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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 shock and most forms of distributive shock.
## Primary Indications
* Acute hypotension.
* First-line agent for septic, cardiogenic, and distributive shock refractory to fluid resuscitation.
## Adult Dosing
* **Initial dose:** 0.01–0.05 mcg/kg/min (or 2–4 mcg/min fixed-rate initial infusion).
* **Titration:** Titrate by 0.01–0.05 mcg/kg/min every 3–5 minutes until target mean arterial pressure (MAP) is achieved.
* **Typical maintenance dose:** 0.05–0.5 mcg/kg/min.
* **Max dose:** No formal maximum; however, doses >1–2 mcg/kg/min are associated with significant tissue ischemia and increased mortality.
## Pediatric Dosing
* **Continuous infusion:** 0.05–0.5 mcg/kg/min.
* **Titration:** Titrate to clinical effect (target perfusion markers).
* **Note:** Dosing varies widely by institutional protocol; verify against local pediatric resuscitation guidelines.
## Dose Adjustments
* **Renal/Hepatic:** No specific dose adjustments provided in labeling; however, caution is warranted in patients with pre-existing vascular disease.
* **Weaning:** Taper doses slowly to avoid rapid hemodynamic collapse.
## Contraindications
* Hypersensitivity to norepinephrine or sulfites (some formulations contain bisulfites).
* Hypotension due to uncorrected hypovolemia (must provide adequate intravascular volume resuscitation concurrently).
## Adverse Effects
* **Cardiovascular:** Tachycardia, arrhythmias, hypertension, myocardial ischemia.
* **Local (Extravasation):** Severe tissue necrosis and sloughing due to intense local vasoconstriction.
* **Other:** Peripheral ischemia (fingers/toes).
## Key Drug Interactions
* **MAO Inhibitors/Tricyclic Antidepressants:** May cause severe, prolonged hypertensive crisis.
* **Beta-blockers:** May cause excessive hypertension and reflex bradycardia due to unopposed alpha-adrenergic stimulation.
* **Inhaled Anesthetics (e.g., halothane, cyclopropane):** Increases myocardial sensitivity to catecholamines, increasing risk of arrhythmias.
## Monitoring
* **Hemodynamics:** Continuous intra-arterial blood pressure monitoring preferred.
* **Perfusion:** MAP, urine output, serum lactate, and capillary refill.
* **Site:** Regularly assess for signs of extravasation. If extravasation occurs, consider phentolamine infiltration.
## Clinical Pearls
* **Line access:** Must be administered through a large-bore, central venous catheter whenever possible to minimize extravasation risk.
* **Compatibility:** Administer in a dedicated line or verify compatibility; norepinephrine is often incompatible with alkaline solutions.
* **Refractory Shock:** If patients require high doses of norepinephrine, consider the early addition of vasopressin (typically fixed dose 0.03 units/min) or systemic corticosteroids per current Surviving Sepsis Campaign guidelines.
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*Disclaimer: This information is for educational purposes only. Clinical protocols vary by institution. Always consult your facility's specific prescribing information, pharmacy policies, and current clinical guidelines before administration.*
