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Flemming Bendtsen - One of the best experts on this subject based on the ideXlab platform.
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Effects of a single Terlipressin administration on cardiac function and perfusion in cirrhosis
European Journal of Gastroenterology & Hepatology, 2010Co-Authors: Aleksander Krag, Christian Mortensen, Jens H. Henriksen, Flemming Bendtsen, Søren MøllerAbstract:BackgroundThe vasoconstrictor Terlipressin is widely used in the treatment of the hepatorenal syndrome and variceal bleeding. However, Terlipressin may compromise cardiac function and induce ischemia.AimTherefore, we aimed to assess the effects of Terlipressin on cardiac function and perfusion.Metho
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Hyponatraemia during Terlipressin therapy
Gut, 2010Co-Authors: Aleksander Krag, Søren Møller, Lise Hobolth, Flemming BendtsenAbstract:We have read with interest the study by Lo et al 1 in a recent issue of Gut . Apart from the findings that short-term therapy with Terlipressin in combination with ligation seems to improve outcome in bleeding oesophageal varices (BOVs) compared to longer treatment with Terlipressin, a shorter treatment period with Terlipressin most likely reduces the risk of severe side effects. Recently, a study observed that during a 5-day Terlipressin treatment with 1 mg/4 h, the serum sodium decreased from 138±5 to 130±9 and in …
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Efficacy and safety of Terlipressin in cirrhotic patients with variceal bleeding or hepatorenal syndrome
Advances in Therapy, 2008Co-Authors: Aleksander Krag, Søren Møller, Tine Borup, Flemming BendtsenAbstract:Terlipressin is an analog of the natural hormone arginine-vasopressin. It is used in the treatment of patients with cirrhosis and bleeding esophageal varices (BEV) and in patients with hepatorenal syndrome (HRS): two of the most dramatic and feared complications of cirrhosis. Terlipressin exerts its main pharmacological effect through stimulation of vasopressin-1 receptors. These receptors are located in vascular smooth muscle and mediate vasoconstriction. In patients with cirrhosis and portal hypertension, treatment with Terlipressin increases mean arterial pressure and decreases portal flow and pressure within minutes of administration. Furthermore, in patients with ascites Terlipressin improves glomerular filtration and excretion of sodium. Terlipressin decreases failure of initial hemostasis by 34%, decreases mortality by 34%, and is considered a first-line treatment for BEV, when available. Terlipressin in combination with albumin reverses type 1 HRS in 33%–60% of cases and is the only treatment with proven efficacy in randomized trials. The safety profile is favorable when considering the clinical efficacy and the high mortality of these clinical entities. Adverse events are mostly cardiovascular and related to vasoconstriction. Mortality and withdrawal of Terlipressin due to adverse events occurs in less than 1% of cases. Mild adverse events related to Terlipressin treatment occur in 10%–20% of patients. The benefit, however, of Terlipressin on long-term survival in HRS remains to be determined. At present, treatment with Terlipressin and albumin is considered the most efficient therapy and should therefore be recommended for the treatment of type 1 HRS-1.
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Terlipressin improves renal function in patients with cirrhosis and ascites without hepatorenal syndrome
Hepatology, 2007Co-Authors: Aleksander Krag, Jens H. Henriksen, Søren Møller, Nielshenrik Holsteinrathlou, Fin Stolze Larsen, Flemming BendtsenAbstract:Patients with advanced cirrhosis and ascites are characterized by circulatory dysfunction with splanchnic vasodilatation and renal vasoconstriction, which often lead to ascites. The vasoconstrictor Terlipressin improves renal function in hepatorenal syndrome (HRS). The aim of this study was to evaluate if Terlipressin also improves renal function in patients with ascites without HRS. Twenty-three patients with cirrhosis participated; 15 with nonrefractory ascites were randomized to either Terlipressin (N group, n = 11) or a placebo (P group, n = 4), and 8 had refractory ascites and received Terlipressin (R group). The glomerular filtration rate (GFR), sodium clearance (CNa), lithium clearance (CLi), osmolal clearance (COsm), and urine sodium concentration (UNa) were assessed before and after the injection of 2 mg of Terlipressin or the placebo. GFR increased in the N group (69 ± 19 versus 92 ± 25 mL/min, P < 0.005) and in the R group (31 ± 19 versus 41 ± 31 mL/min, P < 0.05) after Terlipressin. In the N group, Terlipressin induced an increase in CNa (0.89 ± 0.21 versus 1.52 ± 1.45 mL/min, P < 0.05), CLi (17.3 ± 8.9 versus 21.5 ± 11.6 mL/min, P < 0.05), and COsm (2.10 ± 0.81 versus 3.06 ± 2.0 mL/min, P < 0.05). In the R group, Terlipressin induced an increase in CNa (0.11 ± 0.18 versus 0.35 ± 0.40 mL/min, P < 0.05) and CLi (5.5 ± 4.2 versus 9.5 ± 8.55 mL/min, P < 0.05). UNa increased in both groups after Terlipressin (P < 0.005). Plasma norepinephrine (P < 0.05) and renin (P < 0.05) decreased after Terlipressin. All parameters remained unchanged after the placebo. Conclusion: The vasopressin 1 receptor agonist Terlipressin improves renal function and induces natriuresis in patients with cirrhosis and ascites without HRS. Vasoconstrictors may represent a novel future treatment modality for these patients. (HEPATOLOGY 2007.)
