Impairment of citrate metabolism in acute hepatic failure

Wien Klin Wochenschr. 1997 Feb 28;109(4):123-7.


Aims: To compare the utilization of citrate employed as anticoagulant in patients with acute hepatic failure and subjects with normal liver function.

Patients and methods: Three patients in acute hepatic failure and normal renal function were studied during therapeutic plasma exchange with citrate containing fresh frozen plasma. Six patients receiving immunapheresis or LDL-apheresis anticoagulated with citrate served as controls. Determinations of serum citrate concentrations, of ionized calcium and blood pH were performed before, during, and after the extracorporeal treatment. Total body clearance and elimination half life were calculated in a two compartment model.

Results: Preinfusion citrate levels were higher in the patients with acute hepatic failure than in the controls (n.s.). The citrate level rose to 1.73 +/- 0.2 mmol/l in the liver patients versus 0.99 +/- 0.1 mmol/l in the healthy subjects (p < 0.03). Total body clearance was markedly reduced in patients with acute hepatic failure (3.31 +/- 0.03 ml/kg/min) as compared with the controls (6.34 +/- 0.16 ml/kg/min) (p < 0.02), the elimination half life (t/2 k1e) was prolonged (49.7 +/- 5.4 vs. 32.9 +/- 1.02 min, p < 0.05). In the controls blood pH rose from 7.4 +/- 0.01 to 7.45 +/- 0.01 (p < 0.05) after citrate infusion, whereas in the liver patients no rise in pH was observed, again reflecting the impairment of citrate metabolism. Ionized calcium was lower in the patients with acute hepatic failure at the beginning (1.01 +/- 0.05 vs. 1.21 +/- 0.04 mmol/l, p < 0.05) and the end (0.68 +/- 0.02 vs. 0.93 +/- 0.04 mmol/l, p < 0.05) of the citrate infusion.

Conclusions: Citrate metabolism is severely impaired and the plasmatic calcium stores are reduced in acute hepatic failure and, thus, the risk of adverse effects is high. Therapeutic infusions of citrate should be restricted in patients with acute hepatic failure and, if necessary, therapy should be closely monitored by repeated measurements of ionized calcium to avoid the development of potentially hazardous hypocalcemia.

MeSH terms

  • Adolescent
  • Adult
  • Anticoagulants / administration & dosage
  • Anticoagulants / pharmacokinetics*
  • Blood Component Removal
  • Calcium / blood
  • Citric Acid / administration & dosage
  • Citric Acid / pharmacokinetics*
  • Female
  • Half-Life
  • Hepatic Encephalopathy / physiopathology*
  • Hepatic Encephalopathy / therapy
  • Humans
  • Kidney Function Tests*
  • Male
  • Metabolic Clearance Rate / physiology
  • Middle Aged
  • Plasma
  • Plasma Exchange


  • Anticoagulants
  • Citric Acid
  • Calcium