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# Norepinephrine
## Overview
Norepinephrine is a potent catecholamine acting primarily on alpha-1 (vasoconstriction) and beta-1 (inotropic) adrenergic receptors. It is the first-line vasopressor for septic shock. It is structurally similar to epinephrine but has minimal beta-2 activity, resulting in less tachycardia and bronchodilation.
## Primary Indications
* Hypotension or shock (septic, cardiogenic, or distributive).
* Cardiac arrest (less common than epinephrine; per local ACLS protocols).
## Adult Dosing
* **Initial:** 0.05 to 0.1 mcg/kg/min (or 2–4 mcg/min fixed dose) via continuous IV infusion.
* **Titration:** Titrate to maintain target Mean Arterial Pressure (MAP), typically >65 mmHg.
* **Typical effective range:** 0.1 to 3 mcg/kg/min.
* **Maximum:** No defined absolute maximum; requirements depend on clinical refractoriness to shock.
## Pediatric Dosing
* **Initial:** 0.05 to 0.1 mcg/kg/min continuous IV infusion.
* **Titration:** Titrate by 0.05–0.1 mcg/kg/min every 5–10 minutes based on systemic vascular resistance and blood pressure.
* **Maximum:** 2 mcg/kg/min (consult pediatric intensive care/local guidelines for dose-capping).
## Dose Adjustments
* **Renal/Hepatic:** No specific dosing adjustments required; however, caution is needed due to underlying disease acuity.
* **Geriatric:** Initiate at the lower end of the dosing range due to increased sensitivity and potential for cardiac arrhythmias.
## Contraindications
* Hypersensitivity to norepinephrine or sulfite sensitivity.
* Hypotension secondary to uncorrected hypovolemia (must restore volume status first).
* Mesenteric or peripheral vascular thrombosis (relative contraindication due to risk of ischemia).
## Adverse Effects
* **Cardiovascular:** Hypertension, tachyarrhythmia, bradycardia (reflex), limb ischemia.
* **Local:** Extravasation can lead to severe tissue necrosis and sloughing.
* **Metabolic:** Hyperglycemia, lactic acidosis (at prolonged high doses).
## Key Drug Interactions
* **MAOIs/Linezolid:** May lead to hypertensive crisis due to decreased catecholamine metabolism.
* **Beta-blockers:** May cause unopposed alpha-adrenergic vasoconstriction, leading to extreme hypertension and reflex bradycardia.
* **General Anesthetics:** Halogenated hydrocarbons (e.g., isoflurane) may increase myocardial sensitivity to norepinephrine, increasing arrhythmia risk.
## Monitoring
* **Clinical:** Continuous blood pressure monitoring (arterial line preferred).
* **Safety:** Assess infusion site hourly for signs of extravasation.
* **Laboratory:** Serum lactate (for perfusion adequacy), renal function, and cardiac rhythm (ECG).
## Clinical Pearls
* **Extravasation Management:** If extravasation occurs, discontinue infusion and infiltrate the site with **phentolamine** (5–10 mg in 10 mL saline) as soon as possible.
* **Access:** Must be administered via a large peripheral vein (short-term only, if absolutely necessary) or central venous catheter. Central access is strongly preferred.
* **Compatibility:** Administer through a dedicated line. Do not mix with alkaline solutions as the drug may deactivate.
* **Weaning:** When weaning, reduce dose gradually to avoid hemodynamic collapse.
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**Educational Disclaimer:** This information is for educational purposes only. Clinical protocols vary widely by institution. Always verify dosages, contraindications, and compatibility with your local hospital formulary, clinical guidelines, and the manufacturer’s current prescribing information before administration.
