Central and systemic haemodynamic effects of terlipressin in portal hypertensive patients

Möller, Sören; Hansen, Erik Keith; Becker, Ulrik; Brinch, Kim; Henriksen, Jens H.; Bendtsen, Flemming

doi:10.1034/j.1600-0676.2000.020001051.x

Cited by 129 publications

(108 citation statements)

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“…Terlipressin activates the V1 receptors, which are predominantly located in the vasculature in the splanchnic region, causes vasoconstriction, 28 and thereby reduces the splanchnic arterial vasodilatation and portal pressure and ameliorates the hyperdynamic circulation. 14,29 This improves the effective circulatory volume and renal perfusion pressure. 23,29 In this study, we showed that these improvements in hemodynamics are associated with an increase in GFR and a deactivation of vasoconstrictors and sodium-conserving hormones (that is, norepinephrine and renin).…”

Section: Discussionmentioning

confidence: 99%

“…The mechanisms behind the effect of terlipressin in HRS have not been thoroughly investigated. Terlipressin seems to revert the systemic vasodilatation and increase blood pressure 14 and thereby improve renal perfusion pressure and renal function. As HRS is most often preceded by the development of ascites, vasoconstrictors may also have a beneficial effect in decompensated cirrhosis without severe renal impairment and thereby represent a novel future treatment for ascites.…”

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Terlipressin improves renal function in patients with cirrhosis and ascites without hepatorenal syndrome

et al. 2007

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Patients with advanced cirrhosis and ascites are characterized by circulatory dysfunction with splanchnic vasodilatation and renal vasoconstriction, which often lead to ascites. The vasoconstrictor terlipressin improves renal function in hepatorenal syndrome (HRS). The aim of this study was to evaluate if terlipressin also improves renal function in patients with ascites without HRS. Twenty-three patients with cirrhosis participated; 15 with nonrefractory ascites were randomized to either terlipressin (N group, n ‫؍‬ 11) or a placebo (P group, n ‫؍‬ 4), and 8 had refractory ascites and received terlipressin (R group). The glomerular filtration rate (GFR), sodium clearance (C Na ), lithium clearance (C Li ), osmolal clearance (C Osm ), and urine sodium concentration (U Na ) were assessed before and after the injection of 2 mg of terlipressin or the placebo. GFR increased in the N group (69 ؎ 19 versus 92 ؎ 25 mL/min, P < 0.005) and in the R group (31 ؎ 19 versus 41 ؎ 31 mL/min, P < 0.05) after terlipressin. In the N group, terlipressin induced an increase in C Na (0.89 ؎ 0.21 versus 1.52 ؎ 1.45 mL/min, P < 0.05), C Li (17.3 ؎ 8.9 versus 21.5 ؎ 11.6 mL/min, P < 0.05), and C Osm (2.10 ؎ 0.81 versus 3.06 ؎ 2.0 mL/min, P < 0.05). In the R group, terlipressin induced an increase in C Na (0.11 ؎ 0.18 versus 0.35 ؎ 0.40 mL/min, P < 0.05) and C Li (5.5 ؎ 4.2 versus 9.5 ؎ 8.55 mL/min, P < 0.05). U Na increased in both groups after terlipressin (P < 0.005). Plasma norepinephrine (P < 0.05) and renin (P < 0.05) decreased after terlipressin. All parameters remained unchanged after the placebo. A scites is a serious complication of cirrhosis, occurring in about 50% of patients within 10 years after diagnosis, and it is associated with 50% mortality in 2 years. 1,2 Patients with ascites have hyperdynamic circulation, which is characterized by peripheral and splanchnic arterial vasodilatation and reduced arterial blood pressure and systemic vascular resistance. 3 Portal hypertension and splanchnic vasodilatation are major factors in the development of ascites. 4,5 Secondary to vasodilatation, vasoactive hormones, such as the reninangiotensin-aldosterone system and the sympathetic nervous system, are activated. This leads to renal vasoconstriction and reduced renal perfusion and filtration pressure. The current standard treatment of ascites involves diuretics and paracentesis, which are not designed to improve the underlying pathophysiology. The changes in the renal handling of water and salt seem to develop stepwise from a stage that can be controlled by diuretics to a stage refractory to diuretics and finally to full-blown renal failure, which is known as hepatorenal syndrome (HRS) type 1. 6 Several clinical studies have evaluated the efficacy of the long-term administration of terlipressin [a vasopressin 1 (V1) receptor agonist] in patients with HRS, [7][8][9][10][11][12][13] and there is evidence that terlipressin may improve renal

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Terlipressin improves renal function in patients with cirrhosis and ascites without hepatorenal syndrome

et al. 2007

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“…In the latter patients, the acute administration of terlipressin alone (1-2 mg, intravenous bolus) evokes systemic vasoconstrictor and vasopressor effects associated with bradycardia and a reduction in cardiac output. 30,31 Finally, 2-day terlipressin administration is known to induce an arterial vasopressor effect associated with significant decreases in plasma renin concentrations and significant increases in GFR. 32 The effects of 1 to 2 weeks' administration of ornipressin or terlipressin alone on systemic hemodynamics are unknown.…”

