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# Norepinephrine
## Overview
Norepinephrine (Levophed) is a potent alpha-1 adrenergic agonist and a weaker beta-1 adrenergic agonist. It causes peripheral vasoconstriction and increases myocardial contractility and heart rate, leading to an increase in blood pressure.
## Primary Indications
* Management of severe hypotension unresponsive to adequate fluid resuscitation.
* Septic shock and other distributive shock states.
## Adult Dosing
* **Initiation:** Typically starts at 0.01 to 0.05 mcg/kg/min.
* **Titration:** Gradually increased by 0.01 to 0.05 mcg/kg/min every 5-10 minutes until desired mean arterial pressure (MAP) is achieved (target typically ≥65 mmHg).
* **Maximum:** Doses up to 0.4 mcg/kg/min may be required. Higher doses have been used but are associated with increased risk of adverse events.
## Pediatric Dosing
* **Initiation:** Typically starts at 0.05 to 0.1 mcg/kg/min.
* **Titration:** Gradually increased by 0.05 to 0.1 mcg/kg/min every 5-10 minutes.
* **Maximum:** Doses up to 1-2 mcg/kg/min may be needed.
## Dose Adjustments
* No dose adjustment is necessary for renal or hepatic impairment, but patients with these conditions may be more sensitive to its effects.
* Titration is guided by hemodynamic response and patient tolerance.
## Contraindications
* Hypersensitivity to norepinephrine.
* Hypotension secondary to volume deficit without adequate fluid resuscitation.
* Use during cyclopropane and halogenated hydrocarbon anesthesia due to potential for severe arrhythmias.
## Adverse Effects
* **Cardiovascular:** Arrhythmias (ventricular tachycardia, bradycardia), peripheral ischemia, gangrene, hypertension, palpitations, reflex tachycardia.
* **Extremities:** Coldness, cyanosis.
* **Other:** Headache, anxiety, dizziness, dyspnea, nausea, vomiting.
* **Extravasation:** Tissue necrosis and sloughing. If extravasation occurs, stop the infusion and infiltrate the area with phentolamine.
## Key Drug Interactions
* **Monoamine Oxidase Inhibitors (MAOIs) & Tricyclic Antidepressants (TCAs):** Potentiate the pressor response; avoid concurrent use or use with extreme caution and significantly reduced doses.
* **Beta-blockers:** Can result in unopposed alpha-stimulation, leading to severe hypertension.
* **Oxytocic agents:** May cause severe, sustained hypertension.
* **General anesthetics:** Increased risk of arrhythmias.
## Monitoring
* Continuous electrocardiogram (ECG).
* Continuous blood pressure monitoring (arterial line preferred).
* Central venous pressure (CVP) or other measures of volume status.
* Urine output.
* Peripheral perfusion (skin temperature, color).
* Infusion site for signs of extravasation.
## Clinical Pearls
* Norepinephrine is typically administered via a central venous catheter due to its potent vasoconstrictive properties and risk of tissue necrosis with peripheral administration.
* It should only be initiated after adequate fluid resuscitation has been achieved.
* Titrate slowly to the lowest effective dose to maintain target MAP.
* Monitor closely for signs of peripheral ischemia, especially in patients with compromised circulation.
* Always have a beta-blocker readily available for severe tachyarrhythmias, but use with caution due to potential for unopposed alpha-stimulation.
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*This information is intended for healthcare professionals. Always consult the current prescribing information and relevant clinical guidelines before making therapeutic decisions.*
