Prophylactic levosimendan for the prevention of low cardiac output syndrome and mortality in paediatric patients undergoing surgery for congenital heart disease
Open accessAbstract
BACKGROUND: Low cardiac output syndrome remains a serious complication, and accounts for substantial morbidity and mortality in the postoperative course of paediatric patients undergoing surgery for congenital heart disease. Standard prophylactic and therapeutic strategies for low cardiac output syndrome are based mainly on catecholamines, which are effective drugs, but have considerable side effects. Levosimendan, a calcium sensitiser, enhances the myocardial function by generating more energy-efficient myocardial contractility than achieved via adrenergic stimulation with catecholamines. Thus potentially, levosimendan is a beneficial alternative to standard medication for the prevention of low cardiac output syndrome in paediatric patients after open heart surgery. OBJECTIVES: To review the efficacy and safety of the postoperative prophylactic use of levosimendan for the prevention of low cardiac output syndrome and mortality in paediatric patients undergoing surgery for congenital heart disease. SEARCH METHODS: We identified trials via systematic searches of CENTRAL, MEDLINE, Embase, and Web of Science, as well as clinical trial registries, in June 2016. Reference lists from primary studies and review articles were checked for additional references. SELECTION CRITERIA: We only included randomised controlled trials (RCT) in our analysis that compared prophylactic levosimendan with standard medication or placebo, in infants and children up to 18 years of age, who were undergoing surgery for congenital heart disease. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed risk of bias according to a pre-defined protocol. We obtained additional information from all but one of the study authors of the included studies. We used the five GRADE considerations (study limitations, consistency of effect, imprecision, indirectness, and publication bias) to assess the quality of evidence from the studies that contributed data to the meta-analyses for the prespecified outcomes. We created a 'Summary of findings' table to summarise the results and the quality of evidence for each outcome. MAIN RESULTS: We included five randomised controlled trials with a total of 212 participants in the analyses. All included participants were under five years of age. Using GRADE, we assessed there was low-quality evidence for all analysed outcomes. We assessed high risk of performance and detection bias for two studies due to their unblinded setting. Levosimendan showed no clear effect on risk of mortality (risk ratio (RR) 0.47, 95% confidence interval (CI) 0.12 to 1.82; participants = 123; studies = 3) and no clear effect on low cardiac output syndrome (RR 0.64, 95% CI 0.39 to 1.04; participants = 83; studies = 2) compared to standard treatments. Data on time-to-death were not available from any of the included studies.There was no conclusive evidence on the effect of levosimendan on the secondary outcomes. The length of intensive care unit stays (mean difference (MD) 0.33 days, 95% CI -1.16 to 1.82; participants = 188; studies = 4), length of hospital stays (MD 0.26 days, 95% CI -3.50 to 4.03; participants = 75; studies = 2), duration of mechanical ventilation (MD -0.04 days, 95% CI -0.08 to 0.00; participants = 208; studies = 5), and the risk of mechanical circulatory support or cardiac transplantation (RR 1.49, 95% CI 0.19 to 11.37; participants = 60; studies = 2) did not clearly differ between the groups. Published data about adverse effects of levosimendan were limited. A meta-analysis of hypotension, one of the most feared side effects of levosimendan, was not feasible because of the heterogeneous expression of blood pressure values. AUTHORS' CONCLUSIONS: The current level of evidence is insufficient to judge whether prophylactic levosimendan prevents low cardiac output syndrome and mortality in paediatric patients undergoing surgery for congenital heart disease. So far, no significant differences have been detected between levosimendan and standard inotrope treatments in this setting.The authors evaluated the quality of evidence as low, using the GRADE approach. Reasons for downgrading were serious risk of bias (performance and detection bias due to unblinded setting of two RCTs), serious risk of inconsistency, and serious to very serious risk of imprecision (small number of included patients, low event rates).
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There is no uniform definition or criteria for LCOS in the literature.
“researchers do not use uniform criteria based on specific thresholds to describe the syndrome (definition) (13, 14).”
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Percentages, sums and reported differences re-computed from the paper’s own numbers.
