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PubMed2001

Terlipressin for acute esophageal variceal hemorrhage.

BACKGROUND: Terlipressin (triglycyl lysine vasopressin) is a synthetic analogue of vasopressin, which has been used in the treatment of acute variceal hemorrhage. In contrast to vasopressin, terlipressin can be administered as intermittent injections instead of continuous intravenous infusion and it has a safer adverse reactions profile. However, its effectiveness remains uncertain. OBJECTIVES: To determine if treatment with terlipressin improves outcome in acute esophageal variceal hemorrhage and is safe. SEARCH STRATEGY: Randomized clinical trials were identified by searching the following databases: MEDLINE, EMBASE, the Cochrane Controlled Trials Register, the Cochrane Hepato-Biliary Group Controlled Trials Register, Biosis, and Current Contents. The bibliographies of identified publications were checked. Experts in the field and the manufacturers of terlipressin were contacted. SELECTION CRITERIA: All randomized clinical trials which compared terlipressin with: (a) placebo or no treatment, (b) balloon tamponade, (c) endoscopic treatment, (d) octreotide, (e) somatostatin and (f) vasopressin, in the setting of acute variceal hemorrhage. DATA COLLECTION AND ANALYSIS: Eligibility, trial quality assessment and data extraction were done independently by two reviewers. The primary outcome measure was mortality. Secondary outcomes were failure of initial hemostasis, rebleeding, procedures required for uncontrolled bleeding or rebleeding, transfusion requirements and length of hospitalization. MAIN RESULTS: Twenty studies were identified for all the comparison groups, involving 1609 patients. There were seven studies (with 443 patients) comparing terlipressin to placebo, five of which were considered to be high quality studies based on the Jadad scale. The meta-analysis indicates that terlipressin was associated with a statistically significant reduction in all cause mortality compared to placebo (relative risk 0.66, 95% confidence interval 0.49 to 0.88). Three studies (with 302 patients) were identified comparing terlipressin to somatostatin, two of which were high quality studies; only one high quality study (219 patients) comparing terlipressin to endoscopic treatment was identified. Within the limited power provided by these small numbers of patients, no statistically significant difference was demonstrated between terlipressin and either somatostatin or endoscopic treatment in any of the outcomes. For the remaining comparison groups (terlipressin versus balloon tamponade, terlipressin versus octreotide and terlipressin versus vasopressin) only small, low quality studies were identified and no difference was demonstrated in any of the major outcomes. There was no difference between the terlipressin group and any of the comparison groups in the number of adverse events that caused death or withdrawal of medication. REVIEWER'S CONCLUSIONS: On the basis of a 34% relative risk reduction in mortality, terlipressin should be considered to be effective in the treatment of acute variceal hemorrhage. Further, since no other vasoactive agent has been shown to reduce mortality in single studies or meta-analyses, terlipressin might be the vasoactive agent of choice in acute variceal bleeding.

Acute Disease↗
PubMed2005

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.

Antihypertensive Agents↗
PubMed1993

Randomized controlled trial of desmopressin plus terlipressin vs. terlipressin alone for the treatment of acute variceal hemorrhage in cirrhotic patients: a multicenter, double-blind study. New Italian Endoscopic Club.

1-Deamino-8-D-arginine vasopressin (DDAVP, desmopressin), a synthetic analog of the antidiuretic hormone L-arginine vasopressin, improves hemostasis parameters in cirrhotic patients. Hence its use in combination with a vasoactive drug such as terlipressin might improve the performance of this drug in controlling variceal bleeding. The aim of this trial was to compare the efficacy of desmopressin plus terlipressin with that of terlipressin alone in controlling acute variceal hemorrhage. Cirrhotic patients with active variceal hemorrhage diagnosed endoscopically were randomized within 2 hr of admission to receive desmopressin plus terlipressin or placebo plus terlipressin. Terlipressin (2 mg, intravenous bolus) was given at time 0 and every 4 hr thereafter for 24 hr. Desmopressin (0.3 microgram/kg, intravenously) or placebo was given in saline solution over 30 min at time 0 and at 26 hr. Patients were monitored for 24 hr after cessation of treatment. Treatment failure was defined as recurrence of active bleeding during treatment or within the 24 hr after treatment. After enrolling 51 of the planned 84 patients, we carried out an interim analysis. Treatment failure occurred in 13 of 24 patients randomized to receive desmopressin plus terlipressin (54.2%) and in 6 of 22 patients randomized to receive terlipressin (27.3%) (p = 0.06, Fisher's exact test). The trial was interrupted at this stage because patients treated with the "new" therapy fared worse than those treated with the standard therapy, and the possibility of reversing this trend by completing the trial was deemed remote. The addition of desmopressin does not improve and may worsen the efficacy of terlipressin in controlling acute variceal bleeding in cirrhotic patients.

