Effects of Levosimendan on Endothelial Function and Hemodynamics During Weaning From Veno-Arterial Extracorporeal Life Support

Sangalli, Fabio; Avalli, Leonello; Laratta, Matteo; Formica, Francesco; Maggioni, Elena; Caruso, Rosa; Costa, Maria Cristina Silva; Guazzi, Marco; Fumagalli, Roberto

doi:10.1053/j.jvca.2016.03.139

Cited by 30 publications

(31 citation statements)

References 16 publications

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“…The use of levosimendan in patients undergoing VA-ECMO might be of interest both to reduce the duration of mechanical support and to minimize severe complications. A potential benefit in terms of VA-ECMO weaning success and increased survival has been recently suggested in low cardiac output syndrome following cardiac surgery [12] with the improvement of endothelial function and hemodynamics [13]. We therefore sought to evaluate whether the use of levosimendan could improve weaning of VA-ECMO support in a large cohort of patients undergoing refractory cardiogenic shock.…”

Section: Introductionmentioning

confidence: 99%

Can levosimendan reduce ECMO weaning failure in cardiogenic shock?: a cohort study with propensity score analysis

et al. 2020

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Background: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) has been increasingly used over the last decade in patients with refractory cardiogenic shock. ECMO weaning can, however, be challenging and lead to circulatory failure and death. Recent data suggest a potential benefit of levosimendan for ECMO weaning. We sought to further investigate whether the use of levosimendan could decrease the rate of ECMO weaning failure in adult patients with refractory cardiogenic shock. Methods: We performed an observational single-center cohort study. All patients undergoing VA-ECMO from January 2012 to December 2018 were eligible and divided into two groups: group levosimendan and group control (without levosimendan). The primary endpoint was VA-ECMO weaning failure defined as death during VA-ECMO treatment or within 24 h after VA-ECMO removal. Secondary outcomes were mortality at day 28 and at 6 months. The two groups were compared after propensity score matching. P < 0.05 was considered statistically significant. Results: Two hundred patients were analyzed (levosimendan group: n = 53 and control group: n = 147). No significant difference was found between groups on baseline characteristics except for ECMO duration, which was longer in the levosimendan group (10.6 ± 4.8 vs. 6.5 ± 4.7 days, p < 0.001). Levosimendan administration started 6.6 ± 5.4 days on average following ECMO implantation. After matching of 48 levosimendan patients to 78 control patients, the duration of ECMO was similar in both groups. The rate of weaning failure was 29.1% and 35.4% in levosimendan and control groups, respectively (OR: 0.69, 95%CI: 0.25-1.88). No significant difference was found between groups for all secondary outcomes. Conclusion: Levosimendan did not improve the rate of successful VA-ECMO weaning in patients with refractory cardiogenic shock. Trial registration: ClinicalTrials.gov, NCT04323709.

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Section: Introductionmentioning

confidence: 99%

Can levosimendan reduce ECMO weaning failure in cardiogenic shock?: a cohort study with propensity score analysis

et al. 2020

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“…After baseline data evaluation, levosimendan was administered intravenously at the dose of 0.1 µg/kg/min without a loading dose, which is adopted in the ICU for the treatment of cardiogenic shock or low cardiac output patients [34,35]. In all patients, vasopressor support was implemented by epinephrine (0.01-0.1 µg/kg/min) and in one patient with dopamine (2 µg/kg/min), as well.…”

Section: Methodsmentioning

confidence: 99%

Levosimendan Improves Oxidative Balance in Cardiogenic Shock/Low Cardiac Output Patients