Section: The Use Of Vasoconstrictors For Type 1 Hrsmentioning

confidence: 99%

“…However, no evidence of arterial underfilling was found in an acute hemodynamic study on the effects of the administration of 2 mg terlipressin in patients with cirrhosis. 31 Clearly, hemodynamic studies after 1 to 2 weeks' terlipressin administration are needed.…”

Section: The Use Of Vasoconstrictors For Type 1 Hrsmentioning

confidence: 99%

The use of vasoconstrictors in patients with cirrhosis: Type 1 HRS and beyond

2006

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In patients with cirrhosis and type 1 hepatorenal syndrome (HRS), systemic vasodilation, which is mainly attributable to splanchnic vasodilation, plays a critical role in the activation of endogenous vasoconstrictor systems, resulting in renal vasoconstriction and functional renal failure. It has been suggested that the use of splanchnic (and systemic) vasoconstrictors such as terlipressin (a vasopressin analog) or alpha-1-adrenoceptor agonists (midodrine or noradrenaline) may improve renal function in patients with type 1 HRS. Six studies (with only one randomized study in a small series of patients) have shown that terlipressin improves renal function in these patients. However, there is evidence that terlipressin alone may be less effective than terlipressin combined with intravenous albumin in improving renal function. Future randomized studies should confirm this difference and evaluate the impact of terlipressin therapy (with or without intravenous albumin) on survival. Interestingly, in nonrandomized studies, the use of alpha-1 agonists combined with other therapies (octreotide and albumin for midodrine; furosemide and albumin for noradrenaline) has been shown to improve renal function in patients with type 1 HRS. The efficacy and safety of combined therapies including alpha-1 agonists should be confirmed in randomized studies. Finally, preliminary evidence suggests that vasoconstrictor administration may be a novel therapeutic approach targeting vasodilation involved in the mechanism of: (1) renal failure in type 2 HRS; (2) paracentesis-induced circulatory dysfunction; and (3) arterial hypotension induced by byproducts of gram-negative bacteria. Further studies are needed in all these fields. (HEPATOLOGY 2006;43:385-394.)

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“…1 It is a biologically inactive substance that gains its long half-life of 2-10 hours by being enzymatically cleaved into the biologically active lysine-vasopressin. 13 It has been shown to cause direct vasoconstriction of the systemic arteriolar and splanchnic vasculature. It affects the V 1 vasopressin receptors of systemic vasculature more strongly than the V 2 vasopressin receptors of the kidneys.…”

Section: Hemodynamic Effects Of Terlipressin On Portal Hypertensionmentioning

confidence: 99%

The use of terlipressin in hepatorenal syndrome

Rozov-Ung

Panesar

2010

Dialysis & Transplantation

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Hepatorenal syndrome (HRS) is a potentially reversible cause of acute renal failure that occurs in patients with hepatic failure resulting from advanced cirrhosis. It is characterized by impaired kidney function in the setting of normal renal parenchyma, alterations in cardiovascular function, splanchnic vasodilation, and overactivity of the sympathetic nervous and the renin‐angiotensin systems causing severe arterial vasoconstriction. Clinically, patients will present with the classic signs and symptoms of liver and renal failure, such as ascites, jaundice, coagulopathy, hepatic encephalopathy, and decreased urine output. Patients with cirrhosis are thought to have extreme circulatory dysfunction caused by portal hypertension‐induced release of vasodilators (primarily nitric oxide) into the splanchnic circulation, causing local vasodilation. Terlipressin is a synthetic long‐acting analogue of vasopressin in which lysine is substituted for arginine at position 8 and the N‐triglycyl residue. It has been shown to cause direct vasoconstriction of the systemic arteriolar and splanchnic vasculature. It affects the V1 vasopressin receptors of systemic vasculature more strongly than the V2 vasopressin receptors of the kidneys. Although it is not currently approved by the U.S. Food and Drug Administration, it has been widely studied and is currently being used in other countries for the treatment of HRS. Terlipressin is quickly emerging as a promising treatment of hepatorenal syndrome. Today its best use may be in improving renal function in preparation for liver transplantation, which has shown to reduce post‐transplant morbidity and mortality.

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Central and systemic haemodynamic effects of terlipressin in portal hypertensive patients

Cited by 129 publications

References 0 publications

Terlipressin improves renal function in patients with cirrhosis and ascites without hepatorenal syndrome

Terlipressin improves renal function in patients with cirrhosis and ascites without hepatorenal syndrome

The use of vasoconstrictors in patients with cirrhosis: Type 1 HRS and beyond

The use of terlipressin in hepatorenal syndrome

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