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Published in: Pediatric Cardiology 1/2018

01-01-2018 | Original Article

Use of Levosimendan in Postoperative Setting After Surgical Repair of Congenital Heart Disease in Children

Authors: Vivianne Amiet, Marie-Hélène Perez, David Longchamp, Tatiana Boulos Ksontini, Julia Natterer, Sonia Plaza Wuthrich, Jacques Cotting, Stefano Di Bernardo

Published in: Pediatric Cardiology | Issue 1/2018

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Abstract

Low cardiac output is one of the most common complications after cardiac surgery. Levosimendan, a new inotrope agent, has been demonstrated in adult patient to be an effective treatment for this purpose when classical therapy is not effective. The aim of this study was to evaluate the effect of Levosimendan on cardiac output parameters in cardiac children with low cardiac output syndrome (LCOS.). We carried out a retrospective analysis on 62 children hospitalized in our pediatric intensive care unit (PICU) after cardiac surgery, which demonstrated LCOS not responding to classical catecholamine therapy and who received levosimendan as rescue therapy. LCOS parameters like diuresis, central venous oxygen saturation (SvO2), venous-to-arterial CO2 difference (∆avCO2), and plasmatic lactate were compared before therapy and at 3, 6, 12, and 24 h after the beginning of the levosimendan infusion. We also analyzed the effect on the Vasoactive-inotropic score (VIS), adverse events, and mortality. After the beginning of levosimendan infusion, diuresis (1.1 vs. 3.5 ml/kg/h, p = 0.001) and SvO2 (59.5 vs. 63.3%, p = 0.026) increased significantly during the 24 h of infusion, and at the same time, plasmatic lactate (2.3 vs. 1.3 mmol/l, p < 0.001) decreased. ∆avCO2 (10.8 vs. 9.4 mmHg, p = 0.21) and the VIS (44.5 vs. 22.5, p = 0.143) also decreased, but not significantly. No side effects were noted. The mortality in this patient group was 16%. Levosimendan is an effective treatment in children presenting LCOS after congenital heart surgery. Our study confirms the improvement of cardiac output already shown in other pediatric studies, with no undesirable side effects.
Literature
1.
go back to reference Wernovsky G, Wypij D, Jonas RA, Mayer JE, Hanley FL, Hickey PR, Walsh AZ, Chang AC, Castañeda AR, Newburger JW, Wessel DL (1995) Postoperative course and hemodynamic profile after the arterial switch operation in neonates and infants. A comparison of low-flow cardiopulmonary bypass and circulatory arrest. Circulation 92:2226–2235CrossRefPubMed Wernovsky G, Wypij D, Jonas RA, Mayer JE, Hanley FL, Hickey PR, Walsh AZ, Chang AC, Castañeda AR, Newburger JW, Wessel DL (1995) Postoperative course and hemodynamic profile after the arterial switch operation in neonates and infants. A comparison of low-flow cardiopulmonary bypass and circulatory arrest. Circulation 92:2226–2235CrossRefPubMed
2.
go back to reference Parr GV, Blackstone EH, Kirklin JW (1975) Cardiac performance and mortality early after intracardiac surgery in infants and young children. Circulation 51:867–874CrossRefPubMed Parr GV, Blackstone EH, Kirklin JW (1975) Cardiac performance and mortality early after intracardiac surgery in infants and young children. Circulation 51:867–874CrossRefPubMed
3.
go back to reference Carmona F, Manso PH, Vicente WV, Castro M, Carlotti AP (2008) Risk stratification in neonates and infants submitted to cardiac surgery with cardiopulmonary bypass: a multimarker approach combining inflammatory mediators N-terminal pro-B-type natriuretic peptide and troponin I. Cytokine 42:317–324CrossRefPubMed Carmona F, Manso PH, Vicente WV, Castro M, Carlotti AP (2008) Risk stratification in neonates and infants submitted to cardiac surgery with cardiopulmonary bypass: a multimarker approach combining inflammatory mediators N-terminal pro-B-type natriuretic peptide and troponin I. Cytokine 42:317–324CrossRefPubMed
4.
