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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 cardiac output.
## Primary Indications
* Treatment of hypotension and shock, particularly septic shock and cardiogenic shock.
## Adult Dosing
* **Starting Dose:** 0.01 to 0.02 mcg/kg/min IV.
* **Maintenance Dose:** Typically 0.02 to 0.1 mcg/kg/min IV.
* **Maximum Dose:** Doses up to 1 mcg/kg/min IV have been used, but higher doses are associated with increased risk of adverse events.
* **Titration:** Dose should be titrated to achieve target mean arterial pressure (MAP), often $\geq$ 65 mmHg. Specific target MAP may vary based on patient condition and local protocol.
## Pediatric Dosing
* **Starting Dose:** 0.05 to 0.1 mcg/kg/min IV.
* **Maintenance Dose:** Typically 0.1 to 0.4 mcg/kg/min IV.
* **Maximum Dose:** Up to 1 mcg/kg/min IV or higher in refractory cases, guided by hemodynamic response and local protocol.
* **Titration:** Dose should be titrated to achieve target MAP, often $\geq$ MAP $\geq$ age-adjusted 50th percentile systolic blood pressure.
## Dose Adjustments
* No dose adjustment is typically needed for hepatic or renal impairment, but close monitoring is essential due to potential for altered drug metabolism and excretion.
## Contraindications
* Hypersensitivity to norepinephrine.
* Severe hypotension secondary to hypovolemia (unless used as a temporizing measure to maintain perfusion while initiating fluid resuscitation).
* Use during cyclopropane or halothane anesthesia due to increased risk of serious cardiac arrhythmias.
## Adverse Effects
* **Cardiovascular:** Hypertension, bradycardia, arrhythmias, peripheral ischemia, cardiac tamponade, decreased cardiac output (at very high doses), palpitations.
* **Local:** Extravasation can cause tissue necrosis and sloughing.
* **Other:** Headache, anxiety, dizziness, sweating, tremor, dyspnea.
## Key Drug Interactions
* **Monoamine Oxidase Inhibitors (MAOIs):** Potentiated hypertensive response. Discontinue MAOIs at least 14 days before norepinephrine administration.
* **Tricyclic Antidepressants (TCAs):** Potentiated hypertensive response.
* **Anesthetics (e.g., halogenated):** Increased risk of arrhythmias.
* **Alpha and Beta Blockers:** May antagonize or potentiate effects depending on the specific agent and receptor selectivity.
* **Ergot Alkaloids:** Potentiated vasoconstrictive effects and risk of gangrene.
* **Guanethidine, Guanadrel:** Potentiated pressor effect.
## Monitoring
* **Hemodynamics:** Continuous ECG, arterial blood pressure (MAP), heart rate.
* **Perfusion:** Urine output, peripheral circulation (skin color, temperature, capillary refill), mental status.
* **Fluid Status:** Assess volume status regularly; norepinephrine should not be a substitute for adequate fluid resuscitation.
* **Infusion Site:** Monitor closely for signs of extravasation.
## Clinical Pearls
* Norepinephrine is typically administered via a central venous catheter to reduce the risk of extravasation.
* If extravasation occurs, immediately stop the infusion, aspirate any residual drug from the IV line, remove the catheter, and infiltrate the affected area with phentolamine (an alpha-adrenergic blocker).
* Norepinephrine is light-sensitive; protect infusions from light.
* It is often used in combination with other vasopressors or inotropes to achieve hemodynamic goals.
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*This information is intended for clinical use and does not substitute for professional medical judgment. Always verify current prescribing information and consult relevant guidelines.*