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Effect of Terlipressin on blood volume distribution in patients with cirrhosis.
Scandinavian journal of gastroenterology, 2004Co-Authors: Marianne Kiszka-kanowitz, Jens H. Henriksen, Søren Møller, Erik Feldager Hansen, Flemming BendtsenAbstract:Background: Patients with cirrhosis and portal hypertension have an altered blood volume distribution and a hyperdynamic systemic circulation. Terlipressin is known to reduce portal pressure by decreasing splanchnic inflow, but its effect on the blood volume distribution is unknown. The aim of the study was to investigate changes in regional blood volume distribution and systemic haemodynamics after administration of Terlipressin to patients with cirrhosis. Methods: Blood volume distribution was determined in 13 patients with cirrhosis and portal hypertension by a dual‐head gamma‐camera technique and systemic haemodynamics was measured before and after intravenous administration of Terlipressin (2 mg). Results: Terlipressin increased the blood volume in the thorax region (+6.0%, P
Aleksander Krag - One of the best experts on this subject based on the ideXlab platform.
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Severe hyponatraemia to Terlipressin treatment
Ugeskrift for laeger, 2013Co-Authors: Anja Poulsen, Aleksander KragAbstract:Terlipressin is a vasopressin analogue. The clinical effect is attributable to affinity to vasopressin-1a receptors. However, it also has affinity to renal vasopressin-2 receptors, which can lead to water retention and dilutional hyponatraemia. We report a case of severe hyponatraemia secondary to Terlipressin treatment. A 60-year-old woman with bleeding oesophageal varices was treated with Terlipressin 2 mg every fourth hour. After 24 hours of treatment she was somnolent, and the sodium concentration had dropped from 127 mmol/l to 107 mmol/l. Hyponatraemia is an important adverse event in Terlipressin treatment, and serum sodium should be monitored closely.
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Terlipressin for hepatorenal syndrome
Cochrane Database of Systematic Reviews, 2012Co-Authors: Lise Lotte Gluud, Kurt Christensen, Erik Christensen, Aleksander KragAbstract:Background Clinical trials suggest that Terlipressin improves renal function in hepatorenal syndrome, but the evidence concerning mortality is equivocal. Objectives To assess the beneficial and harmful effects of Terlipressin alone or with albumin versus placebo, no intervention or albumin for hepatorenal syndrome. Search methods Eligible trials were identified through electronic (The Cochrane Library, MEDLINE, EMBASE and Science Citation Index databases) and manual searches until January 2012. Selection criteria Randomised clinical trials involving patients with type 1 or type 2 hepatorenal syndrome were included irrespective of publication status or language. Data collection and analysis The review authors independently extracted data from trial reports and undertook correspondence with the authors. Primary outcome measures included mortality, reversal of hepatorenal syndrome and adverse events. Intention-to-treat, random-effects model meta-analyses were performed and results were expressed as risk ratios (RR) with 95% confidence intervals (CI), and the I2 statistic provided a measure of intertrial heterogeneity. Subgroup, sensitivity, regression and sequential analyses were performed. Main results We identified six randomised clinical trials. All had high risk of bias. Five trials assessed Terlipressin (with albumin in three trials) versus no intervention (with albumin in three trials) and one trial assessed Terlipressin versus albumin. Data from five randomised trials on Terlipressin alone (one trial) or Terlipressin and albumin (four trials) were included in the review. In total, 74 of 155 (47.7%) patients randomised to Terlipressin alone or Terlipressin with albumin versus 98 of 154 (63.6%) patients randomised to no intervention, placebo or albumin died. Random-effects model meta-analysis found that Terlipressin reduced mortality (RR 0.76, 95% CI 0.61 to 0.95). The results were stable when repeated with trials on Terlipressin plus albumin, trials on patients with type 2 hepatorenal syndrome, and trials with a low risk of selection bias. No evidence of bias or small study effects were identified in regression analyses. In a trial sequential analysis on mortality, the cumulative Z curve approached but did not cross the monitoring boundary suggesting that the results were not stable to adjustment for sparse data and multiple comparisons. Analyses of the remaining outcome measures found that Terlipressin and albumin increased the number of patients with reversal of hepatorenal syndrome as well as adverse events, including cardiovascular and gastrointestinal symptoms. Authors' conclusions Terlipressin may reduce mortality and improve renal function in patients with type 1 hepatorenal syndrome. Whether the evidence is strong enough to support the intervention for clinical practice could be debated due to the results of the trial sequential analyses. However, the outcome measures assessed are objective, which reduces the risk of bias.
