What is the proper administration protocol for intravenous (IV) milrinone?

IV Milrinone Administration Protocol

The proper administration of intravenous milrinone requires a loading dose of 50 mcg/kg administered slowly over 10 minutes, followed by a continuous infusion at 0.375-0.75 mcg/kg/min. 1

Loading Dose Administration

• Administer 50 mcg/kg as a loading dose over 10 minutes 1
• The loading dose may be given undiluted, but diluting to a total volume of 10 or 20 mL may simplify visualization of the injection rate 1
• Monitor blood pressure closely during loading dose administration due to risk of hypotension 2
• Consider dividing the bolus into five equal aliquots administered over 10 minutes each if blood pressure stability is a concern 3

Maintenance Infusion

• Standard maintenance dose: 0.5 mcg/kg/min 1
• Dose range:
  • Minimum: 0.375 mcg/kg/min (total daily dose: 0.59 mg/kg) 1
  • Maximum: 0.75 mcg/kg/min (total daily dose: 1.13 mg/kg) 1
• Dilute milrinone prior to maintenance infusion using one of these diluents 1:
  • 0.45% Sodium Chloride Injection USP
  • 0.9% Sodium Chloride Injection USP
  • 5% Dextrose Injection USP

Preparation of Infusion Solution

• To achieve a 200 mcg/mL concentration for infusion 1:
  • 10 mL of milrinone (1 mg/mL) + 40 mL diluent = 50 mL total volume
  • 20 mL of milrinone (1 mg/mL) + 80 mL diluent = 100 mL total volume
• Use a calibrated electronic infusion device for continuous infusion 1

Dosage Adjustment in Renal Impairment

• Renal impairment significantly increases the terminal elimination half-life of milrinone 1
• Adjust infusion rate based on creatinine clearance 1:
  • CrCl 5 mL/min/1.73m²: 0.2 mcg/kg/min
  • CrCl 10 mL/min/1.73m²: 0.23 mcg/kg/min
  • CrCl 20 mL/min/1.73m²: 0.28 mcg/kg/min
  • CrCl 30 mL/min/1.73m²: 0.33 mcg/kg/min
  • CrCl 40 mL/min/1.73m²: 0.38 mcg/kg/min
  • CrCl 50 mL/min/1.73m²: 0.43 mcg/kg/min

Monitoring During Administration

• Monitor hemodynamic parameters closely during infusion 3
• Assess for hypotension, which is the most common side effect 2
• Monitor for cardiac arrhythmias, particularly atrial fibrillation 2
• If hypotension occurs, it can typically be reversed with titrated boluses (5 mL/kg) of isotonic crystalloid or colloid 3
• ECG monitoring for arrhythmias is recommended during milrinone infusion 4

Clinical Response Expectations

• Hemodynamic effects typically occur within 15 minutes after starting administration 5
• Expected hemodynamic effects include 6:
  • 24-42% increase in cardiac index
  • 24-33% decrease in pulmonary capillary wedge pressure
  • 15-31% decrease in systemic vascular resistance
• Significant hemodynamic responses are generally maintained over 48 hours of continuous infusion 6

Important Precautions

• Discontinue milrinone at the first sign of arrhythmia or hypotension caused by excessively diminished systemic vascular resistance 3
• Hypotension-related toxicity can be potentially overcome by beginning norepinephrine or vasopressin 3
• Inspect solution visually before use; do not use if particulate matter or discoloration is present 1
• Milrinone may be preferred over dobutamine in patients on beta-blocker therapy as its mechanism of action is distal to beta-adrenergic receptors 3