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# Norepinephrine
## Overview
Norepinephrine is a potent catecholamine with primary alpha-1 adrenergic agonist activity (vasoconstriction) and secondary beta-1 adrenergic agonist activity (inotropic effect). It is the first-line vasopressor for septic shock.
## Primary Indications
* Acute hypotensive states (e.g., septic shock, cardiogenic shock).
* Hemodynamic support during cardiac arrest (though epinephrine remains the standard).
## Adult Dosing
* **Initial Infusion:** 0.01 to 0.05 mcg/kg/min.
* **Titration:** Titrate to achieve target mean arterial pressure (MAP), typically ≥65 mmHg.
* **Maintenance:** Usual range 0.05 to 0.5 mcg/kg/min; refractory shock may require doses >1 mcg/kg/min.
* **Maximum:** No strict maximum dosage exists; it is limited by clinical response and end-organ perfusion.
## Pediatric Dosing
* **Infusion:** 0.05 to 0.1 mcg/kg/min initial dose.
* **Titration:** Titrate by 0.05 mcg/kg/min increments to achieve goal tissue perfusion.
* **Maximum:** Typically 2 mcg/kg/min.
## Dose Adjustments
* **Hepatic/Renal Impairment:** No standard dosage adjustments provided by manufacturer; use clinical judgment as catecholamine clearance may be altered.
* **Local Protocol:** Always consult institutional guidelines for specific titration intervals and concentration standards (e.g., 4mg/250mL 5% Dextrose vs. 8mg/250mL).
## Contraindications
* Hypersensitivity to norepinephrine or bisulfites.
* Hypotension due to uncorrected blood volume depletion (must correct hypovolemia first).
## Adverse Effects
* **Cardiovascular:** Hypertension, arrhythmias, bradycardia (reflex), peripheral ischemia.
* **Local:** Extravasation can lead to skin necrosis and sloughing.
* **Metabolic:** Hyperglycemia (beta-2 effects secondary to dose-dependent activation).
## Key Drug Interactions
* **MAO Inhibitors / TCAs:** May significantly potentiate pressor response; risk of severe, prolonged hypertension.
* **Non-selective Beta-blockers:** May lead to unopposed alpha-adrenergic vasoconstriction and severe hypertension.
* **Alpha-blockers:** May antagonize the vasopressor effects.
## Monitoring
* **Hemodynamics:** Continuous invasive arterial blood pressure monitoring is strongly recommended.
* **Perfusion:** Monitor heart rate, urine output, skin color/temperature, and serum lactate levels.
* **Access site:** Monitor peripheral IV sites closely for signs of extravasation.
## Clinical Pearls
* **Extravasation Management:** If extravasation occurs, discontinue infusion and infiltrate the area with **phentolamine mesylate** (5–10 mg in 10 mL saline) locally.
* **Drug Compatibility:** Highly sensitive to pH; avoid mixing with alkaline solutions (e.g., sodium bicarbonate).
* **Transition:** Always taper slowly; abrupt cessation can cause profound rebound hypotension.
* **Central Access:** Strongly preferred to use a large-bore central venous catheter to mitigate the risk of severe tissue necrosis.
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*Disclaimer: This information is for educational purposes only. Clinical practice guidelines and institutional protocols may vary significantly. Always verify current prescribing information, compatibility, and safety standards through official pharmacy references or institutional clinical decision support systems before administration.*
