Acute Decompensated Congestive Heart Failure (CHF) with Systolic Dysfunction/Cardiogenic Shock (see Congestive Heart Failure and Cardiogenic Shock)

Clinical Efficacy

• xxx
• 2022 AHA/ACC/HFSA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2022;145(18):e895-e1032. doi:10.1161/CIR.0000000000001063 [MEDLINE]

Postoperative Inotropic Support for Heart Transplant Recipient

• Off-Label Use

Pulmonary Hypertension (see Pulmonary Hypertension)

Clinical Efficacy

• xxxx

Phosphodiesterase Type 3 Inhibitor (Which Inhibits cAMP Degradation) (see Phosphodiesterase Type 3 Inhibitors)

• Increased Myocardial Contractility
• Decreased Pulmonary Vascular Resistance (PVR)
• Vasodilation (Afterload Reduction)

Pharmacokinetics

• Milrinone has a Small Volume of Distribution (Vd)

Metabolism

• Clearance is Highly Dependent on Renal Function

Intravenous (IV)

• Dose
  • Continuous infusion: IV: Initial: 0.125 to 0.25 mcg/kg/minute
    • Titrate based on clinical end point (eg, systemic perfusion or end organ perfusion)
    • Usual dosage range: 0.125 to 0.75 mcg/kg/minute
  • Note: IV bolus loading doses are not recommended due to risk of hypotension

Dose Adjustment

Hepatic Dose Adjustment

• No Manufacturer-Recommended Dosage Adjustments Provided

Renal Dose Adjustment

• CrCl 10-50 mL/min
  • Initial Rate of 0.0625-0.125 μg/kg/min Depending on the Clinical Indication and Degree of Renal Impairment
    • Titrate Cautiously, Especially in the Setting of Worsening Renal Function
    • Titrating to >0.375 μg/kg/min in the Setting of Significant Renal Impairment is Generally Not Recommended Due to the Likelihood for Accumulation
• CrCl <10 mL/min
  • Use is Not Established
    • Consider Alternative Therapy (Cardiol Rev, 2018) [MEDLINE]

Obesity Dose Adjustment

• Class 1, 2, or 3 Obesity (BMI ≥30 kg/m2)
  • Continuous Infusion
    • Use Ideal Body Weight for Initial Weight-Based Dosing
      • Titrate to Hemodynamic Effect and Clinical Response
      • During Therapy, Do Not Change Dosing Weight from One Weight Metric to Another (i.e. Actual Body Weight to/from Ideal Body Weight) (Crit Care, 2021) [MEDLINE]
      • Milrinone has a Small Volume of Distribution (Vd)
      • Adverse Effects May Be More Frequent with Higher Doses or in the Setting of Renal Dysfunction

Use in Pregnancy (see Pregnancy)

• xxx

Use During Breast Feeding

• xxx

Cardiovascular Adverse Effects

Angina Pectoris/Chest Pain (see Chest Pain)

• Epidemiology
  • Angina Pectoris Occurs in ≤1% of Cases

Arrhythmias

• Epidemiology
  • Arrhythmias Occur More Commonly in the Setting of Renal Dysfunction (Acta Anaesthesiol Scand, 2008) [MEDLINE] (Curr Treat Options Cardiovasc Med, 2011) [MEDLINE] (Cardiovasc Pharmacol Ther, 2013) [MEDLINE] (Angiology, 2014) [MEDLINE] (Cardiol Rev, 2018) [MEDLINE] (Circulation, 2022) [MEDLINE]
• Clinical
  • Atrial Fibrillation (AF) (see Atrial Fibrillation)
    • Atrial Fibrillation Has Been Reported in Post-Marketing Studies (Drugs, 2012) [MEDLINE]
  • Supraventricular Arrhythmia (see xxxx)
    • Supraventricular Arrhythmia Occurs in 4% of Cases
  • Ventricular Ectopy (see xxxx)
    • Ventricular Ectopy Occurs in 9% of Cases
  • Ventricular Fibrillation (VF) (see Ventricular Fibrillation)
    • Ventricular Fibrillation Occurs in <1% of Cases
  • Ventricular Tachycardia (VT) (see Ventricular Tachycardia)
    • Ventricular Tachycardia Occurs in 1-3% of Cases

Hypotension (see Hypotension)

• Epidemiology
  • Hypotension Occurs in 3% of Cases
  • Hypotension Occurs More Commonly in the Setting of Renal Dysfunction (Acta Anaesthesiol Scand, 2008) [MEDLINE] (Curr Treat Options Cardiovasc Med, 2011) [MEDLINE] (Cardiovasc Pharmacol Ther, 2013) [MEDLINE] (Angiology, 2014) [MEDLINE] (Cardiol Rev, 2018) [MEDLINE] (Circulation, 2022) [MEDLINE]

Sinus Tachycardia (see Sinus Tachycardia)

• Epidemiology
  • Sinus Tachycardia Has Been Reported in Post-Marketing Studies (Can J Anaesth, 1998) [MEDLINE]

Torsade (see Torsade)

• Epidemiology
  • Torsades de Pointes Has Been Reported in Post-Marketing Studies

Dermatologic Adverse Effects

Rash

• Epidemiology
  • Rash Has Been Reported in Post-Marketing Studies

Gastrointestinal Adverse Effects

Elevated Liver Function Tests (LFT’s) (see Elevated Liver Function Tests)

• Epidemiology
  • Elevated Liver Function Tests Have Been Reported in Post-Marketing Studies

Hematologic Adverse Effects

Thrombocytopenia (see Thrombocytopenia)

• Epidemiology
  • Thrombocytopenia Occurs in <1% of Cases

Imunologic Adverse Effects

Anaphylaxis (see Anaphylaxis)

• Epidemiology
  • Anaphylaxis Has Been Reported in Post-Marketing Studies

Neurologic Adverse Effects

Headache (see Headache)

• Epidemiology
  • Headache Occurs in 3% of Cases

Tremor (see Tremor)

• Epidemiology
  • Tremor Occurs in <1% of Cases

Pulmonary Adverse Effects

Bronchospasm (see Bronchospasm)

• Epidemiology
  • Bronchospasm Has Been Reported in Post-Marketing Studies

Renal Adverse Effects

Hypokalemia (see Hypokalemia)

• Epidemiology
  • Hypokalemia Occurs in <1% of Cases

Other Adverse Effects

Infusion Site Reaction

• Epidemiology
  • Infusion Site Reaction Has Been Reported in Post-Marketing Studies