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The Cochrane Library - Terlipressin for hepatorenal syndrome
The Cochrane database of systematic reviews, 2012Co-Authors: Lise Lotte Gluud, Kurt Christensen, Erik Christensen, Aleksander KragAbstract:Background Clinical trials suggest that Terlipressin improves renal function in hepatorenal syndrome, but the evidence concerning mortality is equivocal. Objectives To assess the beneficial and harmful effects of Terlipressin alone or with albumin versus placebo, no intervention or albumin for hepatorenal syndrome. Search methods Eligible trials were identified through electronic (The Cochrane Library, MEDLINE, EMBASE and Science Citation Index databases) and manual searches until January 2012. Selection criteria Randomised clinical trials involving patients with type 1 or type 2 hepatorenal syndrome were included irrespective of publication status or language. Data collection and analysis The review authors independently extracted data from trial reports and undertook correspondence with the authors. Primary outcome measures included mortality, reversal of hepatorenal syndrome and adverse events. Intention-to-treat, random-effects model meta-analyses were performed and results were expressed as risk ratios (RR) with 95% confidence intervals (CI), and the I2 statistic provided a measure of intertrial heterogeneity. Subgroup, sensitivity, regression and sequential analyses were performed. Main results We identified six randomised clinical trials. All had high risk of bias. Five trials assessed Terlipressin (with albumin in three trials) versus no intervention (with albumin in three trials) and one trial assessed Terlipressin versus albumin. Data from five randomised trials on Terlipressin alone (one trial) or Terlipressin and albumin (four trials) were included in the review. In total, 74 of 155 (47.7%) patients randomised to Terlipressin alone or Terlipressin with albumin versus 98 of 154 (63.6%) patients randomised to no intervention, placebo or albumin died. Random-effects model meta-analysis found that Terlipressin reduced mortality (RR 0.76, 95% CI 0.61 to 0.95). The results were stable when repeated with trials on Terlipressin plus albumin, trials on patients with type 2 hepatorenal syndrome, and trials with a low risk of selection bias. No evidence of bias or small study effects were identified in regression analyses. In a trial sequential analysis on mortality, the cumulative Z curve approached but did not cross the monitoring boundary suggesting that the results were not stable to adjustment for sparse data and multiple comparisons. Analyses of the remaining outcome measures found that Terlipressin and albumin increased the number of patients with reversal of hepatorenal syndrome as well as adverse events, including cardiovascular and gastrointestinal symptoms. Authors' conclusions Terlipressin may reduce mortality and improve renal function in patients with type 1 hepatorenal syndrome. Whether the evidence is strong enough to support the intervention for clinical practice could be debated due to the results of the trial sequential analyses. However, the outcome measures assessed are objective, which reduces the risk of bias.
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Terlipressin for hepatorenal syndrome.
