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# Norepinephrine
## Overview
Norepinephrine is a potent vasopressor and inotropic agent that acts primarily through alpha-1 adrenergic receptors, causing vasoconstriction and increasing systemic vascular resistance. It also has some beta-1 adrenergic activity, which can increase heart rate and contractility.
## Primary Indications
* Treatment of severe hypotension, particularly that associated with shock (e.g., septic shock, cardiogenic shock).
* To restore and maintain blood pressure.
## Adult Dosing
* **Initiation:** Typically started at 2 to 10 mcg/minute (mcg/min) via continuous intravenous infusion.
* **Titration:** Doses can be titrated upward based on patient response (e.g., achieving target mean arterial pressure [MAP] of 65 mmHg or higher).
* **Maximum Dose:** Doses up to 30 mcg/min have been used, but higher doses are associated with increased risk of adverse effects and may not provide additional benefit. Some protocols may allow for higher doses under close supervision.
## Pediatric Dosing
* **Initiation:** Typically 0.05 to 0.1 mcg/kg/minute via continuous intravenous infusion.
* **Titration:** Doses can be titrated up to 1 mcg/kg/minute or higher based on clinical response and institutional protocols. Doses higher than 1 mcg/kg/minute are often reserved for specific situations and require very close monitoring.
## Dose Adjustments
* No specific dose adjustments are typically required for renal or hepatic impairment, as norepinephrine is metabolized rapidly. However, careful titration based on response is crucial in all patients.
## Contraindications
* Hypersensitivity to norepinephrine.
* Severe uncontrolled hypertension.
* Use during general anesthesia with halogenated hydrocarbons or cyclopropane (risk of severe hypertension and arrhythmias).
## Adverse Effects
* **Cardiovascular:** Hypertension, reflex bradycardia, arrhythmias, palpitations, myocardial ischemia, peripheral ischemia, digital ischemia.
* **Local:** Extravasation leading to tissue necrosis and sloughing.
* **Other:** Headache, anxiety, tremors, dyspnea, nausea, vomiting.
## Key Drug Interactions
* **MAO Inhibitors & Tricyclic Antidepressants:** Potentiate hypertensive crisis; avoid concurrent use or use with extreme caution and reduced initial doses.
* **Alpha and Beta Blockers:** May antagonize effects or lead to complex hemodynamic changes.
* **General Anesthetics (Halogenated):** Increased risk of severe hypertension and arrhythmias.
* **Vasodilators (e.g., Nitroglycerin):** May blunt the pressor effect of norepinephrine.
## Monitoring
* **Hemodynamics:** Continuous blood pressure monitoring (arterial line preferred), heart rate, cardiac rhythm.
* **Urine Output:** To assess perfusion.
* **Peripheral Perfusion:** Assess for signs of ischemia (cool extremities, delayed capillary refill, color changes).
* **Infusion Site:** Monitor closely for signs of extravasation.
## Clinical Pearls
* Norepinephrine should be administered via a central venous catheter to minimize the risk of extravasation and local tissue necrosis.
* Have phentolamine readily available for the treatment of extravasation.
* Titrate to achieve desired hemodynamic goals, not just a specific dose.
* Consider weaning gradually when hemodynamically stable to avoid withdrawal hypotension.
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*Disclaimer: This information is for educational purposes only and does not constitute medical advice. Always consult the most current prescribing information and relevant clinical guidelines, and exercise professional judgment when making treatment decisions.*
