Is Levophed (norepinephrine) an inotrope?

Is Levophed (Norepinephrine) an Inotrope?

Norepinephrine (Levophed) is primarily a vasopressor, but it does possess mild inotropic properties through β1-adrenergic receptor stimulation—however, its predominant clinical effect is vasoconstriction via α-adrenergic receptors, not inotropy. 1

Pharmacologic Classification

The FDA label explicitly states that norepinephrine "functions as a peripheral vasoconstrictor (alpha-adrenergic action) and as an inotropic stimulator of the heart and dilator of coronary arteries (beta-adrenergic action)." 1 This dual mechanism is important to understand:

• Primary effect: α-adrenergic mediated vasoconstriction increases systemic vascular resistance and mean arterial pressure 2, 3
• Secondary effect: β1-adrenergic stimulation provides mild positive inotropy and increases stroke volume 4, 1
• Coronary effects: β2-receptor stimulation dilates coronary arteries and increases coronary blood flow 4

Clinical Context: Vasopressor vs. Inotrope

In clinical practice, norepinephrine is classified and used as a vasopressor, not an inotrope, despite having some inotropic activity. 2 The distinction matters for treatment algorithms:

When Norepinephrine is Used (as a vasopressor):

• First-line agent for septic shock and most shock states requiring blood pressure support 2, 5
• Restores mean arterial pressure primarily through vasoconstriction 2, 3
• Preferred over dopamine due to lower arrhythmia risk 2

When True Inotropes are Needed:

• Dobutamine is the first-line inotrope when cardiac output remains inadequate despite adequate preload and blood pressure 2, 6
• Dobutamine is added to norepinephrine (not replaced by it) when myocardial dysfunction with low cardiac output is documented 2, 7
• The Surviving Sepsis Campaign explicitly states: "treatment with a combined inotrope/vasopressor, such as norepinephrine or epinephrine, is recommended if cardiac output is not measured" 2—but when cardiac output monitoring is available, norepinephrine is used separately as the vasopressor, with dobutamine added as the inotrope 2

Key Clinical Distinctions

Norepinephrine's inotropic effects are clinically modest compared to dedicated inotropes:

• Norepinephrine increases cardiac output primarily by increasing venous return (preload recruitment) and afterload optimization, not by dramatically enhancing contractility 2
• The European Society of Cardiology guidelines classify norepinephrine under "vasopressors," not "inotropes," and state it should only be used when inotropes plus fluid challenge fail to restore blood pressure 2
• In cardiogenic shock, norepinephrine is reserved for situations where blood pressure cannot be maintained despite inotropic support—it is not the primary agent for improving contractility 2, 6

Common Pitfalls to Avoid

• Do not use norepinephrine as your primary agent for low cardiac output states—it will increase blood pressure but may worsen cardiac output through excessive afterload if contractility is the primary problem 2
• Do not assume norepinephrine's mild inotropic effects are sufficient to treat myocardial dysfunction—add dobutamine when cardiac output remains inadequate 2, 7
• Recognize that norepinephrine's β1 effects are overshadowed by its α effects in most clinical scenarios, making it functionally a vasopressor 2, 3
• In cardiogenic shock with high systemic vascular resistance, using norepinephrine may further increase afterload and worsen cardiac performance—vasopressors should be used with extreme caution and discontinued as soon as possible in this setting 2

Bottom Line for Clinical Practice

While norepinephrine technically has inotropic properties, it should never be selected when your primary goal is to increase myocardial contractility. 2, 6 It is a vasopressor first and foremost. When you need inotropy, use dobutamine, milrinone, or levosimendan. 2, 6 Norepinephrine's mild inotropic effects are a beneficial side effect when treating hypotension, not a reason to choose it for contractility support. 1, 7