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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 to a lesser extent on beta-1 adrenergic receptors, increasing heart rate and contractility. It is used to treat severe hypotension.
## Primary Indications
* Treatment of septic shock and other distributive shock states characterized by profound hypotension.
* Restoration and maintenance of blood pressure in patients with acute hypotensive states.
## Adult Dosing
* **Initiation:** Typically 2 to 10 mcg/minute (0.02 to 0.1 mcg/kg/minute) via continuous intravenous infusion.
* **Titration:** Titrate infusion rate to achieve target mean arterial pressure (MAP), often 65 mmHg or higher. Doses may be increased up to 30 mcg/minute (0.3 mcg/kg/minute) or higher, depending on patient response and local protocols.
* **Maximum Dose:** No strict maximum dose; titration is guided by clinical response and adverse effects.
## Pediatric Dosing
* **Initiation:** Typically 0.05 to 0.1 mcg/kg/minute via continuous intravenous infusion.
* **Titration:** Titrate infusion rate to achieve target blood pressure or end-organ perfusion. Doses may range from 0.01 to 2 mcg/kg/minute. Specific dosing is often guided by local pediatric advanced life support protocols or institutional guidelines.
## Dose Adjustments
* **Renal Impairment:** No specific dose adjustment recommended, but caution and close monitoring are advised due to potential for altered pharmacokinetics.
* **Hepatic Impairment:** No specific dose adjustment recommended, but caution and close monitoring are advised.
## Contraindications
* Hypersensitivity to norepinephrine.
* During general anesthesia with cyclopropane or halogenated hydrocarbons (risk of severe arrhythmias).
* Patients with hypotension due to relative hypovolemia unless plasma volume is adequately restored first.
## Adverse Effects
* **Cardiovascular:** Hypertension, bradycardia (reflex), arrhythmias, peripheral ischemia, extravasation leading to tissue necrosis.
* **Central Nervous System:** Headache, anxiety, dizziness.
* **Respiratory:** Dyspnea.
* **Metabolic:** Hyperglycemia.
## Key Drug Interactions
* **Monoamine Oxidase Inhibitors (MAOIs):** Potentiates the pressor response; discontinue MAOIs at least 14 days before starting norepinephrine.
* **Tricyclic Antidepressants (TCAs) and other drugs that prolong the QTc interval:** May increase the risk of arrhythmias.
* **Alpha and Beta Blockers:** Can antagonize or potentiate effects depending on the specific agent.
* **Ergot alkaloids:** May cause severe hypertension.
* **Anesthetic agents (e.g., halothane, cyclopropane):** Increased risk of arrhythmias.
## Monitoring
* **Hemodynamics:** Continuous blood pressure monitoring (arterial line preferred), heart rate, cardiac rhythm.
* **Perfusion:** Assess peripheral circulation (skin color, temperature, capillary refill), urine output, mental status.
* **Infusion Site:** Regularly inspect for signs of extravasation. Phentolamine is the recommended antidote for extravasation.
* **Fluid Status:** Monitor intake and output, central venous pressure if available.
## Clinical Pearls
* Norepinephrine is a first-line vasopressor for septic shock.
* Always correct hypovolemia and metabolic derangements before or concurrently with vasopressor initiation.
* Administer via a central venous catheter to minimize the risk of extravasation and tissue necrosis.
* If extravasation occurs, immediately stop the infusion, aspirate any residual drug, and infiltrate the area with phentolamine.
* The goal of therapy is to maintain adequate tissue perfusion and organ function, not just a specific blood pressure number.
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*Disclaimer: This information is intended for healthcare professionals. Always consult the most current prescribing information and institutional guidelines before administering any medication.*
