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# Norepinephrine (Levophed) ## Overview Norepinephrine is a vasopressor and inotropic agent that acts primarily on alpha-1 adrenergic receptors, causing vasoconstriction and increasing blood pressure. It also has some beta-1 adrenergic activity, leading to increased heart rate and contractility. ## Primary Indications * Treatment of severe hypotension and shock, particularly septic shock and cardiogenic shock. * Restoration and maintenance of adequate blood pressure when other means are insufficient. ## Adult Dosing * **Initial Rate:** Typically initiated at **2 mcg/min to 4 mcg/min**. * **Titration:** Increase infusion rate by **2 mcg/min to 4 mcg/min increments** every 5 to 15 minutes as needed to achieve target blood pressure (often a systolic BP of 90-100 mmHg or Mean Arterial Pressure (MAP) of 65-75 mmHg, depending on protocol). * **Maximum Rate:** Doses up to **0.5 mcg/kg/min** have been used, but higher doses are associated with increased risk of adverse effects. Most protocols aim for lower effective doses. ## Pediatric Dosing * **Initial Rate:** **0.05 mcg/kg/min to 0.1 mcg/kg/min**. * **Titration:** Increase by **0.05 mcg/kg/min to 0.1 mcg/kg/min increments** every 10 to 15 minutes as needed. * **Maximum Rate:** Up to **1 mcg/kg/min** may be required, but higher doses should be used with extreme caution. Dosing is highly individualized and dependent on patient response and clinical guidelines. ## Dose Adjustments * **Renal Impairment:** No specific dose adjustment is recommended, but caution is advised due to potential accumulation and increased pressor effect. * **Hepatic Impairment:** No specific dose adjustment is recommended, but caution is advised. ## Contraindications * Hypersensitivity to norepinephrine. * Use as the sole agent to maintain blood pressure in patients with profound volume deficits (correct volume deficits first). * Use in patients with mesenteric or peripheral vascular thrombosis (risk of increasing ischemia). ## Adverse Effects * **Cardiovascular:** Hypertension, reflex bradycardia, arrhythmias (tachycardia, bradycardia, ventricular), peripheral ischemia, skin necrosis at infusion site (extravasation), gangrene, decreased cardiac output (at higher doses). * **Central Nervous System:** Headache, anxiety, confusion, tremor. * **Respiratory:** Dyspnea. * **Other:** Nausea, vomiting. ## Key Drug Interactions * **Monoamine Oxidase Inhibitors (MAOIs) and Tricyclic Antidepressants (TCAs):** Potentiate the pressor effect of norepinephrine; use is generally contraindicated or requires extreme caution and dose reduction. * **Alpha-adrenergic Blockers:** May reduce the pressor effect. * **Beta-adrenergic Blockers:** May antagonize the beta-1 effects of norepinephrine. * **Anesthetics:** Halogenated anesthetics may increase myocardial irritability and potentiate the pressor effect. * **Ergot Alkaloids:** May potentiate the pressor effect. * **Guanethidine:** May prolong and intensify the pressor response. * **Oxytocics:** May cause severe hypertension. ## Monitoring * Continuous blood pressure monitoring (arterial line preferred). * Heart rate and rhythm. * Urine output. * Peripheral perfusion (skin color, temperature, capillary refill). * Central venous pressure (CVP) or pulmonary artery catheter (PAC) measurements if indicated. * Infusion site for signs of extravasation. ## Clinical Pearls * Norepinephrine is a potent vasoconstrictor. The primary goal is to restore adequate organ perfusion. * Always correct hypovolemia before or concurrently with initiating norepinephrine. * Infuse norepinephrine into a large central vein to minimize the risk of extravasation and tissue necrosis. If peripheral infusion is necessary, monitor the site extremely closely and consider diluents with heparin. * Phentolamine is the antidote for extravasation; it should be injected subcutaneously into the blanched area. * Dosing and titration targets should be guided by institutional protocols and patient-specific hemodynamic goals. *** *Disclaimer: This information is intended for clinical decision-making and should not replace independent judgment. Always consult the most current prescribing information and institutional guidelines before administering any medication.*