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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 * Severe hypotension and shock (e.g., septic shock, cardiogenic shock) unresponsive to adequate fluid resuscitation. * To restore and maintain blood pressure. ## Adult Dosing * **Initial Dose:** 2 to 10 mcg/minute IV. * **Titration:** Increase dose by 2 to 4 mcg/minute every 5 to 15 minutes as needed to achieve target blood pressure. * **Maintenance Dose:** Typically 2 to 15 mcg/minute IV, but can range from 0.1 to 3 mcg/kg/minute in severe cases. * **Maximum Dose:** No strict maximum dose, but doses above 0.5 mcg/kg/minute are associated with increased adverse effects. Dosing is often guided by response and local protocol. ## Pediatric Dosing * **Initial Dose:** 0.05 to 0.1 mcg/kg/minute IV infusion. * **Titration:** Increase dose by 0.05 to 0.2 mcg/kg/minute every 5 to 10 minutes as needed to achieve target blood pressure. * **Maintenance Dose:** 0.1 to 2 mcg/kg/minute IV infusion. * **Maximum Dose:** Typically 2 mcg/kg/minute IV infusion, though higher doses may be used under expert guidance. Dosing is highly individualized and dependent on clinical response and local protocols. ## Dose Adjustments * No dose adjustment is typically required for hepatic or renal impairment, as norepinephrine is metabolized in the liver and kidneys and has a short half-life. However, prolonged infusions may necessitate closer monitoring for accumulation or toxicity. ## Contraindications * Hypersensitivity to norepinephrine. * Concurrent use with volatile inhalation anesthetics (risk of arrhythmias). * Known history of severe sulfite sensitivity (if using injectable formulation containing sodium bisulfite). ## Adverse Effects * **Cardiovascular:** Hypertension, reflex bradycardia, arrhythmias, peripheral ischemia, digital ischemia, gangrene, myocardial infarction, palpitations. * **Central Nervous System:** Headache, anxiety, dizziness, tremor, confusion, cerebral hemorrhage. * **Respiratory:** Dyspnea. * **Other:** Extravasation leading to tissue necrosis, decreased blood flow to vital organs (e.g., kidneys, gut). ## Key Drug Interactions * **Monoamine Oxidase Inhibitors (MAOIs) & Tricyclic Antidepressants (TCAs):** Potentiate hypertensive effects. Separate administration by at least 14 days. * **Alpha-adrenergic Blockers (e.g., prazosin, terazosin):** May antagonize the pressor effects. * **Beta-adrenergic Blockers (e.g., propranolol, metoprolol):** May unmask unopposed alpha-receptor stimulation, leading to severe hypertension. * **Ergot Alkaloids:** Potentiate vasoconstrictive effects. * **Oxytocics (e.g., oxytocin):** May cause severe hypertension. * **General Anesthetics:** Increased risk of arrhythmias and hypertension. ## Monitoring * **Hemodynamics:** Continuous blood pressure monitoring (arterial line preferred), heart rate, cardiac rhythm. * **Urine Output:** Assess renal perfusion. * **Peripheral Circulation:** Monitor for signs of ischemia in extremities. * **Infusion Site:** Inspect regularly for signs of extravasation. * **Mental Status:** Assess for central nervous system effects. * **Acid-Base Status and Lactate:** To assess tissue perfusion. ## Clinical Pearls * Norepinephrine is a potent vasoconstrictor and should be administered via a central venous catheter whenever possible to minimize the risk of extravasation and tissue necrosis. * If extravasation occurs, discontinue the infusion immediately and administer phentolamine (an alpha-adrenergic blocker) subcutaneously to the affected area. * Titrate the infusion to the lowest effective dose that maintains adequate mean arterial pressure (MAP), typically > 65 mmHg, or higher depending on patient factors and local protocol. * Watch for reflex bradycardia, which can be managed by adjusting the norepinephrine dose or using atropine if necessary. * Norepinephrine can cause decreased blood flow to peripheral organs, so careful monitoring is essential. *** *Please verify this information with the most current prescribing information and relevant clinical guidelines.*