Hemodynamic effects of a combination of octreotide and terlipressin in patients with viral hepatitis related cirrhosis

BACKGROUND: Terlipressin or octreotide given alone has been used as the first-line pharmacological treatment for acute variceal bleeding. In portal hypertensive animals, pre-infusion of octreotide followed by the addition of terlipressin has an additive or complementary effect on splanchnic hemodynamics. The current study was aimed at evaluating such a combination treatment in patients with cirrhosis and portal hypertension. METHODS: Patients were randomly assigned to receive either a placebo (n = 11) or an intravenous infusion of octreotide 100 microg/h after an initial bolus of 100 microg (n = 13). Thereafter, each patient received an intravenous injection of terlipressin 2 mg. Hemodynamic values were measured basally, 30 min after octreotide or placebo, and 60 min after terlipressin. RESULTS: Placebo administration did not affect any of the hemodynamic values. Terlipressin administration resulted in expected changes in hepatic venous pressure gradient, hepatic blood flow and systemic hemodynamics. In contrast, octreotide administration significantly decreased hepatic blood flow but did not affect other hemodynamic values. After terlipressin administration, significant hemodynamic changes were observed that were similar to the hemodynamic changes with terlipressin alone. The magnitude of changes in hepatic venous pressure gradient, cardiac index and systemic vascular resistance were no different between the two groups of patients. The heart rate was significantly lower in patients receiving octreotide plus terlipressin than those receiving terlipressin alone. CONCLUSION: The current study showed that a combination of octreotide and terlipressin did not exert an additive effect in reducing hepatic venous pressure gradient in patients with cirrhosis. In addition, the systemic hemodynamic changes were comparable between the two groups.     

Hemodynamic Effects of a Combination of Octreotide and Terlipressin Patients with Viral Hepatitis Related Cirrhosis

Background: Terlipressin or octreotide given alone has been used as the first-line pharmacological treatment for acute variceal bleeding. In portal hypertensive animals, pre-infusion of octreotide followed by the addition of terlipressin has an additive or complementary effect on splanchnic hemodynamics. The current study was aimed at evaluating such a combination treatment in patients with cirrhosis and portal hypertension. Methods: Patients were randomly assigned to receive either a placebo ( n = 11) or an intravenous infusion of octreotide 100 μg/h after an initial bolus of 100 μg ( n = 13). Thereafter, each patient received an intravenous injection of terlipressin 2 mg. Hemodynamic values were measured basally, 30 min after octreotide or placebo, and 60 min after terlipressin. Results: Placebo administration did not affect any of the hemodynamic values. Terlipressin administration resulted in expected changes in hepatic venous pressure gradient, hepatic blood flow and systemic hemodynamics. In contrast, octreotide administration significantly decreased hepatic blood flow but did not affect other hemodynamic values. After terlipressin administration, significant hemodynamic changes were observed that were similar to the hemodynamic changes with terlipressin alone. The magnitude of changes in hepatic venous pressure gradient, cardiac index and systemic vascular resistance were no different between the two groups of patients. The heart rate was significantly lower in patients receiving octreotide plus terlipressin than those receiving terlipressin alone. Conclusion: The current study showed that a combination of octreotide and terlipressin did not exert an additive effect in reducing hepatic venous pressure gradient in patients with cirrhosis. In addition, the systemic hemodynamic changes were comparable between the two groups.     

Terlipressin is more effective in decreasing variceal pressure than portal pressure in cirrhotic patients

