MILRINONE
1. BASIC PHARMACOLOGY
- Class: Phosphodiesterase-3 (PDE-3) inhibitor
- Type: Inodilator (↑ inotropy + vasodilation)
Mechanism of Action
Milrinone inhibits PDE-3 → prevents breakdown of cAMP
In cardiac myocytes:
- ↑ cAMP → ↑ intracellular Ca²⁺ → ↑ contractility
In vascular smooth muscle:
- ↑ cAMP → ↓ Ca²⁺ → vasodilation
2. HEMODYNAMIC EFFECTS
|
Parameter |
Effect |
|
Cardiac output |
↑↑ |
|
Stroke volume |
↑ |
|
Heart rate |
Mild ↑ |
|
SVR |
↓↓ |
|
PVR |
↓ |
|
LV filling pressure |
↓ |
|
BP |
↓ (due to vasodilation) |
Key takeaway:
Strong inotrope + potent vasodilator → risk of hypotension
3. INDICATIONS
A. Acute Decompensated Heart Failure (ADHF)
- Especially:
- Low output states
- On chronic beta-blockers (milrinone works independently of β-receptors)
B. Cardiogenic Shock (Selected cases)
- When:
- High SVR + low CO
- Poor response to catecholamines
Usually combined with:
- Norepinephrine to prevent hypotension
C. Right Ventricular Failure / Pulmonary Hypertension
- ↓ PVR → improves RV function
- Useful in:
- Post cardiac surgery
- Acute PE with RV dysfunction (adjunct)
D. Post Cardiac Surgery Low Output Syndrome
- Improves cardiac output
- Reduces afterload
E. Bridge Therapy
- Bridge to:
- LVAD
- Cardiac transplant
4. DOSING
Standard Dose
- Loading dose: 50 mcg/kg over 10 min (often avoided in ICU → hypotension risk)
- Infusion:
0.25 – 0.75 mcg/kg/min
Renal Adjustment
- Milrinone is renally cleared
|
CrCl |
Dose adjustment |
|
30–50 ml/min |
Reduce infusion |
|
<30 ml/min |
Significant reduction |
|
ESRD |
Avoid or very cautious |
Exam pearl:
Accumulation → ↑ arrhythmias + hypotension
5. COMPARISON WITH DOBUTAMINE
|
Feature |
Milrinone |
Dobutamine |
|
Mechanism |
PDE-3 inhibitor |
β1 agonist |
|
β-receptor dependence |
No |
Yes |
|
Effect in β-blocked pts |
Better |
Reduced |
|
Vasodilation |
Strong |
Mild |
|
Tachycardia |
Less |
More |
|
Arrhythmias |
Yes |
Yes (more tachy) |
|
Half-life |
Long (2–4 hr) |
Short (2 min) |
|
Renal adjustment |
Required |
Not required |
Clinical preference:
- On β-blockers → Milrinone preferred
- Hypotensive → Dobutamine preferred
6. ADVERSE EFFECTS
Cardiovascular
- Hypotension (most common)
- Ventricular arrhythmias
- Atrial fibrillation
Others
- Thrombocytopenia (rare)
- Headache
- Electrolyte disturbances
7. MONITORING
Hemodynamic Monitoring
- MAP (risk of hypotension)
- Cardiac output (if advanced monitoring available)
- CVP / PA pressures (if PAC in situ)
Lab Monitoring
- Renal function (daily)
- Electrolytes (K⁺, Mg²⁺)
- Platelet count
8. CLINICAL PEARLS
✔ “Inodilator of choice in β-blocked heart failure patient”
✔ Reduces both preload + afterload
✔ Useful in RV failure (↓ PVR)
✔ Long half-life → not easily titratable
✔ Avoid loading dose in ICU → hypotension
✔ Combine with vasopressor if BP low
9. PRACTICAL ICU SCENARIOS
Scenario 1: ADHF + On β-blocker
Start Milrinone infusion
Avoid dobutamine (poor response)
Scenario 2: Cardiogenic shock + high SVR
Milrinone + Norepinephrine
Scenario 3: RV failure + pulmonary hypertension
Milrinone preferred (↓ PVR)
Scenario 4: Hypotensive cardiogenic shock
Milrinone plus vasopressor