Acute Disease↗
PubMed1999

Portal hypotensive effects of combined terlipressin and DL-028, a synthetic alpha 1 adrenoceptor antagonist administration on anesthetized portal hypertensive rats.

AIMS/BACKGROUND: The purpose of this study was to investigate the therapeutic effects of terlipressin, alone or in combination with DL-028, a synthetic alpha 1-adrenoceptor antagonist on anesthetized portal hypertensive rats. METHODS: Portal hypertension was induced by either partial portal vein ligation (PVL) or bile duct ligation (BDL) in Sprague-Dawley rats. Each portal hypertensive rat received only one of the two regimens: vehicle plus terlipressin or DL-028 plus terlipressin. Terlipressin dosage was 0.017 mg/kg/min infused for 3 min, while vehicle or DL-028 (0.50 microgram/kg/min) was continuously infused for 40 min, starting 10 min before terlipressin infusion. RESULTS: In PVL rats, infusions of vehicle plus terlipressin induced significant, maximum reduction of portal venous pressure (PVP, -11.0 +/- 1.8%) and prominent elevation of mean arterial pressure (MAP, 50.3 +/- 9.0%) from baseline. Infusions of DL-028 plus terlipressin induced maximum PVP reduction (-17.5 +/- 2.8%) and MAP elevation (39.8 +/- 7.4%). In BDL rats, infusion of vehicle plus terlipressin also induced significant, maximum reduction of PVP (-6.8 +/- 2.1%) and prominent elevation of MAP (61.4 +/- 7.8%) from baseline. Infusions of DL-028 plus terlipressin induced maximum PVP reduction (-17.9 +/- 2.2%) and MAP elevation (47.9 +/- 7.4%). Compared to vehicle plus terlipressin, DL-028 significantly enhanced portal hypotensive effects of and attenuated systemic pressor effects of terlipressin in both PVL and BDL rats. CONCLUSIONS: Our results suggest that terlipressin, alone or in combination with DL-028, induced portal hypotensive effects in portal hypertensive rats. The combination of terlipressin with DL-028 was beneficial in enhancing the portal hypotensive effects and ameliorating the systemic pressor effects of terlipressin.

Adrenergic alpha-Antagonists↗
PubMed1997

Haemodynamic responses to a combination of terlipressin and octreotide in portal hypertensive rats.

BACKGROUND: An enhancement of the haemodynamic effects of terlipressin by octreotide (and vice versa) may be useful in the treatment of portal hypertension. The aim of this study was to investigate the short-term effects of terlipressin, octreotide or a combination of these substances on splanchnic and systemic haemodynamics in rats with portal vein stenosis. METHODS: Eight rats received an intravenous (i.v.) infusion of isotonic saline (10 microL/min for 15 min). Eight rats received terlipressin first (0.05 mg/kg) and then an i.v. infusion of octreotide (8 micrograms.h/kg for 15 min) 15 min later. Eight other rats first received an i.v. infusion of octreotide and then terlipressin 15 min later. Splanchnic and systemic haemodynamics (radioactive microsphere method) were measured after saline, after terlipressin or octreotide alone, and after the combined treatments. RESULTS: Terlipressin and octreotide alone significantly decreased portal pressure, portal tributary blood flow and cardiac index. Terlipressin, but not octreotide, significantly increased heptocollateral vascular resistance and arterial pressure. Octreotide administration in rats pre-treated with terlipressin did not change portal pressure, caused portal tributary blood flow to increase and decreased hepatocollateral vascular resistance; it also decreased arterial pressure but not cardiac index. Terlipressin administration in rats pre-treated with octreotide further decreased portal pressure, portal tributary blood flow and increased hepatocollateral vascular resistance; terlipressin increased arterial pressure and further decreased cardiac index. CONCLUSIONS: In rats with portal vein stenosis, octreotide decreased short-term splanchnic and systemic vasoconstriction due to terlipressin. In contrast, terlipressin enhanced the splanchnic and systemic vasoconstriction due to octreotide. Thus, the haemodynamic responses to the combination of octreotide and terlipressin depend on the order of administration of these substances.

