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# Norepinephrine
## Overview
Norepinephrine is a vasopressor and inotrope that acts primarily on alpha-1 adrenergic receptors, causing vasoconstriction and increasing blood pressure. It also has beta-1 adrenergic effects, increasing heart rate and contractility, though less potent than epinephrine.
## Primary Indications
* Management of severe hypotension and shock, particularly distributive shock (e.g., septic shock, neurogenic shock).
* To restore and maintain hemodynamic function.
## Adult Dosing
* **Initial Dose:** Typically initiated as a continuous infusion at 0.01 to 0.05 mcg/kg/min.
* **Titration:** Gradually increase the dose based on hemodynamic response (e.g., mean arterial pressure [MAP], heart rate, clinical signs of perfusion) in increments of 0.005 to 0.01 mcg/kg/min.
* **Maintenance Dose:** Doses can range from 0.01 to 0.3 mcg/kg/min. Higher doses may be required in severe cases.
* **Maximum Dose:** No absolute maximum dose, but doses above 0.3-1 mcg/kg/min are associated with increased risk and may not be tolerated. Dosing is highly individualized and driven by patient response and institutional protocols.
## Pediatric Dosing
* **Initial Dose:** Typically initiated as a continuous infusion at 0.05 to 0.1 mcg/kg/min.
* **Titration:** Gradually increase the dose based on hemodynamic response in increments of 0.05 to 0.1 mcg/kg/min.
* **Maintenance Dose:** Doses can range from 0.1 to 2 mcg/kg/min.
* **Maximum Dose:** Dosing is highly individualized and driven by patient response and institutional protocols.
## Dose Adjustments
* **Renal Impairment:** No specific dose adjustment is typically recommended, but caution and close monitoring are warranted due to potential for accumulation and increased pressor effects.
* **Hepatic Impairment:** No specific dose adjustment is typically recommended, but caution and close monitoring are warranted.
## Contraindications
* Hypersensitivity to norepinephrine.
* Generally not recommended in patients with profound hypovolemia or severe peripheral vascular compromise where vasoconstriction may worsen tissue perfusion.
## Adverse Effects
* **Cardiovascular:** Hypertension, reflex bradycardia, arrhythmias, peripheral ischemia, myocardial ischemia, angina.
* **Local:** Extravasation can lead to severe tissue necrosis and sloughing.
* **Other:** Headache, anxiety, tremors, dyspnea, reduced blood flow to vital organs (kidneys, gut).
## Key Drug Interactions
* **Monoamine Oxidase Inhibitors (MAOIs) & Tricyclic Antidepressants (TCAs):** Potentiate pressor effects, requiring significantly lower starting doses and careful titration. Discontinue MAOIs at least 14 days prior to initiating norepinephrine if possible.
* **Anesthetic Agents:** May increase myocardial irritability and the risk of arrhythmias.
* **Beta-blockers:** Can unmask alpha-adrenergic effects leading to severe hypertension.
* **Alpha-blockers:** May reduce the pressor effect.
* **Diuretics:** May enhance the effects of norepinephrine by causing volume depletion.
## Monitoring
* Continuous electrocardiogram (ECG) for arrhythmias.
* Continuous arterial blood pressure monitoring.
* Central venous pressure or pulmonary artery catheter if available.
* Urine output.
* Peripheral perfusion (skin color, temperature, capillary refill).
* Mental status.
* Infusion site for signs of extravasation.
## Clinical Pearls
* Norepinephrine is typically reconstituted and diluted in a compatible intravenous fluid (e.g., D5W, 0.9% NaCl) for continuous infusion. Refer to specific product labeling for preparation instructions.
* Rapid intravenous administration can cause dangerous hypertension and arrhythmias.
* Administer through a central venous catheter whenever possible to minimize the risk of extravasation and tissue necrosis. If peripheral administration is necessary, use a large vein, monitor the site closely, and discontinue immediately if signs of extravasation appear.
* Have phentolamine readily available as an antidote for extravasation.
* Titration should be guided by the patient's hemodynamic response and clinical signs, not solely by a predetermined dose.
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**Disclaimer:** This information is intended for healthcare professionals. Always consult the most current prescribing information and relevant clinical guidelines before making treatment decisions. Drug information can change rapidly.
