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# Norepinephrine
## Overview
Norepinephrine is a sympathomimetic amine that acts as a vasopressor and inotropic agent. It primarily stimulates alpha-1 adrenergic receptors, causing vasoconstriction and increasing blood pressure. It also has some beta-1 adrenergic activity, which can increase heart rate and contractility, though this effect is less pronounced than with epinephrine.
## Primary Indications
* Management of severe hypotension and shock, particularly septic shock and cardiogenic shock, to restore and maintain hemodynamic function.
## Adult Dosing
* **Initial Infusion Rate:** 0.01 to 0.02 mcg/kg/minute IV.
* **Titration:**titrate infusion rate to achieve target mean arterial pressure (MAP), typically 65-70 mmHg. Doses may range from 0.01 to 0.3 mcg/kg/minute IV.
* **Maximum Dose:** Doses higher than 0.3 mcg/kg/minute IV are generally not recommended due to increased risk of adverse effects without significant additional benefit. Local protocols may vary.
## Pediatric Dosing
* **Initial Infusion Rate:** 0.05 to 0.1 mcg/kg/minute IV.
* **Titration:**titrate infusion rate to achieve target MAP based on age (e.g., MAP > gestational age + 2 in neonates). Doses may range from 0.05 to 2 mcg/kg/minute IV. Local protocols are essential for pediatric dosing.
## Dose Adjustments
* **Renal Impairment:** No specific dose adjustment is typically recommended, but caution and close monitoring are advised due to potential accumulation.
* **Hepatic Impairment:** No specific dose adjustment is typically recommended, but caution and close monitoring are advised.
## Contraindications
* Hypersensitivity to norepinephrine.
* Concurrent use with cyclopropane or halogenated hydrocarbon anesthetics (risk of severe hypertension and arrhythmias).
## Adverse Effects
* **Cardiovascular:** Hypertension, bradycardia (reflex), tachycardia, arrhythmias, peripheral ischemia, extravasation leading to tissue necrosis.
* **Central Nervous System:** Headache, anxiety, tremor, dizziness.
* **Other:** Respiratory distress, decreased renal perfusion.
## Key Drug Interactions
* **Monoamine Oxidase Inhibitors (MAOIs) and Tricyclic Antidepressants (TCAs):** Potentiate pressor response; avoid concurrent use or use with extreme caution and significantly reduced doses.
* **Alpha and Beta-Adrenergic Blockers:** May antagonize effects.
* **Ergot Alkaloids:** Potentiates vasoconstrictive effects.
* **Oxytocics:** May cause severe persistent hypertension.
## Monitoring
* Continuous hemodynamic monitoring (heart rate, blood pressure, MAP).
* Central venous pressure and/or pulmonary artery pressures if available.
* Urine output.
* Peripheral circulation (e.g., skin temperature, color, capillary refill).
* ECG for arrhythmias.
* Infusion site for signs of extravasation.
## Clinical Pearls
* Norepinephrine must be administered via a central venous catheter to minimize the risk of extravasation and subsequent tissue necrosis.
* If extravasation occurs, discontinue the infusion immediately. Local infiltration with phentolamine may be considered.
* Avoid abrupt discontinuation; taper infusion gradually.
* Dilute in compatible IV solutions (e.g., D5W, NS) as per manufacturer guidelines; typically comes in a concentration of 1 mg/mL or 4 mg/10 mL.
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**Disclaimer:** This information is intended for clinical pharmacy professionals. Always consult the most current prescribing information and relevant clinical guidelines for definitive guidance. Dosing can vary based on patient-specific factors and institutional protocols.