go back to reference Gessler P, Knirsch W, Schmitt B, Rousson V, von Eckardstein A (2006) Prognostic value of plasma N-terminal pro-brain natriuretic peptide in children with congenital heart defects and open-heart surgery. J Pediatr 148:372–376CrossRefPubMed Gessler P, Knirsch W, Schmitt B, Rousson V, von Eckardstein A (2006) Prognostic value of plasma N-terminal pro-brain natriuretic peptide in children with congenital heart defects and open-heart surgery. J Pediatr 148:372–376CrossRefPubMed
5.
go back to reference Haikala H, Kaivola J, Nissinen E, Wall P, Levijoki J, Linden IB (1995) Cardiac troponin C as a target protein for a novel calcium sensitizing drug, levosimendan. J Mol Cell Cardiol 27:1859–1866CrossRefPubMed Haikala H, Kaivola J, Nissinen E, Wall P, Levijoki J, Linden IB (1995) Cardiac troponin C as a target protein for a novel calcium sensitizing drug, levosimendan. J Mol Cell Cardiol 27:1859–1866CrossRefPubMed
6.
7.
go back to reference Parissis JT, Panou F, Farmakis D, Adamopoulos S, Filippatos G, Paraskevaidis I, Venetsanou K, Lekakis J, Kremastinos DT (2005) Effects of levosimendan on markers of left ventricular diastolic function and neurohormonal activation in patients with advanced heart failure. Am J Cardiol 96:423–426CrossRefPubMed Parissis JT, Panou F, Farmakis D, Adamopoulos S, Filippatos G, Paraskevaidis I, Venetsanou K, Lekakis J, Kremastinos DT (2005) Effects of levosimendan on markers of left ventricular diastolic function and neurohormonal activation in patients with advanced heart failure. Am J Cardiol 96:423–426CrossRefPubMed
8.
go back to reference Dernellis J, Panaretou M (2005) Effects of levosimendan on restrictive left ventricular filling in severe heart failure: a combined hemodynamic and Doppler echocardiographic study. Chest 128:2633–2639CrossRefPubMed Dernellis J, Panaretou M (2005) Effects of levosimendan on restrictive left ventricular filling in severe heart failure: a combined hemodynamic and Doppler echocardiographic study. Chest 128:2633–2639CrossRefPubMed
9.
go back to reference Sorsa T, Heikkinen S, Abbott MB, Abusamhadneh E, Laakso T, Tilgmann C, Serimaa R, Annila A, Rosevear PR, Drakenberg T, Pollesello P, Kilpelainen I (2001) Binding of levosimendan, a calcium sensitizer, to cardiac troponin C. J Biol Chem 276:9337–9343CrossRefPubMed Sorsa T, Heikkinen S, Abbott MB, Abusamhadneh E, Laakso T, Tilgmann C, Serimaa R, Annila A, Rosevear PR, Drakenberg T, Pollesello P, Kilpelainen I (2001) Binding of levosimendan, a calcium sensitizer, to cardiac troponin C. J Biol Chem 276:9337–9343CrossRefPubMed
10.
go back to reference Michaels AD, McKeown B, Kostal M, Vakharia KT, Jordan MV, Gerber IL, Foster E, Chatterjee K (2005) Effects of intravenous levosimendan on human coronary vasomotor regulation, left ventricular wall stress, and myocardial oxygen uptake. Circulation 111:1504–1509CrossRefPubMed Michaels AD, McKeown B, Kostal M, Vakharia KT, Jordan MV, Gerber IL, Foster E, Chatterjee K (2005) Effects of intravenous levosimendan on human coronary vasomotor regulation, left ventricular wall stress, and myocardial oxygen uptake. Circulation 111:1504–1509CrossRefPubMed
11.
go back to reference Kivikko M, Lehtonen L (2005) Levosimendan: a new inodilatory drug for the treatment of decompensated heart failure. Curr Pharm Des 11:435–455CrossRefPubMed Kivikko M, Lehtonen L (2005) Levosimendan: a new inodilatory drug for the treatment of decompensated heart failure. Curr Pharm Des 11:435–455CrossRefPubMed
12.
