Norepinephrine (Levophed)

Anesthesia Implications

Therapeutic Effects: Vasoconstriction, venoconstriction, positive inotropy, sympathomimetic
Time to Onset: 1-2 minutes

Duration: 5 – 10 minutes; Half-life: 3 minutes.

Primary Considerations

Shock – considered a first-line vasopressor in septic and undifferentiated shock.

Fluids First – Ensure the patient is fluid resuscitated before administering Norepinephrine (see ‘Cardiac Output’ below)

Dilution – dilution to 20 mcg/mL can be achieved by mixing a typical vial of norepinephrine (1mg/ml) with 50 mL of solution.

Cardiac Output – In fluid-resuscitated patients, cardiac output is increased with administration of norepinephrine in most patients. This is due to positive inotropic effects with simultaneous arterial vasoconstriction and increases in preload. In patients that are not fluid-resuscitated, norepinephrine may actually reduce cardiac output.

IV vs central line – Central lines are typically employed if the norepinephrine dose is expected to be continuous. However, a retrospective study (which included 14,385 patients) showed a low incidence of extravasation in administration of diluted norepinephrine (20 mcg/mL) via a peripheral IV. The study included 14,385 patients, only 5 of which extravasated. None of these patients required medical or surgical intervention. Other reviews coincide with these results as long as the IV is large-bore and free flowing. If using a peripheral vein, the vein should be proximal to the anticubital fossa (AC) and optimally the basilic or cephalic vein. Eighty-five percent of extravasation cases happen at or distal to the AC. Dilute IV boluses (4-8 mcg) are typically ok as long as the IV is patent and NOT extravasated.

Phenylephrine comparison – 8 mcg of norepinephrine is roughly equivalent to 100 mcg of phenylephrine.

IV push dose

Increase BP: 4 – 8 mcg dilute solution

IV infusion dose

Increase BP: 1 – 20 mcg/min

Shock: 0.01 to 0.3 mcg/kg/min. For most patients, target a MAP of approximately 65-70 mmHg, urine output ≥0.5 mL/kg per hour, and decreasing serum lactate levels on sequential ABGs.

Method of Action

α1 (high), α2 (high) – vasoconstriction
β1 (moderate) – positive inotropic effects

Metabolism

The enzymes monoamine oxidase and catechol-O-methyltransferase metabolize norepinephrine to 3-methoxy-4-hydroxymandelic acid and 3-methoxy-4-hydroxyphenylglycol (MHPG). MHPG is the major metabolite and can be used to assess the status of the noradrenergic system.

Uptodate. Hemodynamic management during anesthesia in adults. 2022. web link
Uptodate. Intraoperative management of shock in adults. 2022. web link
Uptodate. Use of vasopressors and inotropes. 2021. web link
Wiggins. Emergency cardiovascular pharmacotherapy: a point-of-care guide. 2012. web link