Expected Cardiac Index Increase with Milrinone at 0.375 mcg/kg/min
At a dose of 0.375 mcg/kg/min, milrinone typically increases cardiac index by approximately 0.3-0.5 L/min/m² (15-25% increase from baseline). 1, 2
Milrinone Pharmacodynamics and Cardiac Output Effects
- Milrinone is a phosphodiesterase type III inhibitor (PDEI) with significant inotropic, lusitropic, and peripheral vasodilating effects that increase cardiac output and stroke volume 3
- At the therapeutic plasma concentration range of 100-300 ng/ml, milrinone produces dose-related and plasma concentration-related increases in cardiac index 4, 2
- A milrinone infusion rate of 0.375 mcg/kg/min (the minimum recommended maintenance dose) typically achieves plasma concentrations around 100-150 ng/ml 4, 2
- At plasma concentrations exceeding 100 ng/ml, cardiac index reliably increases by at least 0.4 L/min/m² (range 0.4-1.8 L/min/m²) 2
Dose-Response Relationship
- In dose-finding studies, milrinone at 0.25 mcg/kg/min increased cardiac index by approximately 21%, while 0.5 mcg/kg/min increased it by approximately 26% 1
- The 0.375 mcg/kg/min dose falls between these two studied doses, suggesting an expected cardiac index increase of approximately 23-24% 1, 2
- Early studies demonstrated that even at lower serum concentrations (63±4 ng/ml), milrinone caused significant increases in stroke volume, which contributes directly to cardiac index improvement 5
Clinical Administration Considerations
- The FDA-approved dosing for milrinone includes a loading dose of 50 mcg/kg administered over 10 minutes, followed by a continuous infusion at 0.375-0.75 mcg/kg/min 4
- For patients with renal impairment, dose reduction is necessary as the elimination half-life is significantly prolonged, with 0.33 mcg/kg/min recommended for creatinine clearance of 30 ml/min/1.73m² 4
- Hypotension is the most common side effect of milrinone due to its vasodilatory properties and may require fluid boluses or vasopressors 6, 3
- In patients with low filling pressures, consider starting the infusion without a bolus to avoid excessive hypotension 3
Monitoring and Optimization
- Cardiac index improvements typically occur within 5-15 minutes of initiating therapy 1, 2
- Milrinone may be preferred over dobutamine in patients on concomitant β-blocker therapy as its site of action is distal to beta-adrenergic receptors 3, 6
- For optimal hemodynamic effect, plasma concentrations should be maintained above 100 ng/ml 2, 7
- In advanced heart failure patients with renal dysfunction, lower doses (0.1-0.2 mcg/kg/min) may still achieve therapeutic plasma levels and desired hemodynamic effects 8