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# Norepinephrine
## Overview
Norepinephrine is a potent alpha-1 adrenergic agonist and a weaker beta-1 adrenergic agonist. It causes peripheral vasoconstriction, leading to increased systemic vascular resistance and blood pressure. It also has some positive inotropic and chronotropic effects on the heart.
## Primary Indications
* Severe Hypotension: Primarily in shock states such as septic shock, neurogenic shock, and cardiogenic shock unresponsive to fluid resuscitation.
* Restoration and maintenance of blood pressure.
## Adult Dosing
* **Intravenous Infusion:** Typically initiated at **2 to 4 mcg/minute**.
* **Titration:** Infusion rate should be titrated to achieve the target mean arterial pressure (MAP), usually **≥ 65 mmHg**.
* **Maximum Dose:** Doses can be increased up to **0.5 to 1 mcg/kg/minute** in refractory cases, but higher doses are associated with increased adverse effects. Local protocols often guide maximum titration.
## Pediatric Dosing
* **Intravenous Infusion:** Typically initiated at **0.05 to 0.1 mcg/kg/minute**.
* **Titration:** Titrated to achieve target MAP or specific end-organ perfusion goals.
* **Maximum Dose:** Doses can be increased up to **1 to 2 mcg/kg/minute** based on response and clinical judgment. Local protocols are essential.
## Dose Adjustments
* **Hepatic Impairment:** No specific dose adjustments are routinely recommended, but caution and close monitoring are advised due to potential altered metabolism and increased sensitivity.
* **Renal Impairment:** No specific dose adjustments are routinely recommended, but caution and close monitoring are advised.
## Contraindications
* Hypersensitivity to norepinephrine.
* Hypotension due to conditions where alpha-adrenergic blockade is counterproductive (e.g., sulfite hypersensitivity with concurrent sulfite-containing products, severe uncorrected hypovolemia, distributive shock not adequately resuscitated with fluids).
## Adverse Effects
* **Cardiovascular:** Arrhythmias (tachycardia, bradycardia), hypertension, peripheral ischemia, decreased cardiac output, chest pain, palpitations.
* **Local:** Extravasation leading to severe tissue necrosis, sloughing, and gangrene.
* **Other:** Headache, anxiety, tremors, dyspnea, sweating, nausea.
## Key Drug Interactions
* **MAO Inhibitors & TCAs:** Potentiate hypertensive crisis. Discontinue MAOIs 2 weeks prior to norepinephrine.
* **Beta-Blockers:** Can potentially lead to unopposed alpha-agonism, causing severe hypertension.
* **Alpha-Blockers:** May reduce the pressor effect of norepinephrine.
* **Oxytocic Agents:** May cause severe persistent hypertension.
* **Ergot Alkaloids:** May cause potentiation of vasoconstrictive and hypertensive effects.
## Monitoring
* **Hemodynamics:** Continuous arterial blood pressure monitoring is essential. Heart rate, cardiac rhythm, and cardiac output (if available) should be monitored.
* **Perfusion:** Urine output, capillary refill, skin temperature, mental status.
* **Infusion Site:** Frequent checks for signs of extravasation.
* **Electrolytes & Acid-Base Status:** Especially in critically ill patients.
## Clinical Pearls
* Always administer via a central venous line to minimize the risk of extravasation and tissue necrosis.
* Have phentolamine or another alpha-adrenergic blocker readily available for local treatment of extravasation.
* Ensure adequate volume resuscitation before initiating or significantly increasing norepinephrine, as it is less effective in hypovolemic states.
* Monitor for signs of peripheral ischemia, especially with prolonged infusions or high doses.
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*This information is intended for clinical pharmacists and prescribers. Always consult the most current prescribing information and local institutional protocols for definitive guidance.*