The Cochrane database of systematic reviews, 2012Co-Authors: Lise Lotte Gluud, Kurt Christensen, Erik Christensen, Aleksander KragAbstract:Clinical trials suggest that Terlipressin improves renal function in hepatorenal syndrome, but the evidence concerning mortality is equivocal. To assess the beneficial and harmful effects of Terlipressin alone or with albumin versus placebo, no intervention or albumin for hepatorenal syndrome. Eligible trials were identified through electronic (The Cochrane Library, MEDLINE, EMBASE and Science Citation Index databases) and manual searches until January 2012. Randomised clinical trials involving patients with type 1 or type 2 hepatorenal syndrome were included irrespective of publication status or language. The review authors independently extracted data from trial reports and undertook correspondence with the authors. Primary outcome measures included mortality, reversal of hepatorenal syndrome and adverse events. Intention-to-treat, random-effects model meta-analyses were performed and results were expressed as risk ratios (RR) with 95% confidence intervals (CI), and the I(2) statistic provided a measure of intertrial heterogeneity. Subgroup, sensitivity, regression and sequential analyses were performed. We identified six randomised clinical trials. All had high risk of bias. Five trials assessed Terlipressin (with albumin in three trials) versus no intervention (with albumin in three trials) and one trial assessed Terlipressin versus albumin. Data from five randomised trials on Terlipressin alone (one trial) or Terlipressin and albumin (four trials) were included in the review. In total, 74 of 155 (47.7%) patients randomised to Terlipressin alone or Terlipressin with albumin versus 98 of 154 (63.6%) patients randomised to no intervention, placebo or albumin died. Random-effects model meta-analysis found that Terlipressin reduced mortality (RR 0.76, 95% CI 0.61 to 0.95). The results were stable when repeated with trials on Terlipressin plus albumin, trials on patients with type 2 hepatorenal syndrome, and trials with a low risk of selection bias. No evidence of bias or small study effects were identified in regression analyses. In a trial sequential analysis on mortality, the cumulative Z curve approached but did not cross the monitoring boundary suggesting that the results were not stable to adjustment for sparse data and multiple comparisons. Analyses of the remaining outcome measures found that Terlipressin and albumin increased the number of patients with reversal of hepatorenal syndrome as well as adverse events, including cardiovascular and gastrointestinal symptoms. Terlipressin may reduce mortality and improve renal function in patients with type 1 hepatorenal syndrome. Whether the evidence is strong enough to support the intervention for clinical practice could be debated due to the results of the trial sequential analyses. However, the outcome measures assessed are objective, which reduces the risk of bias.
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Effects of a single Terlipressin administration on cardiac function and perfusion in cirrhosis
European Journal of Gastroenterology & Hepatology, 2010Co-Authors: Aleksander Krag, Christian Mortensen, Jens H. Henriksen, Flemming Bendtsen, Søren MøllerAbstract:BackgroundThe vasoconstrictor Terlipressin is widely used in the treatment of the hepatorenal syndrome and variceal bleeding. However, Terlipressin may compromise cardiac function and induce ischemia.AimTherefore, we aimed to assess the effects of Terlipressin on cardiac function and perfusion.Metho
Søren Møller - One of the best experts on this subject based on the ideXlab platform.
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Effects of a single Terlipressin administration on cardiac function and perfusion in cirrhosis
European Journal of Gastroenterology & Hepatology, 2010Co-Authors: Aleksander Krag, Christian Mortensen, Jens H. Henriksen, Flemming Bendtsen, Søren MøllerAbstract:BackgroundThe vasoconstrictor Terlipressin is widely used in the treatment of the hepatorenal syndrome and variceal bleeding. However, Terlipressin may compromise cardiac function and induce ischemia.AimTherefore, we aimed to assess the effects of Terlipressin on cardiac function and perfusion.Metho
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Hyponatraemia during Terlipressin therapy
Gut, 2010Co-Authors: Aleksander Krag, Søren Møller, Lise Hobolth, Flemming BendtsenAbstract:We have read with interest the study by Lo et al 1 in a recent issue of Gut . Apart from the findings that short-term therapy with Terlipressin in combination with ligation seems to improve outcome in bleeding oesophageal varices (BOVs) compared to longer treatment with Terlipressin, a shorter treatment period with Terlipressin most likely reduces the risk of severe side effects. Recently, a study observed that during a 5-day Terlipressin treatment with 1 mg/4 h, the serum sodium decreased from 138±5 to 130±9 and in …
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Efficacy and safety of Terlipressin in cirrhotic patients with variceal bleeding or hepatorenal syndrome
Advances in Therapy, 2008Co-Authors: Aleksander Krag, Søren Møller, Tine Borup, Flemming BendtsenAbstract:Terlipressin is an analog of the natural hormone arginine-vasopressin. It is used in the treatment of patients with cirrhosis and bleeding esophageal varices (BEV) and in patients with hepatorenal syndrome (HRS): two of the most dramatic and feared complications of cirrhosis. Terlipressin exerts its main pharmacological effect through stimulation of vasopressin-1 receptors. These receptors are located in vascular smooth muscle and mediate vasoconstriction. In patients with cirrhosis and portal hypertension, treatment with Terlipressin increases mean arterial pressure and decreases portal flow and pressure within minutes of administration. Furthermore, in patients with ascites Terlipressin improves glomerular filtration and excretion of sodium. Terlipressin decreases failure of initial hemostasis by 34%, decreases mortality by 34%, and is considered a first-line treatment for BEV, when available. Terlipressin in combination with albumin reverses type 1 HRS in 33%–60% of cases and is the only treatment with proven efficacy in randomized trials. The safety profile is favorable when considering the clinical efficacy and the high mortality of these clinical entities. Adverse events are mostly cardiovascular and related to vasoconstriction. Mortality and withdrawal of Terlipressin due to adverse events occurs in less than 1% of cases. Mild adverse events related to Terlipressin treatment occur in 10%–20% of patients. The benefit, however, of Terlipressin on long-term survival in HRS remains to be determined. At present, treatment with Terlipressin and albumin is considered the most efficient therapy and should therefore be recommended for the treatment of type 1 HRS-1.
