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# Norepinephrine
## Overview
Norepinephrine is a vasopressor and inotropic agent that acts primarily on alpha-1 adrenergic receptors, causing vasoconstriction, and to a lesser extent on beta-1 adrenergic receptors in the heart, increasing heart rate and contractility. It is used to increase blood pressure.
## Primary Indications
* Severe hypotension, particularly that related to shock (e.g., septic shock, cardiogenic shock, anaphylactic shock).
* To restore vascular tone and raise blood pressure in hypotensive states.
## Adult Dosing
* **Initiation:** Typically initiated at 0.01 to 0.05 mcg/kg/minute IV infusion.
* **Titration:** Titrate upwards based on patient's blood pressure response. Doses can range from 0.01 to 0.3 mcg/kg/minute. Higher doses may be necessary in refractory hypotension, but are associated with increased risk of adverse effects.
* **Maximum Dose:** There is no strict maximum dose, but doses exceeding 0.3 mcg/kg/minute are associated with significant risk and should be used with extreme caution.
## Pediatric Dosing
* **Initiation:** Typically initiated at 0.05 to 0.1 mcg/kg/minute IV infusion.
* **Titration:** Titrate to achieve target blood pressure, usually SBP > 70 mmHg + (2 x age in years) or MAP > 40 mmHg. Doses can range from 0.05 to 2 mcg/kg/minute.
* **Maximum Dose:** Doses exceeding 1-2 mcg/kg/minute are generally not recommended due to increased risk of adverse effects. Dosing can be highly individualized based on clinical status and local protocols.
## 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.
* Use with cyclopropane or halothane anesthetics (risk of ventricular arrhythmias).
## Adverse Effects
* **Cardiovascular:** Hypertension, reflex bradycardia, arrhythmias, peripheral ischemia, tissue necrosis (with extravasation), myocardial infarction.
* **Central Nervous System:** Headache, anxiety, dizziness, tremor.
* **Metabolic:** Hyperglycemia.
* **Other:** Dyspnea, piloerection.
## Key Drug Interactions
* **Monoamine Oxidase Inhibitors (MAOIs):** Potentiates hypertensive crisis. Avoid concurrent use. If unavoidable, use with extreme caution and reduced doses.
* **Tricyclic Antidepressants (TCAs):** Potentiates hypertensive response. Use with caution.
* **Beta-Blockers:** May blunt the cardiac effects of norepinephrine and potentially lead to unopposed alpha-receptor stimulation, causing severe hypertension.
* **Ergot Alkaloids:** Can cause severe hypertension and peripheral ischemia.
* **Oxytocics:** May cause severe hypertension.
## Monitoring
* **Hemodynamics:** Continuous blood pressure monitoring (arterial line preferred), heart rate, cardiac output (if available).
* **Perfusion:** Assess peripheral circulation, urine output, mental status.
* **Infusion Site:** Monitor closely for signs of extravasation.
* **Electrolytes:** Particularly potassium, especially with prolonged use.
* **Glucose:** Monitor blood glucose levels.
## Clinical Pearls
* Norepinephrine is typically administered via a central venous catheter to minimize the risk of extravasation and tissue necrosis.
* If extravasation occurs, discontinue the infusion immediately. Local infiltration with phentolamine may be considered.
* Titrate norepinephrine to achieve the desired hemodynamic goal (e.g., target MAP or SBP) rather than a specific dose.
* Norepinephrine can cause peripheral vasoconstriction, leading to cool extremities and decreased urine output.
* It is a potent drug and requires careful and frequent assessment of the patient's response.
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*Disclaimer: This information is intended for healthcare professionals. Always consult the most current prescribing information and relevant clinical guidelines for complete details and to ensure patient safety.*
