Skip to main content
SpringerLink
Log in

Levosimendan infusion in newborns after corrective surgery for congenital heart disease: randomized controlled trial

  • Pediatric Original
  • Published:
Intensive Care Medicine Aims and scope Submit manuscript

Abstract

Purpose

To evaluate the safety and efficacy of levosimendan in neonates with congenital heart disease undergoing cardiac surgery with cardiopulmonary bypass (CPB).

Methods

Neonates undergoing risk-adjusted classification for congenital heart surgery (RACHS) 3 and 4 procedures were randomized to receive either a 72 h continuous infusion of 0.1 μg/kg/min levosimendan or standard post-CPB inotrope infusion.

Results

Sixty-three patients (32 cases and 31 controls) were recruited. There were no differences between groups regarding demographic and baseline clinical data. No side effects were observed. There were no significant differences in mortality (1 vs. 3 patients, p = 0.35), length of mechanical ventilation (5.9 ± 5 vs. 6.9 ± 8 days, p = 0.54), and pediatric cardiac intensive care unit (PCICU) stay (11 ± 8 vs. 14 ± 14 days, p = 0.26). Low cardiac output syndrome occurred in 37 % of levosimendan patients and in 61 % of controls (p = 0.059, OR 0.38, 95 % CI 0.14–1.0). Postoperative heart rate, with a significant difference at 6 (p = 0.008), 12 (p = 0.037), and 24 h (p = 0.046), and lactate levels, with a significant difference at PCICU admission (p = 0.015) and after 6 h (p = 0.048), were lower in the levosimendan group. Inotropic score was significantly lower in the levosimendan group at PCICU admission, after 6 h and after 12 h, (p < 0.0001). According to multivariate analysis, a lower lactate level 6 h after PCICU admission was independently associated with levosimendan administration after correction for CPB time and the need for deep hypothermic circulatory arrest.

Conclusions

Levosimendan infused in neonates undergoing cardiac surgery was well tolerated with a potential benefit of levosimendan on postoperative hemodynamic and metabolic parameters of RACHS 3–4 neonates.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Andropoulos DB, Ogletree ML (2005) Physiology and molecular biology of the developing circulation. In: Andropoulos DB, Stayer SA, Russell IA (eds) Anesthesia for congenital heart disease. Blackwell Futura, Madden, pp 30–45

    Chapter  Google Scholar 

  2. Buijs EA, Danser AH, Meijer NI, Tibboel D (2011) Cardiovascular catecholamine receptors in children: their significance in cardiac disease. J Cardiovasc Pharmacol 58:9–19

    Article  PubMed  CAS  Google Scholar 

  3. Artman M, Mahoney L, Teidel DF (2001) Regulation of myocyte contraction and relaxation. In: Artman M, Mahoney L, Teidel DF (eds) Neonatal cardiology. McGraw Hill, New York, pp 19–37

    Google Scholar 

  4. Than N, Shah N, White J, Lee JA, Orchard CH (1994) Effects of acidosis and hypoxia on the response of isolated ferret cardiac muscle to inotropic agents. Cardiovasc Res 28:1209–1217

    Article  PubMed  CAS  Google Scholar 

  5. Jefferies JL, Hoffman TM, Nelson DP (2010) Heart failure treatment in the intensive care unit in children. Heart Fail Clin 6:531–558

    Article  PubMed  Google Scholar 

  6. Tweddell JS, Hoffman GM (2002) Postoperative management in patients with complex congenital heart disease. Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu 5:187–205

    Article  PubMed  Google Scholar 

  7. Hoffman TM, Wernovsky G, Atz AM, Kulik TJ, Nelson DP, Chang AC, Bailey JM, Akbary A, Kocsis JF, Kaczmarek R, Spray TL, Wessel DL (2003) Efficacy and safety of milrinone in preventing low cardiac output syndrome in infants and children after corrective surgery for congenital heart disease. Circulation 107:996–1002

    Article  PubMed  CAS  Google Scholar 

  8. Milligan DJ, Fields AM (2010) Levosimendan: calcium sensitizer and inodilator. Anesthesiol Clin 28:753–760

    Article  PubMed  CAS  Google Scholar 

  9. Bonios MJ, Terrovitis JV, Drakos SG, Katsaros F, Pantsios C, Nanas SN, Kanakakis J, Alexopoulos G, Toumanidis S, Anastasiou-Nana M, Nanas JN (2011) Comparison of three different regimens of intermittent inotrope infusions for end stage heart failure. Int J Cardiol. doi:10.1016/ij.card.2011.03.013

  10. Lahtinen P, Pitkänen O, Pölönen P, Turpeinen A, Kiviniemi V, Uusaro A (2011) Levosimendan reduces heart failure after cardiac surgery- a prospective, randomized, placebo-controlled trial. Crit Care Med. doi:10.1097/CCM.0b013e3182227b97

  11. Tritapepe L, De Santis V, Vitale D, Santulli M, Morelli A, Nofroni I, Puddu PE, Singer M, Pietropaoli P (2006) Preconditioning effects of levosimendan in coronary artery bypass grafting—a pilot study. Br J Anaesth 96:694–700

    Article  PubMed  CAS  Google Scholar 

  12. Namachivayam P, Crossland DS, Butt WW, Shekerdemian LS (2006) Early experience with levosimendan in children with ventricular dysfunction. Pediatr Crit Care Med 7:445–448

