Conclusions: Octreotide does not affect the portal pressure or hepatic blood flow, whereas it may further contract the central blood volume and thereby exert a potentially harmful effect on central hypovolaemia in patients with cirrhosis.
What are the hemodynamic effects of octreotide infusion?
address this important area by describing portal hemodynamic effects after both multiple boluses and infusion of octreotide, a long-acting somatostatin analogue. It has been shown that octreotide produces a sharp decrease in portal pressure and azygous vein blood flow.
What is the effect of octreotide on blood pressure?
It has been shown that octreotide produces a sharp decrease in portal pressure and azygous vein blood flow.2This is accompanied by a drop in intravariceal pressure and wall tension. These changes in the splanchnic circulation are accompanied by a small decrease in cardiac output and an increase in right heart as well as pulmonary arterial
Can somatostatin and octreotide reduce portal pressure?
Conclusion: Both somatostatin and octreotide can significantly reduce portal pressure, although somatostatin is more potent than octreotide. The underlying mechanisms may involve inhibition of the secretion of GLU, IGF-1 and other hormones as well as a decrease in hepatic metabolism and portal inflow leading to a reduction in portal pressure.
Does octreotide affect central blood flow in cirrhosis?
Effect of octreotide on systemic, central, and splanchnic haemodynamics in cirrhosis Octreotide does not affect the portal pressure or hepatic blood flow, whereas it may further contract the central blood volume and thereby exert a potentially harmful effect on central hypovolaemia in patients with cirrhosis.
How does octreotide decrease portal blood flow?
Octreotide inhibits the release of glucagon, which is a splanchnic vasodilator. It therefore reduces splanchnic blood flow and portal venous pressure.
How does octreotide cause vasoconstriction?
Somatostatin and analogues (octreotide, vapreotide) cause splanchnic vasoconstriction not only through an inhibitory effect on the release of the vasodilator glucagon but also by a local mesenteric vasoconstrictive effect.
How does octreotide work esophageal varices?
Octreotide reduces portal and variceal pressures as well as splanchnic and portal-systemic collateral blood flows [2]. It also prevents postprandial splanchnic hyperemia in patients with portal hypertension [3] and lowers gastric mucosal blood flow in normal and portal hypertensive stomachs [4].
What medication reduces portal pressure?
Medications such as propranolol and isosorbide may be prescribed to lower the pressure in the portal vein and reduce the risk of recurrent bleeding. The drug lactulose can help treat confusion and other mental changes associated with encephalopathy.
How does octreotide work for portal hypertension?
Intravenous infusions of octreotide will lower portal blood pressure and can prevent rebleeding during the patient's initial hospitalization. Vasodilators such as isosorbide mononitrate (ISMN) reduce intrahepatic vascular resistance without decreasing the peripheral or portal-collateral resistance.
How does octreotide increase blood pressure?
Octreotide treatment is associated with an increase of 24-h and nighttime blood pressure, and with loss of circadian blood pressure rhythm. Splanchnic vasoconstriction by this drug, shifting blood to peripheral vessels, may explain this phenomenon.
How does octreotide stop variceal bleeding?
Variceal bleeding: Octreotide decreases the inflow of blood to portal system by constricting the splanchnic arterioles and significantly reduces intravariceal pressure.
What is the mechanism of action of octreotide?
Octreotide binds to somatostatin receptors coupled to phospholipase C through G proteins and leads to smooth muscle contraction in the blood vessels.
How does octreotide work?
It slows down or stops the production of a number of hormones such as insulin and gut hormones. It also controls the emptying of the stomach and bowel. Octreotide is a synthetic version of somatostatin (a somatostatin analogue) and slows down the production of hormones.
How is portal hypertension reduced?
Systemic drugs, such as non-selective beta-blockers, statins, or antibiotics, reduce portal hypertension by decreasing intrahepatic resistance or portal tributary blood flow or by blunting inflammatory stimuli inside and outside the liver.
Which medication is used to decrease portal pressure halting bleeding esophageal varices?
Vasoconstrictors: terlipressin, octreotide (reduce portal pressure)
How does beta-blocker reduce portal hypertension?
These drugs work in two ways: 1) by blocking β1 receptors and reducing cardiac output, and 2) by blocking β2 receptors, producing splanchnic vasoconstriction and reducing portal flow. Consequently, they reduce portal pressure.
What are the side effects of octreotide?
Side effects associated with octreotide are mainly local or gastrointestinal. Local reactions include pain and burning at the site of injection and these rarely last more than 15 minutes. Gastrointestinal side effects include anorexia, nausea, vomiting, cramp like abdominal pain, diarrhoea and steatorrhoea.
How does octreotide help with variceal bleeding?
Variceal bleeding:Octreotide decreases the inflow of blood to portal system by constricting the splanchnic arterioles and significantly reduces intravariceal pressure. Octreotide in a dose of 50 microgram intravenous bolus followed by a continuous infusion of 50 microgram per hour for 48 hours and emergency sclerotherapy have been found to be equally effective in the control of variceal bleeding [6]. This study suggests that octreotide can be administered when injection sclerotherapy is not available and is probably also useful for recurrent bleeding after sclerotherapy.
