48-hour hemodynamic effects of octreotide on postprandial splanchnic hyperemia in patients with liver cirrhosis and portal hypertension: double-blind, placebo-controlled study.
Octreotide is effective during 48 h in the treatment of acute variceal bleeding, probably by reducing variceal blood flow and pressure. Its basal and postprandial effects on splanchnic and systemic hemodynamics, and hormonal changes over this time interval have not yet been studied. Twenty-four patients with cirrhosis and portal hypertension were randomized to receive a liquid meal and either octreotide (Oct, 100 microg bolus intravenous, followed after 2 h by a continuous infusion of 25 microg/hr for 20 hr) or placebo (Plac) given at three consecutive days. Splanchnic (Doppler ultrasound) and systemic hemodynamics (noninvasive cardiac monitoring) were assessed on four consecutive days (one control day and three treatment days) during 2 hr. The postprandial increase in mean blood velocity of the superior mesenteric artery (SMA-V(mean) +44%), portal blood velocity (PV-V(mean), +44%) and total hepatic blood flow (HBF, +40%) observed in the placebo group during the control day was abolished during the first day of treatment (SMA-V(mean), +3%, P < 0.01; PV-V(mean), +6%, P < 0.05; HBF, -25%, P < 0.01) and still reduced after 48 hr in the octreotide group (SMA-V(mean) +28%, P < 0.05; PV-V(mean), +22%, P > 0.05; HBF, -8%, P < 0.05). The postprandial increase in cardiac index (CI, + 10%) and decrease in systemic vascular resistance index (SVRI, -6%) were blunted after the initial injection of octreotide only (CI, -8%, P < 0.05; SVRI, +18%, P < 0.01). Endothelin-1-levels, which were increased at baseline (Plac 25 +/- 17, Oct 16 +/- 13 ng/liter, P > 0.05) decreased significantly after 48 hr of treatment with octreotide (Plac 27 +/- 20, Oct 8 +/- 4 ng/liter, P < 0.05). Octreotide is effective during 48 hr in the prevention of postprandial hyperemia in cirrhotics, even if its efficacy is decreasing over time. Moreover it may have positive effects on systemic vasodilation in cirrhotics. These findings suggest a potential role of this drug in the chronic treatment of portal hypertension.
Ludwig
D
D
Department of Internal Medicine I, University of Lübeck, Germany.
Schädel
S
S
Brüning
A
A
Schiefer
B
B
Stange
E F
EF
D000368:Aged; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004932:Esophageal and Gastric Varices / Q000188:drug therapy; D005260:Female; D006471:Gastrointestinal Hemorrhage / Q000188:drug therapy; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D006940:Hyperemia / Q000188:drug therapy*; D006975:Hypertension, Portal / Q000188:drug therapy*; D008104:Liver Cirrhosis, Alcoholic / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D015282:Octreotide / Q000008:administration & dosage* / Q000009:adverse effects; D019518:Postprandial Period / Q000187:drug effects*; D013152:Splanchnic Circulation / Q000187:drug effects*; D016896:Treatment Outcome; D014662:Vasoconstrictor Agents / Q000008:administration & dosage* / Q000009:adverse effects
D014662:Vasoconstrictor Agents; D015282:Octreotide