Time profile of the haemodynamic effects of terlipressin in portal hypertension.

BACKGROUND/AIMS: Terlipressin is a long-acting vasopressin analogue that has been proved useful in the treatment of variceal haemorrhage. This study investigates the time profile of the haemodynamic effects of terlipressin on portal hypertension as well as the efficacy in decreasing portal-pressure and collateral blood flow of reduced doses, suitable for longer therapy to prevent early rebleeding.

METHODS

Splanchnic and systemic haemodynamics were measured in 23 patients with cirrhosis and portal hypertension in baseline conditions and at 30 min, 1, 2, 3 and/or 4 h after the double-blind administration of a single intravenous injection of 1 mg (n=8) or 2 mg (n=8) of terlipressin, or placebo (n=7).

RESULTS

Placebo caused no significant effects. At 30 min of terlipressin administration, the hepatic venous pressure gradient (1 mg: -16+/-9%, 2 mg: -21+/-11%; p<0.01) and azygos blood flow (1 mg: -19+/-13%, 2 mg: -25+/-17%; p<0.05) were significantly reduced. These effects were still significant at 4 h (2 mg) or 3 h (1 mg). Both doses moderately increased arterial pressure at 1 h. At 4 h, neither arterial pressure nor peripheral vascular resistance was significantly modified by either dose of terlipressin. Terlipressin caused no significant changes in hepatic blood flow.

CONCLUSIONS

In patients with cirrhosis, a single injection of 2 mg of terlipressin significantly and markedly reduces portal pressure and azygos blood flow for up to 4 h. The effects of a reduced dose (1 mg) were almost as pronounced and prolonged, suggesting that after the initial control of variceal bleeding, terlipressin therapy could be maintained for several days at low dosage to reduce the risk of early rebleeding.