BACKGROUND/AIMS: Terlipressin decreases portal pressure. However, its effects on variceal pressure have been poorly investigated. This study investigated the variceal, splanchnic and systemic hemodynamic effects of terlipressin. METHODS: Twenty cirrhotic patients with esophageal varices grade II-III, and portal pressure > or =12 mmHg were studied. Hepatic venous pressure gradient, variceal pressure and systemic hemodynamic parameters were obtained. After baseline measurements, in a double-blind administration, 14 patients received a 2mg/iv injection of terlipressin and six patients received placebo. The same measurements were repeated 60 min later. RESULTS: No demographic or biochemical differences were observed in basal condition between groups. Terlipressin produced significant decreases in intravariceal pressure from 20.9+4.9 to 16.3+/-4.7 mmHg (p<0.01, -21+/- 16%), variceal pressure gradient from 18.9+/-4.8 to 13.5+/-6.0 mmHg (p<0.01, -28+/-27%), estimated variceal wall tension from 78+/-29 to 59+/-31 mmHg x mm (p<0.01, -27+/-22%), and hepatic venous pressure gradient from 19.4+/-4.5 to 16.8+/-5 mmHg (p<0.01, -14+/-12%) at 60 min. The change in variceal pressure after 60 min of terlipressin administration was greater than the change in wedge hepatic venous pressure (-4.7 mmHg vs -0.5 mmHg, respectively, p<0.0001). Terlipressin also caused significant decreases in heart rate and cardiac index and increases in mean arterial pressure and peripheral vascular resistance. CONCLUSIONS: Our results demonstrate that terlipressin produces significant and prolonged decreases in variceal pressure and variceal wall tension and has intrinsic effects on portal pressure and systemic hemodynamics. Variceal pressure provides a better assessment of the effects of terlipressin administration on esophageal varices than hepatic venous pressure gradient.     

Hemodynamic effects of the administration of terlipressin alone or combined with nitroglycerin in patients with cirrhosis]

Terlipressin (Glypressin), a synthetic analog of vasopressin, induces arteriolar vasoconstriction which causes both a portal hypotensive effect and certain side-effects on the systemic circulation (elevated arterial pressure and reduced cardiac output). The combination of nitroglycerin with terlipressin might accentuate the portal hypotensive effect and prevent the side-effects on the systemic circulation. The aim of this study was to examine the systemic and splanchnic hemodynamic responses to terlipressin administered alone or combined with nitroglycerin in patients with cirrhosis. Systemic and splanchnic hemodynamics were measured before and 1 h after a bolus of terlipressin (1 to 2 mg IV) given alone (n = 10) or in association with nitroglycerin infusion (25 micrograms/min, n = 9). Terlipressin alone significantly increased the arterial pressure by 21%, systemic vascular resistance by 60%, and significantly decreased cardiac output by 23%. The right atrial and pulmonary pressures significantly increased and the wedged hepatic venous pressure and hepatic venous pressure gradient significantly decreased by 8% and 16%, respectively. The combined therapy decreased the cardiac output by 20%, but did not significantly modify the other systemic and splanchnic hemodynamic values. No significant differences were found between terlipressin and the combined therapy concerning changes in wedged hepatic venous pressure or hepatic venous pressure gradient. We conclude that in patients with cirrhosis, nitroglycerin prevents the deleterious vasoconstrictor and vasopressor effects of terlipressin. However, the combined therapy, as terlipressin alone, decreases the cardiac output.(ABSTRACT TRUNCATED AT 250 WORDS)     

Splanchnic haemodynamics after intravenous terlipressin in anaesthetised healthy pigs

BACKGROUND/AIMS: Terlipressin is used for the treatment of bleeding oesophageal varices. We evaluated the effects of terlipressin on hepatic haemodynamics, with special focus on the interactions between portal venous flow and hepatic arterial flow over time. Secondly, we evaluated the estimated hepatic blood flow by the ICG clearance method against direct measurements of hepatic blood flow. METHODS: Eight healthy anaesthetised pigs received terlipressin 1 mg or placebo intravenously in a randomised, blind, cross-over design. Hepatic arterial flow, portal venous flow, systemic haemodynamics, and portal vein diameter were recorded simultaneously. Portal venous flow and hepatic arterial flow were measured by transit time ultrasound flowmetry. Estimated hepatic blood flows at baseline and after terlipressin were compared with the sum of the portal venous flow and hepatic arterial flow. RESULTS: Portal venous flow decreased significantly 5 min after administration of terlipressin (p<0.05). At 30 min it had decreased by 34% (p<0.01) and the hepatic arterial flow had increased by 81% (p<0.01). The estimated hepatic blood flow and the hepatic blood flow decreased by 23% (p<0.015). At baseline the estimated hepatic blood flow and the hepatic blood flow correlated significantly (r=0.85, p<0.01), but this correlation disappeared after administration of terlipressin (r=0.06, p=ns). The hepatic blood flow was 12% higher than the estimated hepatic blood flow before and after terlipressin. CONCLUSIONS: Terlipressin decreased the portal venous flow, hepatic blood flow, and estimated hepatic blood flow significantly and was accompanied by a substantial increase in hepatic arterial flow. The estimated hepatic blood flow and hepatic blood flow were strongly correlated at baseline, but after terlipressin the correlation disappeared.     

