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# Norepinephrine
## Overview
Norepinephrine is a vasopressor and inotropic agent that acts primarily on alpha-1 adrenergic receptors, causing vasoconstriction and increased systemic vascular resistance. It also has some beta-1 adrenergic effects, increasing heart rate and contractility.
## Primary Indications
* Severe Hypotension: Particularly in shock states like septic shock, cardiogenic shock, and neurogenic shock, to maintain adequate organ perfusion.
## Adult Dosing
* **Initial Infusion:** 0.01 to 0.03 mcg/kg/min intravenously.
* **Titration:** Titrate infusion rate to achieve target mean arterial pressure (MAP), typically 65 mmHg or higher, or based on local protocol. Doses may range from 0.01 to 2 mcg/kg/min. Higher doses (up to 10 mcg/kg/min or even more in refractory shock) may be used under close monitoring.
## Pediatric Dosing
* **Initial Infusion:** 0.05 to 0.1 mcg/kg/min intravenously.
* **Titration:** Titrate infusion rate to achieve target MAP, typically systolic blood pressure (SBP) > 70 mmHg + (2 x age in years) for children > 1 year, or based on local protocol. Doses can range from 0.05 to 2 mcg/kg/min. Higher doses may be necessary.
## Dose Adjustments
* No specific dose adjustments are typically required for hepatic or renal impairment, as the drug is primarily metabolized by monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT) and its metabolites are renally excreted. However, patients with hepatic impairment may have altered drug metabolism.
## Contraindications
* Hypersensitivity to norepinephrine.
* Hypotension due to volume deficit unless used as a temporizing measure until volume resuscitation is complete.
* Use with volatile inhalation anesthetics (potential for severe arrhythmias).
* Use with cyclopropane anesthesia (potential for severe arrhythmias).
## Adverse Effects
* **Common:** Hypertension, bradycardia (reflex), peripheral ischemia, anxiety, headache, dizziness, tremor.
* **Serious:** Arrhythmias, necrosis of skin or underlying tissues (if extravasation occurs), pulmonary edema.
## Key Drug Interactions
* **MAO Inhibitors:** Potentiate hypertensive crisis. Avoid concurrent use or use with extreme caution and reduced doses if necessary.
* **Tricyclic Antidepressants (TCAs):** May potentiate the pressor effects of norepinephrine.
* **Beta-Blockers:** Can lead to unopposed alpha-1 stimulation, causing severe hypertension.
* **Dobutamine and other beta-agonists:** May antagonize the pressor effects.
* **Ergot Alkaloids:** May potentiate the vasoconstrictive effects.
* **Oxytocic Drugs:** May cause severe persistent hypertension.
* **Certain Anesthetics:** (e.g., halothane, cyclopropane) may increase cardiac irritability and risk of arrhythmias.
## Monitoring
* **Hemodynamic Parameters:** Continuous blood pressure monitoring (arterial line preferred for titration), heart rate, cardiac rhythm.
* **Infusion Site:** Monitor closely for signs of extravasation (pain, blanching, coolness, sloughing).
* **Urine Output:** Assess for adequate renal perfusion.
* **Central Venous Pressure (CVP) or Pulmonary Artery (PA) Catheter:** May be used to assess fluid status and cardiac function.
* **Mental Status:** Assess for signs of adequate cerebral perfusion.
## Clinical Pearls
* Always administer as a continuous intravenous infusion.
* Use a central venous catheter for administration whenever possible to minimize the risk of extravasation and tissue necrosis.
* If extravasation occurs, stop the infusion immediately and administer phentolamine (intradermal injection) to the affected area.
* Norepinephrine has a short half-life, so infusions should not be abruptly stopped. Taper gradually if possible.
* Consider dopamine or other agents if norepinephrine is ineffective or causes unacceptable side effects.
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**Disclaimer:** This information is intended for clinical decision support and does not replace the need for professional judgment. Always refer to the most current prescribing information and institutional guidelines for complete and up-to-date details on drug use.
