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# Norepinephrine
## Overview
Norepinephrine is a potent vasopressor and inotropic agent that acts primarily on alpha-adrenergic receptors, causing vasoconstriction, and to a lesser extent on beta-1 adrenergic receptors, increasing heart rate and contractility.
## Primary Indications
* Severe hypotension, particularly that associated with septic shock and other distributive shock states.
* Cardiogenic shock.
## Adult Dosing
* **Initial Infusion:** 0.01 to 0.05 mcg/kg/min IV.
* **Titration:** Increase infusion rate by 0.005 to 0.01 mcg/kg/min every 5 to 15 minutes until desired blood pressure is achieved.
* **Maximum Dose:** Typically 0.1 to 0.2 mcg/kg/min, but higher doses may be used in refractory shock under close monitoring. Local protocols should be consulted.
## Pediatric Dosing
* **Initial Infusion:** 0.05 to 0.1 mcg/kg/min IV.
* **Titration:** Increase infusion rate by 0.05 to 0.2 mcg/kg/min every 5 to 15 minutes.
* **Maximum Dose:** May be escalated based on response and hemodynamic parameters, often up to 1 to 2 mcg/kg/min. Pediatric critical care guidelines or local protocols should be consulted.
## Dose Adjustments
* **Renal Impairment:** No specific dose adjustment is typically recommended, but prolonged use may warrant closer monitoring due to potential accumulation.
* **Hepatic Impairment:** No specific dose adjustment is typically recommended.
## Contraindications
* Hypersensitivity to norepinephrine.
* Use during general anesthesia with cyclopropane or halogenated hydrocarbons (risk of severe hypertension and arrhythmias).
* Hypotension due to pure hypovolemia unless volume resuscitation is initiated concurrently.
## Adverse Effects
* **Cardiovascular:** Hypertension, bradycardia (reflex), tachycardia, arrhythmias, peripheral ischemia, extravasation leading to tissue necrosis.
* **Central Nervous System:** Headache, anxiety, dizziness.
* **Other:** Decreased urine output, dyspnea.
## Key Drug Interactions
* **MAO Inhibitors & Tricyclic Antidepressants:** Potentiate pressor response; avoid concurrent use or use with extreme caution and reduced initial doses.
* **Beta-Blockers:** May result in unopposed alpha-stimulation, leading to severe hypertension.
* **Ergot Alkaloids & Oxytocics:** May cause severe, persistent hypertension.
* **Anesthetics (Halogenated):** Increased risk of arrhythmias.
## Monitoring
* **Hemodynamics:** Continuous ECG, blood pressure (arterial line preferred), heart rate, central venous pressure.
* **Perfusion:** Urine output, peripheral circulation (skin color, temperature, capillary refill), mental status.
* **Infusion Site:** Monitor closely for signs of extravasation.
## Clinical Pearls
* Norepinephrine is a first-line agent for septic shock refractory to adequate fluid resuscitation.
* Extravasation can cause significant tissue necrosis; an alpha-adrenergic blocking agent (e.g., phentolamine) should be infiltrated locally if extravasation occurs.
* Central venous access is preferred for administration.
* Titrate to the lowest effective dose to achieve target mean arterial pressure (MAP), typically 65 mmHg in septic shock, or individualized based on patient factors.
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*This information is intended for healthcare professionals. Always consult the official prescribing information and relevant clinical guidelines for the most current and comprehensive details.*
