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# Norepinephrine
## Overview
Norepinephrine (Levophed) is a potent sympathomimetic amine that acts primarily as an alpha-1 adrenergic agonist, causing vasoconstriction and increasing systemic vascular resistance and blood pressure. It also has beta-1 adrenergic activity, increasing cardiac contractility and heart rate.
## Primary Indications
* Treatment of severe hypotension and shock unresponsive to adequate fluid resuscitation.
## Adult Dosing
* **Initiation:** Typically started as a continuous infusion at 0.01 to 0.02 mcg/kg/min.
* **Titration:** May be titrated upward to achieve and maintain a target mean arterial pressure (MAP), often 65-75 mmHg. Doses can range from 0.01 to 3 mcg/kg/min, with higher doses sometimes required.
* **Maximum:** No strict maximum dose, titration is guided by patient response and adverse effects.
## Pediatric Dosing
* **Initiation:** Typically started as a continuous infusion at 0.05 to 0.1 mcg/kg/min.
* **Titration:** May be titrated upward to achieve and maintain a target MAP, often 40-60 mmHg or according to local protocol. Doses can range from 0.05 to 2 mcg/kg/min.
* **Maximum:** No strict maximum dose, titration is guided by patient response and adverse effects.
## Dose Adjustments
* No specific dose adjustments are typically required for renal or hepatic impairment, as norepinephrine is metabolized and not cleared by these organs. However, careful titration and monitoring are crucial in patients with these conditions due to potential for altered hemodynamic response.
## Contraindications
* Hypersensitivity to norepinephrine.
* Generally not recommended in patients with mesenteric or peripheral vascular thrombosis due to the risk of exacerbating ischemia.
## Adverse Effects
* **Cardiovascular:** Arrhythmias (tachycardia, bradycardia, ventricular arrhythmias), severe hypertension, peripheral ischemia, gangrene (especially with extravasation), reflex bradycardia.
* **Local:** Extravasation can cause severe tissue necrosis and sloughing.
* **Other:** Headache, anxiety, shortness of breath, reduced blood flow to vital organs with excessive vasoconstriction.
## Key Drug Interactions
* **MAO Inhibitors & Tricyclic Antidepressants:** Can potentiate the pressor effects of norepinephrine, potentially leading to hypertensive crisis. Avoid concurrent use; if necessary, use with extreme caution and reduced norepinephrine doses.
* **Beta-Blockers:** May block the beta-1 effects of norepinephrine, leaving unopposed alpha-1 effects, leading to severe peripheral vasoconstriction and hypertension.
* **Alpha-Blockers:** May antagonize the pressor effects of norepinephrine.
* **Anesthetics (e.g., Halothane):** May increase myocardial irritability and the risk of arrhythmias.
## Monitoring
* **Hemodynamics:** Continuous blood pressure monitoring (intra-arterial preferred), heart rate, cardiac rhythm.
* **Perfusion:** Assess peripheral perfusion, urine output, mental status.
* **Infusion Site:** Regularly check for signs of extravasation.
* **Laboratory:** Electrolytes, lactate.
## Clinical Pearls
* Norepinephrine should be infused via a central venous catheter to minimize the risk of extravasation and tissue necrosis.
* If extravasation occurs, immediately stop the infusion and infiltrate the affected area with phentolamine.
* Titrate infusion rate based on MAP goals and patient's clinical response, not solely on dose.
* Consider concomitant use of other vasopressors or inotropes based on the underlying cause of shock and patient-specific factors.
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*This information is intended for healthcare professionals. Always consult the official prescribing information and relevant clinical guidelines for complete and up-to-date details before making any treatment decisions.*
