Milrinone

Milrinone, an analogue of amrinone, is a bipyridine derivative with inotropic activity that is almost 20 times more potent than that of amrinone and a shorter half-life. Milrinone is an effective inodilator for patients with decompensated HF and low CO after cardiac surgical procedures. 

Suggested administration of milrinone is a loading dose of 50 μg/kg over 10 minutes, followed by an infusion of 0.5 μg/ kg per minute (0.375–0.75 μg/kg per min). By using slower loading doses, high peak concentrations can be prevented, and the vasodilation that is observed with rapid loading can be attenuated. 

A milrinone loading dose of 50 μg/kg in combination with an infusion of 0.5 μg/ kg per minute consistently maintained plasma concentrations more than 100 ng/mL. Clearance was 3.8 ± 1.7 mL/kg per minute, volume of distribution was 465 ± 159 mL/kg, and terminal elimination half-time was 107 ± 77 minutes (values expressed as mean ± standard deviation [SD]). Pharmacokinetic parameters were independent of dose. The relationship between plasma concentration and pharmacodynamic effects produced approximately a 30% improvement in cardiac index with plasma levels of 100 ng/mL, and a curvilinear relationship was noted between plasma levels and improvement in cardiac index. Bailey and colleagues observed that a dose of 50 μg/kg with an infusion rate of 0.5 μg/kg per minute can keep plasma concentrations near the threshold of its therapeutic effects. Compared with amrinone, milrinone has a shorter context-sensitive half-time after administration is stopped without adverse effects on platelet function.

Dosing Modifications

Renal impairment

• CrCl <50 mL/min: 0.43 mcg/kg/min  
• CrCl <40 mL/min/1.73m²: 0.38 mcg/kg/min
• CrCl <30 mL/min/1.73m²: 0.33 mcg/kg/min
• CrCl <20 mL/min/1.73m²: 0.28 mcg/kg/min
• CrCl <10 mL/min/1.73m²: 0.23 mcg/kg/min
• CrCl <5 mL/min/1.73m²: 0.2 mcg/kg/min

Administration

IV Incompatibilities

Additive: Procainamide

Syringe: Furosemide

Y-site: Furosemide, procainamide

IV Compatibilities

Solution: Most common solvents

Additive: Quinidine

Syringe: Atropine, calcium chloride, digoxin, epinephrine, lidocaine, morphine sulfate, propranolol, sodium bicarbonate, verapamil

Y-site (partial list): Acyclovir, amiodarone, calcium chloride, calcium gluconate, ciprofloxacin, digoxin, diltiazem, dobutamine, dopamine, epinephrine, fentanyl, heparin, lorazepam, magnersium sulfate, metronidazole, midazolam, morphine sulfate, nitroglycerin, norepinephrine, potassium chloride, propofol, propranolol, quinidine, sodium nitroprusside, vancomycin

CONTRAINDICATIONS 

Corn hypersensitivity

Idiopathic hypertrophic subaortic stenosis, valvular heart disease in lieu of surgical relief of the obstruction.

Atrial fibrillation, atrial flutter, hypokalemia, hypovolemia

Milrinone use has been associated with ventricular arrhythmias, including ventricular tachycardia. Milrinone produces a slight shortening of AV node conduction time, indicating a potential for an increased ventricular response rate in patients with atrial flutter or atrial fibrillation which is not controlled with digitalis therapy.

Acute myocardial infarction

Milrinone use is not recommended during acute myocardial infarction.

Renal failure, renal impairment

Severe renal impairment significantly increases the half-life of milrinone.

Pregnancy

Breast-feeding