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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 (inotropic effect). It is the first-line vasopressor for most forms of shock.
## Primary Indications
* First-line treatment for septic shock.
* First-line treatment for distributive shock after inadequate response to fluid resuscitation.
* Profound hypotension (systolic BP <70 mmHg) or hemodynamic instability.
## Adult Dosing
* **Initial Infusion:** 0.05–0.1 mcg/kg/min or 2–4 mcg/min (fixed rate).
* **Titration:** Titrate to achieve target Mean Arterial Pressure (MAP), typically 65 mmHg.
* **Maintenance:** 0.01–3 mcg/kg/min.
* **Maximum:** There is no specific absolute maximum dose; however, doses >1–2 mcg/kg/min are associated with significant refractory risks and tissue ischemia.
## Pediatric Dosing
* **Initial Infusion:** 0.05–0.1 mcg/kg/min.
* **Titration:** Titrate by 0.05–0.1 mcg/kg/min every 5–15 minutes based on response.
* **Maximum:** Up to 1–2 mcg/kg/min in severe refractory shock.
* *Note: Always verify pediatric concentrations and titration protocols with local hospital guidelines.*
## Dose Adjustments
* **Renal/Hepatic:** No formal dose adjustments are required, but caution is necessary due to decreased peripheral perfusion.
* **Discontinuation:** Wean gradually to prevent sudden hemodynamic collapse.
## Contraindications
* Hypersensitivity to norepinephrine or bisulfites (usually present as a preservative).
* Hypovolemia (must be corrected/addressed before or concurrently with vasopressor therapy).
* Mesenteric or peripheral vascular thrombosis (due to risk of increased ischemia).
## Adverse Effects
* **Cardiovascular:** Bradycardia (reflex), arrhythmias, myocardial ischemia/infarction.
* **Dermatological:** Extravasation necrosis (use a central line to prevent sloughing and tissue necrosis).
* **Metabolic:** Lactic acidosis (secondary to peripheral vasoconstriction/hypoperfusion).
## Key Drug Interactions
* **MAO Inhibitors / TCAs:** May result in severe, prolonged hypertensive crisis.
* **Beta-blockers:** May result in unopposed alpha-adrenergic vasoconstriction and severe hypertension.
* **Halogenated Anesthetics:** May sensitize the myocardium to arrhythmogenic effects.
## Monitoring
* **Hemodynamics:** Continuous invasive arterial blood pressure monitoring is strongly recommended.
* **Perfusion:** Monitor peripheral pulses, capillary refill, and skin integrity at the infusion site.
* **Labs:** Monitor serum lactate and electrolytes, particularly if used for prolonged periods.
## Clinical Pearls
* **Extravasation Management:** If extravasation occurs, administer **phentolamine** (alpha-antagonist) subcutaneously as soon as possible to counteract localized vasoconstriction.
* **Central access:** Central venous access is preferred; peripheral administration should only be temporary, ideally in large proximal veins, and at the lowest possible concentration.
* **Dosing protocol:** Always reference institution-specific titration protocols, as concentration requirements (e.g., 8 mcg/mL vs. 32 mcg/mL or higher) vary by pharmacy standardization.
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*Disclaimer: This information is for educational purposes only. Prescribing information and local institutional protocols are subject to change. Always verify current, official prescribing information and clinical guidelines before administration.*