go back to reference Slawsky MT, Colucci WS, Gottlieb SS, Greenberg BH, Haeusslein E, Hare J, Hutchins S, Leier CV, LeJemtel TH, Loh E, Nicklas J, Ogilby D, Singh BN, Smith W (2000) Acute hemodynamic and clinical effects of levosimendan in patients with severe heart failure. Study investigators. Circulation 102:2222–2227CrossRefPubMed Slawsky MT, Colucci WS, Gottlieb SS, Greenberg BH, Haeusslein E, Hare J, Hutchins S, Leier CV, LeJemtel TH, Loh E, Nicklas J, Ogilby D, Singh BN, Smith W (2000) Acute hemodynamic and clinical effects of levosimendan in patients with severe heart failure. Study investigators. Circulation 102:2222–2227CrossRefPubMed
13.
go back to reference Nijhawan N, Nicolosi AC, Montgomery MW, Aggarwal A, Pagel PS, Warltier DC (1999) Levosimendan enhances cardiac performance after cardiopulmonary bypass: a prospective, randomized placebo-controlled trial. J Cardiovasc Pharmacol 34:219–228CrossRefPubMed Nijhawan N, Nicolosi AC, Montgomery MW, Aggarwal A, Pagel PS, Warltier DC (1999) Levosimendan enhances cardiac performance after cardiopulmonary bypass: a prospective, randomized placebo-controlled trial. J Cardiovasc Pharmacol 34:219–228CrossRefPubMed
14.
go back to reference Barisin S, Husedzinovic I, Sonicki Z, Bradic N, Barisin A, Tonkovic D (2004) Levosimendan in off-pump coronary artery bypass: a four-times masked controlled study. J Cardiovasc Pharmacol 44:703–708CrossRefPubMed Barisin S, Husedzinovic I, Sonicki Z, Bradic N, Barisin A, Tonkovic D (2004) Levosimendan in off-pump coronary artery bypass: a four-times masked controlled study. J Cardiovasc Pharmacol 44:703–708CrossRefPubMed
15.
go back to reference Follath F, Cleland JG, Just H, Papp JG, Scholz H, Peuhkurinen K, Harjola VP, Mitrovic V, Abdalla M, Sandell EP, Lehtonen L, Study SCaIotLIvDL (2002) Efficacy and safety of intravenous levosimendan compared with dobutamine in severe low-output heart failure (the LIDO study): a randomised double-blind trial. Lancet 360:196–202CrossRefPubMed Follath F, Cleland JG, Just H, Papp JG, Scholz H, Peuhkurinen K, Harjola VP, Mitrovic V, Abdalla M, Sandell EP, Lehtonen L, Study SCaIotLIvDL (2002) Efficacy and safety of intravenous levosimendan compared with dobutamine in severe low-output heart failure (the LIDO study): a randomised double-blind trial. Lancet 360:196–202CrossRefPubMed
16.
go back to reference Husebye T, Eritsland J, Muller C, Sandvik L, Arnesen H, Seljeflot I, Mangschau A, Bjornerheim R, Andersen GO (2013) Levosimendan in acute heart failure following primary percutaneous coronary intervention-treated acute ST-elevation myocardial infarction. Results from the LEAF trial: a randomized, placebo-controlled study. Eur J Heart Fail 15:565–572CrossRefPubMed Husebye T, Eritsland J, Muller C, Sandvik L, Arnesen H, Seljeflot I, Mangschau A, Bjornerheim R, Andersen GO (2013) Levosimendan in acute heart failure following primary percutaneous coronary intervention-treated acute ST-elevation myocardial infarction. Results from the LEAF trial: a randomized, placebo-controlled study. Eur J Heart Fail 15:565–572CrossRefPubMed
17.
