Meta-analysis of the Safety and Efficacy of Levosimendan for Cardiac Insufficiency in Infants and Children

Summary

This meta-analysis of 16 studies suggests that levosimendan has a favorable safety profile in infants and children with cardiac insufficiency and is associated with an early, time-dependent reduction in lactate levels—an indicator of tissue hypoxia and impaired perfusion—without increasing the risk of adverse events.

Abstract

This meta-analysis aimed to evaluate the safety and efficacy of levosimendan for cardiac insufficiency in infants and children, conducted in accordance with PRISMA guidelines and a PROSPERO-registered protocol. Databases including PubMed, Web of Science, Embase, and the Cochrane Library were searched up to October 6, 2024. A total of 276 initial records were screened, and 16 studies (10 randomized controlled trials and 6 retrospective observational studies) were ultimately included. Meta-analyses using Stata and RevMan revealed that at 6 h post-intervention, levosimendan significantly reduced heart rate (WMD=-7.60, 95% CI [-15.16,-0.04]), mean arterial pressure (WMD=-4.04, 95% CI [-6.5,-1.58]), and lactate levels (SMD=-0.29, 95% CI [-0.58,-0.00]) compared with the control group. However, no significant effects on these three indices were observed at 12 or 24 h. Levosimendan showed no significant impacts on central venous pressure, oxygen saturation, B-type natriuretic peptide, ejection fraction, or length of hospitalization. It also did not increase the risks of acute kidney injury, arrhythmia, mortality, or pneumonia, and no publication bias was detected. In conclusion, levosimendan has a favorable safety profile in this pediatric population. Beneficial effects were observed early, mainly manifested by improvements in hypoxia-related indicators and reductions in heart rate and blood pressure within 6 h, without increasing adverse event risk, and the effects were limited to this early 6-h time point.

Introduction

Cardiac insufficiency is a complex clinical syndrome defined by structural or functional cardiac abnormalities that impair the heart’s ability to fill and eject blood¹. This results in insufficient tissue perfusion and an impaired capacity to meet the body’s metabolic demands, rendering it a leading cause of clinical mortality in pediatric populations². In infants and children, the etiology of cardiac insufficiency differs markedly from that in adults, with congenital heart disease and severe myocarditis as the primary pathogenic factors^3,4. Due to th....

Protocol

This meta-analysis was based on previously published clinical studies and did not involve human subjects, specimen collection, or experimental interventions, with ethical approval not required in accordance with international and national research ethics guidelines. This is a prescriptive meta-analysis protocol registered in PROSPERO (CRD420261335583) and fully compliant with the PRISMA reporting guidelines for systematic reviews and meta-analyses, for the systematic evaluation of the safety and efficacy of levosimendan in the treatment of cardiac insufficiency in infants and children. The protocol was initiated on September 1, 2024, as the procedural beginning, with ....

Results

Literature search and characteristics of included studies
This study initially identified 276 records from four databases (PubMed, Web of Science, Embase, Cochrane Library). Eighty-four duplicate records were removed, and the remaining articles were screened against predefined inclusion and exclusion criteria, with 176 articles failing to meet the criteria excluded. Finally, 16 articles were included in the qualitative and quantitative syntheses. The detailed literature screening process is illustrat.......

Discussion

Pediatric cardiac insufficiency is strongly associated with congenital heart disease and fulminant myocarditis and is a major cause of cardiogenic shock and mortality in children³. Traditional positive inotropic agents (e.g., catecholamines, phosphodiesterase inhibitors) are associated with increased mortality, whereas digitalis has a narrow therapeutic window. Pediatric patients' increased sensitivity to digitalis further elevates the risk of toxicity and adverse effects³³

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Excel Office Software 2019	Microsoft Corporation	https://www.microsoft.com/microsoft-365/excel	Data collation and normality verification
RevMan Analysis Software 5.4	The Cochrane Collaboration	https://training.cochrane.org/online-learning/core-software/revman	Forest plot generation and publication bias assessment
Stata Statistical Software 18	StataCorp LLC	https://www.stata.com	Heterogeneity tests and meta-analysis implementation