At what ejection fraction should norepinephrine be chosen over phenylephrine in patients with severe heart failure or cardiogenic shock?

Vasopressor Selection in Heart Failure Based on Ejection Fraction

Norepinephrine should be chosen over phenylephrine when left ventricular ejection fraction is reduced (typically <40-50%) and the patient presents with cardiogenic shock requiring vasopressor support. 1, 2

Primary Recommendation for Reduced Ejection Fraction

• In cardiogenic shock with reduced ejection fraction, norepinephrine is the recommended first-line vasopressor when mean arterial pressure requires pharmacologic support after adequate fluid resuscitation 1, 2

• Norepinephrine is specifically preferred over dopamine in cardiogenic shock, as dopamine causes significantly more arrhythmic events (24.1% vs 12.4%) and is associated with increased mortality in the cardiogenic shock subgroup 3

• The European Society of Cardiology explicitly recommends norepinephrine as the preferred vasopressor to combine with inotropes (such as dobutamine) when blood pressure support is needed in cardiogenic shock 2

Clinical Context for Vasopressor Selection

The choice between vasopressors in heart failure is not strictly determined by a specific ejection fraction threshold, but rather by the hemodynamic profile:

• Patients with dilated, hypokinetic ventricles (reduced EF) in cardiogenic shock should receive dobutamine for inotropic support, with norepinephrine added if systolic blood pressure remains <90 mmHg despite adequate filling 1, 2, 4

• Pure vasopressors like phenylephrine cause peripheral vasoconstriction without inotropic support, which is detrimental in reduced ejection fraction states where cardiac output augmentation is essential 4

• Phenylephrine increases afterload through pure alpha-adrenergic stimulation, which can further compromise an already failing left ventricle with reduced contractility 4

Hemodynamic-Based Algorithm

For patients with reduced ejection fraction (<40-50%) and hypotension:

1. First priority: Ensure adequate fluid resuscitation (if no overt fluid overload) 1

2. Second step: Initiate dobutamine (2-3 μg/kg/min) for inotropic support to increase cardiac output 2, 4

3. Third step: Add norepinephrine if systolic BP <90 mmHg persists despite dobutamine, as it provides both vasopressor and mild inotropic effects 1, 2

4. Avoid phenylephrine in this population, as pure alpha-agonism increases afterload without improving contractility, worsening cardiac output in failing hearts 4

Contemporary Practice Patterns

• In the American Heart Association Cardiogenic Shock Registry (2022-2024), norepinephrine was the most frequently used vasoactive agent (64.7% of cases), reflecting guideline adherence 5

• Inopressors (norepinephrine, epinephrine, dopamine) were used in 73.7% of cardiogenic shock cases, with greater use in acute myocardial infarction-related cardiogenic shock 5

Critical Pitfalls to Avoid

Using phenylephrine in reduced ejection fraction cardiogenic shock is contraindicated because:

• It increases systemic vascular resistance and left ventricular afterload without providing inotropic support 4

• The failing ventricle with reduced contractility cannot overcome the increased afterload, leading to further reduction in cardiac output 4

• Norepinephrine provides both alpha and beta-1 adrenergic effects, offering vasopressor support while maintaining some inotropic augmentation 1, 3

Special Considerations

• **For severe hypotension (SBP <80 mmHg) with reduced EF:** Norepinephrine may be required at higher doses (>0.5 μg/kg/min), potentially indicating need for mechanical circulatory support 1

• Epinephrine should be avoided in cardiogenic shock after myocardial infarction, as it increases refractory shock incidence (37% vs 7% with norepinephrine), causes excessive tachycardia, and worsens lactic acidosis 6

• In preserved ejection fraction (≥50%): The vasopressor choice is less critical regarding contractility concerns, though norepinephrine remains preferred over phenylephrine for its more balanced hemodynamic profile 1