Milrinone Dosing
The recommended dose of milrinone is a 50 mcg/kg loading dose administered over 10 minutes, followed by a continuous infusion of 0.375-0.75 mcg/kg/min, with 0.5 mcg/kg/min being the standard maintenance rate. 1
Standard Dosing Protocol
Loading Dose
- Administer 50 mcg/kg intravenously over 10 minutes 1
- The loading dose may be given undiluted or diluted to 10-20 mL for easier visualization of injection rate 1
- In hypotensive patients (systolic BP <100 mmHg), omit the loading dose and start directly with maintenance infusion 2, 3
- If blood pressure stability is a concern, consider dividing the bolus into five equal aliquots administered over 10 minutes each 3
Maintenance Infusion
- Standard rate: 0.5 mcg/kg/min 1
- Minimum rate: 0.375 mcg/kg/min 1
- Maximum rate: 0.75 mcg/kg/min (not to exceed 1.13 mg/kg/day total) 1
- Dilute to 200 mcg/mL concentration using 0.45% NaCl, 0.9% NaCl, or 5% dextrose 1
Dose Adjustments for Renal Impairment
Milrinone requires dose reduction in renal dysfunction due to prolonged elimination half-life 2, 3:
| Creatinine Clearance | Infusion Rate |
|---|---|
| 50 mL/min | 0.43 mcg/kg/min |
| 40 mL/min | 0.38 mcg/kg/min |
| 30 mL/min | 0.33 mcg/kg/min |
| 20 mL/min | 0.28 mcg/kg/min |
| 10 mL/min | 0.23 mcg/kg/min |
| 5 mL/min | 0.2 mcg/kg/min |
Clinical Context and Monitoring
When to Use Milrinone
- Preferred over dobutamine in patients on beta-blocker therapy, as its mechanism of action (phosphodiesterase-3 inhibition) is distal to beta-adrenergic receptors and maintains full efficacy 2, 3
- Effective for low cardiac output states with cardiac index <2.5 L/min/m² or pulmonary capillary wedge pressure ≥15 mmHg 4, 5
- Produces balanced inotropic and vasodilatory effects, increasing cardiac output while reducing preload and afterload 2, 3
Critical Monitoring Parameters
- Target mean arterial pressure ≥65 mmHg 3
- Continuous ECG telemetry for arrhythmia detection 2
- Hemodynamic parameters: cardiac output, pulmonary capillary wedge pressure, systemic vascular resistance 1
- Hypotension is the most common adverse effect due to vasodilatory properties 3
Managing Hypotension
- If hypotension occurs, reverse with titrated boluses of isotonic crystalloid or colloid 3
- Consider concurrent vasopressor support (norepinephrine or vasopressin) if systolic BP drops below 100 mmHg 3, 6
- Discontinue milrinone at first sign of arrhythmia or excessive hypotension from diminished systemic vascular resistance 3
Evidence-Based Efficacy
Research demonstrates dose-dependent hemodynamic improvements 7:
- Cardiac index increases 21-31% across dosing ranges 7, 8
- Pulmonary capillary wedge pressure decreases 13-41% 7
- Plasma concentrations >100 ng/mL correlate with CI increases ≥0.4 L/min/m² 8
- Effects manifest within 15 minutes of loading dose and are sustained throughout infusion 4, 9
Weaning Strategy
Gradual tapering is essential to prevent acute decompensation 2, 10:
- Decrease by 0.05-0.1 mcg/kg/min every 12-24 hours 10
- Monitor for recurrence of hypotension, congestion, or renal insufficiency 10
- Optimize oral vasodilator therapy (hydralazine, ACE inhibitors) to facilitate discontinuation 10
- Abrupt discontinuation can precipitate hemodynamic collapse 10
Important Caveats
- Use with caution in coronary artery disease, as it may increase medium-term mortality 2
- Long-term use outside palliative care or bridge therapy may be harmful 3
- Elimination half-life is 1-10 hours depending on organ function, requiring 3-30 hours to reach steady state without loading dose 3, 6
- Arrhythmias (particularly atrial fibrillation) can occur due to increased atrial automaticity 3
- Ensure adequate filling pressures before initiation, as vasodilatory effects can unmask hypovolemia 10