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levosimendan in sepsis

Zhongheng Zhang, Kun Chen
The article describes some commonly used vasoactive agents in patients with septic shock. Depending on their distinct pharmacological properties, their effects on vascular bed and cardiac function are different. For example, dopamine has equivalent effect on heart and vasculature, which can result in increases in cardiac output, mean arterial pressure and heart rate. Dobutamine is considered as inodilator because it has potent effect on cardiac systole and vasculature. Patients with sepsis and septic shock sometimes have coexisting cardiac dysfunction that justifies the use of dobutamine...
September 2016: Annals of Translational Medicine
Anthony C Gordon, Gavin D Perkins, Mervyn Singer, Daniel F McAuley, Robert M L Orme, Shalini Santhakumaran, Alexina J Mason, Mary Cross, Farah Al-Beidh, Janis Best-Lane, David Brealey, Christopher L Nutt, James J McNamee, Henrik Reschreiter, Andrew Breen, Kathleen D Liu, Deborah Ashby
Background Levosimendan is a calcium-sensitizing drug with inotropic and other properties that may improve outcomes in patients with sepsis. Methods We conducted a double-blind, randomized clinical trial to investigate whether levosimendan reduces the severity of organ dysfunction in adults with sepsis. Patients were randomly assigned to receive a blinded infusion of levosimendan (at a dose of 0.05 to 0.2 μg per kilogram of body weight per minute) for 24 hours or placebo in addition to standard care. The primary outcome was the mean daily Sequential Organ Failure Assessment (SOFA) score in the intensive care unit up to day 28 (scores for each of five systems range from 0 to 4, with higher scores indicating more severe dysfunction; maximum score, 20)...
October 5, 2016: New England Journal of Medicine
Alessandro Belletti, Umberto Benedetto, Giuseppe Biondi-Zoccai, Carlo Leggieri, Paolo Silvani, Gianni D Angelini, Alberto Zangrillo, Giovanni Landoni
PURPOSE: Inotropes and vasopressors are cornerstone of therapy in septic shock, but search for the best agent is ongoing. We aimed to determine which vasoactive drug is associated with the best survival. MATERIALS AND METHODS: PubMed, BioMedCentral, Embase, and the Cochrane Central Register were searched. Randomized trials performed in septic patients with at least 1 group allocated to an inotrope/vasopressor were included. Network meta-analysis with a frequentist approach was performed...
August 13, 2016: Journal of Critical Care
Margrete Larsen Burns, Hans Jørgen Stensvold, Kari Risnes, Hans Jørgen Guthe, Henriette Astrup, S Marianne Nordhov, Terje Reidar Selberg, Arild Rønnestad, Astri Maria Lang
OBJECTIVE: To describe the use of inotropic drugs and the characteristics of neonates receiving such treatment in a national cohort of patients admitted to neonatal ICUs in Norway. DESIGN: A national registry study of patients included in the Norwegian Neonatal Network database 2009-2014. Demographic and treatment data, including the use of inotropic drugs (dopamine, dobutamine, epinephrine, norepinephrine, milrinone, and levosimendan) and outcomes, were retrieved and analyzed...
October 2016: Pediatric Critical Care Medicine
Antonio Pisano, Giacomo Monti, Giovanni Landoni
PURPOSE OF REVIEW: In the last years, the perioperative use of levosimendan in cardiac surgery patients is spreading. Moreover, newer indications have been suggested such as the treatment of sepsis-associated myocardial dysfunction. In the present review, we discuss the most recent evidences in these settings. RECENT FINDINGS: Levosimendan has been seemingly confirmed to reduce mortality in patients undergoing cardiac surgery. In particular, it appears to be the only inotropic drug to have a favorable effect on survival in any clinical setting...
August 2016: Current Opinion in Anaesthesiology
A Belletti, M L Castro, S Silvetti, T Greco, G Biondi-Zoccai, L Pasin, A Zangrillo, G Landoni
BACKGROUND: Inotropes and vasopressors are frequently administered to critically ill patients in order to improve haemodynamic function and restore adequate organ perfusion. However, some studies have suggested a possible association between inotrope administration and increased mortality. We therefore performed a meta-analysis of randomized trials published in the last 20 yr to investigate the effect of these drugs on mortality. METHODS: BioMedCentral, PubMed, Embase and the Cochrane Central Register were searched (all updated April 8th, 2015)...
November 2015: British Journal of Anaesthesia
Qiang Wang, Hiroki Yokoo, Michinori Takashina, Kimimasa Sakata, Wakana Ohashi, Lobna A Abedelzaher, Takahiro Imaizumi, Takuya Sakamoto, Kohshi Hattori, Naoyuki Matsuda, Yuichi Hattori
OBJECTIVES: The calcium sensitizer levosimendan is used in treatment of decompensated heart failure and may also exhibit anti-inflammatory properties. We examined whether treatment with levosimendan is substantially beneficial in mice with cecal ligation and puncture-induced polymicrobial sepsis, and its arbitration mechanism was explored in the mouse macrophage cell line RAW264.7. DESIGN: Laboratory and animal/cell research. SETTING: University research laboratory...
