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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 increasing peripheral vascular resistance. It also has beta-1 adrenergic effects, increasing heart rate and contractility. It is typically administered as a continuous intravenous infusion.
## Primary Indications
* Management of severe hypotension and shock, particularly septic shock and cardiogenic shock, unresponsive to adequate fluid resuscitation.
## Adult Dosing
* **Starting Dose:** 0.01 to 0.02 mcg/kg/min via continuous IV infusion.
* **Titration:** Increase dose in increments of 0.005 to 0.01 mcg/kg/min every 5-15 minutes until target mean arterial pressure (MAP) is achieved.
* **Usual Range:** 0.01 to 0.3 mcg/kg/min.
* **Maximum Dose:** Doses up to 1-2 mcg/kg/min may be required in severe cases, but higher doses are associated with increased risk of adverse effects. Specific maximums may be dictated by local protocols.
## Pediatric Dosing
* **Starting Dose:** 0.05 to 0.1 mcg/kg/min via continuous IV infusion.
* **Titration:** Increase dose in increments of 0.05 to 0.2 mcg/kg/min every 5-15 minutes.
* **Usual Range:** 0.05 to 1 mcg/kg/min.
* **Maximum Dose:** Doses up to 2 mcg/kg/min may be necessary. Precise titration and maximum doses should align with institutional pediatric critical care guidelines.
## Dose Adjustments
* **Renal Impairment:** No specific dose adjustment recommendations, but caution is advised as renal function may decline with severe hypotension and vasoconstriction.
* **Hepatic Impairment:** No specific dose adjustment recommendations.
## Contraindications
* Hypersensitivity to norepinephrine.
* Should not be used as the sole agent to correct hypotension due to blood volume deficit; fluid resuscitation should be prioritized.
## Adverse Effects
* **Cardiovascular:** Hypertension, reflex bradycardia, arrhythmias, chest pain, myocardial infarction, decreased cardiac output (due to increased afterload), peripheral ischemia, gangrene (especially with extravasation).
* **Central Nervous System:** Headache, anxiety, tremor, dizziness.
* **Respiratory:** Dyspnea.
* **Other:** Extravasation leading to tissue necrosis.
## Key Drug Interactions
* **MAO Inhibitors & Tricyclic Antidepressants:** May potentiate the pressor response; avoid concurrent use or use with extreme caution and lower initial doses.
* **Beta-Blockers:** May cause unopposed alpha stimulation, leading to severe hypertension.
* **Alpha-Blockers:** May antagonize the pressor effects.
* **General Anesthetics:** May increase the risk of arrhythmias.
* **Ergot Alkaloids:** May potentiate the pressor effects.
* **Oxytocics:** May cause severe hypertension.
## Monitoring
* **Hemodynamics:** Continuous arterial blood pressure monitoring (MAP), heart rate, cardiac rhythm.
* **Perfusion:** Peripheral perfusion, urine output, mental status.
* **Infusion Site:** Monitor closely for signs of extravasation.
* **Electrolytes:** Especially potassium, as hypokalemia can be exacerbated.
## Clinical Pearls
* Norepinephrine is a potent vasoconstrictor; adequate volume resuscitation is paramount before and during its use.
* Administer via a central venous catheter to minimize the risk of extravasation and tissue necrosis. If peripheral administration is unavoidable, use a large vein and monitor the site meticulously.
* In case of extravasation, stop the infusion immediately and infiltrate the affected area with phentolamine.
* Titrate to achieve target MAP, typically between 65-70 mmHg, but individualize based on patient factors.
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*Please verify current prescribing information with the most recent product monograph or consult a clinical pharmacist.*
