IMPAIRMENT OF CITRATE METABOLISM IN ACUTE HEPATIC-FAILURE

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 failur e and normal renal function were studied during therapeutic plasma exc hange with citrate containing fresh frozen plasma. Six patients receiv ing immunapheresis or LDL-apheresis anticoagulated with citrate served as controls. Determinations of serum citrate concentrations, of ioniz ed calcium and blood pH were performed before, during, and after the e xtracorporeal treatment. Total body clearance and elimination half lif e were calculated in a two compartment model. Results: Preinfusion cit rate levels were higher in the patients with acute hepatic failure tha n 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 subj ects (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 ha lf life (t/2 k(1e)) 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 patient s no rise in pH was observed, again reflecting the impairment of citra te metabolism. Ionized calcium was lower in the patients with acute he patic 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 sever ely impaired and the plasmatic calcium stores are reduced in acute hep atic failure and, thus, the risk of adverse effects is high. Therapeut ic infusions of citrate should be restricted in patients with acute he patic failure and, if necessary, therapy should be closely monitored b y repeated measurements of ionized calcium to avoid the development of potentially harzardous hypocalcemia.