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Cites
Preferred Reporting Items for Systematic Reviews and Meta-Analyses: the PRISMA statement
Moher, D., Liberati, A., Tetzlaff, J., Altman, D. G., & for the PRISMA Group (2009) · BMJ · doi:10.1136/bmj.b2535 · Cited by 83,823 · see citing works
Preferred reporting items for systematic reviews and meta-analyses: the PRISMA Statement.
(2009) · PubMed Central · Cited by 44,859 · see citing works
Dellinger, R. P., Levy, M. M., Rhodes, A., Annane, D., Gerlach, H., Opal, S. M., Sevransky, J., Sprung, C. L., Douglas, I. S., Jaeschke, R., et al. (2013) · Intensive Care Medicine · doi:10.1007/s00134-012-2769-8 · Cited by 7,282 · see citing works
Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.1. The Cochrane Collaboration
Higgins, J., Green, S. R., & Higgins, J. (2008) · Cited by 5,544 · see citing works
A modified test for small‐study effects in meta‐analyses of controlled trials with binary endpoints
Harbord, R. M., Egger, M., & Sterne, J. A. C. (2006) · Statistics in Medicine · doi:10.1002/sim.2380 · Cited by 2,267 · see citing works
Folláth, F., Cleland, J. G. F., Just, H., Papp, J. G., Scholz, H., PEUHKURINEN, K. J., Harjola, V., Mitrović, V. L., Abdalla, M., Sandell, E.-P., et al. (2002) · The Lancet · doi:10.1016/s0140-6736(02)09455-2 · Cited by 1,180 · see citing works
Wernovsky, G., Wypij, D., Jonas, R. A., Mayer, J. E., Hanley, F. L., Hickey, P. R., Walsh, A. Z., Chang, A. C., Castañeda, A. R., Newburger, J. W., et al. (1995) · Circulation · doi:10.1161/01.cir.92.8.2226 · Cited by 1,010 · see citing works
R Development Core Team (2010): R: A language and environment for statistical computing
Dalgaard, P. (2010) · Cited by 951 · see citing works
Hoffman, T. M., Wernovsky, G., Atz, A. M., Kulik, T. J., Nelson, D. P., Chang, A. C., Bailey, J. M., Akbary, A., Kocsis, J. F., Kaczmarek, R., et al. (2003) · Circulation · doi:10.1161/01.cir.0000051365.81920.28 · Cited by 772 · see citing works
Moiseyev, V. S. (2002) · European Heart Journal · doi:10.1053/euhj.2001.3158 · Cited by 599 · see citing works
Sample size calculations in randomised trials: mandatory and mystical
Schulz, K. F., & Grimes, D. A. (2005) · The Lancet · doi:10.1016/s0140-6736(05)61034-3 · Cited by 549 · see citing works
Overgaard, C. B., & Džavík, V. (2008) · Circulation · doi:10.1161/circulationaha.107.728840 · Cited by 518 · see citing works
Treatment-effect estimates adjusted for small-study effects via a limit meta-analysis
Rücker, G., Schwarzer, G., Carpenter, J. R., Binder, H., & Schumacher, M. C. (2010) · Biostatistics · doi:10.1093/biostatistics/kxq046 · Cited by 284 · see citing works
Elkayam, U., Tasissa, G., Binanay, C. A., Stevenson, L. W., Gheorghiade, M., Warnica, J. W., Young, J. B., Rayburn, B. K., Rogers, J. G., DeMarco, T., et al. (2006) · American Heart Journal · doi:10.1016/j.ahj.2006.09.005 · Cited by 241 · see citing works
Cardiac performance and mortality early after intracardiac surgery in infants and young children.
