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# Norepinephrine
## Overview
Norepinephrine is a potent vasopressor and inotrope that acts primarily on alpha-1 adrenergic receptors, causing peripheral vasoconstriction, and to a lesser extent on beta-1 adrenergic receptors, increasing heart rate and contractility.
## Primary Indications
* Severe hypotension or shock unresponsive to adequate fluid resuscitation.
* Cardiogenic shock.
* Septic shock.
## Adult Dosing
* **Initial Dose:** 0.01 to 0.02 mcg/kg/min IV infusion.
* **Titration:** Titrate infusion rate to achieve target mean arterial pressure (MAP) of 65 mmHg or higher. Doses can be increased up to 0.1 mcg/kg/min, and in refractory cases, may be increased to 0.2 mcg/kg/min or higher.
* **Maximum Dose:** Doses higher than 0.1 mcg/kg/min are associated with increased risk of adverse effects and should be used with extreme caution. Some protocols may allow for higher doses in specific refractory shock states.
## Pediatric Dosing
* **Initial Dose:** 0.05 to 0.1 mcg/kg/min IV infusion.
* **Titration:** Titrate infusion rate to achieve target MAP greater than or equal to gestational age in weeks plus 5 mmHg for neonates, or target systolic blood pressure of 50-70 mmHg in infants and children. Doses can be increased up to 1 mcg/kg/min.
* **Maximum Dose:** 1 mcg/kg/min IV infusion. Higher doses may be used in rare, refractory cases under expert guidance.
## Dose Adjustments
* **Renal Impairment:** No specific dose adjustment is generally recommended, but caution is advised due to potential accumulation and prolonged effects.
* **Hepatic Impairment:** No specific dose adjustment is generally recommended.
## Contraindications
* Hypersensitivity to norepinephrine.
* Hypotension due to pure distributive vasodilation (e.g., septic shock) should be treated with adequate fluid resuscitation and vasopressors *after* fluid challenge. Norepinephrine is generally initiated once adequate fluid resuscitation has been achieved.
* Caution in patients with severe peripheral vascular disease.
## Adverse Effects
* **Cardiovascular:** Hypertension, bradycardia (reflex), arrhythmias, myocardial ischemia, peripheral ischemia, gangrene.
* **Extravasation:** Can cause severe tissue necrosis and sloughing.
* **Other:** Headache, anxiety, tremor, dizziness.
## Key Drug Interactions
* **MAO Inhibitors and Tricyclic Antidepressants:** Potentiate hypertensive effects. Discontinue MAO inhibitors at least 14 days prior to norepinephrine initiation.
* **Beta-blockers:** May unopposed alpha-agonist effects, leading to severe hypertension.
* **Anesthetics:** May increase myocardial irritability and risk of arrhythmias.
* **Ergot alkaloids and Oxytocics:** Can cause severe, persistent hypertension and peripheral ischemia.
## Monitoring
* Continuous blood pressure monitoring (arterial line preferred).
* Heart rate and rhythm.
* Urine output.
* Peripheral perfusion (skin temperature, color, capillary refill).
* Central venous pressure (CVP) or other measures of fluid status.
* Electrolytes.
* Mental status.
## Clinical Pearls
* Administer via a central venous catheter to minimize risk of extravasation.
* If extravasation occurs, stop the infusion immediately and infiltrate the affected area with phentolamine.
* Norepinephrine is light-sensitive; protect infusion bags and tubing from light.
* Taper infusion gradually to avoid abrupt drops in blood pressure.
* In septic shock, norepinephrine is typically the first-line vasopressor after adequate fluid resuscitation has been achieved.
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**Disclaimer:** This information is intended for healthcare professionals and is not a substitute for professional medical advice. Always consult the most current prescribing information and relevant clinical guidelines before making any treatment decisions.