Effects of terlipressin on systemic, hepatic and renal hemodynamics in patients with cirrhosis

Background and Aim: Terlipressin has been shown to be effective in the management of hepatorenal syndrome. However, how terlipressin exerts its effect on the renal artery is unknown. The aim of the present study was to assess the effects of terlipressin on systemic, hepatic and renal hemodynamics in cirrhosis. Methods: Twenty‐eight patients with cirrhosis and portal hypertension were studied. Systemic and hepatic hemodynamics, hepatic and renal arterial resistive indices and neurohumoral factors were measured prior to and 30 min after intravenous administration of 1 mg terlipressin (n = 19) or placebo (n = 9). Results: After terlipressin, there were significant increases in both mean arterial pressure (P < 0.001) and systemic vascular resistance (P < 0.001), whereas heart rate (P < 0.001) and cardiac output (P < 0.001) decreased significantly. There was a significant decrease in the hepatic venous pressure gradient (P < 0.001). Portal venous blood flow also decreased significantly (P < 0.001). The mean hepatic arterial velocity increased significantly (P < 0.001). Although there was a significant decrease in the hepatic arterial resistive index (0.72 ± 0.08 to 0.69 ± 0.08, P < 0.001) and renal arterial resistive index (0.74 ± 0.07 to 0.68 ± 0.07, P < 0.001), portal vascular resistance was unchanged (P = 0.231). Plasma renin activity decreased significantly (P < 0.005), and there was a significant correlation between this decline and the decrease in renal arterial resistive index (r = 0.764, P < 0.005). The effects of terlipressin on systemic, hepatic and renal hemodynamics were observed similarly in patients with and without ascites. Placebo caused no significant effects. Conclusion: Terlipressin decreases hepatic and renal arterial resistance in patients with cirrhosis.     

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.     

Acute hemodynamic effects of octreotide and terlipressin in patients with cirrhosis: a randomized comparison

BACKGROUND: Octreotide and terlipressin are widely used in acute variceal hemorrhage to reduce the bleeding rate. They purportedly act by mesenteric arterial vasoconstriction, thus reducing portal venous flow (PVF) and portal pressure. Little is known about the immediate-early hemodynamic effects of these drugs. AIM: To compare the acute hemodynamic effects of octreotide and terlipressin in patients with cirrhosis. PATIENTS: Forty-two cirrhotic patients with a history of variceal bleeding were randomized to receive either octreotide 100 microg intravenous bolus followed by a continuous infusion at 250 microg/h (n = 21), or terlipressin 2 mg intravenous bolus (n = 21). METHODS: Mean arterial pressure (MAP), heart rate (HR), hepatic venous pressure gradient (HVPG), and PVF, assessed by duplex Doppler ultrasonography, were measured before and at 1, 5, 10, 15, 20, and 25 min after the start of drug administration. RESULTS: Octreotide markedly decreased HVPG (-44.5 +/- 17.8%) and PVF (-30.6 +/- 13.6%) compared to the baseline at 1 min (p < 0.05). Thereafter, both variables rapidly returned toward the baseline, and by 5 min, no significant differences in HVPG (-7.1 +/- 28.9%) and PVF (10.2 +/- 26.2%) were noted. A similar transient effect on MAP and HR was observed. Terlipressin significantly decreased HVPG (-18.3 +/- 11.9%) and PVF (-32.6 +/- 10.5%) at 1 min (p < 0.05) and sustained these effects at all time points. The effects on arterial pressure and HR were also sustained. CONCLUSIONS: Octreotide only transiently reduced portal pressure and flow, whereas the effects of terlipressin were sustained. These results suggest that terlipressin may have more sustained hemodynamic effects in patients with bleeding varices.     

