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      Levosimendan Versus Dobutamine in Myocardial Injury Patients with Septic Shock: A Randomized Controlled Trial

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          Abstract

          Background

          We aimed to investigate the effect of levosimendan on biomarkers of myocardial injury and systemic hemodynamics in patients with septic shock.

          Material/Methods

          After achieving normovolemia and a mean arterial pressure of at least 65 mmHg, 38 septic shock patients with low cardiac output (left ventricular ejective fraction), LEVF ≤45%) were randomly divided into two groups: levosimendan dobutamine. Patients in the levosimendan and dobutamine groups were maintained with intravenous infusion of levosimendan (0.2 μg/kg/minute) and dobutamine (5 μg/kg/minute) for 24 hours respectively. During treatment we monitored hemodynamics and LVEF, and measured levels of heart-type fatty acid binding protein (HFABP), troponin I (TNI), and brain natriuretic peptide(BNP). In addition, the length of mechanical ventilation, intensive care unit (ICU) stay, hospital stay, and 28-day mortality were compared between the two groups.

          Results

          The levosimendan group and the dobutamine group were well matched with respect to age (years, 55.4±1 7.5 versus 50.2±13.6) and gender (males, 68.4% versus 57.9%). Levosimendan-treated patients had higher stroke volume index (SVI), cardiac index (CI), LVEF, and left ventricular stroke work index (LVSWI), and lower extravascular lung water index (EVLWI) compared to dobutamine-treated patients ( p<0.05). HFABP, TNI, and BNP in the levosimendan group were less than in the dobutamine group ( p<0.05). There was no difference in the mechanical ventilation time, length of stay in ICU and hospital, and 28-day mortality between the two groups.

          Conclusions

          Compared with dobutamine, levosimendan reduces biomarkers of myocardial injury and improves systemic hemodynamics in patients with septic shock. However, it does not reduce the days on mechanical ventilation, length of stay in ICU and hospital, or 28-day mortality.

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          Most cited references41

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          Mechanisms of sepsis-induced cardiac dysfunction.

          To review mechanisms underlying sepsis-induced cardiac dysfunction in general and intrinsic myocardial depression in particular. MEDLINE database. Myocardial depression is a well-recognized manifestation of organ dysfunction in sepsis. Due to the lack of a generally accepted definition and the absence of large epidemiologic studies, its frequency is uncertain. Echocardiographic studies suggest that 40% to 50% of patients with prolonged septic shock develop myocardial depression, as defined by a reduced ejection fraction. Sepsis-related changes in circulating volume and vessel tone inevitably affect cardiac performance. Although the coronary circulation during sepsis is maintained or even increased, alterations in the microcirculation are likely. Mitochondrial dysfunction, another feature of sepsis-induced organ dysfunction, will also place the cardiomyocytes at risk of adenosine triphosphate depletion. However, clinical studies have demonstrated that myocardial cell death is rare and that cardiac function is fully reversible in survivors. Hence, functional rather than structural changes seem to be responsible for intrinsic myocardial depression during sepsis. The underlying mechanisms include down-regulation of beta-adrenergic receptors, depressed postreceptor signaling pathways, impaired calcium liberation from the sarcoplasmic reticulum, and impaired electromechanical coupling at the myofibrillar level. Most, if not all, of these changes are regulated by cytokines and nitric oxide. Integrative studies are needed to distinguish the hierarchy of the various mechanisms underlying septic cardiac dysfunction. As many of these changes are related to severe inflammation and not to infection per se, a better understanding of septic myocardial dysfunction may be usefully extended to other systemic inflammatory conditions encountered in the critically ill. Myocardial depression may be arguably viewed as an adaptive event by reducing energy expenditure in a situation when energy generation is limited, thereby preventing activation of cell death pathways and allowing the potential for full functional recovery.
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            Brain natriuretic peptide: A marker of myocardial dysfunction and prognosis during severe sepsis.

