Octreotide October


Q: What is the basis of using octreotide is cases of Variceal Bleeding?


A: Bleeding through esophageal varices is the major cause of death in patients with liver cirrhosis and portal hypertension. (1)

According to the World Gastroenterology Organisation, the gold standard for treatment of acute variceal bleed is endoscopic band ligation and vasoactive pharmacological measures such as octreotide or terlipressin. These drugs can be given as adjunctive therapy, and also as primary therapy in primary centres where facilities for endoscopic evaluation and intervention may not be feasible.

Other measures include, but are not limited to, sclerotherapy, portosystemic shunt surgeries, nonselective beta blockers and nitrates.

In cirrhosis, portal hypertension is developed by a combination of:
a) Increase of Intrahepatic resistance
b) Increase of splanchnic blood flow, both contributing to the development of portal hypertension.(2)

Treatment should thus be targeted at decreasing intrahepatic vascular resistance and/or portal blood flow.

Two types of vasoactive drugs can be used:

  1. Vasodilators: aimed at reducing intrahepatic vascular resistance.
  2. Vasoconstrictors: which reduce portal and portal-systemic collateral blood flow. (3,4)
Somatostatin is the major inhibitory hormone of the GI tract, and suppresses the action of other hormones such as gastrin, cholecystokinin, glucagon, growth hormone, insulin and glucagon.  In 1979, WIlfried Bauer synthesized an artificial and more potent analogue of the natural hormone somatostatin called ‘octreotide’. The standard dose of octreotide for an acute variceal bleed is 50 mcg bolus injection followed by 25–50 mcg/h.

The effects of somatostatin (and by extension, octreotide) in portal hypertension are mediated by its action on G-protein-coupled receptors - mainly SSTR1 and SSTR2.

Somatostatin reduces wedged hepatic venous pressure and estimated hepatic blood flow in cirrhotic patients. (5)

Direct vasoconstriction of mesenteric arteries and portal-systemic collateral veins in the presence of other vasoconstrictors plays a role in acute decrease of flow, and is possibly SSTR2 mediated.

The more long term effect is through decrease in intrahepatic resistance by SSTR1-induced relaxation of hepatic stellate cells.
Octreotide prevents postprandial splanchnic hyperemia in patients with portal hypertension.
This is likely achieved by inhibiting the release of glucagon.(6)
Results of a recent meta-analysis suggested that octreotide significantly improved control of oesophageal variceal haemorrhage compared with placebo or no additional intervention, without benefit on mortality. (7)  


Thus we find a basis for Octreotide use in patients of Variceal bleed.

By Dr Prabhav Vasistha


References :

1. D’Amico G, Pagliaro L, Bosch J. The treatment of portal hypertension: a meta-analytic review. Hepatology 1995; 22: 332–54.
2 Gupta TK, Chen L, Groszmann RJ. Pathophysiology of portal hypertension. Baillieres Clin Gastroenterol 1997; 11: 203–19.
3  D’Amico G, Pagliaro L, Bosch J. Pharmacological treatment of portal hypertension: an evidence-based approach. Semin Liver Dis 1999; 19: 475–505  
4  Lebrec D. Pharmacological treatment of portal hypertension: present and future. J Hepatol 1998; 28: 896–907  
5  Bosch J, Kravetz D, Rodes J. Effects of somatostatin on hepatic and systemic hemodynamics in patients with cirrhosis of the liver: comparison with vasopressin. Gastroenterology 1981; 80: 518–25.
6  Ludwig D, Schadel S, Bruning A, Schiefer B, Stange EF. 48- hour hemodynamic effects of octreotide on postprandial splanchnic hyperemia in patients with liver cirrhosis and portal hypertension: double-blind, placebo-controlled study. Dig Dis Sci 2000; 45: 1019–27
7  Corley DA, Cello JP, Adkisson W, Ko WF, Kerlikowske K. Octreotide for acute esophageal variceal bleeding: a meta-analysis. Gastroenterology 2001; 120: 946–54.

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