Can Levophed (norepinephrine) cause bradycardia?

Does Levophed Cause Bradycardia?

Yes, norepinephrine (Levophed) can cause reflex bradycardia, particularly in cases of overdosage or when blood pressure is elevated significantly. This effect is documented in the FDA drug label for Levophed 1.

Mechanism of Bradycardia with Norepinephrine

Norepinephrine works through multiple mechanisms that can affect heart rate:

1. Direct vs. Reflex Effects:

   • Norepinephrine has direct positive chronotropic effects through β1-adrenergic stimulation
   • However, these effects are often counterbalanced by vagal reflex activity triggered by increased blood pressure 2
   • The reflex bradycardia is a baroreceptor-mediated response to the increase in blood pressure

2. Time-Dependent Effects:

   • The effects of norepinephrine on cardiac function and cardiac output are inconsistent and time-dependent 2
   • Initial positive chronotropic effects may be transient and followed by reflex bradycardia

Clinical Evidence

The FDA drug label for Levophed specifically states that overdosage may result in "reflex bradycardia" along with headache, severe hypertension, marked increase in peripheral resistance, and decreased cardiac output 1.

Research from 1976 demonstrated that during norepinephrine infusion, reflex bradycardia was associated with elevated pressure and was slightly more pronounced in normotensive subjects compared to hypertensive patients, likely due to differences in baroreflex sensitivity 3.

Comparison with Other Vasopressors

Different vasopressors have varying effects on heart rate:

• Norepinephrine: Can cause reflex bradycardia when blood pressure increases significantly 2, 1
• Dopamine: More likely to cause tachycardia at infusion rates of 5-10 μg/kg/min 2
• Epinephrine: Strong β-adrenergic effects that typically increase heart rate 2
• Phenylephrine: More commonly associated with reflex bradycardia due to pure α-adrenergic effects 4

Clinical Management

When bradycardia occurs with norepinephrine:

1. For overdosage:

   • Discontinue norepinephrine until the patient's condition stabilizes 1
   • Monitor blood pressure and heart rate closely

2. For therapeutic dosing:

   • Titrate the dose carefully to achieve desired blood pressure without excessive bradycardia
   • Consider alternative vasopressors if bradycardia becomes clinically significant

Special Considerations

• Combination therapy: Use caution when combining norepinephrine with other medications that can cause bradycardia 5
• Monitoring: Regular assessment of vital signs and hemodynamic parameters is essential during norepinephrine infusion
• Paradoxical response: Rarely, as noted in case reports, low-dose norepinephrine has been associated with tachyarrhythmias rather than bradycardia 6

Conclusion

While norepinephrine has direct positive chronotropic effects, its predominant effect on heart rate in clinical practice is often reflex bradycardia due to the baroreceptor response to increased blood pressure. This effect is most pronounced with higher doses or when blood pressure increases significantly.