Levosimendan does not provide mortality benefit over dobutamine in adult patients with septic shock: A meta-analysis of randomized controlled trials

Bhattacharjee, Sulagna; Soni, Kapil Dev; Maitra, Souvik; Baidya, Dalim Kumar

doi:10.1016/j.jclinane.2017.03.011

Cited by 38 publications

(18 citation statements)

References 24 publications

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“…However, a recent network meta-analysis suggests that levosimendan has the highest probability of being the best treatment in septic shock [25]. Yet, no large randomized trials have provided evidence for a mortality benefit of levosimendan over dobutamine in septic shock [26].…”

Section: Introductionmentioning

confidence: 99%

Current use of inotropes in circulatory shock

Scheeren

Bakker

Kaufmann

et al. 2021

Ann. Intensive Care

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Background Treatment decisions on critically ill patients with circulatory shock lack consensus. In an international survey, we aimed to evaluate the indications, current practice, and therapeutic goals of inotrope therapy in the treatment of patients with circulatory shock. Methods From November 2016 to April 2017, an anonymous web-based survey on the use of cardiovascular drugs was accessible to members of the European Society of Intensive Care Medicine (ESICM). A total of 14 questions focused on the profile of respondents, the triggering factors, first-line choice, dosing, timing, targets, additional treatment strategy, and suggested effect of inotropes. In addition, a group of 42 international ESICM experts was asked to formulate recommendations for the use of inotropes based on 11 questions. Results A total of 839 physicians from 82 countries responded. Dobutamine was the first-line inotrope in critically ill patients with acute heart failure for 84% of respondents. Two-thirds of respondents (66%) stated to use inotropes when there were persistent clinical signs of hypoperfusion or persistent hyperlactatemia despite a supposed adequate use of fluids and vasopressors, with (44%) or without (22%) the context of low left ventricular ejection fraction. Nearly half (44%) of respondents stated an adequate cardiac output as target for inotropic treatment. The experts agreed on 11 strong recommendations, all of which were based on excellent (> 90%) or good (81–90%) agreement. Recommendations include the indications for inotropes (septic and cardiogenic shock), the choice of drugs (dobutamine, not dopamine), the triggers (low cardiac output and clinical signs of hypoperfusion) and targets (adequate cardiac output) and stopping criteria (adverse effects and clinical improvement). Conclusion Inotrope use in critically ill patients is quite heterogeneous as self-reported by individual caregivers. Eleven strong recommendations on the indications, choice, triggers and targets for the use of inotropes are given by international experts. Future studies should focus on consistent indications for inotrope use and implementation into a guideline for circulatory shock that encompasses individualized targets and outcomes.

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Section: Introductionmentioning

confidence: 99%

Current use of inotropes in circulatory shock

Scheeren

Bakker

Kaufmann

et al. 2021

Ann. Intensive Care

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“…Inodilator therapy can be applied in patients experiencing septic shock to restore or prevent contractility derangement that leads to uncoupling. Although the application of drugs that could further reduce the MAP in hypotensive patients seems controversial, a recent study showed that compared to dobutamine, norepinephrine requirements were not higher in patients treated with levosimendan [35].…”

Section: Inodilatorsmentioning

confidence: 99%

“…1h). Although most recent investigations have not clarified the beneficial effect of levosimendan over dobutamine in the treatment of septic shock [35,37], improvements seem to be evident in cellular metabolic alterations caused by sepsis [38]. Moreover, in a recent network meta-analysis, the authors concluded that levosimendan may have a superior beneficial effect on mortality [39•] compared to other drugs.…”

Section: Inodilatorsmentioning

confidence: 99%

Septic Shock and the Heart

Bertini

Guarracino

2019

Curr Anesthesiol Rep

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Purpose of Review The aim of this review is to analyze the cardiovascular pathophysiology of septic shock. Using visual representations of a left ventricular cycle in the pressure/volume plane, we describe hemodynamic derangement occurring in septic shock and subsequent changes at each step of treatment allowing a rapid understanding of complex alterations. Recent Findings Acute circulatory failure during sepsis has to be counterbalanced rapidly and appropriately. The most recent guidelines rely on volume expansion, vasoactive, and inotropic support but underlining patients' pathophysiology is often undetermined. Summary Diagnosis of the hemodynamic substrate needs to be carried out thoroughly, using echocardiography, now commonplace for the intensivist. A pathophysiological approach as we describe might help to understand complicated patterns allowing updates during resuscitation steps. Finally, in our beliefs, clinicians should address septic shock resuscitation using a tailored approach and specific protocols, but their applicability needs to be investigated.

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“…However, subsequent meta-analyses have shown negative results. For example, Bhattacharjee et al selected seven randomized controlled trials and concluded that levosimendan treatment had no beneficial effects compared to dobutamine treatment [64]. In 2018, a meta-analysis of 10 recent randomized controlled trials conducted by Chang et al showed that the levosimendan group had no beneficial results compared to the dobutamine or control groups.…”

Section: Introductionmentioning

confidence: 99%

Multiorgan Drug Action of Levosimendan in Critical Illnesses

Pan

Yang

Zhu

et al. 2019

BioMed Research International

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Cardiotonic drugs mainly include digitalis, catecholamines, phosphodiesterase inhibitors, and calcium sensitizers, which have been successively discovered and applied in clinical practice. However, there are only a few new drugs available in this field, and the selection is very limited. Digitalis, catecholamines, and phosphodiesterase inhibitors increase myocardial contractility by increasing intracellular concentrations of cyclic adenosine monophosphate (cAMP) and Ca2+, and this increase in intracellular calcium ion concentration enhances myocardial oxygen consumption and causes arrhythmia. For these reasons, the research focus on positive inotropic agents has shifted from calcium mobilization to calcium sensitization. Intracellular calcium sensitizers are more effective and safer drugs because they do not increase the intracellular concentration of calcium ions. However, only three calcium sensitizers have been fully developed and used in the past three decades. One of these drugs, levosimendan, has multiple molecular targets and exerts its pharmacological effects by not only increasing myocardial contractility, but also enhancing respiratory muscle function and liver and kidney protection, and it is useful for patients with severe sepsis and septic shock. Recently, more than 60 randomized controlled clinical trials of levosimendan have been reported; however, these clinical trials have occasionally shown different findings. This article reviews the research progress of levosimendan in critical illnesses in recent years.

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Levosimendan does not provide mortality benefit over dobutamine in adult patients with septic shock: A meta-analysis of randomized controlled trials

Cited by 38 publications

References 24 publications

Current use of inotropes in circulatory shock

Current use of inotropes in circulatory shock

Septic Shock and the Heart

Multiorgan Drug Action of Levosimendan in Critical Illnesses

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