Desensitization to the effects of intravenous octreotide in cirrhotic patients with portal hypertension

Background & Aims: Octreotide has keen suggested for the treatment of varic eal bleeding, but detailed dose-finding studies are not available. We perfo rmed a dose-finding study investigating the hemodynamic effects of several forms of intravenous octreotide administration, Methods: Splanchnic hemodyn amics and plasma glucagon levels were measured in 68 cirrhotics in baseline conditions and (1) after a double-blind intravenous injection of octreotid e (50 mug [n = 9] or 500 mug [n = 8]) or placebo (n = 7); (2) after a 50-mu g octreotide bolus followed by continuous infusion of 50 mug/h (n = 8), 250 mug/h (n = 8), or placebo (n = 6); (3) after repeated 50-mug injections of octreotide (n = 9) or placebo (n = 6) after an initial bolus (50 mug octre otide); and (4) after a placebo bolus and continuous octreotide infusion (5 0 mug/h; n = 7), Results: Placebo caused no significant changes, Octreotide caused a marked and transient decrease in portal pressure and azygos blood flow and an increase in mean arterial pressure. These effects lasted only 5 minutes despite addition of continuous octreotide infusions. Repeated oct reotide injections had shorter, less marked effects than the first bolus. A continuous octreotide infusion did not decrease portal pressure. Glucagon levels were markedly reduced by octreotide, but gradually returned to basel ine despite continuous infusions or repeated injections of octreotide, Conc lusions: Octreotide injection caused marked but transient reductions in por tal pressure and azygos blood flow, Adding a continuous octreotide infusion neither maintained nor prolonged its effects, Repeated boluses caused sign ificant tachyphylaxis, This rapid desensitization to the effects of octreot ide may explain the divergent effects achieved with octreotide infusions in acute variceal bleeding.