What effect does norepinephrine (noradrenaline) have on heart rate when used as a pressor in septic or distributive shock?

Norepinephrine Effect on Heart Rate

Norepinephrine causes minimal change in heart rate or a slight decrease in heart rate when used as a vasopressor in septic shock, despite its β₁-adrenergic activity, because the reflex vagal response to increased blood pressure counteracts any direct chronotropic effect. 1, 2

Mechanism of Heart Rate Effect

The heart rate response to norepinephrine reflects competing physiological mechanisms:

• α₁-receptor activation produces potent vasoconstriction and raises mean arterial pressure, which triggers a baroreceptor-mediated vagal reflex that slows heart rate 2
• β₁-receptor stimulation provides modest positive chronotropic effects, but these are typically overwhelmed by the reflex bradycardia from blood pressure elevation 2
• The net result is that norepinephrine-induced increases in heart rate are substantially less than with epinephrine or dopamine 1, 3

Clinical Evidence in Septic Shock

Comparative studies demonstrate norepinephrine's minimal chronotropic effect:

• In septic shock patients, norepinephrine increased mean arterial pressure primarily through vasoconstriction while heart rate decreased by 7% (p < 0.05), whereas dopamine increased cardiac index by 16% without changing heart rate 4
• Norepinephrine raises MAP primarily via increased systemic vascular resistance with little change in heart rate and less increase in stroke volume compared with dopamine 1
• When compared to epinephrine, norepinephrine produces smaller increases in stroke volume and heart rate while achieving similar blood pressure targets 2

Arrhythmia Risk

While norepinephrine has a favorable cardiac rhythm profile compared to other vasopressors, dysrhythmias can still occur:

• Norepinephrine is associated with significantly fewer arrhythmias than dopamine: supraventricular arrhythmias (RR 0.47; 95% CI 0.38–0.58) and ventricular arrhythmias (RR 0.35; 95% CI 0.19–0.66) 1, 3
• In a retrospective cohort of 250 septic shock patients receiving norepinephrine, 34.4% developed dysrhythmias, which were independently associated with longer duration of infusion and higher maximum doses 5
• Patients who developed dysrhythmias had higher mortality (63.9% vs 30.5%; p < 0.001) and worse ICU outcomes 5
• Rare case reports document tachyarrhythmias even at low doses, where heart rate increased with escalating norepinephrine doses and resolved upon discontinuation 6

Clinical Implications for Practice

Norepinephrine is recommended as the first-line vasopressor for septic shock (Grade 1B) based on superior mortality outcomes and lower arrhythmia rates compared to dopamine 1, 2

Key monitoring considerations:

• Expect stable or slightly decreased heart rate during norepinephrine infusion as blood pressure rises 1, 4
• If tachycardia develops or worsens during norepinephrine therapy, investigate alternative causes (hypovolemia, pain, fever, underlying cardiac disease) rather than attributing it to the drug 5, 6
• Minimize duration and dose of norepinephrine when possible, as both are independent risk factors for dysrhythmia development 5
• Dopamine should be reserved only for highly selected patients with absolute or relative bradycardia or low risk of tachyarrhythmias (Grade 2C) 1