Gastroenterology

Gastroenterology

Volume 120, Issue 1, January 2001, Pages 161-169
Gastroenterology

Liver, Pancreas, and Biliary Tract
Desensitization to the effects of intravenous octreotide in cirrhotic patients with portal hypertension,☆☆

https://doi.org/10.1053/gast.2001.20892Get rights and content

Abstract

Background & Aims: 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 μg [n = 9] or 500 μg [n = 8]) or placebo (n = 7); (2) after a 50-μg octreotide bolus followed by continuous infusion of 50 μg/h (n = 8), 250 μg/h (n = 8), or placebo (n = 6); (3) after repeated 50-μg injections of octreotide (n = 9) or placebo (n = 6) after an initial bolus (50 μg octreotide); and (4) after a placebo bolus and continuous octreotide infusion (50 μg/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.

GASTROENTEROLOGY 2001;120:161-169

Section snippets

Patients and methods

The study included 68 patients with cirrhosis, portal hypertension, and esophageal varices who were referred for evaluation to the Hepatic Hemodynamic Laboratory (Barcelona, Spain). Twenty-seven patients were women and 41 were men; the mean age was 55 ± 13 years (mean ± SD; range, 20–75 years). Twenty-four patients had previously bled from varices, whereas the remaining 44 had not. Additional data are shown in Table 1.All patients gave written informed consent to participate in the study, which

Baseline data

There were no statistically significant differences among patients allocated to receive the different schedules of octreotide or placebo administration in age, sex, body weight, etiology of cirrhosis, severity of liver failure, and baseline hemodynamic parameters (Tables 1-5).All patients had severe portal hypertension, as shown by the presence of gastroesophageal varices and by a high baseline HVPG, averaging 18 ± 3.3 mm Hg. In addition, all groups of patients had increased AzBF, CO, and

Discussion

Somatostatin and octreotide are different molecules that bind with a different affinity to somatostatin receptors (SSTR). Octreotide binds with a similar affinity as somatostatin for SSTR2 and SSTR5, has intermediate affinity for SSTR3, and no binding affinity for SSTR1 and SSTR4.2

Although the rationale for the use of octreotide in variceal bleeding comes from the hypothesis that, similar to native somatostatin, it may reduce portal pressure and blood flow, the hemodynamic effects of octreotide

Acknowledgements

The authors thank Àngels Baringo, Laura Rocabert, and Rosa Sáez for providing expert technical assistance.

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    Address requests for reprints to: Jaume Bosch, M.D., Liver Unit, Hospital Clínic, C/ Villarroel, 170, 08036 Barcelona. e-mail: [email protected]; fax: (34) 93-451-5522.

    ☆☆

    Supported in part by grants from the Fondo de Investigaciones Sanitarias (FIS 00/0444) and by Sandoz SA.

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