Milrinone Dosing in Severe Renal Impairment (GFR 27 mL/min)
For a patient with GFR 27 mL/min/1.73 m², milrinone should be administered with a loading dose of 50 mcg/kg over 10 minutes, followed by a continuous infusion of 0.28 mcg/kg/min based on FDA-approved renal dosing adjustments. 1
Loading Dose Administration
- Always administer the full loading dose of 50 mcg/kg over 10 minutes regardless of renal function 1
- The loading dose may be given undiluted or diluted to 10-20 mL for easier visualization of injection rate 1
- For a 70 kg patient, this equals 3.5 mL of milrinone 1 mg/mL concentration 1
Maintenance Infusion Rate Calculation
The FDA label provides specific infusion rates based on creatinine clearance, which directly applies to your patient: 1
- For CrCl 20 mL/min: 0.28 mcg/kg/min
- For CrCl 30 mL/min: 0.33 mcg/kg/min
- For GFR 27 mL/min, interpolate to approximately 0.30 mcg/kg/min 1
This represents a 40% reduction from the standard 0.5 mcg/kg/min maintenance dose used in patients with normal renal function 1
Preparation and Administration
- Dilute milrinone to 200 mcg/mL concentration using 0.45% NaCl, 0.9% NaCl, or 5% Dextrose 1
- For a 70 kg patient at 0.30 mcg/kg/min: infusion rate = 6.3 mL/hr 1
- Use a calibrated electronic infusion device for precise delivery 1
Critical Monitoring Parameters
Plasma concentrations correlate directly with renal function and can accumulate dangerously in severe renal impairment: 2, 3
- Therapeutic plasma concentration range: 100-200 ng/mL 3
- In severe renal failure, plasma concentrations can exceed 700 ng/mL even with reduced dosing 3
- Monitor hemodynamic response closely and adjust infusion rate based on clinical effect, not exceeding 1.13 mg/kg/day total 1
Pharmacokinetic Rationale
The renal clearance of milrinone is highly correlated with creatinine clearance (R² = 0.809), making dose adjustment essential: 2
- In patients with CrCl 30-63 mL/min, plasma half-life increases from 0.94 hours to 1.78 hours 4
- In severe renal impairment (CrCl <30 mL/min), half-life extends to 3.24 hours 4
- Approximately 82% of milrinone is renally excreted unchanged 4
Clinical Validation
The proposed dose modification has been validated in CHF patients with severe renal impairment: 5
- Infusion of 0.35 mcg/kg/min in patients with CrCl 10-30 mL/min achieved steady-state concentrations of 269 ± 32 ng/mL 5
- This dosing maintained therapeutic levels without serious adverse events in 9 of 11 patients 5
- Two patients had levels between 308-353 ng/mL without toxicity 5
Common Pitfalls to Avoid
- Never skip the loading dose - it is essential for rapid therapeutic effect and is not affected by renal function 1
- Do not use standard maintenance dosing (0.5 mcg/kg/min) - this will lead to toxic accumulation in severe renal impairment 2, 3
- Avoid continuous venovenous hemofiltration without further dose reduction - one case report documented plasma levels of 792.7 ng/mL (4x therapeutic) with standard renal dosing during CVVH 3
- Monitor blood pressure closely - milrinone causes vasodilation that may be more pronounced in renal impairment, with maximal BP decrease occurring 2-3 hours post-dose 4