From the Guidelines
Milrinone should be dose-adjusted when the glomerular filtration rate (GFR) falls below 50 mL/min, with a dose reduction of 50% for GFR between 50 and 30 mL/min, and a dose reduction of 75% for GFR less than 30 mL/min. This adjustment is necessary because milrinone is primarily eliminated by the kidneys, with approximately 80-85% of the drug excreted unchanged in the urine 1. Impaired renal function leads to decreased clearance and potential accumulation of the drug, which can increase the risk of adverse effects such as arrhythmias and hypotension. The half-life of milrinone is significantly prolonged in patients with renal dysfunction, further necessitating these dose adjustments. Regular monitoring of renal function and clinical response is essential when administering milrinone to patients with kidney impairment to ensure both efficacy and safety.
Some key points to consider:
- The dose adjustment is based on the GFR, which is a measure of kidney function 1.
- The GFR can be estimated using various formulas, such as the Modification of Diet in Renal Disease (MDRD) formula 1.
- Patients with a GFR less than 30 mL/min are at higher risk of adverse effects and require closer monitoring 1.
- The dose reduction should be individualized based on the patient's renal function and clinical response 1.
It is essential to note that the provided evidence does not directly address the GFR cutoff for milrinone. However, based on the general principles of pharmacology and the importance of renal function in drug elimination, the recommended dose adjustments are reasonable and consistent with the principles of drug dosing in patients with impaired renal function.
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. 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 is not explicitly stated, but the table provides infusion rates for patients with renal impairment based on creatinine clearance.
- The infusion rate is adjusted based on the patient's creatinine clearance, with lower rates for more severe renal impairment.
- The table provides infusion rates for creatinine clearances as low as 5 mL/min/1.73m^2.
- There is no specific GFR cutoff below which Milrinone is contraindicated 2.
From the Research
Milrinone and Glomerular Filtration Rate (GFR) Cutoff
- The relationship between milrinone dosing and GFR is crucial due to the drug's primary clearance through renal excretion 3, 4, 5.
- Studies suggest that dose adjustment may be necessary in patients with renal impairment, as the plasma elimination rate of milrinone is decreased in chronic renal impairment (CRI) 3.
- A proposed dose modification for intravenous milrinone in congestive heart failure patients with moderate and severe renal impairment has been tested, with maintenance infusion rates of 0.45 or 0.35 micrograms kg-1 min-1 for moderate and severe renally impaired subjects, respectively 4.
- The estimated glomerular filtration rate (eGFR) has been used to assess kidney function and modify medication doses, including milrinone, with a median eGFR of 51 mL min(-1) 1.73 m(-2) reported in one study 6.
- However, there is no specific GFR cutoff value mentioned in the provided studies for milrinone dosing, but it is recommended to adjust the dose based on the degree of renal impairment 3, 4, 7, 5.
- The use of urinary biomarkers to guide therapeutic decision making for milrinone dosing in children with acute kidney injury (AKI) has been discussed, highlighting the need for careful consideration of renal function when administering milrinone 7.