Propranolol compared with propranolol plus isosorbide-5-mononitrate for portal hypertension in cirrhosis. A randomized controlled study

OBJECTIVE: To investigate whether isosorbide-5-mononitrate (Is-5-Mn) given with propranolol reduces hepatic portal pressure more than does propranolol alone in patients with cirrhosis. DESIGN: A randomized controlled trial. PATIENTS: Fifty patients with cirrhosis and esophageal varices entered and 42 completed the study. INTERVENTION: Twenty-one patients received oral propranolol at increasing doses until their resting heart rate was reduced by 25%, and 21 patients received oral propranolol (on the same schedule) plus oral Is-5-Mn, 40 mg twice a day. MEASUREMENTS: Hepatic vein pressure gradient, liver function, and splanchnic and systemic hemodynamics before and after 3 months of continuous therapy. MAIN RESULTS: At 3 months, the hepatic venous pressure gradient decreased more (P less than 0.01) in patients given propranolol plus Is-5-Mn (19%, from 18.4 +/- 3.9 to 14.9 +/- 3.8 mm Hg; 95% CI, -2.4 to -4.5 mm Hg) than in those given propranolol alone (10%, from 18.2 +/- 3.5 to 16.3 +/- 3.1 mm Hg; CI, -1.1 to -2.7 mm Hg). The hepatic venous pressure gradient decreased by more than 20% of the baseline value in 10% of patients receiving propranolol, but in 50% of patients receiving combined therapy (P less than 0.02). There were statistically significant decreases in hepatic blood flow and the intrinsic clearance of indocyanine green after propranolol therapy, but not after combined therapy. The treatments caused similar reductions in azygos blood flow and cardiac output. CONCLUSIONS: The long-term combined administration of propranolol plus Is-5-Mn reduces portal pressure more than propranolol alone without adverse effects on hepatic perfusion and liver function. Whether this greater hemodynamic effect translates into better clinical efficacy should be determined in randomized controlled trials.     

Effects of molsidomine, a long acting venous dilator, on portal hypertension. A hemodynamic study in patients with cirrhosis.

The present study investigated the effects of molsidomine, a predominant venous dilator which, contrary to organic nitrates, does not produce pharmacological tolerance on splanchnic and systemic hemodynamics in patients with cirrhosis. Twenty-seven cirrhotic portal hypertensive patients were studied prior to and up to 2 h after the oral administration of 2 mg of molsidomine (n = 11), 4 mg of molsidomine (n = 8) or placebo (n = 8). Molsidomine caused a significant reduction in the hepatic venous pressure gradient. The mean decrease at 60 min was -6.8 +/- 9% after 2 mg (p less than 0.05) and -15.4 +/- 12% after 4 mg (p less than 0.01). The decrease in the hepatic venous pressure gradient was maintained at 120 min: -11% after 2 mg (p less than 0.05) and -19% with 4 mg (p less than 0.01). This was associated with mild changes in azygos blood flow and with a significant decrease in hepatic blood flow (-17%, p less than 0.05). There was a moderate reduction in mean arterial pressure (-12.6% after 2 mg and -13.2% after 4 mg, p less than 0.01), which was due to a reduction in cardiac output, without any significant fall in systemic vascular resistance. Placebo administration did not change systemic or hepatic hemodynamics. This study shows that molsidomine causes a significant and sustained reduction in portal pressure in patients with cirrhosis, suggesting the potential role of this agent in the treatment of portal hypertension.     

Nitroglycerin improves the hemodynamic response to vasopressin in portal hypertension

This study was designed to investigate whether the addition of nitroglycerin to vasopressin infusion could avoid the deleterious systemic effects of vasopressin while maintaining or enhancing the therapeutic benefits of portal pressure reduction. The effect of nitroglycerin on splanchnic and systemic hemodynamics was studied in cirrhotic patients and portal hypertensive dogs receiving i.v. vasopressin. During i.v vasopressin infusion (0.4 units per min), the cardiac output decreased in patients by 14% from 7.6 +/- 0.9 (mean +/- S.E.) to 6.5 +/- 0.7 liters per min, p less than 0.01, the mean arterial pressure increased 21% from 87 +/- 2 to 105 +/- 4, p less than 0.01, and the heart rate decreased 11% from 79 +/- 3 to 71 +/- 3, p less than 0.01. The administration of sublingual nitroglycerin (0.4 mg) returned all the systemic hemodynamic parameters to baseline values. In dogs, vasopressin infusion significantly reduced portal pressure and flow while increasing portal venous resistance. Nitroglycerin when added to the vasopressin infusion reduced portal venous resistance and further decreased portal pressure in dogs. In patients, vasopressin reduced the hepatic blood flow (44%), wedged hepatic venous pressure (11%), and the gradient between wedged and free hepatic venous pressures (23%). Nitroglycerin administration caused a further reduction of the wedged hepatic venous pressure (23.6 +/- 2.3 to 21.1 +/- 2.0, 11%, p less than 0.01). There was a small but not significant further decline (7%) in the hepatic venous pressure gradient. These results provide evidence that the addition of nitroglycerin to an i.v. infusion of vasopressin reversed the detrimental effects of vasopressin while preserving the beneficial effects.     

