What is the recommended dose for milrinone (phosphodiesterase 3 inhibitor) perfusion?

Milrinone Perfusion Dose

The recommended milrinone perfusion dose 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

Loading Dose Administration

• Administer 50 mcg/kg slowly over 10 minutes as the standard loading dose 1
• The loading dose may be given undiluted or diluted to 10-20 mL to simplify visualization of injection rate 1
• In hypotensive patients (systolic BP <100 mmHg), omit the loading dose entirely and start directly with maintenance infusion to avoid precipitous blood pressure drops 2, 3
• If blood pressure stability is a concern, divide the bolus into five equal aliquots administered over 10 minutes each 2

Maintenance Infusion Rates

The FDA-approved dosing ranges are 1:

• Minimum: 0.375 mcg/kg/min (total daily dose 0.59 mg/kg)
• Standard: 0.5 mcg/kg/min (total daily dose 0.77 mg/kg)
• Maximum: 0.75 mcg/kg/min (total daily dose 1.13 mg/kg)

Dilute milrinone to 200 mcg/mL concentration using 0.45% NaCl, 0.9% NaCl, or 5% dextrose before starting maintenance infusion 1. For example, mix 20 mL of milrinone (1 mg/mL) with 80 mL diluent to achieve 100 mL at 200 mcg/mL 1.

Dose Selection Strategy

• Start with 0.5 mcg/kg/min as the standard maintenance rate for most patients with acute heart failure or low cardiac output states 1, 4
• Research demonstrates dose-dependent hemodynamic effects: cardiac index increased 21-31% across the dosing range (0.25-0.75 mcg/kg/min), with higher doses producing greater responses 5, 4
• The 0.5 mcg/kg/min dose achieves plasma concentrations of approximately 150-200 ng/mL, which reliably increases cardiac index by at least 0.4 L/min/m² in most patients 6
• Titrate upward to 0.75 mcg/kg/min if inadequate hemodynamic response, but recognize this increases risk of hypotension and tachycardia 1, 5

Renal Dose Adjustments

Reduce infusion rates in patients with renal impairment based on creatinine clearance 1:

• CrCl 50 mL/min: 0.43 mcg/kg/min
• CrCl 40 mL/min: 0.38 mcg/kg/min
• CrCl 30 mL/min: 0.33 mcg/kg/min
• CrCl 20 mL/min: 0.28 mcg/kg/min
• CrCl 10 mL/min: 0.23 mcg/kg/min
• CrCl 5 mL/min: 0.2 mcg/kg/min

Milrinone has a prolonged elimination half-life (1-10 hours depending on organ function), requiring 3-30 hours to reach steady state without a loading dose 2, 3.

Critical Monitoring and Management

• Monitor hemodynamic parameters continuously during infusion, particularly blood pressure, as systemic hypotension is the most common adverse effect 2
• Target mean arterial pressure ≥65 mmHg in shock states 2
• If hypotension occurs, reverse with titrated boluses of isotonic crystalloid or colloid 2
• Consider starting norepinephrine or vasopressin concurrently if systemic vascular resistance drops excessively 2
• Discontinue milrinone immediately at the first sign of arrhythmia (particularly atrial fibrillation) or severe hypotension 2, 7

Special Clinical Considerations

• Milrinone is preferred over dobutamine in patients on beta-blocker therapy because its mechanism of action (phosphodiesterase-3 inhibition) is distal to beta-adrenergic receptors, maintaining full efficacy 2, 7
• In patients with low filling pressures, start infusion without a bolus to minimize hypotension risk 2, 7
• Use calibrated electronic infusion devices for precise administration 1
• Maximum total daily dose should not exceed 1.13 mg/kg 1