Parr, G. V., Blackstone, E. H., & Kirklin, J. W. (1975) · Circulation · doi:10.1161/01.cir.51.5.867 · Cited by 210 · see citing works
Evidence-based use of levosimendan in different clinical settings
Luca, L. D., Colucci, W. S., NIEMINEN, M., Massie, B. M., & Gheorghiade, M. (2006) · European Heart Journal · doi:10.1093/eurheartj/ehi875 · Cited by 178 · see citing works
Long-term prognosis of congenital heart defects: A systematic review
Verheugt, C. L., Uiterwaal, C. S. P. M., Grobbee, D. E., & Mulder, B. J. M. (2008) · International Journal of Cardiology · doi:10.1016/j.ijcard.2008.06.023 · Cited by 148 · see citing works
Graciano, A. L., Balko, J. A., Rahn, D. S., Ahmad, N., & Giroir, B. P. (2005) · Critical Care Medicine · doi:10.1097/01.ccm.0000170943.23633.47 · Cited by 144 · see citing works
Early experience with Levosimendan in children with ventricular dysfunction*
Namachivayam, P., Crossland, D. S., Butt, W. W., & Shekerdemian, L. S. (2006) · Pediatric Critical Care Medicine · doi:10.1097/01.pcc.0000235251.14491.75 · Cited by 128 · see citing works
Shi, S., Zhao, Z., Liu, X., Shu, Q., Tan, L., Lin, R., Shi, Z., & Fang, X. (2008) · CHEST Journal · doi:10.1378/chest.07-2573 · Cited by 127 · see citing works
Pharmacological Mechanisms Contributing to the Clinical Efficacy of Levosimendan
Papp, Z., Csapó, K., Pollesello, P., Haikala, H., & Edes, I. F. (2005) · Cardiovascular Drug Reviews · doi:10.1111/j.1527-3466.2005.tb00158.x · Cited by 113 · see citing works
Butts, R. J., Scheurer, M. A., Atz, A. M., Zyblewski, S. C., Hulsey, T. C., Bradley, S. M., & Graham, E. M. (2012) · Pediatric Cardiology · doi:10.1007/s00246-012-0193-z · Cited by 95 · see citing works
Causes of death after congenital heart surgery.
Ma, M., Gauvreau, K., Allan, C. K., Mayer, J., & Jenkins, K. (2007) · Annals of Thoracic Surgery · doi:10.1016/j.athoracsur.2006.10.073 · Cited by 89 · see citing works
Levosimendan in Congenital Cardiac Surgery: A Randomized, Double-Blind Clinical Trial
Momeni, M., Rubay, J., Matta, A., Rennotte, M., Veyckemans, F., Poncelet, A. J., de Clety, S. C., Anslot, C., Joomye, R., & Detaille, T. (2010) · Journal of Cardiothoracic and Vascular Anesthesia · doi:10.1053/j.jvca.2010.07.004 · Cited by 84 · see citing works
Pharmacokinetics of levosimendan in pediatric patients evaluated for cardiac surgery
Turanlahti, M., Boldt, T., Palkama, T., Antila, S., Lehtonen, L., & Pesonen, E. J. (2004) · Pediatric Critical Care Medicine · doi:10.1097/01.pcc.0000137355.01277.9c · Cited by 82 · see citing works
Levosimendan for Low Cardiac Output: A Pediatric Experience
Egan, J. R., Clarke, A., Williams, S. P., Cole, A. D., Ayer, J. G., Jacobe, S. J., Chard, R. B., & Winlaw, D. S. (2006) · Journal of Intensive Care Medicine · doi:10.1177/0885066606287039 · Cited by 82 · see citing works
Burkhardt, B. E., Rücker, G., & Stiller, B. (2015) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd009515.pub2 · Cited by 81 · see citing works
Lechner, E., Hofer, A., Leitner-Peneder, G., Freynschlag, R., Mair, R., Weinzettel, R., Rehak, P., & Gombotz, H. (2012) · Pediatric Critical Care Medicine · doi:10.1097/pcc.0b013e3182455571 · Cited by 79 · see citing works
The Search for the Ideal Positive Inotropic Agent
Packer, M. (1993) · New England Journal of Medicine · doi:10.1056/nejm199307153290310 · Cited by 74 · see citing works
Ricci, Z., Garisto, C., Favia, I., Vitale, V., Chiara, L. D., & Cogo, P. E. (2012) · Intensive Care Medicine · doi:10.1007/s00134-012-2564-6 · Cited by 71 · see citing works
Stocker, C., Shekerdemian, L., Nørgaard, M., Brizard, C., Mynard, J., Horton, S., & Penny, D. (2007) · Critical Care Medicine · doi:10.1097/01.ccm.0000251123.70632.4e · Cited by 68 · see citing works
Mechanisms of Action of Novel Cardiotonic Agents