November 2015: Critical Care Medicine
S Wagner, S Schürmann, S Hein, J Schüttler, O Friedrich
Cardiac dysfunction is a common complication in sepsis and is characterized by forward pump failure. Hallmarks of septic cardiomyopathy are decreased myofibrillar contractility and reduced Ca(2+) sensitivity but it is still not clear whether reduced pump efficiency is predominantly a diastolic impairment. Moreover, a comprehensive picture of upstream Ca(2+) handling mechanisms and downstream myosin biomechanical parameters is still missing. Ca(2+)-sensitizing agents in sepsis may be promising but mechanistic insights for drugs like levosimendan are scarce...
September 2015: Basic Research in Cardiology
Alberto Zangrillo, Alessandro Putzu, Fabrizio Monaco, Alessandro Oriani, Giovanna Frau, Monica De Luca, Nora Di Tomasso, Elena Bignami, Vladimir Lomivorotov, Valery Likhvantsev, Giovanni Landoni
PURPOSE: There is controversy about the use of inotropes in the treatment of severe sepsis and septic shock. The objective of this study was to evaluate if levosimendan, as compared with standard inotropic therapy (eg, dobutamine), reduces mortality in septic patients. MATERIALS AND METHODS: BioMedCentral, PubMed, EMBASE, and the Cochrane Central Register were searched for pertinent studies, up to 1st May 2015. Randomized trials on the use of levosimendan in patients with severe sepsis and septic shock were included if reporting mortality data...
October 2015: Journal of Critical Care
Simona Silvetti, Paolo Silvani, Maria Luisa Azzolini, Roberto Dossi, Giovanni Landoni, Alberto Zangrillo
Levosimendan is a calcium-sensitizing agent that improves cardiac function, hemodynamic performance, and survival in critically ill adult patient. Few data exist on its off-label use in paediatric patients. We therefore performed a systematic review updated in September 2013 of all the published articles describing the use of levosimendan in paediatric patients. We identified 24 studies published in the period 2004-2013 that included a total of 623 patients, the largest one being a case series of 293 patients...
2015: Current Vascular Pharmacology
Cheng-Ming Tsao, Kai-Yi Li, Shiu-Jen Chen, Shuk-Man Ka, Wen-Jinn Liaw, Hsieh-Chou Huang, Chin-Chen Wu
INTRODUCTION: The aim of this study was to investigate the effects of levosimendan on rodent septic shock induced by cecal ligation and puncture (CLP). METHODS: Three hours after peritonitis-induced sepsis, male Wistar rats were randomly assigned to receive an intravenous infusion of levosimendan (1.2 μg/kg/min for 10 min and then 0.3 μg/kg/min for 6 h) or an equivalent volume of saline and vehicle (5% dextrose) solution. RESULTS: The levosimendan-treated CLP animals had significantly higher arterial pressure and lower biochemical indices of liver and kidney dysfunction compared to the CLP animals (P < 0...
2014: Critical Care: the Official Journal of the Critical Care Forum
Mingxing Fang, Shimin Dong
OBJECTIVE: To evaluate the effects of levosimendan on hemodynamics and cardiac function in patients with septic shock. METHODS: A prospective single-center randomized controlled trial was conducted. The patients with septic shock admitted to the Department of Critical Care Medicine of the Third Hospital of Hebei Medical University from June 2011 to October 2013 were enrolled. The patients with septic shock received the conventional treatment according to international guidelines for management of severe sepsis and septic shock...
October 2014: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
Xuebing Wang, Shaolin Ma, Yang Liu, Wei Xu, Zhanxia Li
This research is aimed to discover the influence and underling mechanism of combined infusion of arginine vasopressin with levosimendan on acute lung injury in rat septic shock with norepinephrine supplemented. The traditional fecal peritonitis-induced septic shock model was undergone in rats for study. It is observed that the combined infusion supplemented with norepinephrine brought about a lower mean pulmonary artery pressure; lower high-mobility group box 1 levels, pulmonary levels of interleukin-6, and arterial total nitrate/nitrite; lower apoptotic cells scores and total histological scores; but higher pulmonary gas exchange when compared with the separate infusion group and norepinephrine group...
December 2014: Cell Biochemistry and Biophysics
Robert M L'E Orme, Gavin D Perkins, Daniel F McAuley, Kathleen D Liu, Alexina J Mason, Andrea Morelli, Mervyn Singer, Deborah Ashby, Anthony C Gordon
BACKGROUND: Organ dysfunction consequent to infection ('severe sepsis') is the leading cause of admission to an intensive care unit (ICU). In both animal models and early clinical studies the calcium channel sensitizer levosimendan has been demonstrated to have potentially beneficial effects on organ function. The aims of the Levosimendan for the Prevention of Acute oRgan Dysfunction in Sepsis (LeoPARDS) trial are to identify whether a 24-hour infusion of levosimendan will improve organ dysfunction in adults who have septic shock and to establish the safety profile of levosimendan in this group of patients...