Animals↗
PubMed2001

Hemodynamic effects of a combination of prazosin and terlipressin in patients with viral cirrhosis.

OBJECTIVES: Terlipressin reduces portal pressure in cirrhotic patients mainly through intense splanchnic vasoconstriction that decrease portal venous inflow. Hepatic blood flow may also be reduced by terlipressin. Prazosin (an alpha1-adrenoceptor antagonist) has also been proposed to decrease portal pressure in cirrhotic patients possibly through a decrease in the intrahepatic vascular resistance. The current study was aimed to evaluate whether a combination of prazosin and terlipressin exerts more beneficial effects than terlipressin alone. METHODS: Patients were randomly assigned to receive either a placebo (n = 12) or an oral administration of prazosin 2 mg (n = 12). Thereafter, each patient received an intravenous injection of terlipressin 2 mg. Hemodynamic values were measured basally, 30 min after prazosin or placebo, and 30 min after terlipressin. RESULTS: Placebo administration did not affect any hemodynamic values. Terlipressin administration, on the other hand, resulted in expected changes on the hepatic venous pressure gradient, hepatic blood flow, and systemic hemodynamics. In contrast, prazosin significantly decreased hepatic venous pressure gradient with an increased hepatic blood flow and intrinsic hepatic clearance. After terlipressin administration, a further decrease in hepatic venous pressure gradient was observed with preservation of hepatic blood flow and intrinsic hepatic clearance. The magnitude of decrease in hepatic venous pressure gradient was more profound in patients receiving prazosin plus terlipressin than in those receiving terlipressin alone. However, the magnitude of changes in systemic hemodynamics was no different between the two groups of patients. CONCLUSIONS: The current study showed that a combination of prazosin and terlipressin resulted in a more profound reduction of hepatic venous pressure gradient with a preservation of hepatic blood flow and intrinsic hepatic clearance than did terlipressin alone. However, the combined therapy did not modify the systemic hemodynamic effects exerted by terlipressin.

Antihypertensive Agents↗
PubMedDate not supplied

Hemodynamic effects of acute tetrandrine and terlipressin administration on portal hypertensive rats.

The purpose of this study was to investigate the therapeutic effects of tetrandrine and terlipressin, alone or in combination, on anesthetized portal hypertensive rats. Portal hypertension was induced by partial portal vein ligation in Sprague-Dawley rats. Each portal hypertensive rat received one of three regimens: vehicle plus terlipressin, tetrandrine (.50 mg.kg-1.min-1) [corrected] plus terlipressin, or tetrandrine (.75 mg.kg-1.min-1) [corrected] plus terlipressin. Terlipressin dosage was 0.025 mg.kg-1.min-1 [corrected] infused for 3 min. Infusion of vehicle followed by terlipressin induced significant reduction of portal venous pressure (PVP, -24.3 +/- 1.5%) and prominent elevation of mean arterial pressure (MAP, 73.3 +/- 4.6%) as well as total peripheral resistance (TPR, 133 +/- 8%) from baseline, and there was a cardiodepressant response (cardiac index, CI, -30.6 +/- 3.8%; heart rate, HR, -10.4 +/- 2.1%). Infusion of tetrandrine (.50 mg.kg-1.min-1) [corrected] induced significant reduction of PVP (-7.2 +/- 0.9%), MAP (-12.5 +/- 1.6%), and TPR (-14.3 +/- 4.2%) from baseline. Infusions of tetrandrine followed by terlipressin induced significant reduction of PVP (-14.2 +/- 2.4%) but an increase in MAP (22.6 +/- 2.7%) and TPR (71.1 +/- 10.5%). Infusion of tetrandrine (.75 mg.kg-1.min-1) [corrected] induced significant reduction of PVP (-9.9 +/- 0.8%). MAP (-19.2 +/- 2.1%), and TPR (-24.1 +/- 2.1%) from baseline. Infusions of tetrandrine followed by terlipressin induced significant reduction of PVP (-14.0 +/- 1.1%) but an increase in MAP (14.0 +/- 2.7%) and TPR (75.2 +/- 5.2%). Compared with vehicle followed by terlipressin, tetrandrine significantly attenuated systemic pressor (MAP and TPR elevation), cardiodepressant (CI reduction) as well as portal hypotensive (PVP reduction) effects of terlipressin. Our results suggest that tetrandrine and terlipressin, alone or in combination, induced portal hypotensive effects in portal hypertensive rats. Combined tetrandrine and terlipressin administration ameliorated systemic pressor and cardiodepressant effects of terlipressin, but it also attenuated the latter's portal hypotensive effects.

