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# Norepinephrine
## Overview
Norepinephrine is a potent vasopressor and inotrope. It primarily acts on alpha-1 adrenergic receptors, causing vasoconstriction and increasing systemic vascular resistance and blood pressure. It also has some beta-1 adrenergic receptor activity, increasing myocardial contractility.
## Primary Indications
* Treatment of severe hypotension and shock, particularly septic shock and cardiogenic shock, to maintain adequate organ perfusion.
## Adult Dosing
* **Loading Dose:** Not typically used.
* **Maintenance Dose:** Initiate infusion at 0.01 to 0.03 mcg/kg/min.
* **Titration:** Titrate gradually to achieve the target mean arterial pressure (MAP), typically $\geq$ 65 mmHg. Doses can be increased up to 0.1 mcg/kg/min.
* **Maximum Dose:** Doses may be escalated further based on clinical response and institutional protocol, sometimes exceeding 0.1 mcg/kg/min (e.g., up to 1 mcg/kg/min or higher has been reported in severe refractory shock, but extreme caution and close monitoring are required).
## Pediatric Dosing
* **Loading Dose:** Not typically used.
* **Maintenance Dose:** Initiate infusion at 0.05 to 0.1 mcg/kg/min.
* **Titration:** Titrate to achieve target MAP $\geq$ the patient's age in years + 40 mmHg, or as per institutional protocol. Doses can be increased up to 1 mcg/kg/min.
* **Maximum Dose:** Doses may be escalated further based on clinical response and institutional protocol, sometimes exceeding 1 mcg/kg/min in severe refractory shock with extreme caution.
## Dose Adjustments
* **Renal Impairment:** No specific dose adjustment is usually recommended, but caution and close monitoring are advised due to potential accumulation.
* **Hepatic Impairment:** No specific dose adjustment is usually recommended, but caution and close monitoring are advised.
## Contraindications
* Hypersensitivity to norepinephrine.
* Use during general anesthesia with cyclopropane or halogenated hydrocarbons (risk of severe hypertension and arrhythmias).
* Should not be used as the sole agent to treat hypotension due to blood volume deficits; volume resuscitation should be performed first.
## Adverse Effects
* **Common:** Hypertension, reflex bradycardia, peripheral ischemia, tissue necrosis (with extravasation), arrhythmias, anxiety, headache, tremor.
* **Serious:** Severe hypertension, myocardial infarction, cerebral hemorrhage, decreased splanchnic circulation.
## Key Drug Interactions
* **MAO Inhibitors (MAOIs) and Tricyclic Antidepressants (TCAs):** Potentiate the pressor effects of norepinephrine; concurrent use is generally contraindicated or requires extreme caution and dose reduction.
* **General Anesthetics (e.g., Halothane, Cyclopropane):** Increased risk of arrhythmias.
* **Beta-blockers:** May blunt the desired cardiac effects and potentially exacerbate peripheral vasoconstriction.
* **Alpha-blockers:** May antagonize the vasoconstrictive effects.
## Monitoring
* Continuous electrocardiogram (ECG) for arrhythmias.
* Continuous blood pressure monitoring (intra-arterial preferred).
* Central venous pressure (CVP) and pulmonary artery pressures (if available).
* Urine output.
* Peripheral circulation (skin temperature, color).
* Mental status.
* Infusion site for signs of extravasation.
## Clinical Pearls
* Norepinephrine is typically administered via a central venous catheter to minimize the risk of extravasation and tissue necrosis.
* If extravasation occurs, discontinue the infusion immediately and administer phentolamine to the affected area.
* Dosing is highly individualized and titratable based on hemodynamic response.
* The goal is to restore and maintain adequate tissue perfusion, not just to achieve a specific blood pressure number.
* Norepinephrine should be diluted in a compatible IV solution (e.g., D5W, NS) prior to administration.
**Disclaimer:** This information is intended for clinical decision-making and is not a substitute for professional medical advice. Always consult the most current prescribing information and institutional protocols.