What is the treatment for GEP endocrine tumours?
The current treatment modalities for these tumours, i.e. surgery, hepatic artery embolisation, cytotoxic chemotherapy and α-interferon are merely palliative and of relative short lived efficacy. Treatment with octreotide allows symptom free periods for patients with hypersecretory disorders by inhibiting hormone output from the tumours and preventing hormone action on the target tissue. Clinical improvement occurs in 50 to 85 per cent patients during treatment with 150 to 300 microgram of octreotide per day [4].
What receptors are involved in somatostatin?
The various actions of somatostatin are mediated through specific membrane receptors. Five subtypes of human somatostatin receptors have been cloned and characterised. Octreotide binds with high affinity to somatostatin receptor subtype 2 and subtype 5 and with moderate affinity to subtype 3. Subtype 3 receptor is found in the pancreas and subtype 5 in the small intestine. The gastrointestinal effects of octreotide are inhibitory to the azygous blood flow, gastric secretions, splanchnic hemodynamics, pancreatic secretions, intestinal motility and all gastroenteropancreatic (GEP) endocrine secretions.
Does octreotide reduce fluid production?
Pancreatic and gastrointestinal fistula:Octreotide inhibits exocrine pancreatic secretions and thereby reduces the fluid production by pancreatic fistulas. Various studies have shown a higher rate of closure of pancreatic fistulas or at least a significant decrease in the fistula output [7, 8]. In patients with gastrointestinal fistulas octreotide has been shown to decrease the fistula output by 50 to 80 per cent and accelerate the closure of fistula in 80 per cent of these patients [5].
Does octreotide help with diarrhoea?
Diarrhoea:Octreotide prolongs the gastrointestinal transit time, decreases endogenous fluid secretion in the jejunum and stimulates the intestinal absorption of water and electrolytes. In secretory diarrhoeas, in patients with ileostomies, short bowel syndrome and radiation enteritis octreotide in a dose of 50 to 500 microgram per day has been found to be useful [5]. In patients with AIDS related diarrhoea octreotide induces a significant response, thereby improving the quality of life [5].
Why is portal pressure important?
Measurement of portal pressure in patients with portal hypertension is important in the evaluation of the efficacy of different portal-hypotensive pharmacologic therapies.
Why does portal hypertension persist?
However, even when portal blood flow is entirely diverted through collaterals, portal hypertension persists because of a concomitant increase in portal venous inflow, which in turn is caused by splanchnic vasodilatation, 9mostly mediated by an increase in nitric oxide.7.
How does HVPG affect clinical outcomes?
In patients with a history of variceal hemorrhage, a decrease in HVPG to less than 12 mm Hg or a decrease greater than 20% from baseline significantly reduces the risk of recurrent hemorrhage, ascites, encephalopathy, and death.12–14In patients with compensated cirrhosis, even lower reductions in HVPG (>10% from baseline) have been associated with a reduction in the development of varices,1first variceal hemorrhage,15and ascites.15Recent studies show that separate HVPG procedures to assess response to therapy can be obviated by assessing the acute hemodynamic response to intravenous (IV) propranolol (0.15 mg/kg) during a single procedure.15,16
What is portal hypertension?
Portal hypertension is an increase in pressure in the portal vein and its tributaries. It is defined as a portal pressure gradient (the difference in pressure between the portal vein and the hepatic veins) greater than 5 mm Hg. Although this gradient defines portal hypertension, a gradient of 10 mm Hg or greater defines clinically significant portal hypertension, because this pressure gradient predicts the development of varices,1decompensation of cirrhosis,2,3and hepatocellular carcinoma.4The most direct consequence of portal hypertension is the development of gastroesophageal varices that may rupture and lead to the development of variceal hemorrhage. This article reviews the pathophysiologic bases of the different pharmacologic treatments for portal hypertension in patients with cirrhosis and places them in the context of the natural history of varices and variceal hemorrhage.
What is the most potent vasoconstrictor?
Vasopressin is the most potent splanchnic vasoconstrictor available, but it has been abandoned in the therapy for portal hypertension because of its numerous side effects. It is an endogenous nanopeptide that causes vasoconstriction (splanchnic and systemic) by acting on the V1 receptors within the arterial smooth muscle. Having a short half-life, vasopressin can only be administered as a continuous intravenous infusion, and therefore it is only used in an acute setting (ie, in the management of acute variceal hemorrhage). Its continuous intravenous infusion is usually initiated at a dosage of 0.4 units/min that can be titrated up, based on the therapeutic response (cessation of bleeding) and, depending on the development of side effects, to a maximum of 0.8 to 1.0 units/min. Side effects can lead to drug withdrawal in up to 25% of patients, and can include arterial hypertension, myocardial ischemia, arrhythmias, ischemic abdominal pain, and limb gangrene.41Vasopressin should be used in combination with nitrates (see later discussion) to reduce side effects.
