Download Levosimendan - Wellington ICU

Levosimendan
23/3/09
Sylvia Archan and Wolfgang Toller, (2008) “Levosimendan: current status and future
prospects” Current Opinion in Anaesthesiology, 21:78–84
PY Mindmaps
Class – Ca2+ sensitizer (novel inotrope)
Mechanism of Action
- sensitises cardiac muscle to Ca2+ - stabilises troponin C in a conformation that triggers and
maintain contraction.
- doesn’t 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 increases 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 levo)
- also has anti-inflammatory and anti-apoptotic 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
perioperative optimization of cardiac patients with cardiomyopathy
Adverse Effects
-
hypotension
headache
N+V
dysrrhythmias
PK
Jeremy Fernando (2011)
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
- n = 1320
- seeked to prove an mortality reduction of 25%!
-> no difference in 180 day mortality
SUMMARY
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
Jeremy Fernando (2011)