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DOI: 10.1055/s-0039-3400496
Levosimendan Reduces Mortality and Low Cardiac Output Syndrome in Cardiac Surgery
Publication History
13 June 2019
02 October 2019
Publication Date:
26 November 2019 (online)
Abstract
Background There has been conflicting evidence concerning the effect of levosimendan on clinical outcomes in patients undergoing cardiac surgery. Therefore, we performed a systematic review and conducted this meta-analysis to provide evidence for/against the administration of levosimendan in cardiac surgery patients.
Methods We performed a meta-analysis from literature search in PubMed, EMBASE, and Cochrane Library. Only randomized controlled trials comparing the administration of levosimendan in cardiac surgery patients with a control group (other inotrope, standard therapy/placebo, or an intra-aortic balloon pump) were included. In addition, at least one clinical outcome had to be mentioned: mortality, myocardial infarction, low cardiac output syndrome (LCOS), acute kidney injury, renal replacement therapy, atrial fibrillation, prolonged inotropic support, length of intensive care unit, and hospital stay. The pooled treatment effects (odds ratio [OR], 95% confidence intervals [CI]) were assessed using a fixed or random effects model.
Results The literature search retrieved 27 randomized, controlled trials involving a total of 3,198 patients. Levosimendan led to a significant reduction in mortality (OR: 0.67; 95% CI: 0.49–0.91; p = 0.0087). Furthermore, the incidence of LCOS (OR: 0.56, 95% CI: 0.42–0.75; p < 0.0001), acute kidney injury (OR: 0.63; 95% CI: 0.46–0.86; p = 0.0039), and renal replacement therapy (OR: 0.70; 95% CI: 0.50–0.98; p = 0.0332) was significantly decreased in the levosimendan group.
Conclusion Our meta-analysis suggests beneficial effects for the prophylactic use of levosimendan in patients with severely impaired left ventricular function undergoing cardiac surgery. The administration of levosimendan was associated with a reduced mortality, less LCOS, and restored adequate organ perfusion reflected in less acute kidney injury.
* Both senior authors contributed equally to the study.
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References
- 1 Landoni G, Lomivorotov VV, Alvaro G. , et al; CHEETAH Study Group. Levosimendan for hemodynamic support after cardiac surgery. N Engl J Med 2017; 376 (21) 2021-2031
- 2 Lomivorotov VV, Efremov SM, Kirov MY, Fominskiy EV, Karaskov AM. Low-cardiac-output syndrome after cardiac surgery. J Cardiothorac Vasc Anesth 2017; 31 (01) 291-308
- 3 Anastasiadis K, Antonitsis P, Vranis K. , et al. Effectiveness of prophylactic levosimendan in patients with impaired left ventricular function undergoing coronary artery bypass grafting: a randomized pilot study. Interact Cardiovasc Thorac Surg 2016; 23 (05) 740-747
- 4 Cholley B, Caruba T, Grosjean S. , et al. Effect of levosimendan on low cardiac output syndrome in patients with low ejection fraction undergoing coronary artery bypass grafting with cardiopulmonary bypass: the LICORN Randomized Clinical Trial. JAMA 2017; 318 (06) 548-556
- 5 Christoph A, Prondzinsky R, Russ M. , et al. Early and sustained haemodynamic improvement with levosimendan compared to intraaortic balloon counterpulsation (IABP) in cardiogenic shock complicating acute myocardial infarction. Acute Card Care 2008; 10 (01) 49-57
- 6 Nielsen DV, Hansen MK, Johnsen SP, Hansen M, Hindsholm K, Jakobsen CJ. Health outcomes with and without use of inotropic therapy in cardiac surgery: results of a propensity score-matched analysis. Anesthesiology 2014; 120 (05) 1098-1108
- 7 Fellahi JL, Parienti JJ, Hanouz JL, Plaud B, Riou B, Ouattara A. Perioperative use of dobutamine in cardiac surgery and adverse cardiac outcome: propensity-adjusted analyses. Anesthesiology 2008; 108 (06) 979-987
- 8 Toller W, Heringlake M, Guarracino F. , et al. Preoperative and perioperative use of levosimendan in cardiac surgery: European expert opinion. Int J Cardiol 2015; 184: 323-336
