Octreotide blunts postprandial splanchnic hyperemia in cirrhotic patients: A double-blind randomized echo-doppler study

Buonamico, Paolo; Sabbá, Carlo; García–Tsao, Guadalupe; Berardi, Elsa; Antonica, Gianfranco; Ferraioli, Giovanna; Jensen, Jonathan E.; Lerner, Emanuel; Taylor, Kenneth J. W.; Albano, O; Groszmann, Roberto J.

doi:10.1002/hep.1840210123

Cited by 36 publications

(43 citation statements)

References 21 publications

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“…E, Patients with HRS Type 1; F, patients with HRS type 2. [14][15][16][17] or no change in these parameters. 18 These differences may be related to the dosage of the drug, the route of administration (intravenous or subcutaneous), the duration of treatment, the techniques used to measure splanchnic blood flow, and the degree of liver failure in the cirrhotic patients.…”

Section: Discussionmentioning

confidence: 95%

“…23 We did not find any decrease in fasted glucagon plasma levels after octreotide infusion. Previous studies have shown that octreotide could reduce glucagon plasma levels after acute intravenous 17 or subcutaneous administration 14 or after chronic subcutaneous administration. 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.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, it has been repeatedly shown that octreotide administered either intravenously or subcutaneously could blunt the postprandial increase in splanchnic blood flow. 14,15,[19][20][21] The vasoconstrictive effect of octreotide on the splanchnic circulation is thought to be mediated partly by an inhibition of glucagon secretion 22 ; a direct effect on the smooth muscle vasculature has also been suggested. 23 We did not find any decrease in fasted glucagon plasma levels after octreotide infusion.…”

Section: Discussionmentioning

confidence: 99%

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Octreotide in Hepatorenal Syndrome: A Randomized, Double–Blind, Placebo–Controlled, Crossover Study

Pomier‐Layrargues

2003

Hepatology

137

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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: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Octreotide in Hepatorenal Syndrome: A Randomized, Double–Blind, Placebo–Controlled, Crossover Study

Pomier‐Layrargues

2003

Hepatology

137

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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.…”

mentioning

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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“…It might be blunted by octreotide and isosorbide-5-mononitrate (ISMN), whereas propranolol decreases only baseline HVPG [37][38][39][40].…”

Section: Recommendationsmentioning

confidence: 99%

Primary prophylaxis of gastroesophageal variceal bleeding: consensus recommendations of the Asian Pacific Association for the Study of the Liver

et al. 2008

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The Asian Pacific Association for the Study of the Liver (APASL) set up a Working Party on Portal Hypertension in 2002, with a mandate to develop consensus guidelines on various clinical aspects of portal hypertension relevant to disease patterns and clinical practice in the Asia-Pacific region. Variceal bleeding is a consequence of portal hypertension, which, in turn, is the major complication of liver cirrhosis. Primary prophylaxis to prevent the first bleed from varices is one of the most important strategies for reducing the mortality in cirrhotic patients. Experts predominantly from the Asia-Pacific region were requested to identify the different aspects of primary prophylaxis and develop the consensus guidelines. The APASL Working Party on Portal Hypertension evaluated the various therapies that have been used for the prevention of first variceal bleeding. A 2-day meeting was held on January 12 and 13, 2007, at New Delhi, India, to discuss and finalize the consensus statements. Only those statements that were unanimously approved by the experts were accepted. These statements were circulated to all the experts and were subsequently presented at the annual conference of the APASL at Kyoto, Japan, in March 2007.

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Octreotide blunts postprandial splanchnic hyperemia in cirrhotic patients: A double-blind randomized echo-doppler study

Cited by 36 publications

References 21 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

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

Primary prophylaxis of gastroesophageal variceal bleeding: consensus recommendations of the Asian Pacific Association for the Study of the Liver

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