Alkaloids↗
PubMed2006

Meta-analysis: terlipressin therapy for the hepatorenal syndrome.

BACKGROUND: The hepatorenal syndrome is a severe and well-known complication of end-stage liver disease, but its management is controversial. Recent reports have shown the efficacy of terlipressin therapy, a vasopressin analogue, in hepatorenal syndrome patients. AIM: To evaluate the efficacy and safety of terlipressin in the treatment of hepatorenal syndrome. METHODS: We performed a systematic review of the literature with a meta-analysis of clinical trials. The primary outcome (as a measure of efficacy) was the rate of responder patients (i.e. patients who had hepatorenal syndrome reversal after terlipressin therapy). The secondary outcomes were the rate of responders who had hepatorenal syndrome recurrence after terlipressin withdrawal, and the drop-out rate (as a measure of tolerability). We used the random effects model of DerSimonian and Laird with heterogeneity and sensitivity analysis. RESULTS: We identified 10 clinical trials (154 unique patients); two (20.0%) were randomized, controlled trials. The pooled rate of patients who reversed hepatorenal syndrome after terlipressin therapy was 0.52 (95% CI, 0.42; 0.61), P = 0.0001; I2 = 24.6%. The pooled frequency of responder patients who showed hepatorenal syndrome recurrence after terlipressin withdrawal was 0.55 (95% CI, 0.40; 0.69), P = 0.00001; I2 = 44.3%. The pooled rate of patients who showed side-effects to terlipressin therapy was 0.29 (95% CI, 0.17; 0.42), P < 0.0001, I2 = 66.6%. The drop-out rate was 0%. The pooled OR for mortality rate in hepatorenal syndrome patients who were not responders to terlipressin vs. responder patients was 5.746 (95% CI, 1.5; 21.9). We did not find any predictive factor of response to terlipressin therapy. CONCLUSIONS: This meta-analysis shows efficacy and safety of terlipressin in the treatment of hepatorenal syndrome. However, a significant number of responder patients relapsed after terlipressin withdrawal. Further studies are in progress to address the link between terlipressin and survival in hepatorenal syndrome patients.

Clinical Trials as Topic↗
PubMed1993

Effects of terlipressin on hemodynamics and oxygen content in conscious portal vein stenosed and cirrhotic rats receiving propranolol.

Terlipressin is used in patients with variceal bleeding but its effects in patients receiving beta-adrenergic antagonists are unknown. In this study, the hemodynamic effects of terlipressin were evaluated in conscious portal hypertensive rats which had previously received a single dose of propranolol. Moreover, oxygen content and acid-base status were studied. In portal vein stenosed and cirrhotic rats, the addition of terlipressin (0.05 mg/kg) to propranolol (0.4 mg/kg) produced a decrease in portal pressure of 34% and 17%, respectively, and in portal tributary blood flow of 46% and 42%, respectively. In cirrhotic rats, however, the decrease in portal pressure was not significantly different when propranolol was combined with terlipressin than when propranolol was administered alone. Cardiac index also further decreased after terlipressin administration. In both groups of rats, these values were similar to those observed after terlipressin alone. In portal vein stenosed rats but not in cirrhotic rats, arterial pH was significantly lower following the combination of propranolol plus terlipressin than following saline, propranolol or terlipressin alone. In conclusion, terlipressin further reduces both portal pressure and cardiac index in rats with portal hypertension receiving beta-blockers. In portal vein stenosed rats but not in cirrhotic rats, the addition of terlipressin to propranolol induces acidemia. This study suggests that terlipressin might further reduce portal pressure in patients with portal hypertension treated with beta-blockers.