- 9 Desai AS, Jarcho JA. Levosimendan for the low cardiac output syndrome after cardiac surgery. N Engl J Med 2017; 376 (21) 2076-2078
- 10 De Hert SG, Lorsomradee S, Cromheecke S, Van der Linden PJ. The effects of levosimendan in cardiac surgery patients with poor left ventricular function. Anesth Analg 2007; 104 (04) 766-773
- 11 Eriksson HI, Jalonen JR, Heikkinen LO. , et al. Levosimendan facilitates weaning from cardiopulmonary bypass in patients undergoing coronary artery bypass grafting with impaired left ventricular function. Ann Thorac Surg 2009; 87 (02) 448-454
- 12 Tritapepe L, De Santis V, Vitale D. , et al. Levosimendan pre-treatment improves outcomes in patients undergoing coronary artery bypass graft surgery. Br J Anaesth 2009; 102 (02) 198-204
- 13 Levin R, Degrange M, Del Mazo C, Tanus E, Porcile R. Preoperative levosimendan decreases mortality and the development of low cardiac output in high-risk patients with severe left ventricular dysfunction undergoing coronary artery bypass grafting with cardiopulmonary bypass. Exp Clin Cardiol 2012; 17 (03) 125-130
- 14 Harrison RW, Hasselblad V, Mehta RH, Levin R, Harrington RA, Alexander JH. Effect of levosimendan on survival and adverse events after cardiac surgery: a meta-analysis. J Cardiothorac Vasc Anesth 2013; 27 (06) 1224-1232
- 15 Lim JY, Deo SV, Rababa'h A. , et al. Levosimendan reduces mortality in adults with left ventricular dysfunction undergoing cardiac surgery: a systematic review and meta-analysis. J Card Surg 2015; 30 (07) 547-554
- 16 Mehta RH, Leimberger JD, van Diepen S. , et al; LEVO-CTS Investigators. Levosimendan in patients with left ventricular dysfunction undergoing cardiac surgery. N Engl J Med 2017; 376 (21) 2032-2042
- 17 Liberati A, Altman DG, Tetzlaff J. , et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. J Clin Epidemiol 2009; 62 (10) e1-e34
- 18 Deppe AC, Liakopoulos OJ, Choi YH. , et al. Endoscopic vein harvesting for coronary artery bypass grafting: a systematic review with meta-analysis of 27,789 patients. J Surg Res 2013; 180 (01) 114-124
- 19 Jadad AR, Moore RA, Carroll D. , et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary?. Control Clin Trials 1996; 17 (01) 1-12
- 20 Downs SH, Black N. The feasibility of creating a checklist for the assessment of the methodological quality both of randomised and non-randomised studies of health care interventions. J Epidemiol Community Health 1998; 52 (06) 377-384
- 21 Kivikko M, Antila S, Eha J, Lehtonen L, Pentikäinen PJ. Pharmacokinetics of levosimendan and its metabolites during and after a 24-hour continuous infusion in patients with severe heart failure. Int J Clin Pharmacol Ther 2002; 40 (10) 465-471
- 22 Lilleberg J, Laine M, Palkama T, Kivikko M, Pohjanjousi P, Kupari M. Duration of the haemodynamic action of a 24-h infusion of levosimendan in patients with congestive heart failure. Eur J Heart Fail 2007; 9 (01) 75-82
- 23 Leppikangas H, Järvelä K, Sisto T. , et al. Preoperative levosimendan infusion in combined aortic valve and coronary bypass surgery. Br J Anaesth 2011; 106 (03) 298-304
- 24 Eris C, Yavuz S, Toktas F. , et al. Preoperative usages of levosimendan in patients undergoing coronary artery bypass grafting. Int J Clin Exp Med 2014; 7 (01) 219-229
- 25 Ponikowski P, Voors AA, Anker SD. , et al; ESC Scientific Document Group. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC)Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J 2016; 37 (27) 2129-2200
- 26 Guarracino F, Heringlake M, Cholley B. , et al. Use of levosimendan in cardiac surgery: an update after the LEVO-CTS, CHEETAH, and LICORN trials in the light of clinical practice. J Cardiovasc Pharmacol 2018; 71 (01) 1-9
- 27 Husedzinović I, Barisin S, Bradić N, Barisin A, Sonicki Z, Milanović R. Levosimendan as a new strategy during off-pump coronary artery bypass grafting: double-blind randomized placebo-controlled trial. Croat Med J 2005; 46 (06) 950-956
- 28 Jörgensen K, Bech-Hanssen O, Houltz E, Ricksten SE. Effects of levosimendan on left ventricular relaxation and early filling at maintained preload and afterload conditions after aortic valve replacement for aortic stenosis. Circulation 2008; 117 (08) 1075-1081
