Octreotide inhibits the meal-induced increases in the portal venous pressure of cirrhotic patients with portal hypertension: A double-blind, placebo-controlled study

McCormick, P. Aiden; Biagini, Maria Rosa; Dick, Robert; Greenslade, Lynda; Chin, Jun Liong; Cardin, Franco; Wagstaff, D; McIntyre, Neil; Burroughs, Andrew K.

doi:10.1002/hep.1840160513

Cited by 82 publications

(41 citation statements)

References 33 publications

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“…The exact mechanisms of the hemodynamic changes in response to octreotide are partly unknown, 1 and only a transient or no effect on hepatic venous pressure gradient (HVPG) has been demonstrated. [2][3][4][5][6] Lately, a marked increase of lower esophageal sphincter pressure has been described in response to intravenous octreotide in portal hypertensive patients in addition to a sustained suppression of postprandial splanchnic hyperemia. 3,[7][8][9] These effects coincide with a reduction of plasma glucagon, 8,9 and this mechanism has been thought to be responsible for the suppression of splanchnic hyperemia.…”

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confidence: 99%

“…[2][3][4][5][6] Lately, a marked increase of lower esophageal sphincter pressure has been described in response to intravenous octreotide in portal hypertensive patients in addition to a sustained suppression of postprandial splanchnic hyperemia. 3,[7][8][9] These effects coincide with a reduction of plasma glucagon, 8,9 and this mechanism has been thought to be responsible for the suppression of splanchnic hyperemia. However, a recent study indicates that octreotide has direct vasoconstrictive effects in cirrhotic patients unrelated to the effects on glucagon and other vasoactive hormones and neuropeptides 10 that may seriously influence renal function in these patients.…”

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confidence: 99%

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Effects of a long-acting formulation of octreotide on renal function and renal sodium handling in cirrhotic patients with portal hypertension: A randomized, double-blind, controlled trial

et al. 2001

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Octreotide has been widely used for controlling acute variceal bleeding in cirrhotic patients. The exact mechanisms of the hemodynamic changes in response to octreotide are partly unknown, 1 and only a transient or no effect on hepatic venous pressure gradient (HVPG) has been demonstrated. [2][3][4][5][6] Lately, a marked increase of lower esophageal sphincter pressure has been described in response to intravenous octreotide in portal hypertensive patients in addition to a sustained suppression of postprandial splanchnic hyperemia. 3,7-9 These effects coincide with a reduction of plasma glucagon, 8,9 and this mechanism has been thought to be responsible for the suppression of splanchnic hyperemia. However,

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confidence: 99%

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Effects of a long-acting formulation of octreotide on renal function and renal sodium handling in cirrhotic patients with portal hypertension: A randomized, double-blind, controlled trial

et al. 2001

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“…18,19 It has also been shown that octreotide blunts this postprandial increase both in normal subjects 20,21 and cirrhotic patients. [22][23][24] Recently, a new long-acting somatostatin analog, lanreotide, has been developed. 25 The hemodynamic effects of this peptide in humans are yet unknown.…”

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confidence: 99%

Hemodynamic effects of the somatostatin analog lanreotide in humans: Placebo-controlled, cross-over dose-ranging echo-doppler study

Mottet¹,

Sieber²,

Nauer³

et al. 1998

Hepatology

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Because of their vasoactive effects, somatostatin and its analogs are increasingly used in the management of complications of chronic liver diseases such as variceal bleeding. Postprandial hyperemia augments splanchnic blood flow, subsequently increasing portal pressure. The aim of this study was to explore effects of the somatostatin analog, lanreotide, on food-stimulated hemodynamic parameters in healthy human subjects. A dose-response curve was constructed in eight healthy male subjects in a placebo-controlled cross-over study. On 4 different days, either 0 (placebo), 50, 100, or 200 g/h of lanreotide was infused intravenously in random order, starting at 45 minutes for 7 hours. On each day, a liquid test meal (Ensure plus, 1.5 kcal/mL) was perfused intraduodenally at a rate of 3 mL/min over 7 hours after a 45-minute basal period. Diastolic arterial pressure (dBP), heart rate (HR), superior mesenteric arterial (SMA) average flow velocity (SMA-V), SMA pulsatility index (SMA-PI), portal venous volume flow (PV-F), and renal artery (RA) resistance index (RA-RI) were measured on regular intervals (flows using Echo-Doppler technology). Lanreotide at all doses abolished food-stimulated splanchnic hyperemia both in the SMA and PV over 7 hours. The fall in dBP and increase in HR after food perfusion were blunted under lanreotide. Food as well as lanreotide did not modify RA-RI. In summary: 1) lanreotide inhibits food-induced splanchnic hyperemia in normal subjects; 2) in parallel, systemic hemodynamic alterations to food stimulation are abolished with lanreotide; and 3) renal vascular resistance is unchanged. Because of its persistent splanchnic vasoconstrictive effect, lanreotide should be tested in patients with portal hypertension. (HEPATOLOGY 1998;27: 920-925.) Natural somatostatin, and especially its analog, octreotide, are increasingly used in the treatment of esophageal variceal bleeding. [1][2][3][4] In patients with cirrhosis and portal hypertension, it reduces splanchnic and azygos blood flow, 5,6 whereas the action with regard to portal pressure is modest. [5][6][7] Conversely, the effect(s) of natural somatostatin and its analog, octreotide, upon renal hemodynamics and function are unclear and have been a reason for debate. [8][9][10][11] Hemodynamic effects, at least for octreotide, have recently been shown to be only short-lasting, even when the drug is infused constantly. 12 In addition, no clear dose-response with regard to splanchnic hemodynamics has been performed, making a dose justification for the use of this compound difficult.Food is a very potent hyperemic stimulus in the splanchnic vascular area, both in normal subjects, 13-15 as well as in patients with portal hypertension. 16,17 It has been hypothesized that postprandial hyperemia may acutely augment portal pressure, and by this mechanism may probably increase the risk of bleeding from gastroesophageal varices. 18,19 It has also been shown that octreotide blunts this postprandial increase both in normal subjects 20,21 and cirrhotic patients....