Animals↗
PubMed1998

Hemodynamic effects of terlipressin and octreotide administration alone or in combination in portal hypertensive rats.

BACKGROUND/AIMS: The action sites and kinetic effects of octreotide and terlipressin may be different. Therefore, we studied the hemodynamic effects of acute administration of these drugs alone or in combination in rats with portal hypertension due to portal vein ligation. METHODS: In a first study performed in anesthetized rats, hemodynamics were measured before and after drug administration (placebo, octreotide: 8 microg x kg(-1) x h(-1) for 30 min, terlipressin: 50 microg/kg bolus, terlipressin + octreotide at the same doses). The second study, performed in conscious rats, included the same groups and drug doses; hemodynamics were measured every 10 min for 1 h. The third study tested the effect of preinfusion of octreotide on responsiveness to terlipressin. RESULTS: Terlipressin produced more marked systemic effects than octreotide by decreasing heart rate and cardiac output and increasing mean arterial pressure. Terlipressin produced a greater decrease in portal pressure than octreotide: placebo: -3+/-5%, terlipressin: -42+/-8%, octreotide: -16+/-10%, combination: -44+/-8% (conscious rats at 20 min, p<10(-4)). The decrease in portal pressure was immediate and lasted at least 60 min with both drugs. Octreotide significantly decreased spleno-renal shunt blood flow (% variation): placebo: -6+/-8, terlipressin: -15.5+/-20, octreotide: -22.5+/-20, combination: -27+/-10 (p<10(-2)). Octreotide preinfusion significantly increased the responsiveness of arterial pressure and heart rate to terlipressin. CONCLUSIONS: Terlipressin decreases portal pressure significantly more than octreotide, while only octreotide significantly decreases collateral blood flow. Simultaneous administration of these drugs does not have significant additive effects but has complementary effects. The preadministration of octreotide alters systemic response to terlipressin.

Animals↗
PubMed1997

Natriuretic response to the combination of atrial natriuretic peptide and terlipressin in patients with cirrhosis and refractory ascites.

BACKGROUND/AIMS: Refractory ascites, which occurs in certain patients with cirrhosis, is associated with a blunted natriuretic response to exogenous atrial natriuretic peptide (ANP). Since this blunting seems to be related to ANP-induced arterial hypotension, a vasoconstrictor, such as terlipressin (a vasopressin analogue), may restore natriuresis to exogenous ANP. Moreover, since cirrhosis-elicited vasodilation is thought to play a role in sodium retention, a vasoconstriction caused by terlipressin alone may lead to an increase in sodium excretion. This study aimed to evaluate the natriuretic response to either a combination of ANP with terlipressin or terlipressin alone in patients with cirrhosis and refractory ascites. METHODS: Sixteen consecutive patients with cirrhosis and refractory ascites were randomly assigned to receive either a combination of terlipressin (1-2 mg, i.v. bolus) with ANP (35 ng/kg, i.v. bolus followed by 15 ng x kg(-1) x min(-1) for 60 min) (n=8) or terlipressin alone (1-2 mg, i.v. bolus) (n=8). Sodium excretion and urine output, systemic, splanchnic and renal hemodynamics and renal oxygen consumption were measured before and during treatments. RESULTS: Combined therapy did not change arterial pressure but significantly increased urinary sodium excretion and urine output. These effects were associated with a significant increase in glomerular filtration rate and a decrease in renal oxygen consumption. Terlipressin alone significantly increased arterial pressure but did not change urinary sodium excretion or urine output. Moreover, terlipressin did not change either glomerular filtration rate or renal oxygen consumption. CONCLUSIONS: The combination of exogenous ANP with terlipressin, but not terlipressin alone, increases sodium excretion in patients with cirrhosis and refractory ascites.