            To investigate the value of brain natriuretic peptide plasma levels as a marker of systolic myocardial dysfunction during severe sepsis and septic shock. Prospective observational study. Intensive care unit. A total of 34 consecutive patients with severe sepsis (nine patients) or septic shock (25 patients) without previous cardiac, respiratory, or chronic renal failure. None. Myocardial systolic performance was assessed by fractional area contraction (FAC) using echocardiography performed on days 2 (FACD2) and 8. Plasma levels of brain natriuretic peptide were measured at days 1-4 and 8 after the beginning of severe sepsis. Among 34 patients (Simplified Acute Physiology Score II, 43 +/- 2.5), 15 (44%) presented with initial myocardial dysfunction (FACD2 or = 50%) myocardial dysfunction. Plasma levels of brain natriuretic peptide were significantly higher in patients with FACD2 or = 50% (p <.05) from day 2 to day 4. Brain natriuretic peptide levels were also significantly higher on days 2 and 3 in patients who died during their intensive care unit stay (p <.05). Systolic myocardial dysfunction is present in 44% of patient with severe sepsis or septic shock. In this setting, brain natriuretic peptide seems useful to detect myocardial dysfunction, and high plasma levels appear to be associated with poor outcome of sepsis, but further studies are needed.
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              Sepsis-associated myocardial dysfunction: diagnostic and prognostic impact of cardiac troponins and natriuretic peptides.

              Myocardial dysfunction, which is characterized by transient biventricular impairment of intrinsic myocardial contractility, is a common complication in patients with sepsis. Left ventricular systolic dysfunction is reflected by a reduced left ventricular stroke work index or, less accurately, by an impaired left ventricular ejection fraction (LVEF). Early recognition of myocardial dysfunction is crucial for the administration of the most appropriate therapy. Cardiac troponins and natriuretic peptides are biomarkers that were previously introduced for diagnosis and risk stratification in patients with acute coronary syndrome and congestive heart failure, respectively. However, their prognostic and diagnostic impact in critically ill patients warrants definition. The elevation of cardiac troponin levels in patients with sepsis, severe sepsis, or septic shock has been shown to indicate left ventricular dysfunction and a poor prognosis. Troponin release in this population occurs in the absence of flow-limiting coronary artery disease, suggesting the presence of mechanisms other than thrombotic coronary artery occlusion, probably a transient loss in membrane integrity with subsequent troponin leakage or microvascular thrombotic injury. In contrast to the rather uniform results of studies dealing with cardiac troponins, the impact of raised B-type natriuretic peptide (BNP) levels in patients with sepsis is less clear. The relationship between BNP and both LVEF and left-sided filling pressures is weak, and data on the prognostic impact of high BNP levels in patients with sepsis are conflicting. Mechanisms other than left ventricular wall stress may contribute to BNP release, including right ventricular overload, catecholamine therapy, renal failure, diseases of the CNS, and cytokine up-regulation. Whereas cardiac troponins may be integrated into the monitoring of myocardial dysfunction in patients with severe sepsis or septic shock to identify those patients requiring early and aggressive supportive therapy, the routine use of BNP and other natriuretic peptides in this setting is discouraged at the moment.
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                Author and article information

                Journal
                Med Sci Monit
                Med. Sci. Monit
                Medical Science Monitor
                Medical Science Monitor : International Medical Journal of Experimental and Clinical Research
                International Scientific Literature, Inc.
                1234-1010
                1643-3750
                2016
                03 May 2016
                : 22
                : 1486-1496
                Affiliations
                [1 ]Department of Intensive Care Unit, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejang, P.R. China
                [2 ]Department of Ultrasonography, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejang, P.R. China
                Author notes
                Corresponding Author: Geng Zhang, e-mail: zg_tdicu12@ 123456163.com
                [A]

                Study Design

                [B]

                Data Collection

                [C]

                Statistical Analysis

                [D]

                Data Interpretation

                [E]

                Manuscript Preparation

                [F]

                Literature Search

                [G]

                Funds Collection

                [*]

                Jian-biao Meng, Ma-hong Hu, and Zhi-zhen Lai contributed equally to this work

                Article
                898457
                10.12659/MSM.898457
                4861009
                27138236
                8502c987-f975-4e09-9f66-fef4b81a076b
                © Med Sci Monit, 2016

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License

                History
                : 11 March 2016
                : 05 April 2016
                Categories
                Clinical Research

                cardiomyopathies,fatty acid-binding proteins,hemodynamics,shock, septic

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