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Terlipressin improves renal function in patients with cirrhosis and ascites without hepatorenal syndrome
Hepatology, 2007Co-Authors: Aleksander Krag, Jens H. Henriksen, Søren Møller, Nielshenrik Holsteinrathlou, Fin Stolze Larsen, Flemming BendtsenAbstract:Patients with advanced cirrhosis and ascites are characterized by circulatory dysfunction with splanchnic vasodilatation and renal vasoconstriction, which often lead to ascites. The vasoconstrictor Terlipressin improves renal function in hepatorenal syndrome (HRS). The aim of this study was to evaluate if Terlipressin also improves renal function in patients with ascites without HRS. Twenty-three patients with cirrhosis participated; 15 with nonrefractory ascites were randomized to either Terlipressin (N group, n = 11) or a placebo (P group, n = 4), and 8 had refractory ascites and received Terlipressin (R group). The glomerular filtration rate (GFR), sodium clearance (CNa), lithium clearance (CLi), osmolal clearance (COsm), and urine sodium concentration (UNa) were assessed before and after the injection of 2 mg of Terlipressin or the placebo. GFR increased in the N group (69 ± 19 versus 92 ± 25 mL/min, P < 0.005) and in the R group (31 ± 19 versus 41 ± 31 mL/min, P < 0.05) after Terlipressin. In the N group, Terlipressin induced an increase in CNa (0.89 ± 0.21 versus 1.52 ± 1.45 mL/min, P < 0.05), CLi (17.3 ± 8.9 versus 21.5 ± 11.6 mL/min, P < 0.05), and COsm (2.10 ± 0.81 versus 3.06 ± 2.0 mL/min, P < 0.05). In the R group, Terlipressin induced an increase in CNa (0.11 ± 0.18 versus 0.35 ± 0.40 mL/min, P < 0.05) and CLi (5.5 ± 4.2 versus 9.5 ± 8.55 mL/min, P < 0.05). UNa increased in both groups after Terlipressin (P < 0.005). Plasma norepinephrine (P < 0.05) and renin (P < 0.05) decreased after Terlipressin. All parameters remained unchanged after the placebo. Conclusion: The vasopressin 1 receptor agonist Terlipressin improves renal function and induces natriuresis in patients with cirrhosis and ascites without HRS. Vasoconstrictors may represent a novel future treatment modality for these patients. (HEPATOLOGY 2007.)
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Effect of Terlipressin on blood volume distribution in patients with cirrhosis.
Scandinavian journal of gastroenterology, 2004Co-Authors: Marianne Kiszka-kanowitz, Jens H. Henriksen, Søren Møller, Erik Feldager Hansen, Flemming BendtsenAbstract:Background: Patients with cirrhosis and portal hypertension have an altered blood volume distribution and a hyperdynamic systemic circulation. Terlipressin is known to reduce portal pressure by decreasing splanchnic inflow, but its effect on the blood volume distribution is unknown. The aim of the study was to investigate changes in regional blood volume distribution and systemic haemodynamics after administration of Terlipressin to patients with cirrhosis. Methods: Blood volume distribution was determined in 13 patients with cirrhosis and portal hypertension by a dual‐head gamma‐camera technique and systemic haemodynamics was measured before and after intravenous administration of Terlipressin (2 mg). Results: Terlipressin increased the blood volume in the thorax region (+6.0%, P
Martin Westphal - One of the best experts on this subject based on the ideXlab platform.