Adult↗
PubMed2003

Systematic review: terlipressin in acute oesophageal variceal haemorrhage.

BACKGROUND: Controversy exists surrounding pharmacological therapy in acute variceal bleeding. AIM: To determine the efficacy and safety of terlipressin. METHODS: Randomized trials were identified and duplicate, independent, review identified 20 randomized trials involving 1609 patients that compared terlipressin with placebo, balloon tamponade, endoscopic treatment, octreotide, somatostatin or vasopressin for treatment of acute oesophageal variceal haemorrhage. RESULTS: Meta-analysis showed that compared to placebo, terlipressin reduced mortality (relative risk 0.66, 95% CI 0.49-0.88), failure of haemostasis (relative risk 0.63, 95% CI 0.45-0.89) and the number of emergency procedures per patient required for uncontrolled bleeding or rebleeding (relative risk 0.72, 95% CI 0.55-0.93). When used as an adjuvant to endoscopic sclerotherapy, terlipressin reduced failure of haemostasis (relative risk 0.75, 95% CI 0.58-0.96), and had an effect on reducing mortality that approached statistical significance (relative risk 0.74, 95% CI 0.53-1.04). No significant difference was demonstrated between terlipressin and endoscopic sclerotherapy, balloon tamponade, somatostatin or vasopressin. Haemostasis was achieved more frequently with octreotide compared to terlipressin (relative risk 1.62, 95% CI 1.05-2.50), but this result was based on unblinded studies. Adverse events were similar between terlipressin and the other comparison groups except for vasopressin, which caused more withdrawals due to adverse events. CONCLUSIONS: Terlipressin is a safe and effective treatment for acute oesophageal variceal bleeding, with or without adjuvant endoscopic sclerotherapy. Terlipressin appears to reduce mortality in acute oesophageal variceal bleeding compared to placebo, and is the only pharmacological agent shown to do so. Future studies will be required to detect potential mortality differences between terlipressin and other therapeutic approaches.

Esophageal and Gastric Varices↗
PubMed2002

Clinical course, predictive factors and prognosis in patients with cirrhosis and type 1 hepatorenal syndrome treated with Terlipressin: a retrospective analysis.

BACKGROUND AND AIM: Terlipressin has been proposed to treat renal failure in patients with type 1 hepatorenal syndrome (HRS). However, the predictive factors for improved renal function and survival are unknown in patients with type 1 HRS treated with terlipressin. The aim of the present retrospective study was to investigate the predictive factors and prognosis of patients with type 1 HRS treated with terlipressin. METHODS: The clinical charts of 18 consecutive patients with cirrhosis and type 1 HRS treated with terlipressin were studied. The predictive factors for improved renal function and survival were identified using univariate analyses. RESULTS: Improved renal function, indicated by a significant decrease in serum creatinine (61 +/- 4%), occurred in 11 (60%) patients. The only predictive factor for improved renal function was a Child-Pugh's score < or =13 at the time of diagnosis of HRS (P = 0.02). Fifteen patients (83%) died at 45 days and the median survival was 24 days. Of the three patients who survived, two underwent successful orthotopic liver transplantation. Three predictive factors for survival were identified: absence of a precipitating factor for HRS (P = 0.012); improved renal function during terlipressin therapy (P = 0.05); and a dose of terlipressin > or =3 mg/day (P = 0.04). CONCLUSIONS: In patients with type 1 HRS treated with terlipressin, patients with improved renal function had less severe cirrhosis (Child-Pugh >10 but < or =13) than patients without. The predictive factors for survival were the absence of a precipitating factor for HRS, the terlipressin-induced improvement in renal function and a dose of terlipressin of at least 3 mg/day. These findings suggest that a randomized controlled trial investigating the effect of terlipressin on survival in patients with type 1 HRS should be performed.

Adult↗
PubMed2002

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.

Aged↗
PubMedDate not supplied

A randomized controlled study of low-dose and high-dose terlipressin in the control of acute oesophageal variceal haemorrhage.

