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Annals of Cardiac Anaesthesia Annals of Cardiac Anaesthesia Annals of Cardiac Anaesthesia
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Table of Contents
INVITED COMMENTARY  
Year : 2013  |  Volume : 16  |  Issue : 2  |  Page : 99-101
Invited Commentary


Director Anaesthesia, Pushpanjali Crosslay Hospital, Ghaziabad, India

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Date of Web Publication29-Mar-2013
 

How to cite this article:
Kapoor MC. Invited Commentary. Ann Card Anaesth 2013;16:99-101

How to cite this URL:
Kapoor MC. Invited Commentary. Ann Card Anaesth [serial online] 2013 [cited 2019 Sep 23];16:99-101. Available from: http://www.annals.in/text.asp?2013/16/2/99/109738


Levosimendan use is associated with dose-dependent increase in cardiac output, stroke volume and heart rate, and decrease in left and right heart filling pressures, systemic arterial pressure and systemic vascular resistance. [1] Cardiac performance is improved without significant increases in oxygen consumption and no potentially malignant arrhythmia have been reported with its use. Levosimendan has been shown to be superior to dobutamine in increasing cardiac output and decreasing cardiac filling pressures in patients with decompensated heart failure. [2] In the presence of beta-blockade, levosimendan has more favorable effects than dobutamine. Additionally, it has been reported to provide myocardial preconditioning in patients for coronary surgery [3] and protect the ischemic myocardium when administered before and during myocardial ischemia. [4]

The clinical use of levosimendan is presently restricted to enhancement of cardiac output in patients with compromised left ventricular (LV) function; however, it has been used to improve perioperative hemodynamics in cardiac surgical patients with normal LV function. [5] It has potent hemodynamic actions in patients with decompensated heart failure due to LV systolic dysfunction and there is evidence that its use in combination with dobutamine improves outcomes in patients with decompensated heart failure refractory to dobutamine alone. [6] Apart from levosimendan, no inotropic drug has been shown to improve outcome in randomized controlled studies. [7]

Reduced post-operative cardiac troponin release with the use of levosimendan illustrates its cardioprotective effects [7] and these cardioprotective effects could result in a reduced post-operative mortality. [8] Activation of the ATP-dependent potassium (K ATP ) channels is important for ischemic and anesthetic cardioprotection. [9] Both mitochondrial and sarcolemmal K ATP channels, responsible for ischemic pre-conditioning, are opened by levosimendan. [10] Levosimendan also dilates the peripheral and coronary vessels by opening K ATP channels in vascular smooth muscle [11] and decreasing sensitivity to calcium. [12] In higher doses, levosimendan has selective phosphodiesterase III (PDE III) inhibitory effects on the myocardium [13] and vascular smooth muscle. [14] Levosimendan; thus, benefits patients with myocardial oxygen imbalance requiring inotropic support and probably offers more advantage than PDE III inhibitors in patients with a compromised myocardial oxygen balance. [15],[16] Levosimendan may arguably be labeled as an ideal inotrope for patients undergoing myocardial revascularization.

During off pump coronary artery bypass (OPCAB) surgery, lifting of the heart out of the pericardial sac is necessary for the exposure of lateral and posterior coronary vessels. This displacement of the heart is associated with alterations in filling pressures; a reduction in cardiac output; blood to flow upwards into the ventricular cavities; distortion of the mitral and tricuspid valve anatomy with a resultant significant regurgitation; and finally restriction of ventricular wall motion with reduction in ventricular dimensions by the retractor placed on the ventricular wall to facilitate coronary anastomosis. [17],[18] The management of these changes involves maintaining a high perfusion pressure and a low myocardial oxygen consumption using the Trendelenburg position, administration of fluids and infusion of a vasopressor. In such situations, enhancement of cardiac output with the traditional inotropes may not benefit, as these drugs increase cytosolic cyclic adenosine monophosphate (cAMP) concentrations, which increases oxygen consumption. Moreover, stronger muscular contraction and movements due to increased inotropy may hinder the surgical process. Unlike traditional inotropes, levosimendan improves the myocardial contractility by binding to cardiac troponin C and enhancing myocardial contractile protein sensitivity to calcium without increasing its intracellular concentration. [19],[20] No rise in cAMP production is needed to mobilise calcium and thus, there is no increase in myocardial oxygen consumption. [15]

