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# Norepinephrine
## Overview
Norepinephrine is a potent catecholamine acting primarily on alpha-1 adrenergic receptors, with moderate beta-1 activity. It serves as a potent vasoconstrictor and inotropic agent. It is rapidly metabolized by catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO), necessitating continuous intravenous infusion.
## Primary Indications
* Severe hypotensive states (e.g., septic shock, distributive shock).
* First-line vasopressor for hypotension unresponsive to adequate fluid resuscitation.
* Cardiac arrest (less common, usually reserved for refractory cases).
## Adult Dosing
* **Initial Infusion:** 0.01 to 0.05 mcg/kg/min.
* **Titration:** Titrate by 0.01 to 0.05 mcg/kg/min every 3–5 minutes to achieve target Mean Arterial Pressure (MAP; typically ≥65 mmHg).
* **Maintenance:** Usual range is 0.05 to 0.5 mcg/kg/min.
* *Note: Dosing is highly dependent on institutional protocols and clinical severity.*
## Pediatric Dosing
* **Initial Infusion:** 0.05 to 0.1 mcg/kg/min.
* **Titration:** Titrate to effect in increments of 0.05 mcg/kg/min; maximum typically 2–3 mcg/kg/min.
* *Note: Weight-based dosing is mandatory in pediatric populations.*
## Dose Adjustments
* **Renal/Hepatic Impairment:** No formal dosage adjustments; however, proceed with caution due to potential altered sensitivity.
* **Tapering:** Must be tapered slowly to prevent rebound hypotension.
## Contraindications
* Hypersensitivity to norepinephrine or sulfites.
* Hypotension due to uncorrected uncorrected hypovolemia (must correct volume status before or concurrently with initiation).
## Adverse Effects
* **Cardiovascular:** Hypertension, arrhythmias (tachycardia or bradycardia), myocardial ischemia.
* **Extravasation:** Tissue necrosis and sloughing due to intense vasoconstriction.
* **Metabolic:** Metabolic acidosis, increased oxygen demand.
* **Peripheral:** Digital ischemia and peripheral vasoconstriction.
## Key Drug Interactions
* **MAO Inhibitors/Tricyclic Antidepressants:** May cause severe, prolonged hypertension.
* **General Anesthetics (e.g., Halothane, Cyclopropane):** Increase risk of ventricular arrhythmias.
* **Beta-Blockers:** May cause severe hypertension or paradoxical bradycardia (unopposed alpha-adrenergic stimulation).
## Monitoring
* **Continuous ECG:** Monitor for rate and rhythm abnormalities.
* **Blood Pressure:** Arterial line preferred for titration; frequent NIBP if line unavailable.
* **Perfusion:** Monitor urine output, skin perfusion, and capillary refill.
* **Extravasation Site:** Monitor for infiltration; treat extravasation immediately with phentolamine (alpha-blocker) if required.
## Clinical Pearls
* **Route:** Must be administered via a **central venous catheter** whenever possible to minimize risk of extravasation injury. If peripheral administration is necessary, use a large-bore proximal vein and limit duration/concentration.
* **Compatibility:** Administer in D5W or NS. Do not mix with alkaline solutions (e.g., sodium bicarbonate) as it may inactivate the drug.
* **Concentration:** Standardize concentrations (e.g., 4 mg/250 mL or 8 mg/250 mL) to reduce medication programming errors.
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*Disclaimer: This information is for educational purposes only. Drug protocols, concentrations, and indications vary by institution and clinical context. Always verify dosages and compatibility against current local pharmacy guidelines, package inserts, and hospital policy before prescribing or administering medications.*
