Effect of Levosimendan on Renal Outcome in Cardiac Surgery Patients With Chronic Kidney Disease and Perioperative Cardiovascular Dysfunction: A Substudy of a Multicenter Randomized Trial

Zangrillo, Alberto; Alvaro, Gabriele; Belletti, Alessandro; Pisano, Antonio; Brazzi, Luca; Calabrò, Maria Grazia; Guarracino, Fabio; Bove, Tiziana; Grigoryev, Evgeny; Monaco, Fabrizio; Boboshko, Vladimir; Лихванцев, В. В.; Scandroglio, Anna Mara; Paternoster, Gianluca; Lembo, Rosalba; Frassoni, Samuele; Comis, Marco; Pasyuga, Vadim; Navalesi, Paolo; Lomivorotov, Vladimir V.

doi:10.1053/j.jvca.2018.02.039

Cited by 25 publications

(15 citation statements)

References 48 publications

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“…Zangrillo et al 40 have recently published the findings of a subgroup analysis of the CHEETAH study linking levosimendan with a lower rate of post-operative acute kidney injury vis-à-vis placebo (30% vs. 52%, P = 0.035) in patients undergoing mitral valve surgery who developed post-operative myocardial dysfunction/low CO syndrome. These findings are consistent with other meta-analyses that have suggested a renal-protective benefit of levosimendan in a range of clinical situations 41 , 42 but, particularly because the REVIVE programme—to date the largest randomized study of levosimendan in AHF—produced no indications of significant impact on renal function, 12 such post hoc exercises must be regarded as in need of validation in prospective, randomized, controlled trials.…”

Section: Renal Effects Of Levosimendanmentioning

confidence: 99%

Use of levosimendan in acute heart failure

Harjola

Giannakoulas

Lewinski

et al. 2018

European Heart Journal Supplements

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As a calcium sensitizer and inodilator that augments cardiac contractility without increasing myocardial oxygen demand or exacerbating ischaemia, levosimendan may be well configured to deliver inotropic support in cases of acute heart failure (AHF). Other factors favouring levosimendan in this setting include its extended duration of action due to the formation of an active metabolite and the lack of any attenuation of effect in patients treated with beta-blockers. Effects of levosimendan on systemic haemodynamics include its significant, dose-dependent increases in cardiac output, stroke volume and heart rate, and decreases in right and left ventricular filling and total peripheral resistance. Rapid and sustained reduction in levels of natriuretic peptides is a consistent effect of levosimendan use and potentially favourable effects on other neurohormonal indicators of cardiac distress are also observed. Levosimendan has repeatedly been shown to be effective in relief of symptoms of AHF, notably dyspnoea and fatigue, while mortality data from clinical trials and registries suggest that levosimendan is markedly less likely than catecholaminergic inotropes to worsen prognosis. The vasodilator pharmacology of levosimendan is also pertinent to the drug’s use in AHF, in which setting organ under-perfusion is often a key pathology. These considerations suggest that levosimendan may have a more favourable impact on the circumstances of the majority of AHF patients than adrenergic agents that act only or primarily as cardiac stimulants. They also suggest that levosimendan may advantageously be integrated into a comprehensive strategy of early intervention designed and intended to prevent cardiac destabilization worsening to the point where hospitalization is necessary. Levosimendan should be used with caution and with tightened haemodynamic monitoring in patients who have low baseline blood pressure (systolic blood pressure <100 mmHg; diastolic blood pressure <60 mmHg), or who are at risk of a hypotensive episode.