A randomized controlled trial was designed to investigate whether a high dose of terlipressin could control acute variceal haemorrhage more effectively than a low dose of terlipressin. Forty cirrhotic patients with bleeding oesophageal varices were included, with low-dose terlipressin in 21 patients and high-dose terlipressin in 19 patients. The two groups of patients were similarly matched for all parameters on admission. High-dose terlipressin (84%) seemed to be more effective in the initial control of bleeding than low-dose terlipressin (67%); however this difference was not significant. Complete control of bleeding during 24 h of drug infusion was achieved in 53% of patients receiving high-dose terlipressin and in 48% of those treated with low-dose terlipressin (P greater than 0.05). There were no major complications in either group. Mortality in relation to variceal bleeding and transfusion requirements were similar in the two groups. This study shows that high dose terlipressin is not superior to low dose terlipressin in acute variceal bleeding.

Aged↗
PubMedDate not supplied

Terlipressin in bleeding esophageal varices: a placebo-controlled, double-blind study.

The effect of terlipressin (N-alpha-triglycyl-8-lysine-vasopressin) in bleeding esophageal varices was evaluated in a prospective placebo-controlled study. Fifty bleeding episodes from esophageal varices in 34 patients were randomized. Standard therapy with transfusions, fluid and electrolyte correction, and lactulose was performed in both groups. Balloon tamponade was used in 20 bleeding episodes in the terlipressin group and in 19 bleeding episodes in the control group. In the terlipressin group, hemorrhage was controlled in all bleeding episodes (25/25) whereas in the placebo group, only 20 of 25 bleeding episodes could be stopped within 36 hr (p less than 0.05). Sclerotherapy was performed in five bleeding episodes in the terlipressin group and in seven bleeding episodes in the placebo group. Treatment failures, including patients who required sclerotherapy, occurred in five bleedings in the terlipressin group and in 12 in the control group (p less than 0.05). The hospital mortality rate was 12% (3/25) in the terlipressin group and 32% (8/25) in the control group. Patients in the terlipressin group required fewer transfusions, the balloon needed to be inflated for a shorter time and the duration of bleeding was shorter than in the control group. However, these differences were not significant. These data do not allow conclusions concerning monotherapy with terlipressin, but they indicate that the addition of terlipressin to standard therapy may increase the control rate in acute variceal hemorrhage.

Adult↗
PubMed1996

Hemodynamic and metabolic effects of terlipressin in patients with cirrhosis receiving a nonselective beta-blocker.

Terlipressin (Glypressin), a vasopressin analog, may be administered to patients with cirrhosis receiving a beta-adrenergic antagonist. Since terlipressin alone and beta-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 beta-blockade. Thus, the present study examined hemodynamic and metabolic responses to terlipressin in 12 patients receiving nonselective beta-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 beta-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 beta-adrenergic blocker.

Adrenergic beta-Antagonists↗
PubMed2004

A prospective double blind randomized study comparing the need for blood transfusion with terlipressin or a placebo during early excision and grafting of burns.

INTRODUCTION: Early excision and skin grafting has become the standard of good burn management, but it is associated with major blood loss. AIM: To determine the haemostatic effect of terlipressin compared with placebo. MATERIAL AND METHODS: Fifty-one patients with burns of 10-20% total body surface area had early excision and split skin grafting of deep burns. The surface area of the burn wound and of the healed graft were measured by planimetry. The patients were randomly allocated to medication, either terlipressin or placebo. Blood loss and number of transfused units of blood were recorded. RESULTS: Twenty-one patients received terlipressin, 13 received terlipressin late (cross-over) and 17 received placebo. Six out of 21 patients exposed to terlipressin were transfused with eleven units of packed red blood cells. Seven out of 13 patients crossed over from placebo to terlipressin (late terlipressin) were transfused with 17 units of blood. Eight out of 17 patients exposed to the placebo were transfused with 22 units of blood (P < 0.05). Graft healing was 1055 +/- 609 cm2 out of 1452 +/- 11 cm2 in terlipressin and 914 +/- 633 cm2 out of 1288 +/- 720 cm2 in the placebo group (n.s.). CONCLUSION: Terlipressin reduced the need for blood transfusion by a factor of 2.5 compared to a placebo without impairment of graft healing.

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