Levosimendan

CLASS

  • 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

PHARMACEUTICS

DOSE

  • loading dose: 6-24mcg/kg over 10 min
  • infusion for 24 hours of 0.05-0.2mcg/kg/min

INDICATIONS

  • heart failure (acute and chronic)
  • sepsis
  • post resuscitation myocardial dysfunction
  • peri-operative optimization of cardiac patients with cardiomyopathy

ADVERSE EFFECTS

  • hypotension
  • headache
  • N+V
  • dysrhythmias

PHARMACOKINETICS

  • 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.

EVIDENCE

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
  • inodilator
  • ?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.

CCC 700 6

Critical Care

Compendium

Chris is an Intensivist and ECMO specialist at the Alfred ICU in Melbourne. He is also the Innovation Lead for the Australian Centre for Health Innovation at Alfred Health and Clinical Adjunct Associate Professor at Monash University. He is a co-founder of the Australia and New Zealand Clinician Educator Network (ANZCEN) and is the Lead for the ANZCEN Clinician Educator Incubator programme. He is on the Board of Directors for the Intensive Care Foundation and is a First Part Examiner for the College of Intensive Care Medicine. He is an internationally recognised Clinician Educator with a passion for helping clinicians learn and for improving the clinical performance of individuals and collectives.

After finishing his medical degree at the University of Auckland, he continued post-graduate training in New Zealand as well as Australia’s Northern Territory, Perth and Melbourne. He has completed fellowship training in both intensive care medicine and emergency medicine, as well as post-graduate training in biochemistry, clinical toxicology, clinical epidemiology, and health professional education.

He is actively involved in in using translational simulation to improve patient care and the design of processes and systems at Alfred Health. He coordinates the Alfred ICU’s education and simulation programmes and runs the unit’s education website, INTENSIVE.  He created the ‘Critically Ill Airway’ course and teaches on numerous courses around the world. He is one of the founders of the FOAM movement (Free Open-Access Medical education) and is co-creator of litfl.com, the RAGE podcast, the Resuscitology course, and the SMACC conference.

His one great achievement is being the father of two amazing children.

On Twitter, he is @precordialthump.

| INTENSIVE | RAGE | Resuscitology | SMACC

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