Norepinephrine (Levophed®)

• Core dose: 0.1–0.5 mcg/kg/min IV infusion; titrate to MAP goal (typically ≥65 mmHg); max ~30 mcg/min in severe shock
• Onset/duration: Onset immediate (seconds); half-life 2–3 min; effects dissipate within minutes of stopping
• Key danger: Extravasation causes severe tissue necrosis—use central line; excessive vasoconstriction can worsen organ perfusion; arrhythmias at high doses
• Special: First-line vasopressor for septic shock per Surviving Sepsis; potent α1-agonist with mild β1 activity; maintains cardiac output better than pure vasoconstrictors

• Generic Name: Norepinephrine bitartrate
• Brand Names: Levophed®

Endogenous catecholamine; potent α1-adrenergic agonist with β1 activity (minimal β2)

Mechanism of Action:

• Stimulates α1-adrenergic receptors on vascular smooth muscle causing potent vasoconstriction and increased SVR
• β1 stimulation increases inotropy (with minimal chronotropic effect)
• Net effect is increased MAP with generally minimal effect on heart rate due to baroreflex

Pharmacokinetics:

• Onset: 1–2 min
• Duration: Very short; only while infusion runs
• Metabolism: Rapid neuronal and hepatic metabolism
• Elimination: Primarily renal excretion of metabolites

• Restoration of blood pressure in acute hypotensive states (septic shock, anesthesia-related hypotension, neurogenic shock)
• Post–cardiac arrest hypotension
• Adjunct in cardiac arrest and profound hypotension
• First-line vasopressor for adults with septic shock after adequate volume resuscitation

• Septic shock
• Distributive shock (anaphylactic, neurogenic)
• Post-cardiac arrest hypotension
• Anesthesia-related hypotension
• Refractory hypotensive states

Available Forms:

• Vial: 1 mg/mL norepinephrine base (as bitartrate) for dilution
• Typical infusion concentration (institution-specific): 4 mg in 1000 mL D5W (4 mcg/mL)

Preparation:

• Avoid mixing with sodium bicarbonate
• Administer via dedicated line
• Central venous access preferred as soon as feasible

Adult Dosing (Septic/Distributive Shock):

• Start: 0.01–0.1 mcg/kg/min IV; titrate to achieve target MAP (initial adult target 65 mmHg)
• Common fixed-start alternative: 4 mcg/min, titrate to effect
• Reported maximum: Around 3 mcg/kg/min

Pediatric Dosing:

• Start: 0.05–0.2 mcg/kg/min IV
• Titrate: Increase by 0.02–0.05 mcg/kg/min to hemodynamic goals
• Higher doses: Up to ~1–2 mcg/kg/min may be used in refractory shock
• Current pediatric sepsis guidance permits either epinephrine or norepinephrine as initial vasoactive agent; selection should be tailored to origin of shock and myocardial function

Contraindications:

• Uncorrected hypovolemia (except as a temporizing measure)
• Mesenteric or peripheral vascular thrombosis (risk of worsening ischemia)
• Concomitant use with certain volatile anesthetics (e.g., cyclopropane, halothane) due to arrhythmia risk

Ischemic Complications:

• Digital/skin ischemia
• Mesenteric ischemia
• Limb ischemia
• Extravasation-induced tissue necrosis

Cardiac:

• Arrhythmias
• Reflex bradycardia
• Hypertension
• Stress cardiomyopathy with overdose

Metabolic:

• Mild hyperglycemia

• MAO inhibitors/linezolid, tricyclics/SNRIs: Risk of hypertensive crisis or potentiation—avoid or monitor closely
• Ergot alkaloids: Additive vasospasm—contraindicated
• Inhaled anesthetics (e.g., isoflurane): Arrhythmia risk—avoid
• Insulin/antidiabetics: Opposing glycemic effects; monitor glucose

Hemodynamic Monitoring:

• Continuous BP monitoring
• Invasive arterial pressure monitoring recommended when feasible
• Initial MAP target 65 mmHg in adults

End-Organ Perfusion:

• Mental status
• Capillary refill and skin perfusion
• Urine output ≥0.5 mL/kg/h
• Lactate trends

Infusion Safety:

• Central venous access when possible
• Frequent site checks if peripheral initiation
• Extravasation management ready (phentolamine)

• 1. Evans, L., Rhodes, A., Alhazzani, W., Antonelli, M., Coopersmith, C. M., French, C., ... & Levy, M. (2021). Surviving Sepsis Campaign: International guidelines for management of sepsis and septic shock 2021. Intensive Care Medicine, 47, 1181–1247. https://doi.org/10.1007/s00134-021-06506-y
• 2. Medscape. (2024). Levarterenol, Levophed (norepinephrine) – dosing, indications, interactions. https://reference.medscape.com/drug/levarterenol-levophed-norepinephrine-342443
• 3. Pfizer. (2018). LEVOPHED (norepinephrine bitartrate injection) Prescribing Information. https://webfiles.pfizer.com/file/2aa809f8-b0a8-4654-b494-5879aa27cf26
• 4. Papadopoulos, J. (2007). Pocket Guide to Critical Care Pharmacotherapy. Humana Press.
• 5. Weiss, S. L., Peters, M. J., Alhazzani, W., Agus, M. S. D., Flori, H. R., Inwald, D. P., ... & Kissoon, N. (2020). Surviving Sepsis Campaign International Guidelines for the Management of Septic Shock and Sepsis-Associated Organ Dysfunction in Children. Pediatric Critical Care Medicine, 21(2), e52–e106. https://doi.org/10.1097/PCC.0000000000002198
• 6. American Academy of Pediatrics. (2023). Pediatric Sepsis: Diagnosis, Management, and Sub-classification. Pediatrics, 153(1), e2023062967.