Norepinephrine
Norepinephrine
Generic Name
Norepinephrine
Mechanism
- α₁‑adrenergic agonist → vasoconstriction of arterioles & venules → ↑ systemic vascular resistance (SVR) & blood pressure.
- α₂‑adrenergic agonist (minor) → central inhibition of norepinephrine release, producing modest baroreflex-mediated BP rise.
- β₁‑adrenergic agonist (low affinity) → ↑ cardiac contractility (inotropy) and heart rate, supporting cardiac output during shock.
- Net effect: Rapid restoration of mean arterial pressure (MAP) with minimal tachycardia compared to vasopressin or dopamine.
Pharmacokinetics
| Parameter | Details |
| Route | Intravenous (IV) infusion (no oral/IM form) |
| Absorption | Immediate, 100 % bioavailability |
| Distribution | Widely distributed; lipophilic; crosses placenta & BBB in small amounts |
| Metabolism | Monoamine oxidase (MAO) and catechol-O‑methyltransferase (COMT) → catecholamine breakdown |
| Elimination | Primary hepatic metabolism; renal secretion of metabolites |
| Half‑life | ~2–9 min (rapid) |
| Protein binding | ~6 % (low) |
| Key factors | Fast clearance → tight infusion control needed; altered MAO/COMT activity in liver disease changes half‑life |
Indications
- Cardiogenic shock (post‑cardiac‑surgery, myocardial infarction)
- Septic shock or distributive shock when MAP < 65 mmHg despite fluids
- Hypotension during anesthesia or major surgery
- Resuscitation in advanced life support protocols (adult ACLS, Pediatric Advanced Life Support)
- Underlying arrhythmias secondary to low preload or aftershock
Contraindications
- Absolute: Hypersensitivity to norepinephrine or any excipients; severe coronary artery disease with impaired left ventricular function (risk of ischemia).
- Relative:
- Patients with uncontrolled hypertension or history of vasospastic disorders (e.g., Prinzmetal’s angina)
- Severe peripheral arterial disease (increased risk of digital ischemia)
- Severe intrathoracic pressure (e.g., tension pneumothorax) due to additive peak pressures
- Warnings:
- Use caution in patients with arrhythmic risk profiles (Brugada, QT prolongation);
- Avoid peripheral administration without a central line if dose > 1 µg/kg/min due to extravasation risk.
Dosing
- Loading dose: Generally not administered; immediate infusion preferred.
- Starting infusion: 0.01–0.03 µg/kg/min in ICU; titrate by 0.01 µg/kg/min increments every 5‑10 min until MAP 65‑70 mmHg.
- Maximum: 3 µg/kg/min (rarely exceeded in shock states).
- Route: Central venous line preferred; peripheral line acceptable for short duration (< 24 h) at < 2 µg/kg/min with needle aspiration.
- Concentration: 4 µg/mL (100 µg/mL) in 10‑mL diluted 0.9 % NaCl; adjust per institutional protocol.
- Adjuncts: Add vasopressin or epinephrine in refractory shock after adequate norepinephrine dosing.
Adverse Effects
- Common
- Local site pain / vasoconstriction (if extravasated)
- Reflex bradycardia
- Elevated systolic BP spikes
- Serious
- Arrhythmias (PVCs, SVT, VF) due to tachycardia/high BP
- Myocardial ischemia/infraction (especially in CAD)
- Transient ischemic attacks, gangrene from extravasation
- Hypersensitivity reactions (rare)
Monitoring
- Hemodynamics: Continuous MAP & HR; target MAP 65–70 mmHg (or individualized goal)
- Vascular access: Watch for extravasation and phlebitis; clamp if infiltration suspected.
- Laboratory:
- Serum lactate (shunt/ischemia indicator)
- Cardiac enzymes if ischemic symptoms develop
- Metabolic panel for kidney/liver function (metabolism)
- Fluid balance: Maintain euvolemia; avoid excessive fluid overload.
- Sedation & analgesia: Ensure adequate depth to prevent sympathetic surges.
Clinical Pearls
1. Start low, titrate fast – Norepinephrine’s potent vasoconstriction demands a *microdose approach*; small increases dramatically raise MAP.
2. Central line first – Even if peripheral infusion is used for short term, place a central line within the first hour “just in case” and move the infusion promptly.
3. Plate detection – A rising serum lactate ahead of MAP changes may predict impending shock; consider earlier norepinephrine even when MAP is near goal.
4. Avoid “bridging” to epinephrine – Norepinephrine is preferred for shock; only switch to epinephrine if tachyarrhythmias or septic arrest remains uncontrolled.
5. Layer of Support – Pair levitation patient [hospital standing positions & leg elevation] to reduce venous stasis while on vasopressors if feasible.
6. Extravasation – If leakage occurs, immediately aspirate waste fluid, apply warm compress & administer phentolamine 4 mg IV push; surgical consultation if skin ischemia persists.
7. Data-Driven – Adopt smart infusion pumps with built‑in alarm ranges (e.g., 0.01–3 µg/kg/min) to prevent overdosing, especially in mixed‑protocol stays.
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• Key pharmacology terms: vasopressor, α‑adrenergic agonist, mean arterial pressure, septic shock, catecholamine metabolism, tachyarrhythmia, extravasation.
Use this card as a quick reference when managing life‑threatening hypotension in acute care settings.