Levosimendan has an active metabolite, OR-1896, which exhibits positive inotropic and vasodilatory effects on the myocardium and vasculature respectively, similar to levosimendan. The elimination half-life of levosimendan is about 1 h but OR-1896 has a half-life of approximately 80 h. Due to the formation of OR-1896, the hemodynamic effects are maintained up to several days after stopping levosimendan infusion. [21] There is no sign of development of tolerance even with a prolonged infusion up to 48 h.

In this issue of Annals of Cardiac Anaesthesia, Kodalli et al., describe levosimendan use in patients with normal LV function undergoing OPCAB surgery. [22] The authors have reported better outcomes 6 h postoperative and beyond, in terms of cardiac index and systemic vascular resistance, with the perioperative infusion of levosimendan @ 1 μg/kg/min. Although, the authors have not demonstrated any benefit with the use of the drug for OPCAB grafting per se, they have shown better out-comes with the perioperative use of levosimendan. Perhaps, the true benefits of levosimendan are not apparent as the number of patients included is small and because the subjects had normal LV function. If the authors had included patients with LV dysfunction, its benefits would have possibly become apparent. Husedzinović et al., have earlier reported better outcomes with use of levosimendan, administered as a bolus dose, 12 μg/kg, in patients with normal LV function for OPCAB surgery; however, unfortunately their report did not specify whether better cardiac indices were achieved during the performance of the OPCAB grafting. [5] More studies are required to unearth the true potentials of levosimendan.

 
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1.Slawsky MT, Colucci WS, Gottlieb SS, Greenberg BH, Haeusslein E, Hare J, et al. Acute hemodynamic and clinical effects of levosimendan in patients with severe heart failure. Study Investigators. Circulation 2000;102:2222-7.  Back to cited text no. 1
    
2.Bergh CH, Andersson B, Dahlström U, Forfang K, Kivikko M, Sarapohja T, et al. Intravenous levosimendan vs. dobutamine in acute decompensated heart failure patients on beta-blockers. Eur J Heart Fail 2010;12:404-10.  Back to cited text no. 2
    
3.Tritapepe L, De Santis V, Vitale D, Santulli M, Morelli A, Nofroni I, et al. Preconditioning effects of levosimendan in coronary artery bypass grafting - A pilot study. Br J Anaesth 2006;96:694-700.  Back to cited text no. 3
    
4.Kersten JR, Montgomery MW, Pagel PS, Warltier DC. Levosimendan, a new positive inotropic drug, decreases myocardial infarct size via activation of K (ATP) channels. Anesth Analg 2000;90:5-11.  Back to cited text no. 4
    
5.Husedzinoviæ I, Barisin S, Bradiæ N, Barisin A, Sonicki Z, Milanoviæ R. Levosimendan as a new strategy during off-pump coronary artery bypass grafting: Double-blind randomized placebo-controlled trial. Croat Med J 2005;46:950-6.  Back to cited text no. 5
    
6.Cavusoglu Y. The use of levosimendan in comparison and in combination with dobutamine in the treatment of decompensated heart failure. Expert Opin Pharmacother 2007;8:665-77.  Back to cited text no. 6
    
7.Zangrillo A, Biondi-Zoccai G, Mizzi A, Bruno G, Bignami E, Gerli C, et al. Levosimendan reduces cardiac troponin release after cardiac surgery: A meta-analysis of randomized controlled studies. J Cardiothorac Vasc Anesth 2009;23:474-8.  Back to cited text no. 7
    
