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# Norepinephrine
## Overview
Norepinephrine is a potent catecholamine acting primarily on alpha-1 adrenergic receptors (vasoconstriction) and, to a lesser extent, beta-1 adrenergic receptors (inotropic effect). It is the first-line vasopressor for septic shock.
## Primary Indications
* Acute hypotensive states (e.g., septic shock, cardiogenic shock).
* Treatment of hypotension refractory to fluid resuscitation.
## Adult Dosing
* **Initial Infusion:** 0.01 to 0.05 mcg/kg/min IV.
* **Titration:** Titrate to achieve target mean arterial pressure (MAP), typically 65 mmHg. Usual range is 0.01 to 3 mcg/kg/min.
* **Max Dose:** No absolute maximum; doses >3 mcg/kg/min are associated with significant risk of severe vasoconstriction and end-organ ischemia.
## Pediatric Dosing
* **Continuous Infusion:** 0.05 to 0.1 mcg/kg/min IV.
* **Titration:** Titrate to clinical effect (e.g., perfusion, target blood pressure for age).
* **Max Dose:** Generally 1 to 2 mcg/kg/min.
* *Note: Always verify with local institutional guidelines, as weight-based protocols vary.*
## Dose Adjustments
* **Renal/Hepatic Impairment:** No standard dose reduction required. Monitor closely for signs of decreased peripheral perfusion.
* **Discontinuation:** Always taper gradually to prevent rebound hypotension.
## Contraindications
* Hypersensitivity to norepinephrine or sulfites.
* Hypotension due to uncorrected blood volume deficit (except as an emergency measure to maintain perfusion while replacing volume).
* Mesenteric or peripheral vascular thrombosis.
## Adverse Effects
* **Cardiovascular:** Hypertension, arrhythmias (tachycardia or bradycardia), myocardial ischemia.
* **Local:** Extravasation can lead to tissue necrosis and sloughing (treat with phentolamine infiltration).
* **Metabolic:** Lactic acidosis (secondary to peripheral vasoconstriction/hypoperfusion).
## Key Drug Interactions
* **MAO Inhibitors/TCAs:** May cause severe, prolonged hypertension due to inhibited metabolism.
* **Beta-blockers:** May lead to unopposed alpha-adrenergic stimulation, causing severe hypertension and reflex bradycardia.
* **Cyclopropane/Halothane anesthetics:** May increase cardiac irritability and risk of arrhythmias.
## Monitoring
* **Hemodynamics:** Continuous blood pressure monitoring (preferably arterial line) and heart rate.
* **Perfusion:** Urine output, capillary refill, mental status, and lactate levels.
* **IV Site:** Assess frequently for signs of infiltration. Use a large-bore, central venous catheter whenever possible.
## Clinical Pearls
* **First-line:** Norepinephrine is currently the vasopressor of choice for septic shock (Surviving Sepsis Campaign).
* **Fluid First:** Ensure adequate volume resuscitation prior to initiating vasopressors to prevent worsening tissue ischemia.
* **Receptor profile:** Minimal effect on beta-2 receptors, minimizing beta-mediated vasodilation compared to epinephrine, making it a more consistent peripheral vasoconstrictor.
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**Educational Disclaimer:** This information is for educational purposes only. Clinical practice protocols vary by institution. Always verify specific dosing, safety precautions, and contraindications by consulting current FDA-approved labeling, institutional formularies, and clinical pharmacy specialists before prescribing or administering medication.