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Section: Renal Effects Of Levosimendanmentioning

confidence: 99%

Use of levosimendan in acute heart failure

Harjola

Giannakoulas

Lewinski

et al. 2018

European Heart Journal Supplements

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“…Our findings of a lack of effect of levosimendan on GFR in postoperative AKI, are in line with the findings of those trials. In a sub-study of the CHEETAH trial [ 15 ], however, levosimendan was found to reduce the risk of AKI in a high-risk population, when used for treatment of the low cardiac output syndrome, postoperatively. Thus, one can speculate that levosimendan may exert beneficial effects on renal function only when used for treatment of heart failure as shown by the CHEETAH sub-study [ 15 ] and by our group demonstrating that levosimendan, but not dobutamine, increased GFR in patients with the cardiorenal syndrome [ 17 ].…”

Section: Discussionmentioning

confidence: 99%

“…Levosimendan is a calcium sensitizing agent used as an inodilator in cardiac failure. Although three major trials have failed to demonstrate a superiority of levosimendan over placebo regarding prevention of major adverse outcomes after cardiac surgery such as acute kidney injury [ 9 – 11 ], other studies have shown that levosimendan may have beneficial effects on renal function in several clinical situations [ 12 – 15 ]. More specifically, levosimendan increases RBF through renal vasodilation with preference for the afferent arterioles, resulting in higher intra-glomerular pressure and increased filtration [ 16 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

Effects of levosimendan on renal blood flow and glomerular filtration in patients with acute kidney injury after cardiac surgery: a double blind, randomized placebo-controlled study

2021

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Background Acute kidney injury (AKI) is a common and serious complication after cardiac surgery, and current strategies aimed at treating AKI have proven ineffective. Levosimendan, an inodilatating agent, has been shown to increase renal blood flow and glomerular filtration rate in uncomplicated postoperative patients and in patients with the cardiorenal syndrome. We hypothesized that levosimendan through its specific effects on renal vasculature, a preferential vasodilating effect on preglomerular resistance vessels, could improve renal function in AKI-patients with who did not have clinical indication for inotropic support. Methods In this single-center, double-blind, randomized controlled study, adult patients with postoperative AKI within 2 days after cardiac surgery, who were hemodynamically stable with a central venous oxygen saturation (ScvO2) ≥ 60% without inotropic support were eligible for inclusion. After randomization, study drug infusions, levosimendan (n = 16) or placebo (n = 13) were given for 5 h. A bolus infusion of levosimendan (12 µg/kg), were given for 30 min followed by 0.1 µg/kg/min for 5 h. Renal blood flow and glomerular filtration rate were measured using infusion clearance of para-aminohippuric acid and a filtration marker, respectively. As a safety issue, norepinephrine was administered to maintain mean arterial pressure between 70–80 mmHg. Intra-group differences were tested by Mann–Whitney U-tests, and a linear mixed model was used to test time and group interaction. Results Twenty-nine patients completed the study. At inclusion, the mean serum creatinine was higher in the patients randomized to levosimendan (148 ± 29 vs 127 ± 22 µmol/L, p = 0.030), and the estimated GFR was lower (46 ± 12 vs 57 ± 11 ml/min/1.73 m2, p = 0.025). Levosimendan induced a significantly (p = 0.011) more pronounced increase in renal blood flow (15%) compared placebo (3%) and a more pronounced decrease in renal vascular resistance (− 18% vs. − 4%, respectively, p = 0.043). There was a trend for a minor increase in glomerular filtration rate with levosimendan (4.5%, p = 0.079), which did differ significantly from the placebo group (p = 0.440). The mean norepinephrine dose was increased by 82% in the levosimedan group and decreased by 29% in the placebo group (p = 0.012). Conclusions In hemodynamically stable patients with AKI after cardiac surgery, levosimendan increases renal blood flow through renal vasodilatation. Trial registration NCT02531724, prospectly registered on 08/20/2015. https://clinicaltrials.gov/ct2/show/NCT02531724?cond=AKI&cntry=SE&age=1&draw=2&rank=1

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“…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. 167 'Decatecholaminisation' of the medical armamentarium is a developing line of practice in the management of critically ill patients.…”

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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Effect of Levosimendan on Renal Outcome in Cardiac Surgery Patients With Chronic Kidney Disease and Perioperative Cardiovascular Dysfunction: A Substudy of a Multicenter Randomized Trial

Cited by 25 publications

References 48 publications

Use of levosimendan in acute heart failure

Use of levosimendan in acute heart failure

Effects of levosimendan on renal blood flow and glomerular filtration in patients with acute kidney injury after cardiac surgery: a double blind, randomized placebo-controlled study

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

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