Levosimendan does not reduce the mortality of critically ill adult patients with sepsis and septic shock

Feng, Fang; Chen, Yu; Yuan, Jiaojiao; Chang, Xue-Ni; Dong, Chenming

doi:10.1097/cm9.0000000000000197

Cited by 10 publications

(4 citation statements)

References 17 publications

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“…Randomized controlled studies of levosimendan versus either inotropic drugs or placebo for the treatment of sepsis or septic shock were included in the second recent meta-analysis. Feng and colleagues [ 27 ] identified 20 such trials that enrolled an aggregate of 1467 patients (levosimendan, n = 738; control, n = 729). Findings very similar to those of Liu et al were documented, with indications of improved cardiac function in the levosimendan group, plus reduction in serum lactate, but no robust impact on mortality.…”

Section: Septic Shockmentioning

confidence: 99%

Levosimendan in intensive care and emergency medicine: literature update and expert recommendations for optimal efficacy and safety

Girardis

Béttex

Bojan

et al. 2022

J Anesth Analg Crit Care

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The inodilator levosimendan, in clinical use for over two decades, has been the subject of extensive clinical and experimental evaluation in various clinical settings beyond its principal indication in the management of acutely decompensated chronic heart failure. Critical care and emergency medicine applications for levosimendan have included postoperative settings, septic shock, and cardiogenic shock. As the experience in these areas continues to expand, an international task force of experts from 15 countries (Austria, Belgium, China, Croatia, Finland, France, Germany, Greece, Hungary, Italy, the Netherlands, Spain, Sweden, Switzerland, and the USA) reviewed and appraised the latest additions to the database of levosimendan use in critical care, considering all the clinical studies, meta-analyses, and guidelines published from September 2019 to November 2021. Overall, the authors of this opinion paper give levosimendan a “should be considered” recommendation in critical care and emergency medicine settings, with different levels of evidence in postoperative settings, septic shock, weaning from mechanical ventilation, weaning from veno-arterial extracorporeal membrane oxygenation, cardiogenic shock, and Takotsubo syndrome, in all cases when an inodilator is needed to restore acute severely reduced left or right ventricular ejection fraction and overall haemodynamic balance, and also in the presence of renal dysfunction/failure.

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Section: Septic Shockmentioning

confidence: 99%

Levosimendan in intensive care and emergency medicine: literature update and expert recommendations for optimal efficacy and safety

Girardis

Béttex

Bojan

et al. 2022

J Anesth Analg Crit Care

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“…This may be due to the inclusion of patients with septic shock and cardiogenic shock in addition to those with HFrEF and cardiac surgery. Previous meta‐analyses 126,127 have also shown that levosimendan did not improve mortality rates in patients with septic shock and cardiogenic shock. To identify the subgroup of patients with greater survival benefit from levosimendan treatment, we performed subgroup analyses, which showed (Supporting Information, Figure ) that levosimendan significantly reduced mortality in patients with advanced heart failure.…”

Section: Discussionmentioning

confidence: 92%

Effect of levosimendan on ventricular remodelling in patients with left ventricular systolic dysfunction: a meta‐analysis