Endoh, M. (2002) · Journal of Cardiovascular Pharmacology · doi:10.1097/00005344-200209000-00001 · Cited by 67 · see citing works
A Population Pharmacokinetic Analysis of Milrinone in Pediatric Patients After Cardiac Surgery
Bailey, J., Hoffman, T., Wessel, D., Nelson, D., Atz, A., Chang, A. C., Kulik, T., Spray, T., Akbary, A., Miller, R. P., et al. (2004) · Journal of Pharmacokinetics and Pharmacodynamics · doi:10.1023/b:jopa.0000029488.45177.48 · Cited by 64 · see citing works
Lim, J. Y., Deo, S. V., Rababa’h, A. M., Altarabsheh, S. E., Cho, Y. H., Hang, D., McGraw, M. P., Avery, E. G., Markowitz, A., & Park, S. J. (2015) · Journal of Cardiac Surgery · doi:10.1111/jocs.12562 · Cited by 62 · see citing works
Phase 1 study of two inodilators in neonates undergoing cardiovascular surgery
Pellicer, A., Riera, J., López‐Ortego, P., Bravo, M. C., Madero, R., Pérez‐Rodríguez, J., de Lera, C. L., Quero, J., Soto, A. B., Castro, L., et al. (2012) · Pediatric Research · doi:10.1038/pr.2012.154 · Cited by 55 · see citing works
Treatment of acute heart failure in an infant after cardiac surgery using levosimendan
BRAUN, J., SCHNEIDER, M., Kastrup, M., & LIU, J. (2004) · European Journal of Cardio-Thoracic Surgery · doi:10.1016/j.ejcts.2004.03.034 · Cited by 54 · see citing works
Ebade, A., Khalil, M. A., & Mohamed, A. K. (2012) · Journal of Anesthesia · doi:10.1007/s00540-012-1537-9 · Cited by 45 · see citing works
Bravo, M. C., López, P., Cabañas, F., Pérez‐Rodríguez, J., Pérez‐Fernández, E., & Pellicer, A. (2010) · Neonatology · doi:10.1159/000314955 · Cited by 39 · see citing works
First experiences with intraoperative Levosimendan in pediatric cardiac surgery
Osthaus, W. A., Boethig, D., Winterhalter, M., Huber, D., Goerler, H., Sasse, M., & Sümpelmann, R. (2009) · European Journal of Pediatrics · doi:10.1007/s00431-008-0834-7 · Cited by 38 · see citing works
Treatment for paediatric low cardiac output syndrome: results from the European EuLoCOS-Paed survey
Vogt, W., & Läer, S. (2011) · Archives of Disease in Childhood · doi:10.1136/archdischild-2011-300370 · Cited by 32 · see citing works
[Levosimendan, a new inotropic drug: experience in children with acute heart failure].
Magliola, R., Moreno, G., Vassallo, J. C., Landry, L. M., Althabe, M., Balestrini, M. R., Charroqui, A., Salgado, G. H., Lataza, E., & Chang, A. C. (2009) · PubMed · doi:10.1590/s0325-00752009000200008 · Cited by 30 · see citing works
Newer Inotropes in Pediatric Heart Failure
Hoffman, T. M. (2011) · Journal of Cardiovascular Pharmacology · doi:10.1097/fjc.0b013e3182163ba0 · Cited by 25 · see citing works
A Systematic Review on Levosimendan in Paediatric Patients
Silvetti, S., Silvani, P., Azzolini, M. L., Dossi, R., Landoni, G., & Zangrillo, A. (2014) · Current Vascular Pharmacology · doi:10.2174/1570161112666141127163536 · Cited by 23 · see citing works
Vela, J. L. P., Benitez, J. C. M., González, M. C., López, M. Á. D. L. C., Pérez, R. H., Meneses, V. S., & Sáez, F. D. N. (2012) · Medicina Intensiva · doi:10.1016/j.medin.2012.01.016 · Cited by 22 · see citing works
Froese, N. R., Sett, S. S., Mock, T., & Krahn, G. (2009) · Critical Care and Resuscitation · doi:10.1016/s1441-2772(23)01535-1 · Cited by 19 · see citing works
Chiara, L. D., Ricci, Z., Garisto, C., Morelli, S., Giorni, C., Vitale, V., Donato, R. M. D., & Picardo, S. G. (2009) · Pediatric Cardiology · doi:10.1007/s00246-009-9571-6 · Cited by 17 · see citing works
Vela, J. L. P., Benitez, J. C. M., González, M. C., López, M. Á. D. L. C., Pérez, R. H., Meneses, V. S., & Sáez, F. D. N. (2012) · Medicina Intensiva (English Edition) · doi:10.1016/j.medine.2012.01.007 · Cited by 17 · see citing works
Lobacheva, G. V., Kharkin, A. V., Manerova, A. F., & Роландовна, Д. Е. (2010) · PubMed · Cited by 12 · see citing works
