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# Norepinephrine
## Overview
Norepinephrine is a potent vasopressor and inotropic agent that acts primarily on alpha-1 adrenergic receptors, causing vasoconstriction, and on beta-1 adrenergic receptors, increasing cardiac contractility and heart rate.
## Primary Indications
* Severe hypotension, particularly shock unresponsive to adequate fluid resuscitation.
* Cardiogenic shock.
* Septic shock.
## Adult Dosing
* **Initiation:** Typically started at 0.01 to 0.02 mcg/kg/min intravenously.
* **Titration:** titrated to achieve and maintain a target mean arterial pressure (MAP) of 65 mmHg or higher. Doses may be increased by 0.01 to 0.05 mcg/kg/min every 5-15 minutes as needed.
* **Maximum Dose:** Doses can range up to 0.2 mcg/kg/min or higher in refractory shock, though higher doses are associated with increased risk of adverse events. Exact maximum dose may depend on local protocol.
## Pediatric Dosing
* **Initiation:** Typically started at 0.05 to 0.1 mcg/kg/min intravenously.
* **Titration:** titrated to achieve desired hemodynamic response. Doses may be increased by 0.05 to 0.1 mcg/kg/min every 10-15 minutes.
* **Maximum Dose:** Doses can range up to 1 mcg/kg/min or higher in refractory shock. Exact maximum dose may depend on local protocol.
## Dose Adjustments
No specific dose adjustments for hepatic or renal impairment are established. Dosing is primarily guided by hemodynamic response and patient tolerance.
## Contraindications
* Hypersensitivity to norepinephrine.
* Certain patients during cyclopropane or halogenated hydrocarbon anesthesia (risk of severe hypertension or arrhythmias).
## Adverse Effects
* **Cardiovascular:** Hypertension, bradycardia (reflex), arrhythmias, peripheral ischemia, extravasation leading to tissue necrosis.
* **Central Nervous System:** Headache, anxiety, dizziness.
* **Respiratory:** Dyspnea.
## Key Drug Interactions
* **Monoamine Oxidase Inhibitors (MAOIs) and Tricyclic Antidepressants (TCAs):** Can potentiate the pressor effects of norepinephrine, leading to severe hypertension. Avoid concurrent use or use with extreme caution and reduced doses.
* **Beta-blockers:** May unmask unopposed alpha-adrenergic receptor stimulation, leading to severe hypertension.
* **Alpha-blockers:** May reduce the pressor effects of norepinephrine.
* **Ergot alkaloids and Oxytocics:** May potentiate the pressor response and cause severe hypertension.
## Monitoring
* **Hemodynamics:** Continuous ECG monitoring for arrhythmias, frequent blood pressure monitoring (MAP target typically $\geq$ 65 mmHg).
* **Perfusion:** Monitor for signs of adequate tissue perfusion (e.g., urine output, mental status, lactate levels).
* **Infusion Site:** Assess frequently for signs of extravasation (pain, pallor, edema, blistering).
## Clinical Pearls
* Norepinephrine should be administered via a central venous catheter to minimize the risk of extravasation and tissue necrosis.
* In case of extravasation, stop the infusion immediately. Consider infiltration of the area with phentolamine.
* Taper the infusion gradually to avoid abrupt hypotension.
* Concurrent use with vasopressin or epinephrine may be considered in refractory shock states.
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**Disclaimer:** This information is intended for healthcare professionals and is a summary. Always consult the most current official prescribing information and institutional protocols before making clinical decisions.