Modulation of splanchnic circulation:Role in perioperative management of liver transplant patients

Splanchnic circulation is the primary mechanism thatregulates volumes of circulating blood and systemic blood pressure in patients with cirrhosis accompanied by portal hypertension. Recently, interest has been expressed in modulating splanchnic circulation in patients with liver cirrhosis, because this capability might produce beneficial effects in cirrhotic patients undergoing a liver transplant. Pharmacologic modulation of splanchnic circulation by use of vasoconstrictors might minimize venous congestion, replenish central blood flow, and thus optimize management of blood volume during a liver transplant operation. Moreover, splanchnic modulation minimizes any high portal blood flow that may occur following liver resection and the subsequent liver transplant. This effect is significant, because high portal flow impairs liver regeneration, and thus adversely affects the postoperative recovery of a transplant patient. An increase in portal blood flow can be minimized by either surgical methods(e.g., splenic artery ligation, splenectomy or portocaval shunting) or administration of splanchnic vasoconstrictor drugs such as Vasopressin or terlipressin. Finally, modulation of splanchnic circulation can help maintain perioperative renal function. Splanchnic vasoconstrictors such as terlipressin may help protect against acute kidney injury in patients undergoing liver transplantation by reducing portal pressure and the severity of a hyperdynamic state. These effects are especially important in patients who receive a too small for size graft. Terlipressin selectively stimulates V1 receptors, and thus causes arteriolar vasoconstriction in the splanchnic region, with a consequent shift of blood from splanchnic to systemic circulation. As a result, terlipressin enhances renal perfusion by increasing both effective blood volume and mean arterial pressure.     

Central and systemic haemodynamic effects of terlipressin in portal hypertensive patients

AIMS/BACKGROUND: Cirrhotic patients exhibit a hyperdynamic and hyporeactive circulation with central hypovolaemia which may influence the course of the disease. As terlipressin, a vasopressin analogue, may modify systemic haemodynamics in these patients, the aim of the present study was to assess the acute effects of terlipressin on central and systemic haemodynamics. METHODS: Sixteen patients with alcoholic cirrhosis and portal hypertension had their systemic, central, and splanchnic haemodynamics determined at baseline and after a blind randomised bolus infusion (2 mg) of terlipressin/placebo. RESULTS: After terlipressin, the arterial blood pressure and the systemic vascular resistance increased by 26% and 61%, respectively (both p<0.001), and the cardiac output, heart rate, and arterial compliance decreased by 18%, 11%, and 32%, respectively (all p<0.001). The central circulation time increased by 36% (p<0.001), whereas the central and arterial blood volume only increased by 4% (p= 0.07). As expected, both portal pressure and hepatic blood flow decreased (17% and 29%, both p<0.001). The decrease in portal pressure after terlipressin was significantly related to the increase in systemic vascular resistance (r=-0.52, p<0.05) and the central circulation time (r=-0.80, p<0.0001). CONCLUSIONS: Terlipressin significantly attenuates the hyperdynamic circulation in portal hypertensive patients without a further contraction of the central and arterial blood volume. The systemic haemodynamic response to terlipressin is moreover associated with the decrease in portal pressure. Terlipressin may therefore have potentially beneficial effects on the hyperdynamic circulation in cirrhosis in addition to its effects on portal pressure.     

Reduction of Portal Pressure by Chronic Administration of Isosorbide Dinitrate in Patients with Cirrhosis: Effects on Systemic and Splanchnic Hemodynamics and Liver Function

We investigated the chronic effects of isosorbide dinitrate on systemic and splanchnic hemodynamics and liver function in 13 patients with liver cirrhosis and portal hypertension. Placebo administration for 4 wk (n = 4) had no significant effects on these parameters. In contrast, oral administration of 40 mg/day of isosorbide dinitrate for 4 wk (n = 9) caused a significant fall in portal pressure (-18%, p less than 0.02), as evaluated by measurements of the hepatic venous pressure gradient with no modification in hepatic blood flow (from 0.72 +/- 0.29 to 0.71 +/- 0.34 L/min, NS), suggesting decreased intrahepatic or collateral vascular resistance. On the other hand, there was no significant correlation between the changes in mean arterial pressure and hepatic venous pressure gradient (r = 0.42). Thus, it seems unlikely that a reduction in portal blood inflow by baroreceptor-mediated reflex splanchnic vasoconstriction contributed to the fall in portal pressure. In addition, this drug had no adverse effects on liver function, as evaluated by measurements of the intrinsic clearance. These results suggest that chronic administration of isosorbide dinitrate could be a potentially useful and associated with cirrhosis.     