Grossini¹,

Farruggio²,

Pierelli

et al. 2020

JCM

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The beneficial effects exerted by levosimendan against cardiac failure could be related to the modulation of oxidative balance. We aimed to examine the effects of levosimendan in patients with cardiogenic shock or low cardiac output on cardiac systo-diastolic function and plasma oxidants/antioxidants (glutathione, GSH; thiobarbituric acid reactive substances, TBARS). In four patients undergoing coronary artery bypass grafting or angioplasty, cardiovascular parameters and plasma GSH and TBARS were measured at T0 (before levosimendan infusion), T1 (1 h after the achievement of the therapeutic dosage of levosimendan), T2 (end of levosimendan infusion), T3 (72 h after the end of levosimendan infusion), and T4 (end of cardiogenic shock). We found an improvement in the indices of systolic (ejection fraction, cardiac output, cardiac index) and diastolic (E to early diastolic mitral annular tissue velocity, E/'; early to late diastolic transmitral flow velocity, EA) cardiac function at early T2. A reduction of central venous pressure and pulmonary wedge pressure was also observed. Plasma levels of GSH and TBARS were restored by levosimendan at T1, as well. The results obtained indicate that levosimendan administration can regulate oxidant/antioxidant balance as an early effect in cardiogenic shock/low cardiac output patients. Modulation of oxidative status on a mitochondrial level could thus play a role in exerting the cardio-protection exerted by levosimendan in these patients.

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“…150 A range of ICU situations has been identified in which levosimendan may offer clinical benefits, either as an adjunct to existing interventions or as an alternative to conventional therapies. These situations include haemodynamic support in cardiac critical care, 151 haemodynamic support in septic cardiomyopathy, 152,153 weaning from the ventilator, 154 weaning from venoarterial extracorporeal membrane oxygenation after cardiac surgery, [155][156][157][158][159] and renal failure and kidney protection in cardiorenal syndrome. 97,130,132,[160][161][162][163][164][165][166] In several of these areas, notably low CO syndrome, cardiogenic shock, takotsubo cardiomyopathy and sepsis, a substantial element of any benefit accruing from use of levosimendan may be attributable to the substitution of a non-adrenergic stimulant for conventional catecholaminergic agents, such as dobutamine, thereby averting some of the potential toxic complications of adrenergic overstimulation.…”

Section: The Next 20 Years Of Levosimendanmentioning

confidence: 99%

Levosimendan Efficacy and Safety: 20 years of SIMDAX in Clinical Use

Papp¹,

Agostoni²,

Álvarez³

et al. 2020

Cardiac Failure Review

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Levosimendan was first approved for clinic use in 2000, when authorisation was granted by Swedish regulatory authorities for the haemodynamic stabilisation of patients with acutely decompensated chronic heart failure. In the ensuing 20 years, this distinctive inodilator, which enhances cardiac contractility through calcium sensitisation and promotes vasodilatation through the opening of adenosine triphosphate-dependent potassium channels on vascular smooth muscle cells, has been approved in more than 60 jurisdictions, including most of the countries of the European Union and Latin America. Areas of clinical application have expanded considerably and now include cardiogenic shock, takotsubo cardiomyopathy, advanced heart failure, right ventricular failure and pulmonary hypertension, cardiac surgery, critical care and emergency medicine. Levosimendan is currently in active clinical evaluation in the US. Levosimendan in IV formulation is being used as a research tool in the exploration of a wide range of cardiac and non-cardiac disease states. A levosimendan oral form is at present under evaluation in the management of amyotrophic lateral sclerosis. To mark the 20 years since the advent of levosimendan in clinical use, 51 experts from 23 European countries (Austria, Belgium, Croatia, Cyprus, Czech Republic, Estonia, Finland, France, Germany, Greece, Hungary, Italy, the Netherlands, Norway, Poland, Portugal, Russia, Slovenia, Spain, Sweden, Switzerland, UK and Ukraine) contributed to this essay, which evaluates one of the relatively few drugs to have been successfully introduced into the acute heart failure arena in recent times and charts a possible development trajectory for the next 20 years.

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Effects of Levosimendan on Endothelial Function and Hemodynamics During Weaning From Veno-Arterial Extracorporeal Life Support

Cited by 30 publications

References 16 publications

Can levosimendan reduce ECMO weaning failure in cardiogenic shock?: a cohort study with propensity score analysis

Can levosimendan reduce ECMO weaning failure in cardiogenic shock?: a cohort study with propensity score analysis

Levosimendan Improves Oxidative Balance in Cardiogenic Shock/Low Cardiac Output Patients

Levosimendan Efficacy and Safety: 20 years of SIMDAX in Clinical Use

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