What is the appropriate dosage of Milrinone for an adult patient in cardiogenic shock?

Inotrope Selection and Dosing in Cardiogenic Shock

For adult patients in cardiogenic shock, milrinone is administered with a loading dose of 50 mcg/kg over 10 minutes, followed by a continuous infusion of 0.375-0.75 mcg/kg/min, titrated to hemodynamic response, with the loading dose omitted in hypotensive patients (SBP <100 mmHg). 1, 2

Standard Milrinone Dosing Protocol

Loading Dose

• Administer 50 mcg/kg slowly over 10 minutes in hemodynamically stable patients (SBP ≥100 mmHg) 1
• Omit the loading dose entirely in hypotensive patients with systolic blood pressure <100 mmHg and proceed directly to maintenance infusion 2, 3
• The loading dose may be given undiluted or diluted to 10-20 mL for easier visualization of injection rate 1

Maintenance Infusion

• Standard starting dose: 0.5 mcg/kg/min as continuous IV infusion 1
• Dose range: 0.375-0.75 mcg/kg/min, titrated to hemodynamic response 1, 2
• Maximum dose should not exceed 1.13 mg/kg/day (0.75 mcg/kg/min) 1
• Dilute to 200 mcg/mL concentration using 0.45% NaCl, 0.9% NaCl, or 5% dextrose 1

Hemodynamic Targets

• Mean arterial pressure ≥65 mmHg 2
• Cardiac index >2 L/min/m² 2, 4
• Resolution of hypoperfusion signs: improved urine output, mental status, lactate clearance, and warming of extremities 2, 4

Dose Adjustments in Renal Impairment

Milrinone requires significant dose reduction in renal dysfunction due to prolonged elimination half-life 1, 3:

Creatinine Clearance	Infusion Rate
50 mL/min	0.43 mcg/kg/min
40 mL/min	0.38 mcg/kg/min
30 mL/min	0.33 mcg/kg/min
20 mL/min	0.28 mcg/kg/min
10 mL/min	0.23 mcg/kg/min
5 mL/min	0.20 mcg/kg/min

1, 3

Clinical Indications for Milrinone Over Dobutamine

Milrinone is specifically preferred in three clinical scenarios:

• Patients on chronic beta-blocker therapy, as milrinone's mechanism (phosphodiesterase-3 inhibition) is distal to beta-adrenergic receptors and maintains full efficacy despite beta-blockade, whereas dobutamine requires higher doses to overcome receptor blockade 2, 4, 3
• Right ventricular failure or pulmonary hypertension, as milrinone reduces both systemic and pulmonary vascular resistance 2, 4
• Post-cardiac surgery low cardiac output syndrome, where milrinone has demonstrated efficacy in prevention and treatment 5

Comparative Efficacy: Milrinone vs Dobutamine

The most recent high-quality randomized trial (DOREMI, 2021) found no significant difference in mortality or major outcomes between milrinone and dobutamine in cardiogenic shock 6:

• Primary composite outcome: 49% (milrinone) vs 54% (dobutamine), RR 0.90 (95% CI 0.69-1.19, p=0.47) 6
• In-hospital mortality: 37% vs 43%, RR 0.85 (95% CI 0.60-1.21) 6
• No differences in mechanical circulatory support, cardiac arrest, or renal replacement therapy 6

However, adverse event profiles differ significantly 7:

• Arrhythmias more common with dobutamine: 62.9% vs 32.8% (p<0.01) 7
• Hypotension-related discontinuation more common with milrinone: 13.1% vs 0% (p<0.01) 7
• Each 1 mcg/kg/min increase in dobutamine dose associated with 15% increased mortality risk 8

Critical Management of Hypotension

Hypotension is the most common and clinically significant adverse effect of milrinone due to potent vasodilatory properties 2, 3:

• Add norepinephrine as first-line vasopressor if SBP remains <90 mmHg despite adequate fluid resuscitation 2, 4
• Starting dose: 2-3 mL/min (8-12 mcg/min), titrated to maintain SBP 80-100 mmHg 4
• The combination of milrinone and norepinephrine is particularly beneficial: milrinone improves cardiac output by reducing afterload while norepinephrine maintains coronary and systemic perfusion pressure 4
• Consider fluid boluses with isotonic crystalloid or colloid for acute hypotension 3

Essential Monitoring Requirements

Invasive arterial blood pressure monitoring is mandatory during milrinone administration 2:

• Continuous ECG telemetry for arrhythmia detection (milrinone increases atrial automaticity) 2, 3
• Hemodynamic parameters: cardiac output/index, pulmonary artery pressures 2
• Signs of improved perfusion: urine output, mental status, lactate clearance, extremity warmth 2, 4

Important Safety Considerations

• Use the lowest effective dose for the shortest duration, as all inotropes increase myocardial oxygen consumption and arrhythmia risk 2
• Long-term use outside of palliative care or bridge therapy may be harmful, particularly in ischemic heart failure 2, 3
• Observe patients for at least 48 hours after discontinuation to assess stability 3
• Gradual tapering is essential to prevent acute decompensation 3
• Milrinone has synergistic effects when combined with beta-agonists (dobutamine, epinephrine) due to cAMP accumulation mechanism 3