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“…In the light of our results, we can hypothesize that other physiologic situations known to transiently increase portal pressure and/or AzBF, such as moderate physical exercise 11,12 or meals, [13][14][15][16][17][18][19][20] may cause significant increases in variceal pressure. It is of interest to note that propranolol therapy has been shown to prevent the changes in HVPG associated with moderate exercise.…”

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confidence: 95%

Increasing intra-abdominal pressure increases pressure, volume, and wall tension in esophageal varices

et al. 2002

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Many daily activities cause acute elevations of intra-abdominal pressure (IAP). In portal hypertensive cirrhotic patients, increased IAP increases absolute portal pressure and azygos blood flow, suggesting that it may have detrimental consequences at the esophageal varices. The aim of this study was to investigate the effects of increased IAP on variceal pressure, size, and wall tension. Endosonography and a noninvasive endoscopic pressure gauge were used to measure variceal pressure, radius, wall tension, and volume in baseline conditions and after increasing IAP by 10 mm Hg using an inflatable girdle in 14 patients with cirrhosis and esophageal varices. Increasing IAP markedly increased variceal pressure (from 13.3 ؎ 4.2 to 17.4 ؎ 4.6 mm Hg; P ‫؍‬ .0001) and radius (from 2.9 ؎ 1.0 to 3.9 ؎ 1.1 mm; P ‫؍‬ .0001). Consequently, wall tension dramatically increased (from 38.7 ؎ 13.6 to 65.9 ؎ 23.8 mm Hg ⅐ mm, ؉78%; P ‫؍‬ .0001). Variceal volume increased significantly from 1,264 ؎ 759 to 2,025 ؎ 1,129 mm 3 (P ‫؍‬ .0001). In conclusion, in portal hypertensive cirrhotic patients, increases in IAP have deleterious effects on variceal hemodynamics, markedly increasing the volume, pressure, and wall tension of the varices. Increases in IAP may contribute to the progressive dilatation that precedes the rupture of the varices in portal hypertension. V ariceal wall tension is thought to represent the key factor determining variceal rupture. 1,2 Wall tension is the inwardly directed force that opposes the expanding force that the increased intravascular pressure and blood flow exert on the variceal wall. 1 It is calculated by Frank's modification of Laplace's law, as the transmural pressure at the varices (the difference between intravariceal and esophageal luminal pressures) times the radius of the varix, divided by the thickness of the variceal wall. 1 Several efforts have been made to obtain objective measurements of variceal wall tension. In that regard, we have previously shown that the combination of endosonography and endoscopic measurement of transmural variceal pressure allows a quantitative, objective, and reproducible estimation of variceal wall tension. 3 In addition, endosonography allows for estimation of variceal volume in the distal esophagus. 3 Elevations of intra-abdominal pressure (IAP) in cirrhotic patients have significant effects on both the systemic and the splanchnic circulation. A previous study from our laboratory showed that brief mechanical elevations of IAP increased azygos blood flow (AzBF), an index of gastroesophageal collateral blood flow, and the absolute portal pressure, estimated by the wedged hepatic venous pressure. 4 Therefore, an elevated IAP may be associated with acute increments of both variceal pressure and variceal blood flow.Moreover, Kravetz et al. 5 showed that in cirrhotic patients with ascites releasing an increased IAP by means of total volume paracentesis decreased intravariceal pressure. These effects of total volume paracentesis may be related to a significant decrease ...

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Octreotide inhibits the meal-induced increases in the portal venous pressure of cirrhotic patients with portal hypertension: A double-blind, placebo-controlled study

Cited by 82 publications

References 33 publications

Effects of a long-acting formulation of octreotide on renal function and renal sodium handling in cirrhotic patients with portal hypertension: A randomized, double-blind, controlled trial

Effects of a long-acting formulation of octreotide on renal function and renal sodium handling in cirrhotic patients with portal hypertension: A randomized, double-blind, controlled trial

Hemodynamic effects of the somatostatin analog lanreotide in humans: Placebo-controlled, cross-over dose-ranging echo-doppler study

Increasing intra-abdominal pressure increases pressure, volume, and wall tension in esophageal varices

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