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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 blood pressure. It also has some beta-1 adrenergic effects, increasing heart rate and contractility.
## Primary Indications
* Treatment of severe hypotension and shock, particularly distributive shock (e.g., septic shock, neurogenic shock).
* Restoration and maintenance of blood pressure.
## Adult Dosing
* **Initial dose:** Typically starts at **2 mcg/min to 10 mcg/min** via continuous intravenous infusion.
* **Titration:** Dose is titrated to achieve and maintain a target mean arterial pressure (MAP) of **at least 65 mmHg**. Some protocols may target a higher MAP.
* **Maximum dose:** Doses can range up to **0.1 mcg/kg/min (or 6 mcg/kg/hr)**, but higher doses are associated with increased risk of adverse effects and may indicate the need for adjunctive therapies.
*Dosing is highly individualized and often guided by institutional protocols and patient response.*
## Pediatric Dosing
* **Initial dose:** Typically **0.05 mcg/kg/min** via continuous intravenous infusion.
* **Titration:** Dose is titrated to achieve and maintain a target MAP appropriate for age (e.g., greater than or equal to gestational age + 2 mmHg in neonates, or greater than or equal to 50 mmHg in older children).
* **Maximum dose:** Doses can range up to **2 mcg/kg/min**.
*Dosing is highly individualized and often guided by institutional protocols and patient response.*
## Dose Adjustments
* **Renal impairment:** No specific dose adjustment is established. Use with caution, as clearance may be reduced.
* **Hepatic impairment:** No specific dose adjustment is established. Use with caution.
## Contraindications
* Hypersensitivity to norepinephrine.
* Use during general anesthesia with cyclopropane or halogenated hydrocarbons (risk of severe hypertension and arrhythmias).
* Hypotension due to pure hypovolemia (requires volume resuscitation prior to or concurrent with vasopressor initiation).
## Adverse Effects
* **Common:** Hypertension, bradycardia (reflex), peripheral ischemia, local tissue necrosis at infusion site (extravasation), anxiety, headache, dizziness, arrhythmias.
* **Serious:** Severe hypertension, cardiac arrhythmias, myocardial infarction, stroke, limb ischemia, gangrene, pulmonary edema.
## Key Drug Interactions
* **Monoamine Oxidase Inhibitors (MAOIs):** Potentiated pressor response. Avoid concurrent use. If necessary, reduce norepinephrine dose significantly.
* **Tricyclic Antidepressants (TCAs):** Potentiated pressor response. Use with caution and consider reducing norepinephrine dose.
* **Guanethidine, debrisoquine, methyldopa:** May reduce the antihypertensive effect of these agents.
* **Beta-blockers:** May unmask or potentiate unopposed alpha-adrenergic effects, leading to severe hypertension and reflex bradycardia.
* **Ergot alkaloids, oxytocin:** May cause severe hypertension.
## Monitoring
* **Hemodynamics:** Continuous blood pressure monitoring (arterial line preferred), heart rate, central venous pressure (CVP), pulmonary artery pressures (if available).
* **Perfusion:** Urine output, mental status, skin color and temperature, capillary refill.
* **Infusion site:** Closely monitor for signs of extravasation.
## Clinical Pearls
* Norepinephrine is typically the first-line vasopressor for septic shock.
* Adequate volume resuscitation is crucial before or concurrent with norepinephrine initiation to ensure efficacy and minimize adverse effects.
* Administer via a central venous catheter to minimize the risk of extravasation and tissue necrosis. If peripheral administration is necessary, use a large vein and monitor the site very closely.
* Have phentolamine readily available to treat extravasation.
* Taper norepinephrine gradually to avoid sudden drops in blood pressure.
**Please verify the current prescribing information and institutional protocols before administering any medication.**
