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

Abstract

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.)

Meta‐analysis: terlipressin therapy for the hepatorenal syndrome

“…The efficacy and safety of vasoconstrictors to stop active variceal bleeding has been repeatedly emphasized whereas their clinical use in the management of HRS is preliminary in nature. 28 Many centres have started to use terlipressin in patients with HRS but only small-sized, uncontrolled trials are available. Although a beneficial effect of terlipressin therapy has been suggested by many investigators, no review has summarized the size and consistency of terlipressin's effect on hepatorenal syndrome.…”

Treatment of type 2 hepatorenal syndrome in patients awaiting transplantation: Effects on kidney function and transplantation outcomes

“…5 In the last decade, an effective pharmacological therapy based on the use of vasoconstrictors, particularly terlipressin (but also noradrenalin), associated with the administration of albumin has been introduced. [1][2][3][4]7 This treatment causes a marked increase in GFR in approximately 50% of patients and improves survival in type 1 HRS. [8][9][10][11][12] Therefore, this pharmacological treatment has become the standard of care for this condition.…”

Effects of terlipressin on the aquaretic system: evidence of antidiuretic effects

“…Plasma sodium decreased 1.1 mmol/l (P Ͻ 0.01). An increase in AQP2 excretion and a decrease in C H 2 O and distal water excretion after terlipressin despite water loading is a clear indication of activation of the antidiuretic system (V 2 receptor effect).aquaporin-2; vasopressin; hepatorenal syndrome; cirrhosis; ascites THE VASOPRESSIN ANALOG TERLIPRESSIN is widely used in the treatment of type 1 hepatorenal syndrome (HRS) (15,22). Patients with HRS are characterized by avid sodium and water retention.…”

“…THE VASOPRESSIN ANALOG TERLIPRESSIN is widely used in the treatment of type 1 hepatorenal syndrome (HRS) (15,22). Patients with HRS are characterized by avid sodium and water retention.…”