Levosimendan 

1. Introduction

Levosimendan is a calcium sensitizer + inodilator used in acute decompensated heart failure (ADHF) and selected cardiogenic shock states.

• Unlike catecholamines, it improves contractility without increasing intracellular Ca²⁺
• Produces inotropy + vasodilation (inodilator)
• Has prolonged action due to active metabolites

2. Mechanism of Action

A. Calcium Sensitization

• Binds to troponin C
• Enhances actin–myosin interaction
• No increase in intracellular Ca²⁺ → no increase in myocardial oxygen consumption

 Key exam point:
✔ Improves contractility without tachycardia or increased O₂ demand

B. KATP Channel Opening

• Opens ATP-sensitive K⁺ channels
• Vascular smooth muscle → vasodilation
• Mitochondria → cardioprotection

C. Net Hemodynamic Effects

Effect	Mechanism
↑ Cardiac output	Positive inotropy
↓ SVR	Vasodilation
↓ Preload	Venodilation
↓ Pulmonary pressures	Pulmonary vasodilation

3. Pharmacokinetics 

Parameter	Value
Route	IV infusion
Onset	Within minutes
Half-life (parent drug)	~1 hour
Active metabolite (OR-1896)	Half-life ~70–80 hours
Duration of action	Up to 7–10 days

✔ Effects persist even after stopping infusion

4. Indications in ICU 

A. Acute Decompensated Heart Failure (ADHF)

• Especially:
• Low cardiac output
• Beta-blocker use (catecholamine-resistant)

B. Cardiogenic Shock (Selected cases)

• Not first-line
• Consider when:
• Poor response to noradrenaline/dobutamine
• Need to avoid tachyarrhythmia

C. Right Ventricular Failure

• Pulmonary vasodilation + RV contractility improvement

D. Weaning from VA-ECMO

• Improves myocardial recovery

5. Dose & Administration

Standard Regimen

• Loading dose: 6–12 µg/kg over 10 min (often avoided in ICU)
• Infusion: 0.05–0.2 µg/kg/min for 24 hours

 ICU practice:

• Avoid bolus → prevents hypotension
• Start low dose (0.05–0.1 µg/kg/min)

6. Hemodynamic Profile vs Other Inotropes

Drug	Inotropy	Vasodilation	HR effect	O₂ demand
Dobutamine	↑↑	↑	↑↑	↑
Milrinone	↑↑	↑↑	↑	↑
Levosimendan	↑↑	↑↑	Minimal	↔

Unique advantage:
✔ No significant increase in myocardial oxygen consumption

7. Advantages 

• Works independent of β-receptors
• Effective in patients on beta-blockers
• No tachyphylaxis
• Prolonged action
• Improves:
• Cardiac output
• Renal perfusion
• Pulmonary pressures

8. Adverse Effects

Common

• Hypotension (most important)
• Headache
• Nausea

Serious

• Arrhythmias (less than catecholamines)
• Hypokalemia

 Key point:
✔ Hypotension limits use in shock

9. Contraindications

• Severe hypotension
• Severe hypovolemia
• Significant arrhythmias
• Severe renal/hepatic failure (caution due to metabolite accumulation)

10. Evidence & Trials 

A. SURVIVE Trial

• Compared levosimendan vs dobutamine
• No mortality benefit
• Better hemodynamics

B. REVIVE Trials

• Symptom improvement
• More hypotension and arrhythmias

C. CHEETAH Trial (Cardiac surgery)

• No mortality benefit

11. Guideline Recommendations

European Society of Cardiology (ESC HF Guidelines)

• May be considered in:
• ADHF with low output
• Especially on β-blockers
• Not first-line in cardiogenic shock

American Heart Association / American College of Cardiology

• Limited recommendation
• Not routine first-line
• Consider as adjunct in refractory cases

12. Comparison with Milrinone 

Feature	Levosimendan	Milrinone
Mechanism	Ca sensitizer	PDE-3 inhibitor
β-receptor dependence	No	No
Hypotension	Moderate	Significant
Duration	Very long	Short
Arrhythmia risk	Less	More

13. Special ICU Situations

A. Septic Cardiomyopathy

• Mixed evidence
• Not routine

B. Cardiorenal Syndrome

• Improves renal perfusion via:
• Increased CO
• Renal vasodilation

C. Pulmonary Hypertension

• Useful due to pulmonary vasodilation