Baysal, A., Şaşmazel, A., Yıldırım, A., Koçak, T., Sunar, H., & Zeybek, R. (2010) · PubMed · Cited by 9 · see citing works
de Palencia-Espinosa, M. F., Cárceles, M. D., Blázquez-Álvarez, M. J., Casañ, V. A., & de la Rubia-Nieto, A. (2012) · Revista Española de Anestesiología y Reanimación · doi:10.1016/j.redar.2012.06.002 · Cited by 6 · see citing works
Samadi, M., Malaki, M., Ghaffari, S., & Khalili, R. G. (2012) · Journal of Cardiovascular and Thoracic Research · doi:10.5681/jcvtr.2012.010 · Cited by 4 · see citing works
Flagged first, then by citations
2 of the 53 references couldn’t be matched to a known paper.
Research works printed but not linked: 2
- Fernández de Palencia-Espinosa MA, Cárceles-Barón MD, Blázquez-Álvarez MJ, Arocas-Casañ V, de la Rubia-Nieto A. [Retrospective descriptive study about the use of levosimendan in children undergoing surgical correction for congenital heart disease]. Revista Española de Anestesiología y Reanimación 2012;59(9):489-96.
- animal/ or nonhuman/) not human/ 93. 91 not 92 94. 75 and 93 Prophylactic levosimendan for the prevention of low cardiac output syndrome and mortality in paediatric patients undergoing surgery for congenital heart disease (Review) Copyright © 2017 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
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Sorted by citations
Schoonen, A., van Klei, W. A., van Wolfswinkel, L., & van Loon, K. (2022) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2022.926957 · Cited by 74 · see citing works
“However, despite the obvious interest in LCOS from a clinical perspective, researchers do not use uniform criteria based on specific thresholds to describe the syndrome (definition) (13, 14).”
BackgroundRoeleveld, P. P., & de Klerk, J. C. A. (2018) · World Journal for Pediatric and Congenital Heart Surgery · doi:10.1177/2150135117731725 · Cited by 51 · see citing works
“The current level of evidence is insufficient to judge whether prophylactic levosimendan prevents LCOS and mortality in pediatric patients undergoing surgery for congenital heart disease.(74) The use of levosimendan is reported by 5% of respondents of this survey.”
BackgroundWang, A., Cui, C., Fan, Y., Zi, J., Zhang, J., Wang, G., Wang, F., Wang, J., & Tan, Q. (2019) · Critical Care · doi:10.1186/s13054-019-2704-2 · Cited by 44 · see citing works
“The 2019 report of cardiovascular disease in China indicated that there are roughly 2 million individuals suffering from congenital heart disease (CHD), with over 110, 000 pediatric patients undergoing surgical treatment for this condition annually.”
BackgroundInfluentialSong, B., Dang, H., & Dong, R. (2021) · Journal of Cardiothoracic Surgery · doi:10.1186/s13019-021-01518-7 · Cited by 41 · see citing works
“A further increase in resistance increases the right ventricular afterload, which further leads to the occurrence of right heart failure and LCOS [24].”
BackgroundManagement of Neonatal Hypotension and Shock
Schwarz, C. E., & Dempsey, E. M. (2020) · Seminars in Fetal and Neonatal Medicine · doi:10.1016/j.siny.2020.101121 · Cited by 37 · see citing works
Silvetti, S., Belletti, A., Bianzina, S., & Momeni, M. (2021) · Journal of Cardiothoracic and Vascular Anesthesia · doi:10.1053/j.jvca.2021.09.018 · Cited by 28 · see citing works
An Update on Pharmacologic Management of Neonatal Hypotension: When, Why, and Which Medication
Agakidou, E., Chatziioannidis, I., Kontou, A., Stathopoulou, T., Chotas, W., & Sarafidis, K. (2024) · Children · doi:10.3390/children11040490 · Cited by 26 · see citing works
“The observed side effects have included tachycardia, arrythmia, and hypotension; however, the hypotension did not require intervention, or discontinuation of LEVO, only close monitoring [186].”