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Effects of two different dosing regimens of Terlipressin on organ functions in ovine endotoxemia
Inflammation Research, 2011Co-Authors: Matthias Lange, Andrea Morelli, Christian Ertmer, Sebastian Rehberg, Gabriele Köhler, Tim G. Kampmeier, Hugo Aken, Martin WestphalAbstract:Objective and design To test the hypothesis that a continuous infusion of the vasopressin analog Terlipressin is associated with less organ dysfunction as compared to intermittent bolus infusion in an ovine sepsis model. Subjects Twenty-seven adult female sheep. Treatment All sheep were subjected to a Salmonella typhosa endotoxin infusion (10 ng/kg/min). After 16 h of endotoxemia, the surviving animals ( n = 24) were randomized to (1) an untreated control group, (2) a continuous Terlipressin group (2 mg/24 h), or (3) a Terlipressin bolus group (1 mg/6 h). Methods Hemodynamic variables were measured and blood was withdrawn at specific time points for the assessment of organ functions. Results Continuous Terlipressin infusion was associated with improved surrogate parameters of myocardial, renal, and hepatic function as compared with Terlipressin bolus infusion. Reduced vascular hyperpermeability was evidenced by an attenuated decrease in plasma protein concentrations in sheep treated with continuous Terlipressin infusion as compared to bolus injection or no treatment. Conclusions Continuous infusion of low-dose Terlipressin preserved several surrogate parameters of organ function better than intermittent bolus injections in sheep with systemic inflammation.
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Terlipressin a promising vasoactive agent in hemodynamic support of septic shock
Expert Opinion on Pharmacotherapy, 2009Co-Authors: Andrea Morelli, Christian Ertmer, P Pietropaoli, Martin WestphalAbstract:Background: At present, Terlipressin is predominantly used for the management of bleeding gastric and esophageal varices, as well as hepato-renal syndrome secondary to liver cirrhosis. Owing to its high and relatively selective affinity to vascular V1 receptors, Terlipressin is also increasingly used as an adjunct vasopressor agent in the management of vasodilatory hyperdynamic septic shock. Objective: This review article aims to summarize the available knowledge related to hemodynamic support with Terlipressin in septic shock. Methods: For literature search, PubMed and specific keywords from the MeSH Database were used. Results/conclusions: Terlipressin represents an effective pressor agent in patients with catecholamine-unresponsive septic shock. However, caution should be exercised, as Terlipressin may contribute dose-dependently to vasoconstriction and a reflectory decrease in cardiac output. Additional studies are needed to clarify: i) the optimal time of therapy institution; ii) the efficacy and the...
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“Terlipressin in the treatment of septic shock: the earlier the better?”
Best practice & research. Clinical anaesthesiology, 2008Co-Authors: Andrea Morelli, Christian Ertmer, Martin WestphalAbstract:Terlipressin, a long-acting vasopressinergic V 1 agonist, is increasingly used to increase mean arterial blood pressure in the common setting of catecholamine-refractory septic shock. Traditionally, Terlipressin has been used as drug of last resort and administered as intermittent high-dose bolus infusion (1–2mg every 4 to 6 hours). Recent experimental and clinical evidence, however, suggests that Terlipressin may also be used as a low-dose continuous infusion (1–2μgkg −1 h −1 ) in the early course of the disease. This approach may sufficiently increase systemic blood pressure and thereby prevent unwanted side effects, such as exaggerating increases in peripheral resistance or rebound hypotension. Small-scale clinical studies suggest that low-dose Terlipressin, when given as a first-line vasopressor agent, is safe. Randomised, clinical multicenter trials are now needed to investigate whether or not early institution of low-dose continuous Terlipressin infusion improves overall outcome of patients suffering from vasodilatory shock states.
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Rebound hypotension following Terlipressin bolus infusion can be prevented by continuous low-dose infusion of Terlipressin
Critical Care, 2007Co-Authors: Matthias Lange, Christian Ertmer, Katrin Bröking, C. Hucklenbruch, Hugo Van Aken, Daniel L. Traber, Martin WestphalAbstract:Bolus infusion of Terlipressin, a vasopressin analog, increases the mean arterial pressure (MAP) in patients with sepsis-related arterial hypotension. However, bolus infusion of Terlipressin may be associated with severe side effects like excessive systemic and pulmonary vasoconstriction. We hypothesized that continuous low-dose infusion of Terlipressin may reverse arterial hypotension with reduced side effects.