    Article  PubMed  Google Scholar 

  13. Stocker CF, Shekerdemian LS, Nørgaard MA, Brizard CP, Mynard JP, Horton SB, Penny DJ (2007) Mechanisms of a reduced cardiac output and the effects of milrinone and levosimendan in a model of infant cardiopulmonary bypass. Crit Care Med 35:252–259

    Article  PubMed  CAS  Google Scholar 

  14. Haikala H, Linden IB (1995) Mechanisms of action of calcium-sensitizing drugs. J Cardiovasc Pharmacol 26:S10–S19

    PubMed  CAS  Google Scholar 

  15. Lilleberg J, Ylonen V, Lehtonen L, Toivonen L (2004) The calcium sensitizer levosimendan and cardiac arrhythmias: an analysis of the safety database of heart failure treatment studies. Scand Cardiovasc J 38:80–84

    Article  PubMed  CAS  Google Scholar 

  16. Kopustinskiene D, Pollesello P, Saris N (2001) Levosimendan is a mitochondrial KATP channel opener. Eur J Pharmacol 428:311–314

    Article  PubMed  CAS  Google Scholar 

  17. Pollesello P, Mebazaa A (2004) ATP-dependent potassium channels as a key target for the treatment of myocardial and vascular dysfunction. Curr Opin Crit Care 10:436–441

    Article  PubMed  Google Scholar 

  18. Soeding PE, Royse CF, Wright CE, Royse AG, Angus JA (2007) Inoprotection: the perioperative role of levosimendan. Anaesth Intensive Care 35:845–862

    PubMed  CAS  Google Scholar 

  19. Jenkins KJ, Gauvreau K, Newburger JW, Spray TL, Moller JH, Iezzoni LI (2002) Consensus-based method for risk adjustment for surgery for congenital heart disease. J Thorac Cardiovasc Surg 123:110–118

    Article  PubMed  Google Scholar 

  20. 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 11:234–238

    Article  PubMed  Google Scholar 

  21. Graciano AL, Balko JA, Rahn DS, Ahmad N, Giroir BP (2005) The Pediatric Multiple Organ Dysfunction Score (P-MODS): development and validation of an objective scale to measure the severity of multiple organ dysfunction in critically ill children. Crit Care Med 33:1484–1491

    Article  PubMed  Google Scholar 

  22. Mebazaa A, Nieminen MS, Packer M, Cohen-Solal A, Kleber FX, Pocock SJ, Thakkar R, Padley RJ, Põder P, Kivikko M, SURVIVE Investigators (2007) Levosimendan vs dobutamine for patients with acute decompensated heart failure: the SURVIVE Randomized Trial. JAMA 297:1883–1891

    Article  PubMed  CAS  Google Scholar 

  23. Tasouli A, Papadopoulos K, Antoniou T, Kriaras I, Stavridis G, Degiannis D, Geroulanos S (2007) Efficacy and safety of perioperative infusion of levosimendan in patients with compromised cardiac function undergoing open-heart surgery: importance of early use. Eur J Cardiothorac Surg 32:629–633

    Article  PubMed  Google Scholar 

  24. Molina Hazan V, Gonen Y, Vardi A, Keidan I, Mishali D, Rubinshtein M, Yakov Y, Paret G (2010) Blood lactate levels differ significantly between surviving and nonsurviving patients within the same risk-adjusted classification for congenital heart surgery (RACHS-1) group after pediatric cardiac surgery. Pediatr Cardiol 31:952–960

    Article  PubMed  Google Scholar 

  25. Wood L, Egger M, Gluud LL, Schulz KF, Jüni P, Altman DG, Gluud C, Martin RM, Wood AJ, Sterne JA (2008) Empirical evidence of bias in treatment effect estimates in controlled trials with different interventions and outcomes: meta-epidemiological study. BMJ 336:601–605

    Article  PubMed  Google Scholar 

  26. Hoffman TM, Wernovsky G, Atz AM, Bailey JM, Akbary A, Kocsis JF, Nelson DP, Chang AC, Kulik TJ, Spray TL, Wessel DL (2002) Prophylactic intravenous use of milrinone after cardiac operation in pediatrics (PRIMACORP) study. Am Heart J 143:15–21

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Pediatric Cardiac Anesthesia/Intensive Care Unit, Department of Pediatric Cardiology and Cardiac Surgery, Bambino Gesù Children’s Hospital, Piazza S.Onofrio 4, 00165, Rome, Italy

    Zaccaria Ricci, Cristiana Garisto, Isabella Favia, Vincenzo Vitale, Luca Di Chiara & Paola E. Cogo

Authors
  1. Zaccaria Ricci
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Cristiana Garisto
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Isabella Favia
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Vincenzo Vitale
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Luca Di Chiara
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Paola E. Cogo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Zaccaria Ricci.

Additional information

Trial registration: ClinicalTrials.gov NCT01120106.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ricci, Z., Garisto, C., Favia, I. et al. Levosimendan infusion in newborns after corrective surgery for congenital heart disease: randomized controlled trial. Intensive Care Med 38, 1198–1204 (2012). https://doi.org/10.1007/s00134-012-2564-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00134-012-2564-6

Keywords

Search

Navigation