Citrate Toxicity
OVERVIEW
Citrate toxicity is primarily a result of hypocalcaemia and metabolic effects of excess citrate
CITRATE METABOLISM
- citrate is metabolised to HCO3 with NADH generation via the Kreb’s cycle
- metabolism occurs predominately in the liver, kidneys and skeletal muscle
RISK FACTORS FOR CITRATE TOXICITY
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
CLINICAL AND BIOCHEMICAL FEATURES
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)
MANAGEMENT
- 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 Toxicology Series
General
Approach to acute poisoning, ECGs in Tox, Evidenced-based Tox, Toxicology literature summaries, Does anti-venom work?
Toxins / Overdose
Amphetamines, Barbituates, Benzylpiperazine, Beta Blockers, Calcium Channel Blocker, Carbamazepine, Carbon Monoxide, Ciguatera, Citrate, Clenbuterol, Cocaine, Corrosive ingestion, Cyanide, Digoxin, Ethanol, Ethylene Glycol, Iron, Isoniazid, Lithium, Local anaesthetic, Methanol, Monoamine oxidase inhibitor (MAOI), Mushrooms (non-hallucinogenic), Opioids, Organophosphate, Paracetamol, Paraquat, Plants, Polonium, Salicylate, Scombroid, Sodium channel blockers, Sodium valproate, Theophylline, Toxic alcohols, Tricyclic antidepressants (TCA)
Envenomation
Marine, Snakebite, Spider, Tick paralysis
Syndromes
Alcohol withdrawal, Anticholinergic syndrome, Cholinergic syndrome, Drug withdrawals in ICU, Hyperthermia associated toxidromes, Malignant hyperthermia (MH), Neuroleptic malignant syndrome (NMS), Opioid withdrawal, Propofol Infusion Syndrome (PrIS) Sedative toxidrome, Serotonin syndrome, Sympatholytic toxidrome, Sympathomimetic toxidrome
Decontamination
Activated Charcoal, Gastric lavage, GI Decontamination
Enhanced Elimination
Enhanced elimination, Hyperbaric therapy for CO
Antidotes
Antidote summary, Digibind, Glucagon, Flumazenil, HIET – High dose euglycaemic therapy, Intralipid, Methylene Blue, N-Acetylcysteine (NAC), Naloxone
Miscellaneous
Cocaine chest pain, Digoxin and stone heart theory, Hyperbaric oxygen, Hypoxaemia in tox, Liver failure in tox, Liver transplant for paracetamol, Methaemoglobinaemia, Urine drug screen
Critical Care
Compendium
Chris is an Intensivist and ECMO specialist at The Alfred ICU, where he is Deputy Director (Education). He is a Clinical Adjunct Associate Professor at Monash University, the Lead for the Clinician Educator Incubator programme, and a CICM First Part Examiner.
He is an internationally recognised Clinician Educator with a passion for helping clinicians learn and for improving the clinical performance of individuals and collectives. He was one of the founders of the FOAM movement (Free Open-Access Medical education) has been recognised for his contributions to education with awards from ANZICS, ANZAHPE, and ACEM.
His one great achievement is being the father of three amazing children.
On Bluesky, he is @precordialthump.bsky.social and on the site that Elon has screwed up, he is @precordialthump.
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