In which types of shock are adrenaline (epinephrine) and milrinone used?

Adrenaline and Milrinone Use in Shock

Adrenaline (epinephrine) is primarily used in distributive shock (particularly septic shock) as a second-line agent when norepinephrine fails, while milrinone is used in cardiogenic shock as an inotrope to improve cardiac output in patients with myocardial dysfunction. 1, 2

Adrenaline (Epinephrine)

Primary Indication: Distributive/Septic Shock

• Second-line vasopressor when norepinephrine alone is insufficient 1
• Can be used as a single agent alternative to norepinephrine plus dobutamine, achieving similar shock reversal rates 1
• No survival advantage demonstrated over norepinephrine in randomized trials 1

Important Caveats

However, recent evidence suggests epinephrine may cause harm: it significantly increases refractory shock risk (OR 8.24) and mortality (OR 1.63 vs. norepinephrine) 3. The 2018 guidelines note that drugs with positive chronotropic effects (including epinephrine) may be associated with higher mortality risk 1.

When NOT to Use

• Avoid as first-line therapy in septic shock
• Use cautiously in patients at risk for tachyarrhythmias
• Not recommended in cardiogenic shock due to increased myocardial oxygen consumption

Milrinone

Primary Indication: Cardiogenic Shock

Milrinone is an inotrope and vasodilator used specifically in cardiogenic shock to improve cardiac output in patients with myocardial dysfunction 1, 2. The FDA label confirms it is indicated for heart failure associated with cardiac surgery and myocardial infarction 2.

Mechanism and Benefits

• Phosphodiesterase III inhibitor that increases cardiac contractility and causes vasodilation 2
• Superior outcomes in cardiogenic shock: Recent meta-analyses show milrinone has the lowest mortality and adverse event rates among inotropes for cardiogenic shock 4
• In acute decompensated heart failure with cardiogenic shock, milrinone shows lower 30-day mortality (HR 0.52) compared to dobutamine 5
• Particularly effective in ICU settings: Dobutamine shows 2.85-fold higher mortality than milrinone in ICU cardiogenic shock patients 6

Specific Clinical Scenarios

1. Cardiogenic shock with myocardial depression: First-line inotrope choice 1, 7
2. Acute heart failure with shock: Preferred over dobutamine based on 2023-2026 evidence 5, 6
3. When combined with norepinephrine: Improves hemodynamics and reduces organ dysfunction 8

Emerging Role in Septic Shock

While traditionally not first-line, recent 2025 data shows milrinone may benefit septic shock patients with persistent tissue hypoperfusion despite norepinephrine, significantly improving cardiac output at 6 hours 9. Guidelines suggest considering inotropes like milrinone when septic shock involves myocardial depression 1.

Critical Contraindications and Warnings

• Do NOT use in severe aortic or pulmonic stenosis - may worsen outflow obstruction 2
• Avoid in hypertrophic obstructive cardiomyopathy - aggravates outflow tract obstruction 2
• Causes more profound hypotension than dobutamine due to longer half-life 1
• Monitor closely for arrhythmias (12.1% incidence of ventricular arrhythmias) 2
• Requires dose adjustment in renal impairment

Practical Dosing Considerations

• Therapeutic plasma concentrations: 100-300 ng/mL 2
• Monitor blood pressure and heart rate continuously; slow or stop infusion if excessive hypotension occurs 2
• Limited experience beyond 48 hours of continuous infusion 2
• Correct hypokalemia before use to prevent arrhythmias 2

Key Algorithmic Approach

For Cardiogenic Shock:

1. Start norepinephrine if hypotensive (MAP <65 mmHg) 1, 7
2. Add milrinone (not dobutamine) as first-line inotrope for myocardial dysfunction 5, 6, 7
3. Avoid epinephrine due to adverse metabolic effects and increased refractory shock risk 3, 7

For Septic Shock:

1. Norepinephrine is first-line vasopressor 1
2. If persistent hypotension: add vasopressin (up to 0.03 U/min) 1
3. If myocardial depression present: consider epinephrine as single agent OR add milrinone to norepinephrine 1, 9
4. Avoid epinephrine if possible given recent safety concerns 3

Critical Pitfall: Do not use milrinone in valvular obstruction (aortic/pulmonic stenosis) or hypertrophic cardiomyopathy - this can be fatal 2.