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# Norepinephrine
## Overview
Norepinephrine is a potent endogenous catecholamine and sympathomimetic amine that acts primarily as an alpha-adrenergic agonist, causing vasoconstriction, and also as a beta-1 adrenergic agonist, increasing cardiac output. It is available as a solution for intravenous infusion.
## Primary Indications
* Severe hypotension and shock, particularly in settings of distributive shock (e.g., septic shock) and cardiogenic shock when other measures are insufficient.
* Cardiac arrest as part of advanced cardiac life support (ACLS) protocols.
## Adult Dosing
* **Hypotension/Shock:** Initiate infusion at 0.01 to 0.02 mcg/kg/min. Titrate to maintain systolic blood pressure of 90-100 mmHg or mean arterial pressure (MAP) of 65-75 mmHg. Doses can be increased up to 0.1 mcg/kg/min, and in some cases, higher doses (up to 0.5 mcg/kg/min or more) may be required.
* **Cardiac Arrest:** Typically administered as 1 mg IV/IO every 3-5 minutes as per ACLS guidelines.
## Pediatric Dosing
* **Hypotension/Shock:** Initiate infusion at 0.05 to 0.1 mcg/kg/min. Titrate to maintain adequate blood pressure and perfusion. Doses may range from 0.05 to 2 mcg/kg/min.
* **Cardiac Arrest:** Typically administered as 0.01 mg/kg IV/IO (10 mcg/kg) every 3-5 minutes as per PALS guidelines.
## Dose Adjustments
No specific dose adjustments are typically required based on renal or hepatic impairment, as norepinephrine is extensively metabolized and has a short half-life. However, close monitoring is essential in all patients.
## Contraindications
* Hypersensitivity to norepinephrine.
* Generally not recommended in patients with profound hypoxemia or specific types of shock (e.g., hemorrhagic shock) unless corrected rapidly.
* Tromboembolic occlusion (relative contraindication due to vasoconstrictive properties).
## Adverse Effects
Common adverse effects include bradycardia (reflex), peripheral ischemia, anxiety, headache, dizziness, tremor, and tissue necrosis at the infusion site due to extravasation. Hypertensive crisis can occur with excessive doses.
## Key Drug Interactions
* **MAO Inhibitors and Tricyclic Antidepressants:** May potentiate the pressor effects of norepinephrine, leading to hypertensive crisis. Discontinue MAO inhibitors at least 14 days before administering norepinephrine.
* **Anesthetic Agents:** Some anesthetic agents can sensitize the myocardium to catecholamines, increasing the risk of arrhythmias.
* **Beta-blockers:** Can unmask unopposed alpha-adrenergic receptor stimulation, leading to severe hypertension.
* **Alpha-blockers:** Can antagonize the vasoconstrictive effects.
## Monitoring
* Continuous arterial blood pressure monitoring.
* Heart rate and rhythm.
* Urine output.
* Peripheral perfusion (skin color, temperature, capillary refill).
* Central venous pressure and pulmonary artery pressures if available and indicated.
* Infusion site for signs of extravasation.
## Clinical Pearls
* Always administer via a central venous catheter to minimize the risk of extravasation and tissue necrosis.
* If extravasation occurs, discontinue the infusion immediately and infiltrate the area with phentolamine (an alpha-adrenergic blocker).
* Norepinephrine's short half-life requires continuous infusion for sustained effect.
* Titration should be guided by clinical endpoints (e.g., blood pressure, perfusion) rather than specific dose ranges alone.
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*Please verify current prescribing information and local protocols for definitive guidance.*
