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Recent advances – levosimendan
Dr. S. Parthasarathy
MD., DA., DNB, MD (Acu), Dip. Diab. DCA,
Dip. Software statistics,
PhD(physiology)
Inodilators
• Increase contractility
• But slightly vasodilate to cause decreased
afterload
• Dobutamine , phophodiesterase inhibitors
• Levosimendan
• Increased intracellular calcium with others – - arrhythmias
• But this is a calcium sensitizer
• Especially in systole
The first action
• It binds to cardiac troponin C in a calcium-dependent
manner and stabilises troponin C.
• This
causes
increasing
actin-myosin
myocardial
cross-bridges,
consumption
of
without
adenosine
triphosphate (ATP).
• The
cardiac
performance
and
contractility
are
significantly improved with no increase in the total
myocardial energy demand and oxygen consumption.
• No effect in diastole
• Normal relaxation
• Normal diastolic function
• Less arrhythmias
The second action
• Levosimendan also causes venous, arterial and
coronary vasodilation, probably by opening ATP
sensitive potassium channels in smooth muscle.
• Dose-dependant hypotension may occur.
• Levosimendan reduces pulmonary vascular resistancebenefit in RV strains
• Elimination half life – one hour
• Active metabolite – 70 hours may be
• Hence after infusion – may have action
• We can stop catecholamines in between
• Tolerance settled
• Children with alpha blockers – no catecholamines
– but this is ok
Decompensated chronic heart failure !!
• The usual dosage of intravenous levosimendan used in
clinical trials of patients with heart failure is 6 to 12
µg/kg loading dose over 10 minutes
• followed by 0.05 to 0.2 µg/kg/min as a continuous
infusion
• Levosimendan is available in the strength of 2.5 mg
per 5 mL per ampoule and 10mL per ampoule
• Post CABG LCOS
Rs 427 / 12.5 mg
• Liver dysfunction
• Not much studied – can use with normal dose
and titrate
• Severe renal dysfunction – levels are high a 50 %
dose reduction is OK
• But no clear cut studies
Side effects
•
•
•
•
•
Usually well tolerated
Headache
Hypotension
Rarely arrhythmias
No interaction with digoxin, frusemide and
amiodarone , other inotropes
• Stop other vasodilators if possible
• Levosimendan has been found to be a safe and useful
drug when given to the sickest children with acute
heart failure refractory to standard anti-failure
medications.
• Even in septic shock in children
• But do we need long acting drugs ?
Tips ??
• Chronic heart failure – trigger – fluid
imbalance, infection, drug non compliant etc, ------ decompensation
• Stabilize
• Infusion of levosimendan – 24 hours
• Discharge the patient
• Stable for one week – by the time the trigger
is undone
Summary
• Enantiomer of simendan
• Inotrope without increasing oxygen
consumption of heart
• Vasodilation – mechanisms
• No action through adrenergic receptors
• Decompensated Chronic heart failure , septic
shock in children, RV strain, LCOS etc..
• 6-12 and 0.2 microgram
• Headache hypotension
• Prolonged action