Desensitization to the effects of intravenous octreotide in cirrhotic patients with portal hypertension.
OBJECTIVE
Octreotide has been suggested for the treatment of variceal bleeding, but detailed dose-finding studies are not available. We performed a dose-finding study investigating the hemodynamic effects of several forms of intravenous octreotide administration.


METHODS
Splanchnic hemodynamics and plasma glucagon levels were measured in 68 cirrhotics in baseline conditions and (1) after a double-blind intravenous injection of octreotide (50 microg [n = 9] or 500 microg [n = 8]) or placebo (n = 7); (2) after a 50-microg octreotide bolus followed by continuous infusion of 50 microg/h (n = 8), 250 microg/h (n = 8), or placebo (n = 6); (3) after repeated 50-microg injections of octreotide (n = 9) or placebo (n = 6) after an initial bolus (50 microg octreotide); and (4) after a placebo bolus and continuous octreotide infusion (50 microg/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 octreotide 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 baseline despite continuous infusions or repeated injections of octreotide.


CONCLUSIONS
Octreotide injection caused marked but transient reductions in portal pressure and azygos blood flow. Adding a continuous octreotide infusion neither maintained nor prolonged its effects. Repeated boluses caused significant tachyphylaxis. This rapid desensitization to the effects of octreotide may explain the divergent effects achieved with octreotide infusions in acute variceal bleeding.
Escorsell
A
A
Hepatic Hemodynamic Laboratory, Liver Unit, Institut de Malalties Digestives, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Hospital Clínic, University of Barcelona, Barcelona.
Bandi
J C
JC
Andreu
V
V
Moitinho
E
E
García-Pagán
J C
JC
Bosch
J
J
Rodés
J
J
D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000187:drug effects; D004361:Drug Tolerance; D005260:Female; D005765:Gastrointestinal Agents / Q000008:administration & dosage*; D005934:Glucagon / Q000097:blood; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006975:Hypertension, Portal / Q000188:drug therapy* / Q000209:etiology; D007275:Injections, Intravenous; D008103:Liver Cirrhosis / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D015282:Octreotide / Q000008:administration & dosage*; D010919:Placebos; D013152:Splanchnic Circulation / Q000187:drug effects
D005765:Gastrointestinal Agents; D010919:Placebos; D005934:Glucagon; D015282:Octreotide