Citrate pharmacokinetics and metabolism in cirrhotic and noncirrhotic critically ill patients.
OBJECTIVE
To investigate pharmacokinetics and metabolism of sodium citrate in critically ill patients. To determine the risk of citrate accumulation in the setting of liver dysfunction (cirrhosis, hepatorenal syndrome).


METHODS
Prospective cohort study.


METHODS
Intensive Care Unit, Department of Medicine IV, University Hospital Vienna.


METHODS
Consecutive critically ill cirrhotic (n = 16) and noncirrhotic patients (n = 16).


METHODS
Infusion of sodium citrate (0.5 mmol.kg-1.hr-1) and calcium chloride (0.17 mmol.kg-1.hr-1) for 2 hrs. Analysis of serial arterial blood samples.


RESULTS
Total body clearance of citrate was normal in noncirrhotic critically ill patients but significantly reduced in cirrhotic patients (710 vs. 340 mL/min, p =.008). Citrate peak concentrations and concentration over time were increased by 65% and 114% in cirrhotic patients (p <.001), respectively; volumes of distribution were similar. Net metabolic changes were quantitatively similar, with pH and plasma bicarbonate concentrations increasing more slowly in cirrhotic patients. No citrate-related side effects were noted. Citrate clearance could not be predicted by standard liver function tests and was not appreciably influenced by renal function and Acute Physiology and Chronic Health Evaluation II scores.


CONCLUSIONS
This first systematic study on citrate pharmacokinetics and metabolism in critically ill patients confirms a major role of hepatic citrate metabolism by demonstrating reduced citrate clearance in cirrhotic patients. Pharmacokinetic data could provide a basis for the clinical use of citrate anticoagulation in critically ill patients. Provided dose adaptation and monitoring of ionized calcium, citrate anticoagulation seems feasible even in patients with decompensated cirrhosis. Metabolic consequences of citrate infusion were not different between groups in this study but may be more pronounced in prolonged infusion.
Kramer
Ludwig
L
Department of Medicine IV, University of Vienna Medical School, Austria.
Bauer
Edith
E
Joukhadar
Christian
C
Strobl
Wolfram
W
Gendo
Alexandra
A
Madl
Christian
C
Gangl
Alfred
A
D018806:APACHE; D019540:Area Under Curve; D016022:Case-Control Studies; D002951:Citrates / Q000378:metabolism / Q000493:pharmacokinetics; D005260:Female; D006207:Half-Life; D006801:Humans; D008103:Liver Cirrhosis / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D011446:Prospective Studies; D000077559:Sodium Citrate
D002951:Citrates; D000077559:Sodium Citrate