citrate is metabolised to HCO3 with NADH generation via the Kreb’s cycle
  • metabolism occurs predominately in the liver, kidneys and skeletal muscle


Citrate administration

  • massive transfusion (citrate is used as a preservative)
  • regional citrate anticoagulation for RRT

Decreased citrate clearance

  • liver failure
  • decreased cardiac output

Exacerbating factors

  • hypocalcemia
  • hypoalbuminemia


Hypocalcaemia (decreased iCa, normal total Ca as bound to citrate)

  • anxiety, paraesthesia, carpopedal spasm, tetany, seizures
  • nausea and vomiting
  • long QT, dysrhythmias
  • negative inotropy and vasoplegia, hypotension
  • systemic hypocoagulability

Other metabolic and electrolyte disturbances

  • Metabolic alkalosis due to HCO3 formation (3 HCO3 for each citrate molecule)
  • HAGMA due to citrate accumulation
  • hypernatremia (due to sodium load from sodium citrate)
  • hypomagnesemia (due to citrate chelation)
  • hypokalemia (due to low magnesium and metabolic alkalosis)


  • stop citrate administration
  • treat life-threatening hypocalcemia with IV calcium (either calcium gluconate or chloride)
  • optimise cardiac output and liver function to enhance citrate clearance
  • consider RRT to correct metabolic derangement and enhance citrate clearance

References and Links

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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