- 29 Putzu A, Clivio S, Belletti A, Cassina T. Perioperative levosimendan in cardiac surgery: a systematic review with meta-analysis and trial sequential analysis. Int J Cardiol 2018; 251: 22-31
- 30 Baysal A, Yanartas M, Dogukan M, Gundogus N, Kocak T, Koksal C. Levosimendan improves renal outcome in cardiac surgery: a randomized trial. J Cardiothorac Vasc Anesth 2014; 28 (03) 586-594
- 31 Yilmaz MB, Grossini E, Silva Cardoso JC. , et al. Renal effects of levosimendan: a consensus report. Cardiovasc Drugs Ther 2013; 27 (06) 581-590
- 32 Bragadottir G, Redfors B, Ricksten S-E. Effects of levosimendan on glomerular filtration rate, renal blood flow, and renal oxygenation after cardiac surgery with cardiopulmonary bypass: a randomized placebo-controlled study. Crit Care Med 2013; 41 (10) 2328-2335
- 33 Erb J, Beutlhauser T, Feldheiser A. , et al. Influence of levosimendan on organ dysfunction in patients with severely reduced left ventricular function undergoing cardiac surgery. J Int Med Res 2014; 42 (03) 750-764
- 34 Järvelä K, Maaranen P, Sisto T, Ruokonen E. Levosimendan in aortic valve surgery: cardiac performance and recovery. J Cardiothorac Vasc Anesth 2008; 22 (05) 693-698
- 35 Juhl-Olsen P, Jakobsen CJ, Rasmussen LA. , et al. Effects of levosimendan in patients with left ventricular hypertrophy undergoing aortic valve replacement. Acta Anaesthesiol Scand 2015; 59 (01) 65-77
- 36 Kodalli RK, Sundar AS, Vakamudi M. , et al. Effect of levosimendan on hemodynamic changes in patients undergoing off-pump coronary artery bypass grafting: a randomized controlled study. Ann Card Anaesth 2013; 16 (02) 94-99
- 37 Lahtinen P, Pitkänen O, Pölönen P, Turpeinen A, Kiviniemi V, Uusaro A. Levosimendan reduces heart failure after cardiac surgery: a prospective, randomized, placebo-controlled trial. Crit Care Med 2011; 39 (10) 2263-2270
- 38 Lilleberg J, Nieminen MS, Akkila J. , et al. Effects of a new calcium sensitizer, levosimendan, on haemodynamics, coronary blood flow and myocardial substrate utilization early after coronary artery bypass grafting. Eur Heart J 1998; 19 (04) 660-668
- 39 Shah B, Sharma P, Brahmbhatt A. , et al. Study of levosimendan during off-pump coronary artery bypass grafting in patients with LV dysfunction: a double-blind randomized study. Indian J Pharmacol 2014; 46 (01) 29-34
- 40 Sharma P, Malhotra A, Gandhi S, Garg P, Bishnoi A, Gandhi H. Preoperative levosimendan in ischemic mitral valve repair. Asian Cardiovasc Thorac Ann 2014; 22 (05) 539-545
- 41 Al-Shawaf E, Ayed A, Vislocky I, Radomir B, Dehrab N, Tarazi R. Levosimendan or milrinone in the type 2 diabetic patient with low ejection fraction undergoing elective coronary artery surgery. J Cardiothorac Vasc Anesth 2006; 20 (03) 353-357
- 42 Mishra A, Kumar B, Dutta V, Arya VK, Mishra AK. Comparative effect of levosimendan and milrinone in cardiac surgery patients with pulmonary hypertension and left ventricular dysfunction. J Cardiothorac Vasc Anesth 2016; 30 (03) 639-646
- 43 Gandham R, Syamasundar A, Ravulapalli H. , et al. A comparison of hemodynamic effects of levosimendan and dobutamine in patients undergoing mitral valve repair / replacement for severe mitral stenosis. Ann Card Anaesth 2013; 16 (01) 11-15
- 44 Kandasamy A, Simon HA, Murthy P, Annadurai M, Ali MM, Ramanathan G. Comparison of levosimendan versus dobutamine in patients with moderate to severe left ventricular dysfunction undergoing off-pump coronary artery bypass grafting: a randomized prospective study. Ann Card Anaesth 2017; 20 (02) 200-206
- 45 Salgado Filho MF, Barral M, Barrucand L, Cavalcanti IL, Verçosa N. A randomized blinded study of the left ventricular myocardial performance index comparing epinephrine to levosimendan following cardiopulmonary bypass. PLoS One 2015; 10 (12) e0143315
- 46 Lomivorotov VV, Boboshko VA, Efremov SM. , et al. Levosimendan versus an intra-aortic balloon pump in high-risk cardiac patients. J Cardiothorac Vasc Anesth 2012; 26 (04) 596-603