Nor%252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252520epinephrine

# Norepinephrine ## Overview Norepinephrine is a potent vasopressor and inotropic agent. It primarily acts on alpha-1 adrenergic receptors, causing vasoconstriction and increasing systemic vascular resistance. It also has some beta-1 adrenergic effects, increasing heart rate and contractility. ## Primary Indications * Severe hypotension, particularly distributive shock (e.g., septic shock, neurogenic shock). * Cardiogenic shock refractory to other treatments. ## Adult Dosing * **Loading Dose:** Not typically used. * **Maintenance Dose:** Administer via continuous intravenous infusion. * **Initial:** 0.01 to 0.3 mcg/kg/min. * **Titration:** Titrate to achieve and maintain target mean arterial pressure (MAP), often >65 mmHg. Some protocols may target a specific MAP based on patient condition or comorbidities. * **Maximum:** Doses up to 2 mcg/kg/min have been used, but higher doses are associated with increased risk and limited additional benefit. Doses exceeding 1-2 mcg/kg/min warrant careful reevaluation of the patient's condition and potential for alternative or adjunct therapies. ## Pediatric Dosing * **Initial:** 0.05 to 0.1 mcg/kg/min. * **Titration:** Titrate to achieve target MAP based on age (e.g., MAP > gestational age + 2 years in neonates and infants, or MAP > 50 mmHg in older children). * **Maximum:** Higher doses may be required (e.g., up to 1 mcg/kg/min), but use with caution and close monitoring. ## Dose Adjustments * **Renal Impairment:** No specific dose adjustment, but prolonged use or higher doses may be less well tolerated. * **Hepatic Impairment:** No specific dose adjustment. * **Dose adjustments are primarily guided by hemodynamic response and patient tolerance.** ## Contraindications * Known hypersensitivity to norepinephrine. * Use with volatile inhalation anesthetics (e.g., halothane) due to increased risk of arrhythmias. * Use with cyclopropane anesthesia. ## Adverse Effects * **Cardiovascular:** Hypertension, reflex bradycardia, arrhythmias (including ventricular), peripheral ischemia, angina, decreased cardiac output at very high doses. * **Extravasation:** Tissue necrosis, sloughing, and gangrene. If extravasation occurs, stop the infusion, aspirate any residual drug, and infiltrate the area with phentolamine. * **Other:** Headache, anxiety, apprehension, dizziness, nausea, vomiting, sweating, decreased urine output (due to vasoconstriction). ## Key Drug Interactions * **Monoamine Oxidase Inhibitors (MAOIs) and Tricyclic Antidepressants (TCAs):** Potentiate the pressor response and may lead to severe hypertension. Discontinue MAOIs at least 14 days before starting norepinephrine. * **Beta-adrenergic Blockers:** May unmask or potentiate alpha-adrenergic effects, leading to severe hypertension. * **Alpha-adrenergic Blockers:** May reduce the pressor effect. * **Ergot Alkaloids:** May potentiate the vasopressor effects and cause vasoconstriction. * **Anesthetics:** Increased risk of arrhythmias, especially with halogenated anesthetics. ## Monitoring * Continuous ECG monitoring for arrhythmias. * Frequent blood pressure monitoring (invasive arterial line preferred for titratable infusions). * Central venous pressure (CVP) and pulmonary artery pressures (if available). * Urine output. * Peripheral circulation (skin color, temperature, capillary refill). * Mental status. * Lactate levels. ## Clinical Pearls * Norepinephrine is typically prepared by diluting the standard concentrate (e.g., 4 mg/10 mL) to a final concentration of 40 mcg/mL (e.g., 4 mg in 100 mL D5W or NS). * Always administer via a central venous catheter if possible to minimize the risk of peripheral extravasation. If peripheral administration is necessary, use a large, intact vein and monitor the site closely. * Reversal of extravasation is critical; phentolamine is the recommended antidote. * The choice of diluent (D5W vs. NS) may depend on institutional policy and patient-specific factors, though norepinephrine is generally more stable in D5W. * Titrate to effect, aiming for adequate perfusion rather than a specific MAP target alone. **Disclaimer:** This information is intended for clinical pharmacists and healthcare professionals. It is not a substitute for comprehensive drug information resources or professional judgment. Always consult the official prescribing information and institutional guidelines for the most current and complete information before making any treatment decisions. Dosing and administration may vary based on patient-specific factors and local protocols.