- Calcium sensitizer (novel inotrope, also considered an inodilator like milrinone)
MECHANISM OF ACTION
- sensitizes cardiac muscle to Ca2+
- stabilises troponin C in a conformation that triggers and maintain contraction.
- does not impair diastolic relaxation
- also produces vasodilation by opening ATP-sensitive K+ channels in vascular smooth muscle
-> reduces preload, afterload, improves O2 supply to myocardium, increases coronary blood flow and renal blood flow.
- increases: Q, SV, HR and coronary blood flow.
- decreases: SVR, SBP, PCWP, PAP, coronary vascular resistance, myocardial oxygen consumption.
- shown to improve symptoms, and BNP in cardiac failure (but, unfortunately not survival)
- can be used with beta-blockers (doesn’t compete with levos)
- also has anti-inflammatory and anti-apoptotic effects
- has weak cAMP-PDE inhibitory effects
- loading dose: 6-24mcg/kg over 10 min
- infusion for 24 hours of 0.05-0.2mcg/kg/min
- heart failure (acute and chronic)
- post resuscitation myocardial dysfunction
- peri-operative optimization of cardiac patients with cardiomyopathy
- Absorption – IV or PO
- Distribution – highly protein bound, peak concentrations reached after 2 days of treatment
- Metabolism – hepatic, active metabolite with t1/2 of 70 hours
- Elimination – dose adjust in renal insufficiency, eliminated in urine and faeces.
Mebazza, (2007) SURVIVE – Levosimendan vs Dobutamine in patients with acute decompensated heart failure, JAMA (pubmed)
- n = 1320
- sought to prove an mortality reduction of 25%!
- -> no difference in 180 day mortality
- initial reduction in plasma B-type natriuretic peptide level in patients in the levosimendan group
- higher rates of AF, hypoK and headache in levosimendan group
De Keulenaer, B. L. (2008) – “The case for Levosimendan” Critical Care and Resuscitation, Volume 10 (3) page 180
- decreased arrhythmias
- decreased myocardial oxygen consumption
- ?prevention of apoptosis and preservation of mitochondrial function
- improved right ventricular function in ARDS and in acute PE
References and Links
- De Keulenaer, B. L. (2008) The case for Levosimendan. Critical Care and Resuscitation, Volume 10 (3) page 180 [pdf]
- Pathak A, Lebrin M, Vaccaro A, Senard JM, Despas F. Pharmacology of levosimendan: inotropic, vasodilatory and cardioprotective effects. J Clin Pharm Ther. 2013 Apr 18. PMID: 23594161.