What is the portal vein?
Anatomically, the portal vein is formed by the union of the superior mesenteric vein and the splenic vein. The mesenteric vein collects blood from the splanchnic circulation. Thus, portal venous inflow is determined by the state of constriction or dilatation of splanchnic arterioles.
What is the most common cause of portal hypertension?
The most common cause of portal hypertension is cirrhosis. In cirrhosis, the increased resistance is mostly caused by hepatic architectural distortion (fibrosis and regenerative nodules) but about a third of the increased resistance is caused by intrahepatic vasoconstriction, amenable to vasodilators.5This is caused by the activation of stellate cells with active contraction of myofibroblasts and vascular smooth muscle cells in portal venules,6which in turn is caused by increased endogenous vasoconstrictors, such as endothelin, and reduced nitric oxide bioavailability.7,8
What does octreotide do to the gastrointestinal system?
Octreotide decreases the splanchnic blood flow (blood flow in the gastrointestinal region) and can be used in a hospital.
What is the best treatment for portal hypertension?
Liver transplantation is the only effective treatment for cirrhosis and portal hypertension. Liver transplantation means your diseased liver is replaced with a healthy one from deceased donors or living donors who donate portions of the liver. The surgery is long and complex, requiring the removal and replacement of your body's largest solid organ. However, this option offers the highest survival rate and chance of complete rehabilitation.
How to stop variceal bleeding?
Balloon tamponade: This is done to control severe variceal bleeding through compressing the vein. We inflate a small balloon within your stomach or esophagus to apply pressure to the bleeding veins. This compresses and stops the bleeding. This is a complex procedure that should only be performed by experienced physicians.
What is the main complication of portal hypertension?
The main complication of portal hypertension is bleeding from the varices, and many of the treatment options aim to manage the bleeding.
How to treat variceal hemorrhage?
During an endoscopy, your doctor places small elastic rings over the vein. The rings block the blood supply to each varix. You will undergo the initial banding session and then return for subsequent sessions in order to completely obliterate the varices, which is usually achieved after four to five procedures.
Can beta blockers be used for varices?
Beta blockers can be used to decrease portal pressure, although there are side effects. However, if you have cirrhosis but no varices, beta blockers cannot be used to prevent varices from developing. Studies have shown that the side effects of the medication outweigh the possible benefits.
How does a vasodilator affect the portal?
Vasodilators have been shown to exert a small effect on the reduction of portal flow, an increase in portal resistance, and decrease on portal pressure. These agents reduce intrahepatic vascular resistance without decreasing peripheral or portal-collateral resistance.
What is the best vasoconstrictors for portal hypertension?
The vasoconstrictors somatostatin and octreotide are used to treat acute bleeding in patients with portal hypertension before performing endoscopy. [ 47, 51] Intravenous infusions of octreotide will lower portal blood pressure and can prevent rebleeding during the patient's initial hospitalization. Vasodilators such as isosorbide mononitrate (ISMN) reduce intrahepatic vascular resistance without decreasing the peripheral or portal-collateral resistance.
Why do endoscopists use vasoactive agents?
The main advantages to using vasoactive agents include the ability of these drugs to treat variceal bleeding in the emergency department, lower portal pressure, and offer the endoscopist a clearer view of varices because of less active bleeding. Vasoactive agents represent an ideal treatment for sources of portal hypertensive bleeding other than esophageal varices (eg, gastric varices >2 cm below the gastroesophageal junction or portal hypertensive gastropathy). [ 8, 15]
Why do vasoconstrictors reduce blood flow?
Therefore, these drugs reduce blood flow in the gastroesophageal collaterals because of their vasoactive effects on the splanchnic vascular system.
What is the effect of beta blockers on the cardiac output?
Beta-blockers lower the cardiac output (via blockade of beta1 adrenoreceptors) and cause splanchnic vasoconstriction (via blockade of vasodilatory adrenoreceptors of the splanchnic circulation), reducing portal and collateral blood flow. Next: Somatostatin Analogs.
What is the purpose of beta blockers?
Beta-blockers, which include propranolol, nadolol, and timolol, are used to provide primary and secondary prophylaxis. Beta-blockers lower the cardiac output (via blockade ...
What is the digital subtraction venous phase of a superior mesenteric artery angiogram?
Digital subtraction venous phase of a superior mesenteric artery angiogram (same patient as in the previous 2 images) shows retrograde flow into the left gastric vein (curved arrow) and the inferior mesenteric vein (straight arrow). Note the flow defect of the distal portal vein caused by retrograde flow (open arrowhead). The final diagnosis was hepatitis C cirrhosis, hepatocellular carcinoma of the left hepatic lobe (which had ruptured into the peritoneum), and portoarterial fistula (which had developed inside the ruptured tumor, giving rise to severe portal hypertension).