From the FDA Drug Label
Data obtained from patients with severe renal impairment (creatinine clearance = 0 to 30 mL/min) but without congestive heart failure have demonstrated that the presence of renal impairment significantly increases the terminal elimination half-life of milrinone lactate. Reductions in infusion rate may be necessary in patients with renal impairment For patients with clinical evidence of renal impairment, the recommended infusion rate can be obtained from the following table: Creatinine Clearance (mL/min/1.73m 2) Infusion Rate (mcg/kg/min) 5 0.2 10 0.23 20 0.28 30 0.33 40 0.38 50 0.43
The GFR cutoff for Milrinone therapy is not explicitly stated, but the table provides infusion rates based on creatinine clearance levels.
- For a creatinine clearance of 5 mL/min/1.73m^2, the infusion rate is 0.2 mcg/kg/min.
- For a creatinine clearance of 10 mL/min/1.73m^2, the infusion rate is 0.23 mcg/kg/min.
- For a creatinine clearance of 20 mL/min/1.73m^2, the infusion rate is 0.28 mcg/kg/min.
- For a creatinine clearance of 30 mL/min/1.73m^2, the infusion rate is 0.33 mcg/kg/min.
- For a creatinine clearance of 40 mL/min/1.73m^2, the infusion rate is 0.38 mcg/kg/min.
- For a creatinine clearance of 50 mL/min/1.73m^2, the infusion rate is 0.43 mcg/kg/min 1.
From the Research
Milrinone therapy should be used with caution in patients with impaired renal function, with dose adjustments recommended for patients with a GFR below 50 mL/min. The most recent and highest quality study 2 suggests that patients with severe renal dysfunction (GFR <30 mL/min) may experience adverse effects with milrinone therapy.
Key Considerations
- For patients with a GFR of 10-50 mL/min, the loading dose should remain standard (50 μg/kg over 10 minutes) but the maintenance infusion rate should be reduced by 50% (from 0.375-0.75 μg/kg/min to 0.2-0.375 μg/kg/min) 2.
- For patients with severe renal impairment (GFR <10 mL/min), the maintenance dose should be further reduced to about 25% of normal.
- Regular monitoring of renal function, blood pressure, and heart rate is essential during milrinone therapy, particularly in patients with compromised kidney function 3.
Rationale
Milrinone is primarily eliminated by the kidneys, with approximately 80-85% excreted unchanged in urine. Without dose adjustments, patients with renal impairment may experience drug accumulation, leading to increased risk of adverse effects such as hypotension, arrhythmias, and thrombocytopenia 4.
Additional Guidance
The choice of inotrope therapy should consider the potential effects on renal function, with levosimendan potentially having a renoprotective effect compared to milrinone 3. However, the decision to use milrinone should be based on individual patient needs and careful consideration of the potential risks and benefits.