Effects of glypressin on the splanchnic and systemic circulation in patients with cirrhosis

Although not demonstrated in patients with cirrhosis, it is generally claimed that administration of vasopressin in the form of triglycyl-lysine-vasopressin (glypressin) may prevent untoward systemic effects of this former hormone. The aim of this study was to assess the effects of intravenous administration of 2 mg of glypressin on splanchnic and systemic hemodynamics in 9 patients with cirrhosis under stable circulatory conditions. One hour after the injection, the following statistically significant changes were observed as compared to the baseline values (m +/- SEM): wedged hepatic venous pressure, -9 +/- 2 p. 100; hepatic venous pressure gradient, -16 +/- 3 p. 100; azygos blood flow, -24 +/- 6 p. 100; heart rate, -16 +/- 3 p. 100; cardiac index, -23 +/- 2 p. 100; systemic vascular resistances, +47 +/- 11 p. 100; wedged pulmonary arterial pressure, +44 +/- 15 p. 100. In conclusion, in patients with cirrhosis in a stable hemodynamic condition, intravenous administration of glypressin decreased portal venous pressure and blood flow into the superior portal systemic collateral circulation but did not prevent the untoward systemic hemodynamic effects of vasopressin.     

Systemic, splanchnic and renal hemodynamic effects of a dopaminergic dose of dopamine in patients with cirrhosis

The effects of dopamine on kidney function have not been elucidated in patients with cirrhosis. Moreover, although increased portal pressure has been observed with supradopaminergic doses of dopamine in these patients, the splanchnic hemodynamic effects of low doses of dopamine have not been previously studied. Thus we studied the acute systemic, splanchnic and renal hemodynamic effects of a dopaminergic dose of dopamine (1.5 micrograms/kg body wt min) in nine cirrhotic patients. Plasma dopamine levels increased markedly from 35 +/- 20 pg/ml to 31,400 +/- 4,900 pg/ml during dopamine administration. A significant diastolic pressure decrease of 10% was associated with a 15% increase in heart rate. Cardiac output was not altered. Although dopamine significantly increased azygos blood flow by 16%, wedged and free hepatic venous pressures were not altered. Dopamine significantly increased renal blood flow by 31%, but did not change the glomerular filtration rate. We conclude that a dopaminergic dose of dopamine increases azygos blood flow but not the hepatic venous pressure gradient. Finally, although it increases renal blood flow, dopamine does not seem to have any beneficial effects on glomerular filtration rate in cirrhotic patients.     

Portal hemodynamics during nitroglycerin administration in cirrhotic patients

Nitroglycerin is a potent venous dilator and a mild arterial vasodilator that has been shown to improve the hemodynamic response to vasopressin in portal hypertensive patients and to decrease portal pressure in experimental animals. In order to determine the effect of nitroglycerin on portal venous hemodynamics, we studied 11 patients with alcoholic cirrhosis before and during the administration of sublingual nitroglycerin (0.4 and 0.6 mg). The hepatic venous pressure gradient (which was obtained by subtracting the free hepatic venous pressure from the wedged hepatic venous pressure) decreased from 17.9 +/- 6.5 mm Hg (mean +/- S.D.) to 15.1 +/- 5.1 mm Hg (p less than 0.02) at the peak of the effect, which occurred from 2 to 12 min after nitroglycerin administration. The mean arterial pressure was reduced from 96 +/- 10 mm Hg to a peak decrease of 76 +/- 18 mmHg (p less than 0.001). The peak change in the hepatic venous pressure gradient induced by nitroglycerin correlated directly with the peak change in mean arterial pressure (r = 0.79, p less than 0.01). There was a moderate increase in heart rate in response to the decrease in blood pressure (73 +/- 15 to 83 +/- 15 beats per min, p less than 0.001). Two of the 11 patients did not reduce their hepatic venous pressure gradient after 0.6 mg nitroglycerin. Reductions in portal pressure were observed with both increases and moderate decreases in azygos blood flow, suggesting that, as observed in experimental animals, the portal-pressure-reducing effect of nitroglycerin could be due to two different and independent mechanisms, a reduction in portal blood flow or portal-collateral vasodilatation.     

