EFFECT OF CLONIDINE ON LIVER OXYGEN EXTRACTION DURING ALCOHOL-WITHDRAWAL IN MAN

Since catecholamines can alter splanchnic oxygen transport and extract ion, the suppression of sympathetic overactivity during alcohol withdr awal might improve hepatic oxygen extraction. Therefore, this study in vestigated the effects of clonidine, a centrally-acting alpha(2)-agoni st which reduces sympathetic nervous outflow, on splanchnic oxygen tra nsport and extraction in 13 patients with chronic alcoholism during al cohol withdrawal. All patients had elevated transaminases and steatosi s at liver biopsy and were withdrawn from alcohol 51+/-15 h (mean+/-SD ) before the study. Hepatic blood flow, cardiac output and the oxygen contents were measured in the radial and pulmonary arteries and in the hepatic veins before and 45 min after intravenous administration of c lonidine, 150 mu g. Basal hepatic blood flow was inversely correlated with norepinephrine plasma concentrations (r=-0.63, p<0.025). After cl onidine administration, the decrease in plasma norepinephrine correlat ed with the norepinephrine basal value (r=0.889, p<0.001), and splanch nic oxygen extraction increased (from 40+/-15 to 49+/-17%, p<0.025). A fter clonidine administration, splanchnic oxygen extraction was correl ated with the decrease in plasma norepinephrine (r=0.72, p<0.01). Arte rial lactate concentration decreased (from 0.74+/-0.20 to 0.64+/-0.23 mmol/l, p<0.01). These results suggest that defective liver oxygen ext raction might occur during alcohol withdrawal as a result of sympathet ic nervous hyperactivity. Alterations in the hepatic microcirculation during withdrawal might be related to catecholamine secretion and be c ontrolled by pharmacological manipulation. (C) Journal of Hepatology.