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# Norepinephrine
## Overview
Norepinephrine is a sympathomimetic amine that acts as a potent vasoconstrictor and has a positive inotropic effect on the heart. It primarily acts on alpha-1 adrenergic receptors, causing peripheral vasoconstriction and increasing blood pressure. It also has some beta-1 adrenergic receptor activity, increasing heart rate and contractility.
## Primary Indications
* Treatment of severe hypotension and shock, particularly septic shock and cardiogenic shock, to restore and maintain blood pressure.
## Adult Dosing
* **Usual starting dose:** 0.01 to 0.02 mcg/kg/min intravenously (IV).
* **Titration:** Titrate infusion rate based on patient's hemodynamic response (e.g., mean arterial pressure [MAP], heart rate) and clinical signs of perfusion.
* **Maximum dose:** Doses up to 0.3 mcg/kg/min have been used, but higher doses are associated with increased risk of adverse events. Specific maximums may be dictated by local protocol.
## Pediatric Dosing
* **Usual starting dose:** 0.05 to 0.1 mcg/kg/min intravenously (IV) by continuous infusion.
* **Titration:** Titrate infusion rate based on patient's hemodynamic response and clinical signs of perfusion.
* **Maximum dose:** Doses up to 1-2 mcg/kg/min may be required in some cases, but higher doses increase risks. Dosing is highly individualized and often guided by expert consensus or local protocol.
## Dose Adjustments
* **Renal Impairment:** No specific dose adjustment is typically recommended, as norepinephrine is metabolized in the liver and tissues. However, close hemodynamic monitoring is essential.
* **Hepatic Impairment:** No specific dose adjustment is typically recommended. Close hemodynamic monitoring is essential.
## Contraindications
* Hypersensitivity to norepinephrine.
* Should generally not be used in patients with mesenteric or peripheral vascular thrombosis due to risk of increasing ischemia.
## Adverse Effects
* **Cardiovascular:** Arrhythmias, bradycardia (reflex), hypertension, tachycardia, vasoconstriction leading to peripheral ischemia, tissue necrosis at infusion site.
* **Central Nervous System:** Headache, anxiety, dizziness, tremor.
* **Respiratory:** Dyspnea.
* **Other:** Extravasation leading to tissue sloughing.
## Key Drug Interactions
* **Monoamine Oxidase Inhibitors (MAOIs):** Potentiates pressor effect; avoid use or use with extreme caution and significantly reduced doses.
* **Tricyclic Antidepressants (TCAs):** Potentiates pressor effect; use with caution and reduced doses.
* **General Anesthetics:** May increase risk of arrhythmias.
* **Beta-Adrenergic Blockers:** May unmask unopposed alpha-adrenergic receptor stimulation, leading to severe hypertension.
* **Alpha-Adrenergic Blockers:** May reduce pressor effect.
## Monitoring
* Continuous arterial blood pressure monitoring.
* Heart rate and rhythm.
* Central venous pressure (CVP) or pulmonary artery catheter (PAC) if indicated.
* Urine output.
* Signs of peripheral perfusion (e.g., skin temperature, color, capillary refill).
* Infusion site for signs of extravasation.
## 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. Administer phentolamine mesylate subcutaneously to the affected area to counteract vasoconstriction.
* Titrate infusion to achieve target MAP (often 65 mmHg or higher, depending on patient condition and local protocol) and adequate end-organ perfusion, rather than solely titrating to a specific dose.
* The duration of infusion should be minimized as clinically feasible.
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***Disclaimer:** This information is intended for clinical pharmacists and other healthcare professionals. It is essential to consult the most current prescribing information and relevant clinical guidelines for definitive guidance. Dosing and management decisions should be individualized based on patient-specific factors and institutional protocols.*
