The use of vasoconstrictors in patients with cirrhosis: type 1 HRS and beyond.
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.
INSERM, U773, Centre de Recherche Biomédicale Bichat-Beaujon CRB3, and Service d'Hépatologie, Hôpital Beaujon, Clichy, France. rmoreau@bichat.inserm.fr
Richard
R
Moreau
Didier
D
Lebrec
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000209:etiology; D004359:Drug Therapy, Combination; D006530:Hepatorenal Syndrome / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000503:physiopathology; D008236:Lypressin / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D019152:Paracentesis / Q000009:adverse effects; D012772:Shock, Septic / Q000188:drug therapy; D013152:Splanchnic Circulation / Q000187:drug effects / Q000502:physiology; D000077585:Terlipressin; D014662:Vasoconstrictor Agents / Q000494:pharmacology / Q000627:therapeutic use*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D000316:Adrenergic alpha-Agonists; D014662:Vasoconstrictor Agents; D008236:Lypressin; D000077585:Terlipressin