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# Norepinephrine
## Overview
Norepinephrine is a potent vasopressor and inotropic agent that acts primarily on alpha-adrenergic receptors, causing vasoconstriction, and to a lesser extent on beta-1 adrenergic receptors, increasing heart rate and contractility.
## Primary Indications
* Management of severe hypotension unresponsive to adequate fluid resuscitation.
* Septic shock.
* Cardiogenic shock.
## Adult Dosing
* **Initiation:** Typically started at **2 mcg/min to 10 mcg/min** IV infusion.
* **Titration:** titrated to achieve and maintain target mean arterial pressure (MAP), often **65 mmHg or higher**. Titration increments are usually **0.5 mcg/min to 1 mcg/min** every 5-15 minutes.
* **Maximum Dose:** Doses can range up to **0.5 mcg/kg/min (or higher in some protocols)**, but higher doses are associated with increased adverse effects. Specific maximums often dictated by local protocol or institutional guidelines.
## Pediatric Dosing
* **Initiation:** **0.05 mcg/kg/min to 0.1 mcg/kg/min** IV infusion.
* **Titration:** Titrated to achieve target MAP (e.g., target systolic BP > 70 mmHg + 2x age in years, or specific institutional goals). Titration increments typically **0.05 mcg/kg/min** every 10-15 minutes.
* **Maximum Dose:** **2 mcg/kg/min**. Higher doses may be used in refractory shock, but require close monitoring.
## Dose Adjustments
* **Renal Impairment:** No specific dose adjustment, but patients may have altered responses.
* **Hepatic Impairment:** No specific dose adjustment, but patients may have altered responses.
* **General:** Dosing is primarily driven by hemodynamic response (MAP, heart rate, signs of perfusion).
## Contraindications
* Known hypersensitivity to norepinephrine.
* Hypotension due to absolute or relative hypovolemia (must be corrected with fluid resuscitation first).
* Use with volatile anesthetic agents during general anesthesia.
## Adverse Effects
* **Cardiovascular:** Arrhythmias (especially ventricular), bradycardia (reflex), hypertension, peripheral ischemia, tissue necrosis (extravasation), palpitations, increased myocardial oxygen demand.
* **Respiratory:** Dyspnea.
* **Gastrointestinal:** Nausea, vomiting.
* **Central Nervous System:** Anxiety, headache, dizziness.
* **Metabolic:** Hyperglycemia.
## Key Drug Interactions
* **Monoamine Oxidase Inhibitors (MAOIs):** Potentiates pressor response; avoid concurrent use. If unavoidable, reduce norepinephrine dose significantly.
* **Tricyclic Antidepressants (TCAs) & Atomoxetine:** Can potentiate pressor response; use with caution.
* **Beta-Blockers:** May cause unopposed alpha-stimulation leading to severe hypertension.
* **Ergot Alkaloids:** Potentiates pressor effect.
* **Guanethidine/Reserpine:** Potentiates pressor effect.
* **Oxytocin:** Potential for severe hypertension.
* **Dopamine:** Co-administration may lead to complex hemodynamic effects.
* **Beta-agonists:** Additive effects on heart rate and contractility.
## Monitoring
* **Hemodynamic Parameters:** Continuous arterial blood pressure monitoring (MAP), heart rate, cardiac output (if available).
* **Signs of Perfusion:** Urine output, mental status, skin temperature and color, lactate levels.
* **Infusion Site:** Monitor closely for signs of extravasation (e.g., blanching, coolness, edema).
* **ECG:** For arrhythmias.
* **Electrolytes & Glucose:** Especially in patients with diabetes or receiving long-term infusions.
## Clinical Pearls
* Norepinephrine should be administered via a central venous catheter to minimize the risk of extravasation and tissue necrosis.
* If extravasation occurs, stop the infusion immediately. Local infiltration with phentolamine may be considered.
* Titrate to achieve target MAP, not necessarily a specific dose. Goal is to restore perfusion, not induce hypertension.
* Norepinephrine is a potent vasoconstrictor and can reduce splanchnic and renal blood flow at higher doses. Monitor urine output and signs of end-organ perfusion.
* When discontinuing, taper the infusion gradually to avoid abrupt hypotension.
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**Disclaimer:** This information is intended for educational purposes and does not replace comprehensive drug information resources. Always consult the most current prescribing information and relevant institutional protocols before making clinical decisions.