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Effects of simultaneously infused Terlipressin and dobutamine in septic shock
Critical Care, 2007Co-Authors: Andrea Morelli, Christian Ertmer, P Pietropaoli, Matthias Lange, Katrin Broeking, Alessandra Orecchioni, Monica Rocco, H. Van Aken, Martin WestphalAbstract:Terlipressin is increasingly used in the treatment of sepsis-associated hypotension. However, Terlipressin may reduce cardiac output and global oxygen supply.
Didier Lebrec - One of the best experts on this subject based on the ideXlab platform.
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clinical course predictive factors and prognosis in patients with cirrhosis and type 1 hepatorenal syndrome treated with Terlipressin a retrospective analysis
Journal of Gastroenterology and Hepatology, 2002Co-Authors: I Colle, Francois Durand, Didier Lebrec, Fabienne Pessione, Emmanuel Rassiat, Jacques Bernuau, Eric Barriere, Dominiquecharles Valla, Richard MoreauAbstract: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 ≤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 ≥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 ≤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. © 2002 Blackwell Publishing Asia Pty Ltd
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beneficial effects of the 2 day administration of Terlipressin in patients with cirrhosis and hepatorenal syndrome
Journal of Hepatology, 1998Co-Authors: Antoine Hadengue, Adrian Gadano, Moreau Richard, E Giostra, Francois Durand, Dominique Valla, Serge Erlinger, Didier LebrecAbstract:Abstract Background/Aims: A treatment to induce a sustained increase in glomerular filtration rate in patients with hepatorenal syndrome has not yet been identified. Thus, the aim of the present study was to investigate the effecs of Terlipressin for 2 days on the glomerular filtration rate in patients with cirrhosis and hepatorenal syndrome. Methods: A double-blind, cross-over randomized study was performed in nine patients. Patients received terlipression (2 mg/day for 2 days) and a placebo for 2 days in a randomized order. Results: Terlipressin administration significantly increased creatinine clearance (from 15±2 ml/min to 27±4 ml/min) and urine output (from 628±67 ml/day to 811±76 ml/day), but did not significantly change urinary sodium concentrations. Urinary sodium excretion was not significantly different after placebo administration (0.6±0.1 mmol/24 h) and Terlipressin administration (9.3±7.2 mmol/24 h). Terlipressin administration significantly decreased plasma concentrations of renin and aldosterone but not atrial natriuretic peptide levels. Placebo elicited no significant effects. Conclusions: This study shows that 2-day Terlipressin administration increases the glomerular filtration rate in patients with cirrhosis and hepatorenal syndrome.
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Haemodynamic responses to a combination of Terlipressin and octreotide in portal hypertensive rats.
Alimentary pharmacology & therapeutics, 1997Co-Authors: Richard Moreau, Dominique Valla, Stéphane Cailmail, Didier LebrecAbstract: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 μL/min for 15 min). Eight rats received Terlipressin first (0.05 mg/kg) and then an i.v. infusion of octreotide (8 μg.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.
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Hemodynamic and metabolic effects of Terlipressin in patients with cirrhosis receiving a nonselectiveβ-blocker
Digestive diseases and sciences, 1996Co-Authors: Florence Vachiery, Antoine Hadengue, Adrian Gadano, Richard Moreau, Stéphane Cailmail, Song Yang, Phillippe Sogni, Thierry Soupison, Didier LebrecAbstract:Terlipressin (Glypressin), a vasopressin analog, may be administered to patients with cirrhosis receiving aβ-adrenergic antagonist. Since Terlipressin alone andβ-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-termβ-blockade. Thus, the present study examined hemodynamic and metabolic responses to Terlipressin in 12 patients receiving nonselectiveβ-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 nonselectiveβ-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 aβ-adrenergic blocker.
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Hemodynamic effects of the administration of Terlipressin alone or combined with nitroglycerin in patients with cirrhosis
Gastroenterologie clinique et biologique, 1992Co-Authors: Richard Moreau, Antoine Hadengue, Philippe Sogni, Olivier Soubrane, Christophe Gaudin, Gerhard Kleber, Didier LebrecAbstract: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)
