Effects of somatostatin, terlipressin and somatostatin plus terlipressin on portal and systemic hemodynamics and renal sodium excretion in patients with cirrhosis.

BACKGROUND AND AIM: Terlipressin and somatostatin are the most preferable agents for the control of variceal bleeding in cirrhotic patients. The present study evaluated the hemodynamic effects of somatostatin, terlipressin and somatostatin plus terlipressin in cirrhotic patients with portal hypertension, as well as the effect of each regimen on renal sodium excretion.

METHODS: Twenty-four patients with esophageal varices were randomly assigned to receive either an intravenous infusion of a placebo (n = 12) or somatostatin 250 microg/h after an initial bolus of 250 microg (n = 12) for 60 min. Thereafter, each patient received an intravenous injection of terlipressin 2 mg while the intravenous infusion of either somatostatin or placebo was maintained. Portal and systemic hemodynamic parameters, assessed by Doppler sonography, and urinary sodium excretion were evaluated at baseline, 60 min after placebo or somatostatin, and 30 min after terlipressin.

RESULTS: Placebo had no effect on the patients studied. After terlipressin, portal vein velocity, portal flow volume and cardiac output (CO) significantly decreased (0.09 vs 0.15 m/s, 0.56 vs 1 L/min and 6.4 vs 7.6 L/min, respectively [values are medians]), while mean arterial pressure (MAP) and systemic vascular resistance significantly increased (103.3 vs 89.9 mmHg and 1541 vs 1108dyn.s/cm(5), respectively). Fractional sodium excretion significantly increased in patients without ascites (0.43 vs 0.16%) while it did not change in patients with ascites. Somatostatin did not alter portal hemodynamics whereas it significantly reduced MAP, heart rate (HR) and CO (86.9 vs 98.6 mmHg, 65 vs 73 bpm and 8.4 vs 9.1 L/min, respectively) and, in patients with ascites, sodium excretion (0.13 vs 0.23%). The addition of terlipressin to somatostatin induced similar changes to those observed after terlipressin alone. The magnitude of increase in MAP was significantly higher in patients receiving terlipressin alone than in those receiving somatostatin plus terlipressin (15 vs 5.3%), while CO was conversely affected (-28.5 vs-20.9%).

CONCLUSIONS: Combined treatment with somatostatin and terlipressin does not exert an additive portal hypotensive effect in cirrhotic patients as compared to terlipressin alone, whereas somatostatin alone may impair systemic hemodynamics. Compared with somatostatin, terlipressin exerts a more beneficial effect on renal sodium excretion in patients with or without ascites.