go back to reference Altenberger J, Parissis JT, Costard-Jaeckle A, Winter A, Ebner C, Karavidas A, Sihorsch K, Avgeropoulou E, Weber T, Dimopoulos L, Ulmer H, Poelzl G (2014) Efficacy and safety of the pulsed infusions of levosimendan in outpatients with advanced heart failure (LevoRep) study: a multicentre randomized trial. Eur J Heart Fail 16:898–906CrossRefPubMed Altenberger J, Parissis JT, Costard-Jaeckle A, Winter A, Ebner C, Karavidas A, Sihorsch K, Avgeropoulou E, Weber T, Dimopoulos L, Ulmer H, Poelzl G (2014) Efficacy and safety of the pulsed infusions of levosimendan in outpatients with advanced heart failure (LevoRep) study: a multicentre randomized trial. Eur J Heart Fail 16:898–906CrossRefPubMed
18.
go back to reference Turanlahti M, Boldt T, Palkama T, Antila S, Lehtonen L, Pesonen E (2004) Pharmacokinetics of levosimendan in pediatric patients evaluated for cardiac surgery. Pediatr Crit Care Med 5:457–462CrossRefPubMed Turanlahti M, Boldt T, Palkama T, Antila S, Lehtonen L, Pesonen E (2004) Pharmacokinetics of levosimendan in pediatric patients evaluated for cardiac surgery. Pediatr Crit Care Med 5:457–462CrossRefPubMed
19.
go back to reference Lechner E, Moosbauer W, Pinter M, Mair R, Tulzer G (2007) Use of levosimendan, a new inodilator, for postoperative myocardial stunning in a premature neonate. Pediatr Crit Care Med 8:61–63CrossRefPubMed Lechner E, Moosbauer W, Pinter M, Mair R, Tulzer G (2007) Use of levosimendan, a new inodilator, for postoperative myocardial stunning in a premature neonate. Pediatr Crit Care Med 8:61–63CrossRefPubMed
20.
go back to reference Braun JP, Schneider M, Kastrup M, Liu J (2004) Treatment of acute heart failure in an infant after cardiac surgery using levosimendan. Eur J Cardiothorac Surg 26:228–230CrossRefPubMed Braun JP, Schneider M, Kastrup M, Liu J (2004) Treatment of acute heart failure in an infant after cardiac surgery using levosimendan. Eur J Cardiothorac Surg 26:228–230CrossRefPubMed
21.
go back to reference Egan JR, Clarke AJ, Williams S, Cole AD, Ayer J, Jacobe S, Chard RB, Winlaw DS (2006) Levosimendan for low cardiac output: a pediatric experience. J Intensive Care Med 21:183–187CrossRefPubMed Egan JR, Clarke AJ, Williams S, Cole AD, Ayer J, Jacobe S, Chard RB, Winlaw DS (2006) Levosimendan for low cardiac output: a pediatric experience. J Intensive Care Med 21:183–187CrossRefPubMed
22.
go back to reference Namachivayam P, Crossland DS, Butt WW, Shekerdemian LS (2006) Early experience with Levosimendan in children with ventricular dysfunction. Pediatr Crit Care Med 7:445–448CrossRefPubMed Namachivayam P, Crossland DS, Butt WW, Shekerdemian LS (2006) Early experience with Levosimendan in children with ventricular dysfunction. Pediatr Crit Care Med 7:445–448CrossRefPubMed
23.
go back to reference Suominen PK (2011) Single-center experience with levosimendan in children undergoing cardiac surgery and in children with decompensated heart failure. BMC Anesthesiol 11:18CrossRefPubMedPubMedCentral Suominen PK (2011) Single-center experience with levosimendan in children undergoing cardiac surgery and in children with decompensated heart failure. BMC Anesthesiol 11:18CrossRefPubMedPubMedCentral
24.
go back to reference Gaies MG, Gurney JG, Yen AH, Napoli ML, Gajarski RJ, Ohye RG, Charpie JR, Hirsch JC (2010) Vasoactive-inotropic score as a predictor of morbidity and mortality in infants after cardiopulmonary bypass. Pediatr Crit Care Med 11:234–238CrossRefPubMed Gaies MG, Gurney JG, Yen AH, Napoli ML, Gajarski RJ, Ohye RG, Charpie JR, Hirsch JC (2010) Vasoactive-inotropic score as a predictor of morbidity and mortality in infants after cardiopulmonary bypass. Pediatr Crit Care Med 11:234–238CrossRefPubMed
25.