BackgroundWang, H.-B., Luo, Q., Li, Y.-N., Zhang, L., Wu, X., & Yan, F.-X. (2020) · Frontiers in Pediatrics · doi:10.3389/fped.2020.00456 · Cited by 21 · see citing works
“primarily investigated the effect of prophylactic levosimendan on mortality and LCOS incidence in pediatric patients undergoing surgery for congenital heart disease (9).”
BackgroundExploratory Assessment of Levosimendan in Infants With Congenital Diaphragmatic Hernia
Schroeder, L., Gries, K., Ebach, F., Mueller, A., & Kipfmueller, F. (2021) · Pediatric Critical Care Medicine · doi:10.1097/pcc.0000000000002665 · Cited by 22 · see citing works
“However, due to the design of these studies, evidence is still limited (21).”
BackgroundWang, P., Fu, C., Bai, G., Cuan, L., Tang, X., Jin, C., Jin, H., Zhu, J., & Xie, C. (2023) · Frontiers in Pediatrics · doi:10.3389/fped.2022.954427 · Cited by 20 · see citing works
Jothinath, K., Balakrishnan, S., Raju, V., Menon, S., & Osborn, J. (2021) · Annals of Cardiac Anaesthesia · doi:10.4103/aca.aca_160_19 · Cited by 18 · see citing works
Congenital Heart Disease: The State-of-the-Art on Its Pharmacological Therapeutics
Varela-Chinchilla, C. D., Sánchez-Mejía, D. E., & Trinidad-Calderón, P. A. (2022) · Journal of Cardiovascular Development and Disease · doi:10.3390/jcdd9070201 · Cited by 18 · see citing works
Effects of Vasopressin Infusion After Pediatric Cardiac Surgery: A Meta-analysis
Farias, J. S., Villarreal, E. G., Flores, S., Mastropietro, C. W., Vogel, M., Schulz, K., Culichia, C., Iliopoulos, I. D., Bronicki, R. A., & Loomba, R. S. (2020) · Pediatric Cardiology · doi:10.1007/s00246-020-02496-8 · Cited by 16 · see citing works
“Preventative medications include milrinone and levosimendan, while medications to manage low cardiac output syndrome include a variety of vasoactive agents such as dopamine, dobutamine, epinephrine, norepinephrine, and vasopressin [17, 18].”
BackgroundAbril-Molina, A., Gómez-Luque, J. M., Perín, F., Esteban-Molina, M., Ferreiro-Marzal, A., Fernández-Guerrero, C., & Ocete‐Hita, E. (2020) · Drugs in R&D · doi:10.1007/s40268-020-00332-1 · Cited by 15 · see citing works
“No fatal adverse effects have been reported [16].”
BackgroundMethodAre outcomes in congenital cardiac surgery better than ever?
Holcomb, R. M., & Ündar, A. (2022) · Journal of Cardiac Surgery · doi:10.1111/jocs.16225 · Cited by 14 · see citing works
“Unfortunately, these findings are similar to recently reported data.(69) This is problematic as LCOS is associated with poor clinical outcomes including prolonged ventilation time and hospital length of stay.”
BackgroundResultIacobelli, R., Ricci, Z., Marinari, E., Haiberger, R., Molfetta, A. D., Toscano, A., & Chiara, L. D. (2019) · Interactive Cardiovascular and Thoracic Surgery · doi:10.1093/icvts/ivz319 · Cited by 14 · see citing works
Wang, C., Gong, J., Shi, S., Wang, J., Gao, Y., Wang, S., Peng, Y., Song, J., & Wang, Y. (2018) · Frontiers in Pediatrics · doi:10.3389/fped.2018.00225 · Cited by 11 · see citing works
“The meta-analysis mentioned previously (19) summarized that prophylactic levosimendan had no positive influence on mortality.”
BackgroundLevosimendan for Perioperative Cardioprotection: Myth or Reality?