Wang,

Zhao,

Wang

et al. 2024

ESC Heart Failure

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Heart failure is the final stage of several cardiovascular diseases, and the key to effectively treating heart failure is to reverse or delay ventricular remodelling. Levosimendan is a novel inotropic and vasodilator agent used in heart failure, whereas the impact of levosimendan on ventricular remodelling is still unclear. This study aims to investigate the impact of levosimendan on ventricular remodelling in patients with left ventricular systolic dysfunction. Electronic databases were searched to identify eligible studies. A total of 66 randomized controlled trials involving 7968 patients were included. Meta‐analysis results showed that levosimendan increased left ventricular ejection fraction [mean difference (MD) = 3.62, 95% confidence interval (CI) (2.88, 4.35), P < 0.00001] and stroke volume [MD = 6.59, 95% CI (3.22, 9.96), P = 0.0001] and significantly reduced left ventricular end‐systolic volume [standard mean difference (SMD) = −0.52, 95% CI (−0.67, −0.37), P < 0.00001], left ventricular end‐diastolic volume index [SMD = −1.24, 95% CI (−1.61, −0.86), P < 0.00001], and left ventricular end‐systolic volume index [SMD = −1.06, 95% CI (−1.43, −0.70), P < 0.00001]. In terms of biomarkers, levosimendan significantly reduced the level of brain natriuretic peptide [SMD = −1.08, 95% CI (−1.60, −0.56), P < 0.0001], N‐terminal pro‐brain natriuretic peptide [SMD = −0.99, 95% CI (−1.41, −0.56), P < 0.00001], and interleukin‐6 [SMD = −0.61, 95% CI (−0.86, −0.35), P < 0.00001]. Meanwhile, levosimendan may increase the incidence of hypotension [risk ratio (RR) = 1.24, 95% CI (1.12, 1.39), P < 0.0001], hypokalaemia [RR = 1.57, 95% CI (1.08, 2.28), P = 0.02], headache [RR = 1.89, 95% CI (1.50, 2.39), P < 0.00001], atrial fibrillation [RR = 1.31, 95% CI (1.12, 1.52), P = 0.0005], and premature ventricular complexes [RR = 1.86, 95% CI (1.27, 2.72), P = 0.001]. In addition, levosimendan reduced all‐cause mortality [RR = 0.83, 95% CI (0.74, 0.94), P = 0.002]. In conclusion, our study found that levosimendan might reverse ventricular remodelling when applied in patients with left ventricular systolic dysfunction, especially in patients undergoing cardiac surgery, decompensated heart failure, and septic shock.

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“…Авторы комментария к исследованию LeoPARDS пришли к интересному выводу: это исследование не добавляет ничего нового, кроме информации о том, что использование левосимендана у пациентов с сепсисом, с низким системным сосудистым сопротивлением в отсутствие клинических признаков дисфункции миокарда не отличается по клинической эффективности от плацебо [64]. В дальнейшем в серии метаанализов авторам также не удалось выявить достоверной разницы в основных клинических исходах при использовании левосимендана у пациентов с тяжелым сепсисом/септическим шоком по сравнению с добутамином [65] или другими инотропными препаратами [66], однако стоит отметить, что в данные анализы были включены пациенты из исследования LeoPARDS, к интерпретации данных которого нужно подходить с учетом вышеупомянутых ограничений.…”

Section: сепсисunclassified

Levosimendan: current and possible areas of clinical application: A review

Boboshko,

Zibareva,

Lomivorotov

2023

Annals of Critical Care

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Levosimendan belongs to the class of calcium sensitizers, which exhibits its positive inotropic effects by increasing the affinity of troponin from the myocardium to calcium without additional myocardial oxygen demand, what favorably distinguishes it from catecholamines and their negative effects (myocardial ischemia, arrhythmias, vasoconstriction, hyperglycemia). In 2000, the drug was first used for the short-term treatment of decompensated chronic heart failure. After more than 20 years, the clinical use of levosimendan has covered a wide area among patients with pathology of the cardiovascular system and its use has gone far beyond the primary indications. To date, the drug has been studied in more than 200 randomized trials in patients with various clinical profiles: acute decompensation of chronic heart failure, progressive heart failure, acute myocardial infarction, cardiogenic shock, therapy of low cardiac output syndrome in cardiac surgery, perioperative use in pediatric cardiac surgery, septic shock, pulmonary hypertension, right ventricular failure, Takotsubo cardiomyopathy, patients with mechanical circulatory support devices. This review highlights the pharmacological features of the drug and key randomized clinical trials on the use of levosimendan in various categories of patients, in addition to officially recommended indications. The article also provides a brief overview of current and planned randomized trials.

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Levosimendan does not reduce the mortality of critically ill adult patients with sepsis and septic shock

Abstract: Supplemental Digital Content is available in the text

Cited by 10 publications

References 17 publications

Levosimendan in intensive care and emergency medicine: literature update and expert recommendations for optimal efficacy and safety

Levosimendan in intensive care and emergency medicine: literature update and expert recommendations for optimal efficacy and safety

Effect of levosimendan on ventricular remodelling in patients with left ventricular systolic dysfunction: a meta‐analysis

Levosimendan: current and possible areas of clinical application: A review

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