go back to reference Ricci Z, Garisto C, Favia I, Vitale V, Di Chiara L, Cogo PE (2012) Levosimendan infusion in newborns after corrective surgery for congenital heart disease: randomized controlled trial. Intensiv Care Med 38:1198–1204CrossRef Ricci Z, Garisto C, Favia I, Vitale V, Di Chiara L, Cogo PE (2012) Levosimendan infusion in newborns after corrective surgery for congenital heart disease: randomized controlled trial. Intensiv Care Med 38:1198–1204CrossRef
26.
go back to reference Salmenpera M, Eriksson H (2009) Levosimendan in perioperative and critical care patients. Curr Opin Anaesthesiol 22:496–501CrossRefPubMed Salmenpera M, Eriksson H (2009) Levosimendan in perioperative and critical care patients. Curr Opin Anaesthesiol 22:496–501CrossRefPubMed
27.
go back to reference Eriksson HI, Jalonen JR, Heikkinen LO, Kivikko M, Laine M, Leino KA, Kuitunen AH, Kuttila KT, Perakyla TK, Sarapohja T, Suojaranta-Ylinen RT, Valtonen M, Salmenpera MT (2009) Levosimendan facilitates weaning from cardiopulmonary bypass in patients undergoing coronary artery bypass grafting with impaired left ventricular function. Ann Thorac Surg 87:448–454CrossRefPubMed Eriksson HI, Jalonen JR, Heikkinen LO, Kivikko M, Laine M, Leino KA, Kuitunen AH, Kuttila KT, Perakyla TK, Sarapohja T, Suojaranta-Ylinen RT, Valtonen M, Salmenpera MT (2009) Levosimendan facilitates weaning from cardiopulmonary bypass in patients undergoing coronary artery bypass grafting with impaired left ventricular function. Ann Thorac Surg 87:448–454CrossRefPubMed
28.
go back to reference Landoni G, Mizzi A, Biondi-Zoccai G, Bignami E, Prati P, Ajello V, Marino G, Guarracino F, Zangrillo A (2010) Levosimendan reduces mortality in critically ill patients. A meta-analysis of randomized controlled studies. Minerva Anestesiol 76:276–286PubMed Landoni G, Mizzi A, Biondi-Zoccai G, Bignami E, Prati P, Ajello V, Marino G, Guarracino F, Zangrillo A (2010) Levosimendan reduces mortality in critically ill patients. A meta-analysis of randomized controlled studies. Minerva Anestesiol 76:276–286PubMed
29.
go back to reference Lilleberg J, Laine M, Palkama T, Kivikko M, Pohjanjousi P, Kupari M (2007) Duration of the haemodynamic action of a 24-h infusion of levosimendan in patients with congestive heart failure. Eur J Heart Fail 9:75–82CrossRefPubMed Lilleberg J, Laine M, Palkama T, Kivikko M, Pohjanjousi P, Kupari M (2007) Duration of the haemodynamic action of a 24-h infusion of levosimendan in patients with congestive heart failure. Eur J Heart Fail 9:75–82CrossRefPubMed
30.
go back to reference Kivikko M, Lehtonen L, Colucci WS (2003) Sustained hemodynamic effects of intravenous levosimendan. Circulation 107:81–86CrossRefPubMed Kivikko M, Lehtonen L, Colucci WS (2003) Sustained hemodynamic effects of intravenous levosimendan. Circulation 107:81–86CrossRefPubMed
Metadata
Title
Use of Levosimendan in Postoperative Setting After Surgical Repair of Congenital Heart Disease in Children
Authors
Vivianne Amiet
Marie-Hélène Perez
David Longchamp
Tatiana Boulos Ksontini
Julia Natterer
Sonia Plaza Wuthrich
Jacques Cotting
Stefano Di Bernardo
Publication date
01-01-2018
Publisher
Springer US
Published in
Pediatric Cardiology / Issue 1/2018
Print ISSN: 0172-0643
Electronic ISSN: 1432-1971
DOI
https://doi.org/10.1007/s00246-017-1718-2

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