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 actin-myosin cross-bridges, without increasing myocardial consumption of 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 resistance- benefit 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