Vasopressor · Catecholamine

Norepinephrine (Levophed)

Also called Levophed

Reviewed by Alex G, BSN, RN, CEN, CCRN, CMC, NREMT-P · From the Reference tab of the app

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Vasopressors Made Simple: Receptors, Drugs and MAP Targets

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Indications

• Septic shock: first-line vasopressor (SSC 2026)
• Other vasodilatory shock (vasoplegia after bypass) and neurogenic shock, where β1 offsets bradycardia
• Cardiogenic shock with hypotension, plus an inotrope for low output
• RV failure or massive PE, to keep the RV perfused
• Severe hypotension during anesthesia
• Hepatorenal syndrome with albumin when terlipressin is not used (off-label)

Dosing

Mechanism of action

Norepinephrine, the sympathetic neurotransmitter, is an α1 and β1 agonist with little β2 activity. Vascular α1 receptors couple to Gq: IP3 releases calcium from the sarcoplasmic reticulum, and calcium–calmodulin activates myosin light-chain kinase, constricting arterioles and veins. Cardiac β1 receptors couple to Gs: cAMP and protein kinase A phosphorylate L-type calcium channels and phospholamban, strengthening contraction. With so little β2 action, nothing offsets the vasoconstriction.

Pharmacology

• Cardiovascular: α1 > β1 with little β2, so SVR, MAP and venous return rise
• Cardiovascular: β1 keeps or slightly raises contractility and cardiac output, while the baroreflex leaves heart rate unchanged or slower
• Renal: constricts renal arterioles, but in vasodilatory shock restoring MAP usually improves urine output
• Metabolic: small rise in glucose; far less lactate and glucose effect than epinephrine
• Other: skin, digital and splanchnic vasoconstriction; no CNS effect, since it does not cross the blood–brain barrier

Pharmacokinetics

Chemistry

• Catecholamine: catechol ring, β-hydroxyl and a primary amine; without epinephrine's N-methyl group it has little β2 action
• Natural l-(R) isomer (levarterenol, hence Levophed); the d-isomer is much weaker
• Amine pKa about 8.6 (PubChem): ionized and water-soluble at pH 7.4, so it stays out of the brain
• 1 mg/mL as base (2 mg of the bitartrate is about 1 mg base), with sodium metabisulfite, pH 3.0–4.5
• Oxidizes with light, air and alkaline pH: keep it in the carton, dilute in dextrose (label), discard if pink or brown, never mix with bicarbonate

Adverse effects and cautions

In the one-pagers

• Vasopressors and InotropesReceptors and effects: Norepinephrine: α1 > β1 (little β2): ↔ / ↑ / ↑↑
• Shock Types at a GlanceFindings and first treatments: Cardiogenic: Cool, mottled; crackles, JVD; low urine output: Reperfuse an MI; norepinephrine; add an inotrope; MCS if failing
• Sepsis and Septic Shock BundleVasopressors and MAP: 1st: Norepinephrine: First-line; may start peripherally
• After Cardiac SurgeryTamponade, low output or vasoplegia?: Vasoplegia: MAP under 65, CI over 2.2, SVR under 800 (risks: long bypass, preop ACE inhibitors). Norepinephrine plus vasopressin; if refractory, methylene blue 1 to 2 mg/kg (serotonin syndrome with SSRIs, falsely low SpO2, G6PD hemolysis) or hydroxocobalamin 5 g (red urine, lab interference, CRRT blood-leak alarms). Follow your institution's protocols.
• Pulmonary EmbolismSupporting the failing RV: Norepinephrine first: keeps aortic above RV pressure; vasopressin second
• Right Heart Failure and Pulmonary HypertensionManagement priorities: Pressure: norepinephrine, then vasopressin; MAP 65 or more (WSPH 2024: 70–75), aortic above PA pressure.

In the algorithms

• New Hypotension
• New Fever in the ICU
• Flash Pulmonary Edema (SCAPE)
• Sepsis: Hour-1 Bundle
• Anaphylaxis
• Massive Pulmonary Embolism

Other vasopressor drugs

• Epinephrine
• Vasopressin
• Phenylephrine
• Dopamine
• Angiotensin II
• Ephedrine

Sources

1. FDA label: Levophed (2023)
2. Surviving Sepsis Campaign guideline (2026)
3. PubChem: norepinephrine

For education and exam preparation only. Follow your institution’s protocols. Typical adult values for study. Follow the order, the label and your institution's protocols.