Hemodynamic changes of systemic,hepatic, and splenic circulation following triglycyl-lysin-vasopressin administration in alcoholic cirrhosis

Triglycyl-lysin-vasopressin is a long-acting vasopressin derivative which is under consideration for the treatment of acute variceal bleeding in cirrhosis. However, its splanchnic hemodynamic effects have not been investigated thoroughly. In 11 patients with alcoholic cirrhosis, systemic and splanchnic hemodynamics were evaluated before and 20–40 min after intravenous administration of 2 mg triglycyl-lysin-vasopressin. Following the drug administration, heart rate decreased by 10% and cardiac index by 22% on the average, respectively; mean arterial pressure increased by 14% and systemic vascular resistence index by 48%. Hepatic venous pressure gradient showed a marked and persistent fall, averaging 31%. Hepatic and splenic blood flow decreased by 31% and 56%, respectively. A significant correlation was found between the decrease in hepatic venous pressure gradient and in splenic blood flow. By contrast, the decrease in the hepatic venous pressure gradient was not significantly correlated to the decrease in hepatic blood flow or in cardiac index. We conclude that in patients with alcoholic cirrhosis, triglycyl-lysin-vasopressin decreases portal pressure as well as hepatic and splenic blood flows. The decrease in portal pressure was due to the decrease in splanchnic blood inflow and not to the decrease in cardiac index.This work was supported in part by a grant from the Italian Ministry of Education (National Project Liver Cirrhosis).     

Hemodynamic evaluation of molsidomine: a vasodilator with antianginal properties in patients with alcoholic cirrhosis

Organic nitrates were reported to reduce portohepatic venous pressure gradient in patients with cirrhosis. However, these drugs lower arterial pressure and are well known to induce tolerance. The aim of the present study was to assess the hemodynamic effects of molsidomine, an antianginal agent, which does not induce tolerance and has little effect on arterial pressure in patients with normal liver, in 13 patients with alcoholic cirrhosis. Wedged hepatic vein pressure (-11%, p less than 0.01), portohepatic venous pressure gradient (-15%, p less than 0.005), hepatic blood flow (-17.4%, p less than 0.005), mean arterial pressure (-13.5%, p less than 0.01) and cardiac output (-17%, p less than 0.001) were significantly reduced by molsidomine. Free hepatic vein pressure, intrinsic hepatic clearance indocyanine green, heart rate and systemic vascular resistances were not significantly modified. There was no correlation between the decrease in portohepatic venous pressure gradient and the reduction in mean arterial pressure on one hand and the decrease in cardiac output on the other hand. We therefore conclude that in patients with cirrhosis, molsidomine has effects similar to nitrates on systemic and splanchnic hemodynamics.     

Hemodynamic and metabolic effects of terlipressin in patients with cirrhosis receiving a nonselectiveβ-blocker

Terlipressin (Glypressin), a vasopressin analog, may be administered to patients with cirrhosis receiving a-adrenergic antagonist. Since terlipressin alone and-blockers alone both decrease portal pressure, a combination of these substances may have additional portal hypotensive effects. However, the negative side effects of terlipressin may be accentuated by long-term-blockade. Thus, the present study examined hemodynamic and metabolic responses to terlipressin in 12 patients receiving nonselective-blockers (propranolol or nadolol). Hemodynamics and oxygen (O₂) -derived variables were measured prior to and 30 min after the administration (intravenous bolus) of terlipressin (1 to 2 mg, according to body weight). The hepatic venous pressure gradient and azygos blood flow significantly decreased (from 15.3±1.1 to 12.5±1.1 mm Hg, and from 0.6±0.1 to 0.5±0.1 liters/min, respectively). Arterial and pulmonary wedged pressures significantly increased. Heart rate, cardiac index, and O₂ consumption were not significantly affected by terlipressin. In conclusion, in patients with cirrhosis being treated with a nonselective-blocker, terlipressin administration decreased portal pressure. Moreover, terlipressin induced only mild systemic hemodynamic effects in these patients. These results suggest that terlipressin can be administered in patients receiving a-adrenergic blocker.This work was supported in part by Ferring S.A.