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# Norepinephrine
## Overview
Norepinephrine is a potent catecholamine with primary alpha-1 adrenergic agonist activity (vasoconstriction) and moderate beta-1 adrenergic activity (inotropy). It is the first-line vasopressor for septic and distributive shock.
## Primary Indications
* Acute hypotensive states (e.g., septic, cardiogenic, or neurogenic shock)
* Adjunct in cardiac arrest (less common, usually epinephrine preferred)
## 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 clinical goal (usually Mean Arterial Pressure ≥65 mmHg). Typical range is 0.01 to 3 mcg/kg/min.
* **Maximum:** No absolute maximum dose defined in shock protocols; however, high doses correlate with increased mortality and refractory ischemia. Dose-dependent requirements vary by institution.
## Pediatric Dosing
* **Initial:** 0.05 to 0.1 mcg/kg/min continuous IV infusion.
* **Titration:** Titrate in increments based on hemodynamic response (MAP/SBP). Common range is 0.05 to 1 mcg/kg/min.
* **Max:** Generally considered 1–2 mcg/kg/min in severe refractory shock. Higher doses require specialized pediatric critical care oversight.
## Dose Adjustments
* **Hepatic/Renal Impairment:** No standard dose adjustment required; however, monitor closely for accumulation and tissue hypoperfusion.
* **Weaning:** Taper slowly to avoid rebound hypotension.
## Contraindications
* Hypersensitivity to norepinephrine or sulfites (some formulations contain sodium metabisulfite).
* Hypotension due to uncorrected blood volume deficit (except as an emergency measure before volume replacement).
* Mesenteric or peripheral vascular thrombosis (risk of worsening ischemia).
## Adverse Effects
* **Common:** Arrhythmias (bradycardia or tachycardia), hypertension, headache, anxiety.
* **Serious:** Tissue necrosis/sloughing upon extravasation, limb ischemia, mesenteric ischemia, bowel infarction, renal failure (secondary to extreme vasoconstriction).
## Key Drug Interactions
* **MAO Inhibitors/Tricyclic Antidepressants:** May cause severe, prolonged hypertensive crises.
* **Beta-Blockers:** May lead to unopposed alpha-mediated vasoconstriction and severe hypertension.
* **Cyclopropane/Halogenated Hydrocarbon Anesthetics:** Increase cardiac sensitivity to catecholamines, raising the risk of arrhythmias.
## Monitoring
* **Hemodynamics:** Continuous intra-arterial blood pressure (ideal) or high-frequency non-invasive cycling.
* **Safety:** Continuous cardiac telemetry (arrhythmia watch).
* **Peripheral:** Frequent assessment of IV site for extravasation; monitor peripheral pulses and extremity temperature/color.
* **End-organ:** Urine output (renal perfusion) and serum lactate (tissue perfusion).
## Clinical Pearls
* **Extravasation Management:** Phentolamine mesylate is the antidote. If extravasation occurs, stop the infusion immediately and infiltrate the area with phentolamine (5–10 mg in 10 mL saline).
* **IV Access:** Must be administered via a large-bore central venous catheter whenever possible. Peripheral administration is acceptable in emergent settings through a large, proximal vein for short durations, but carries high risk of tissue necrosis.
* **Compatibility:** Administer only in D5W or D5NS; epinephrine/norepinephrine are inactivated in alkaline solutions (e.g., sodium bicarbonate).
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*Disclaimer: This information is for educational purposes only. Dosing, titration, and protocols vary significantly by institution and patient status. Always verify current prescribing information and follow local hospital clinical guidelines before administration.*
