Effects of long-term propranolol and octreotide on postprandial hemodynamics in cirrhosis: A randomized, controlled trial

Vorobioff, Julio; Gamen, Marcelo; Kravetz, David; Picabea, Eduardo; Villavicencio, R; Bordato, Juan; Ruf, Andrés E.; Bessone, Fernando; Romero, Gustavo; Palazzi, Jorge; Nicora, Alicia; Passamonti, María; Tanno, Hugo

doi:10.1053/gast.2002.32395

Cited by 35 publications

(18 citation statements)

References 33 publications

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“…24 This discrepancy can be related to the severity of liver failure observed in our patients or to a desensitization to the effects of octreotide. 25 Also, it must be noticed that octreotide can blunt the postprandial increase in glucagon release in cirrhotic patients, 14,20,21,26 an observation that parallels the findings of octreotide effects on splanchnic blood flow described earlier.…”

Section: Discussionsupporting

confidence: 57%

Octreotide in hepatorenal syndrome: A randomized, double-blind, placebo-controlled, crossover study

Pomier‐Layrargues

2003

Hepatology

136

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The hepatorenal syndrome (HRS) is related to vasoconstriction of the renal cortex induced by systemic hypovolemia that follows splanchnic vasodilatation as the primary event in the cascade of hemodynamic changes associated with portal hypertension. We evaluated the effects of octreotide, a splanchnic vasoconstrictor, on HRS in cirrhotic patients. We compared the effects of octreotide infusion (50 g/h) to placebo using a randomized, doubleblind, cross-over design over 2, 4-day periods. Nineteen patients were included, and 14 patients could complete the 2 phases of the study (group 1: placebo first; n ‫؍‬ 8 and group 2: octreotide first; n ‫؍‬ 6) The end point of the study was to evaluate improvement in renal function as defined by a 20% decrease in serum creatinine value after a 4-day treatment as compared with baseline. In all the patients, a normal central venous pressure was maintained by daily intravenous administration of 2 units of albumin. The 2 groups were similar with regard to demographic data and liver and kidney function parameters at baseline. Improvement in renal function was observed in 2 patients after the placebo and 1 patient after octreotide infusion in group 1 and in 2 patients after octreotide infusion and 1 patient after placebo in group 2 (P ‫؍‬ not significant). In addition, treatment with octreotide infusion did not result in significant changes in creatinine clearance, daily urinary sodium, plasma renin activity, plasma aldosterone and glucagon levels, or renal and mesenteric artery resistance indices as measured by Doppler ultrasonography. In conclusion, the present study demonstrates that, under our experimental conditions, octreotide infusion combined with albumin is not effective for the treatment of HRS in cirrhotic patients. (HEPATOLOGY 2003;38:238-243.) T he hepatorenal syndrome (HRS) is a functional renal disorder associated with severe acute or chronic liver failure. It is always potentially reversible because no anatomic damage can be demonstrated in the kidney. This syndrome carries a very bad prognosis because it is always the consequence of severe liver insufficiency, the only definitive treatment being liver transplantation. 1 The pathophysiology of renal failure is thought to be mediated primarily by splanchnic vasodilatation leading to systemic hypovolemia; a cascade of vasoactive mechanisms is then initiated including compensatory activation of vasoconstrictor catecholamines, renin, aldosterone, antidiuretic hormone, and endothelin; a marked vasoconstriction of the renal cortex ensues, glomerular filtration decreases, and the kidney function deteriorates. 2 Over recent years, several attempts have been made to correct the cortical renal vasoconstriction by using splanchnic vasoconstrictors, in the hope of reversing splanchnic vasodilatation, which is thought to be the primary pathogenetic event. The efficacy of ornipressin, 3-5 terlipressin, 6-10 and octreotide alone 11 or combined with midodrine 12 has been tested in small uncontrolled pilot trials. Terlipressin appe...

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Section: Discussionsupporting

confidence: 57%

Octreotide in hepatorenal syndrome: A randomized, double-blind, placebo-controlled, crossover study

Pomier‐Layrargues

2003

Hepatology

136

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“…15 More importantly, the study demonstrates that the administration of a low dose of ISMN (10 mg), but not of placebo, largely prevented the postprandial increase in portal pressure. Again, this effect was also observed in patients under continued propranolol therapy.…”