Santillo, E., Migale, M., Massini, C., & Incalzi, R. A. (2018) · Current Cardiology Reviews · doi:10.2174/1573403x14666180322104015 · Cited by 10 · see citing works
“Hummel J, 2017, [94] Studies on levosimendan versus standard”
BackgroundLevosimendan in paediatric cardiac anaesthesiology
Lapere, M., Rega, F., & Rex, S. (2022) · European Journal of Anaesthesiology · doi:10.1097/eja.0000000000001711 · Cited by 6 · see citing works
Ferraro, S., Biganzoli, E. M., Mannarino, S., Lanzoni, M., Zuccotti, G., Plebani, M., & Kavsak, P. A. (2024) · Clinical Chemistry · doi:10.1093/clinchem/hvad215 · Cited by 9 · see citing works
Burkhardt, B. E. U., Hummel, J., Rücker, G., & Stiller, B. (2024) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd013707.pub2 · Cited by 7 · see citing works
Asfari, A., Wolovits, J. S., Gazit, A. Z., Abbas, Q., Macfadyen, A. J., Cooper, D. S., Futterman, C., Penk, J. S., Kelly, R. B., Salvin, J. W., et al. (2023) · Critical Care Explorations · doi:10.1097/cce.0000000000001013 · Cited by 6 · see citing works
Burkhardt, B. E. U., Hummel, J., Rücker, G., & Stiller, B. (2020) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd013707 · Cited by 4 · see citing works
Beretta‐Piccoli, X., Biarent, D., Bels, D. D., Honoré, P. M., & Redant, S. (2020) · Critical Care · doi:10.1186/s13054-020-2812-z · Cited by 4 · see citing works
“, their total 864-patient sample size was calculated based on the incidence of mortality [7].”
BackgroundWannaz, L., Boillat, L., Perez, M., & Bernardo, S. D. (2023) · Frontiers in Pediatrics · doi:10.3389/fped.2023.1205971 · Cited by 3 · see citing works
“Most other teams in pediatrics use prophylactic Levosimendan perioperative or immediately after surgery, as described in Cochrane 2017 (26).”
BackgroundMethodInfluentialLevosimendan in pediatric and neonatal practice – Pro and Contra
Golomidov, A. V., Задворнов, А. А., Ivanova, A. V., Kryuchkova, O. G., Grigoryev, E. V., Moses, V. G., & Мозес, К. Б. (2023) · Messenger of Anesthesiology and Resuscitation · doi:10.24884/2078-5658-2023-20-3-84-93 · Cited by 3 · see citing works
Gayatri, D., Tongers, J., Efremov, L., Mikolajczyk, R., Sedding, D., & Schumann, J. E. (2024) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd013781.pub2 · Cited by 2 · see citing works
Yamaguchi, T., Tomonari, Y., Utsunomiya, S., Fujioka, N., & Asano, T. (2025) · Pediatric Cardiology · doi:10.1007/s00246-025-04041-x · Cited by 1 · see citing works
Liu, H. (2020) · Turkish Journal of Thoracic and Cardiovascular Surgery · doi:10.5606/tgkdc.dergisi.2020.20088 · Cited by 1 · see citing works
“[1-5] However, many patients need long-term mechanical ventilation after cardiac surgery, due to complications such as low cardiac output syndrome postoperatively.[6-9] The use of heat and moisture exchanger (HME) has been increasingly used in the intensive care unit (ICU) for patients requiring long-term mechanical v…”
BackgroundCardiopulmonary bypass in neonates and infants
Ündar, A., Patel, K., Holcomb, R. M., & Dan, Y. (2023) · Elsevier eBooks · doi:10.1016/b978-0-443-18918-0.00022-x · Cited by 1 · see citing works
Maître, G., Schaffner, D., Lava, S. A. G., Perez, M., & Bernardo, S. D. (2024) · European Journal of Pediatrics · doi:10.1007/s00431-024-05597-1 · Cited by 1 · see citing works
“…it should be acknowledged that despite a careful and restrictive scoring system, the retrospective definition of LCOS, albeit frequently used in pediatric studies [22–24], and probably the best research tool currently available to measure its occurrence, still suffers from some imprecision.”