8.Landoni G, Mizzi A, Biondi-Zoccai G, Bruno G, Bignami E, Corno L, et al. Reducing mortality in cardiac surgery with levosimendan: A meta-analysis of randomized controlled trials. J Cardiothorac Vasc Anesth 2010;24:51-7.  Back to cited text no. 8
    
9.Nanas JN, Papazoglou PP, Terrovitis JV, Kanakakis J, Dalianis A, Tsolakis E, et al. Hemodynamic effects of levosimendan added to dobutamine in patients with decompensated advanced heart failure refractory to dobutamine alone. Am J Cardiol 2004;94:1329-32.  Back to cited text no. 9
    
10.Gross GJ, Peart JN. KATP channels and myocardial preconditioning: An update. Am J Physiol Heart Circ Physiol 2003;285:H921-30.  Back to cited text no. 10
    
11.Yokoshiki H, Katsube Y, Sunagawa M, Sperelakis N. Levosimendan, a novel Ca2+ sensitizer, activates the glibenclamide-sensitive K+ channel in rat arterial myocytes. Eur J Pharmacol 1997;333:249-59.  Back to cited text no. 11
    
12.Bowman P, Haikala H, Paul RJ. Levosimendan, a calcium sensitizer in cardiac muscle, induces relaxation in coronary smooth muscle through calcium desensitization. J Pharmacol Exp Ther 1999;288:316-25.  Back to cited text no. 12
    
13.Sato S, Talukder MA, Sugawara H, Sawada H, Endoh M. Effects of levosimendan on myocardial contractility and Ca2+ transients in aequorin-loaded right-ventricular papillary muscles and indo-1-loaded single ventricular cardiomyocytes of the rabbit. J Mol Cell Cardiol 1998;30:1115-28.  Back to cited text no. 13
    
14.Gruhn N, Nielsen-Kudsk JE, Theilgaard S, Bang L, Olesen SP, Aldershvile J. Coronary vasorelaxant effect of levosimendan, a new inodilator with calcium-sensitizing properties. J Cardiovasc Pharmacol 1998;31:741-9.  Back to cited text no. 14
    
15.Ukkonen H, Saraste M, Akkila J, Knuuti J, Karanko M, Iida H, et al. Myocardial efficiency during levosimendan infusion in congestive heart failure. Clin Pharmacol Ther 2000;68:522-31.  Back to cited text no. 15
    
16.Lilleberg J, Nieminen MS, Akkila J, Heikkilä L, Kuitunen A, Lehtonen L, 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;19:660-8.  Back to cited text no. 16
    
17.Hett DA. Anaesthesia for off-pump coronary artery surgery. Contin Educ Anaesth Crit Care Pain 2006;6:60-2.  Back to cited text no. 17
    
18.Mathison M, Edgerton JR, Horswell JL, Akin JJ, Mack MJ. Analysis of hemodynamic changes during beating heart surgical procedures. Ann Thorac Surg 2000;70:1355-60.  Back to cited text no. 18
    
19.Toller WG, Stranz C. Levosimendan, a new inotropic and vasodilator agent. Anesthesiology 2006;104:556-69.  Back to cited text no. 19
    
20.Raja SG, Rayen BS. Levosimendan in cardiac surgery: Current best available evidence. Ann Thorac Surg 2006;81:1536-46.  Back to cited text no. 20
    
21.Kivikko M, Lehtonen L. Levosimendan: A new inodilatory drug for the treatment of decompensated heart failure. Curr Pharm Des 2005;11:435-55.  Back to cited text no. 21
    
22.Kodalli RK, Sundar AS, Vakamudi M, Ravulapali H, Nandipati S, Chandrasekaran N, 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;16:94-8.  Back to cited text no. 22
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Correspondence Address:
Mukul Chandra Kapoor
Department of Anaesthesia, Pushpanjali Crosslay Hospital, Ghaziabad
India
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