2014: Trials
Alessandra Torraco, Rosalba Carrozzo, Fiorella Piemonte, Anna Pastore, Giulia Tozzi, Daniela Verrigni, Marco Assenza, Alessandra Orecchioni, Annalia D'Egidio, Elisa Marraffa, Giovanni Landoni, Enrico Bertini, Andrea Morelli
Mitochondrial dysfunction is key feature of septic shock and contributes to the development of sepsis related organ dysfunction. It is characterized by a variable reduction of the respiratory chain (RC) activities, altered mitochondrial morphology and reactive oxygen species production. Recent data have reported the efficacy of levosimendan, a calcium sensitizer, in improving heart performance and organ perfusion in critically ill patients. Moreover, it has been demonstrated that Levosimendan has antioxidant properties...
July 2014: Biochimie
Konstanze Plaschke, Franziska Bent, Sören Wagner, Markus Zorn, Jürgen Kopitz
Levosimendan shows protective myocardial characteristics and is administered to enhance cardiac contractility in patients. However, currently little is known about levosimendan's effect on brain. The aim of this pilot study was to investigate the long-term effect of levosimendan on brain and during mild rat sepsis in comparison to its peripheral mode of action. Adult rats (n=40) were divided into four groups with n=10 per group: (I) sham, (II) levosimendan (283 μg/kg body weight i.v.), (III) lipopolysaccharide (LPS, 8 mg/kg body weight i...
February 7, 2014: Neuroscience Letters
Mehmet B Yilmaz, Elena Grossini, José C Silva Cardoso, István Édes, Francesco Fedele, Piero Pollesello, Matti Kivikko, Veli-Pekka Harjola, Julia Hasslacher, Alexandre Mebazaa, Andrea Morelli, Jos le Noble, Anders Oldner, Ignacio Oulego Erroz, John T Parissis, Alexander Parkhomenko, Gerhard Poelzl, Sebastian Rehberg, Sven-Erik Ricksten, Luís M Rodríguez Fernández, Markku Salmenperä, Mervyn Singer, Sascha Treskatsch, Bojan Vrtovec, Gerhard Wikström
Renal dysfunction is common in clinical settings in which cardiac function is compromised such as heart failure, cardiac surgery or sepsis, and is associated with high morbidity and mortality. Levosimendan is a calcium sensitizer and potassium channel opener used in the treatment of acute heart failure. This review describes the effects of the inodilator levosimendan on renal function. A panel of 25 scientists and clinicians from 15 European countries (Austria, Finland, France, Hungary, Germany, Greece, Italy, Portugal, the Netherlands, Slovenia, Spain, Sweden, Turkey, the United Kingdom, and Ukraine) convened and reached a consensus on the current interpretation of the renal effects of levosimendan described both in non-clinical research and in clinical study reports...
December 2013: Cardiovascular Drugs and Therapy
Alain Rudiger, Mervyn Singer
Septic shock is characterized by circulatory compromise, microcirculatory alterations and mitochondrial damage, which all reduce cellular energy production. In order to reduce the risk of major cell death and a diminished likelihood of recovery, adaptive changes appear to be activated. As a result, cells and organs may survive in a non-functioning hibernation-like condition. Sepsis-induced cardiac dysfunction may represent an example of such functional shutdown. Sepsis-induced myocardial dysfunction is common, corresponds to the severity of sepsis, and is reversible in survivors...
March 1, 2013: Current Vascular Pharmacology
Paola Papoff, Elena Caresta, Paolo Versacci, Raffaella Pinto, Corrado Moretti, Fabio Midulla
Although international guidelines for hemodynamic support of pediatric septic shock suggest considering the potent calcium sensitizer inodilator levosimendan as a second-line inotropic agent to treat cold hypodynamic shock resistant to catecholamines, clinical experience in septic infants is lacking. We report the beneficial effects of levosimendan infusion in 2 infants (39 and 64 days old) with low cardiac output septic shock (ejection fraction, 29% and 33%; fractional shortening, 10% and 16% respectively) refractory to volume replacement and to the catecholamines dopamine and dobutamine...
October 2012: Pediatric Emergency Care
Franziska Bent, Konstanze Plaschke
Although studies have evaluated the efficacy of levosimendan in heart failure during sepsis, it still is a subject of controversy whether levosimendan produces an effect on platelets. In this study, the short- and long-term effects of levosimendan on platelet aggregation were investigated in untreated animals and in a rat model of sepsis. Therefore, adult rats (n = 40) were randomly divided into four groups with n = 10 per group: (I) sham, (II) levosimendan (bolus 53 µg/kg + 285 µg/kg/hour, intravenously (i...
2013: Platelets
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