BackgroundMethodCardiovascular Pharmacology in Adult Patients Undergoing Cardiac Surgery
Dabbagh, A., Tajbakhsh, A., Talebi, Z., & Rajaei, S. (2018) · Springer eBooks · doi:10.1007/978-3-319-75747-6_4 · Cited by 1 · see citing works
Current Trends and Critical Care Considerations for the Management of Single Ventricle Neonates
Wong, V. L., El-Said, H. G., Mueller, D. M., Nigro, J. J., Suttner, D. M., & Werho, D. K. (2020) · Current Pediatrics Reports · doi:10.1007/s40124-020-00227-4 · Cited by 1 · see citing works
Song, Y.-N., Chen, W., Pan, Y., Zhang, M., & Chen, H. (2023) · Translational Pediatrics · doi:10.21037/tp-22-498 · Cited by 1 · see citing works
“2 L·min·m, (II) vasoactive inotropic score >20 (13), (III) lactic acid >3 mmol/L (27 mg/dL) or at least 2 mmol/L (18 mg/dL) higher than the baseline, (IV) urine output <1 mL·kg·h, (V) core body-peripheral skin temperature difference >7 degrees, (VI) central venous oxygen saturation <50% or arterial-central venous oxyg…”
Herzinsuffizienz und Hypoxämie bei Kindern und Jugendlichen
Kramer, H. H. (2019) · Springer Reference Medizin · doi:10.1007/978-3-642-54671-6_200-2
Falla cardíaca en pacientes pediátricos. Fisiopatología y tratamiento. Parte II
Cassalett-Bustillo, G. (2018) · Revista Colombiana de Cardiología · doi:10.1016/j.rccar.2018.03.005
Another Outcome Lost to the Benefits of Levosimendan?*
Alexander, P. M. A., Akcan‐Arikan, A., & Shekerdemian, L. S. (2019) · Pediatric Critical Care Medicine · doi:10.1097/pcc.0000000000002019
“996 17April201925April2019 single-ventricle circulations (7).”
BackgroundEhrmann, D. E., Kaufman, J., & Gist, K. M. (2020) · Current Treatment Options in Pediatrics · doi:10.1007/s40746-020-00200-9
Development the Low Cardiac Output Syndrome Risk Score for Children after Congenital Heart SurgeryPreprint
Zhang, M., Chen, X., Xu, Y., Chen, Y., Zhang, Z., & Xu, Z. (2024) · Research Square · doi:10.21203/rs.3.rs-4740647/v1
Challenges in the treatment of hypotension in an extremely preterm neonate
Palić, I., Jovanovic-Krisulovic, B., Jovičić, M., & TODOROVIC, M. K. (2025) · Srpski arhiv za celokupno lekarstvo · doi:10.2298/sarh240711072p
- Authors
- Hummel, J., Rücker, G., & Stiller, B.
- Affiliations
- University of Freiburg (DE)
- Venue
- Cochrane Database of Systematic Reviews
- Publisher
- Wiley
- Published
- 2017-08-02
- Volume
- 2017
- Issue
- 8
- Pages
- CD011312-CD011312
- ISSN
- 1361-6137 (ISSN-L)
- 1465-1858
- PMC
- PMC6483297
- OpenAlex
- W2594672943
- Cited by
- 40
- References
- 53
- Citations by year
- 2025: 2 · 2024: 6 · 2023: 6 · 2022: 4 · 2021: 4 · 2020: 9 · 2019: 4 · 2018: 4 · 2017: 1
- FWCI
- 0.65
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cochrane Database of Systematic Reviews (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Epidemiology › Congenital Heart Disease Studies
- Health Sciences › Medicine › Surgery › Hemodynamic Monitoring and Therapy
- Health Sciences › Medicine › Surgery › Cardiac and Coronary Surgery Techniques
- Keywords
- levosimendan, low cardiac output syndrome, congenital heart disease, pediatric cardiac surgery, postoperative mortality, infants, postoperative complications
- MeSH terms
- Simendan, Assisted Circulation, Cardiac Output, Low, Cardiotonic Agents, Child, Preschool, Heart Defects, Congenital, Humans, Hydrazones, Infant, Length of Stay, Postoperative Complications, Pyridazines, Respiration, Artificial, Syndrome, Intensive Care Units, Pediatric, Randomized Controlled Trials as Topic
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