Norepinephrine

What is Norepinephrine? 1

  • Norepinephrine is produced endogenously and is one of the main neurotransmitters of the sympathetic nervous system
  • Norepinephrine is used as a vasopressor in many clinical scenarios and can be given as an infusion or a bolus.

Mechanism of Action 1

  • Norepinephrine stimulates α1- and β1-adrenergic receptors, causing vasoconstriction and maintains heart rate and contractility.
  • compared to PhenylephrinePhenylephrine
    , norepinephrine generally does not cause reflex bradycardia
  • It causes significant increases in systolic, diastolic, and mean arterial pressures, with minimal metabolic effects (i.e., no hyperglycemia).

Pharmacology 2

  • Onset: ~ 1 minute
  • Duration: ~2.5 minute half-life, requiring continuous infusion for sustained effect.
  • Elimination: Primarily by reuptake with only a small portion metabolized and excreted in the urine.
Drug α1 α2 β1 β2
NorepinephrineNorepinephrine
What is Norepinephrine? 1

Norepinephrine is produced endogenously and is one of the main neurotransmitters of the sympathetic nervous system
Norepinephrine is used as a vasopressor in many cli...
++ ++ + +
Epinephrine Private or Broken Links
The page you're looking for is either not available or private!
++ ++ ++ ++
EphedrineEphedrine
Mechanism of Action 1

Ephedrine is a sympathomimetic with both indirect and direct effects on catecholamine receptors:

Indirect: promotes the release of endogenous norepinephrine whic...
+ + + +
PhenylephrinePhenylephrine
++ ++ 0 0

Indications 1

  • Hypotension: First-line agent in treating hypotension during severe sepsis or septic shock.

Dosage 2

Norepinephrine is generally prepared as 64 mcg/mL in the ICU. 'Dilute' norepinephrine in the OR is generally 10 mcg/mL

  • Continuous Infusion: wide variety of dosing
    • Low Dose: 0 - 0.1 mcg/kg/min
    • Medium Dose: 0.1-0.3 mcg/kg/min
    • High Dose: > 0.3 mcg/kg/min
  • Bolus Dose: 10 mcg IV push
    • Long durations of infusions should be delivered via central venous access due to the risk of extravasation and tissue necrosis.
    • Short infusions (up to ~6 hours in sepsis) can be delivered through peripheral catheters. Dilute solutions (< 20 mcg/mL have been observed to be safe in peripheral catheters)

Complications 1

  • Tachycardia and Arrhythmias: While less arrhythmogenic than epinephrine, norepinephrine can still cause tachycardia, especially at higher doses.
  • End-Organ Ischemia: Excessive vasoconstriction may lead to renal, splanchnic, and peripheral ischemia, potentially resulting in organ failure
  • Extravasation Injury: Extravasation of norepinephrine can lead to tissue necrosis.

Clinical Pearls 1

  • Balanced Use in Coronary Artery Disease: Norepinephrine is useful in increasing perfusion pressure, but caution must be taken to balance the resultant increase in afterload.
  • Splanchnic Blood Flow: May improve splanchnic perfusion in hypotensive patients but can also reduce flow at high doses due to extreme vasoconstriction.
  • Vasoconstriction Risk: Central venous administration is essential to avoid peripheral vasoconstriction and necrosis from extravasation.

References

  1. Flood P, Rathmell J, Shafer S. Stoelting’s Pharmacology & Physiology in Anesthetic Practice. 5th ed. Philadelphia, PA: Wolters Kluwer Health; 2015.  2 3 4 5

  2.  2