Milrinone

Milrinone is a phosphodiesterase-3 inhibitor (PDE3-I) used as a potent inotropic and vasodilator agent. It increases intracellular cyclic AMP (cAMP), enhancing cardiac contractility (inotropy) and relaxation (lusitropy) while inducing vasodilation. Milrinone is especially beneficial in acute heart failure and right ventricular failure.

Uses

• Acute Heart Failure: Improves hemodynamics by enhancing cardiac output and reducing vascular resistance.
• Cardiogenic Shock: Supports cardiac function in critical conditions by increasing myocardial contractility.
• Post-Cardiac Surgery: Used for inotropic support after cardiac procedures.
• Right Ventricular Failure: Particularly beneficial post-cardiac surgery due to its pulmonary vasodilatory effects.
• Pulmonary Hypertension: Effective in lowering pulmonary artery pressure and improving hemodynamics.

Dosage and Administration

Adults:

• Loading Dose: 50 mcg/kg IV over 10 minutes.
• Maintenance Dose: 0.375-0.75 mcg/kg/min IV infusion, adjusted based on hemodynamic response.

Pediatric:

• Loading Dose: 50-75 mcg/kg IV over 30-60 minutes.
• Maintenance Dose: 0.25-0.75 mcg/kg/min IV infusion.

Dose Adjustment in Different Diseases

• Renal Impairment:
  • Dosage reduction is recommended in patients with renal dysfunction.
  • Monitor renal function during therapy.
• Hepatic Impairment:
  • No specific dosage adjustment guidelines, but caution is advised.
• Geriatric Patients:
  • Start at the lower end of the dosage range due to potential decreased renal function.

Presentation/Form

• IV Solution: 10 mg/10 cc

Pharmacokinetics

• Absorption: Not applicable (administered intravenously).
• Onset: 5-15 minutes.
• Distribution: Widely distributed in the body.
• Metabolism: Hepatic and renal pathways.
• Elimination: Primarily renal; half-life approximately 2.3 hours.
• Duration: 3-6 hours after infusion is stopped.

Pharmacodynamics

• Enhances myocardial contractility by inhibiting PDE3, leading to increased cAMP levels.
• Vasodilatory effects reduce both preload and afterload.
• Promotes myocardial relaxation, improving lusitropy.

Drug Interactions

• Furosemide (Lasix): Avoid mixing in the same IV line due to precipitation.
• Inotropes: Caution with concurrent use due to the risk of arrhythmias.
• Vasodilators: Increased risk of hypotension.
• Beta-blockers: Effects may be counterbalanced by beta-blocker activity.

Precautions and Special Considerations

• Hemodynamic Monitoring: Continuous monitoring of blood pressure and heart rate is essential.
• Renal Function: Monitor renal function closely; adjust dosage in renal impairment.
• Right Ventricular Failure: Particularly beneficial due to its pulmonary vasodilatory effects.
• Pulmonary Hypertension: Effective in lowering pulmonary vascular resistance.
• Pediatric Use: Widely used for postoperative inotropic support in pediatric cardiac patients.
• Elderly: Initiate treatment at the lower dosage range.
• Hypotension Risk: Use cautiously in patients prone to hypotension.

Side Effects

• Common: Hypotension, arrhythmias (especially ventricular tachycardia), headache.
• Serious: Thrombocytopenia, worsening renal function, increased risk of mortality with prolonged use in heart failure.
• Rare: Skin rashes, elevated liver enzymes.

Recent Updates and Guidelines

• Heart Failure Guidelines: Recent updates highlight the role of inotropic agents like milrinone in short-term management of severe heart failure.
• Post-Cardiac Surgery: Increased adoption for right heart support and pulmonary hypertension management.
• Combination Therapy: Emerging studies suggest benefits of using milrinone with vasopressors for cardiogenic shock.

References

• Milrinone - NCBI StatPearls: https://www.ncbi.nlm.nih.gov/books/NBK532943/
• Goodman & Gilman’s The Pharmacological Basis of Therapeutics, 13th Edition.
• Current Heart Failure Management Guidelines (2025 update).
• Recent Clinical Trials on Milrinone in Pediatric and Adult Cardiac Care.
• Clinical Pharmacokinetics and Pharmacodynamics of Milrinone: A Review Article.