Section: Discussionmentioning

confidence: 78%

“…[1][2][3][4]6,7 On the other hand, in cirrhotic patients, the postprandial hyperemia determines a significant increase of portal and collateral blood flow, which results in an increased hepatic venous pressure gradient (HVPG). 3,[7][8][9][10][11][12][13][14][15] This is observed rapidly, the maximum changes in splanchnic hemodynamics being observed at 30 minutes after the meal, returning to basal levels at 120 minutes. 3,8,9,[11][12][13][14] These data suggest that, in cirrhotic patients, the repeated increase in portal venous pressure because of food intake may contribute to the progressive portal-systemic collateral dilation and to the development and dilation of the varices that eventually lead to variceal bleeding.…”

mentioning

confidence: 99%

“…15 Several recent studies have shown that the cirrhotic liver exhibits endothelial dysfunction that results in a defective or absent vasodilatory response to acetylcholine and in an insufficient nitric oxide (NO) production by endothelial nitric oxide synthase in the intrahepatic vascular bed. [17][18][19] Such a deficient NO production increases the hepatic vascular tone and may decrease the intrahepatic vasodilatory adaptive response to sudden increases in blood flow.…”

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confidence: 99%

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Low doses of isosorbide mononitrate attenuate the postprandial increase in portal pressure in patients with cirrhosis

Bellis¹,

Berzigotti

Abraldes

et al. 2003

Hepatology

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Postprandial hyperemia is associated with a significant increase in portal pressure in cirrhosis, which may contribute to progressive dilation and rupture of gastroesophageal varices. In cirrhosis, an insufficient hepatic production of nitric oxide (NO) may impair the expected hepatic vasodilatory response to increased blood flow, further exaggerating the postprandial increase in portal pressure. This study was aimed at investigating whether low doses of an oral NO donor might counteract the postprandial peak in portal pressure. Twenty-three portal hypertensive cirrhotics, 8 of them under propranolol therapy, were randomized to receive orally 5-isosorbide mononitrate (ISMN; 10 mg; n ‫؍‬ 11) or placebo (n ‫؍‬ 12) and a standard liquid meal 15 minutes later. S everal studies have shown that, in normal subjects, food intake induces marked changes in splanchnic hemodynamics. [1][2][3][4][5] The main finding is a postprandial increase in splanchnic blood flow, caused by splanchnic arteriolar vasodilatation occurring in the submucosal and mucosal layers of the small intestine. This postprandial splanchnic vasodilatation and hyperemia occur owing to the interaction of intrinsic mechanisms (such as changes in arteriolar transmural pressure and/or increase in vasodilator tissue metabolites) and extrinsic mechanisms (action of autonomic nervous system) and to the effect of gastrointestinal hormones. [1][2][3][4]6,7 On the other hand, in cirrhotic patients, the postprandial hyperemia determines a significant increase of portal and collateral blood flow, which results in an increased hepatic venous pressure gradient (HVPG). 3,[7][8][9][10][11][12][13][14][15] This is observed rapidly, the maximum changes in splanchnic hemodynamics being observed at 30 minutes after the meal, returning to basal levels at 120 minutes. 3,8,9,[11][12][13][14] These data suggest that, in cirrhotic patients, the repeated increase in portal venous pressure because of food intake may contribute to the progressive portal-systemic collateral dilation and to the development and dilation of the varices that eventually lead to variceal bleeding.Propranolol administration has been reported to reduce the postprandial peak in portal pressure, 10 but sub-

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“…26,27 OCT has been shown to prevent postprandial increase in portal pressure in stable cirrhotics but its practical role in BEVs is still unclear. 28 Furthermore, a previous study found that OCT injection in cirrhotic patients caused marked but transient reductions in portal pressure and azygos blood flow because of rapid development of desensitization. 29 Adding a continuous OCT infusion neither maintained nor prolonged its effects.…”

Section: Discussionmentioning

confidence: 99%

Clinical trial: the effect of somatostatin vs. octreotide in preventing post‐endoscopic increase in hepatic venous pressure gradient in cirrhotics with bleeding varices

Vlachogiannakos

Kougioumtzian

Triantos

et al. 2007

Aliment Pharmacol Ther

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Effects of long-term propranolol and octreotide on postprandial hemodynamics in cirrhosis: A randomized, controlled trial

Cited by 35 publications

References 33 publications

Octreotide in hepatorenal syndrome: A randomized, double-blind, placebo-controlled, crossover study

Octreotide in hepatorenal syndrome: A randomized, double-blind, placebo-controlled, crossover study

Low doses of isosorbide mononitrate attenuate the postprandial increase in portal pressure in patients with cirrhosis

Clinical trial: the effect of somatostatin vs. octreotide in preventing post‐endoscopic increase in hepatic venous pressure gradient in cirrhotics with bleeding varices

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