Nor%252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252520epinephrine

# Norepinephrine ## Overview Norepinephrine is a potent sympathomimetic amine that acts as a neurotransmitter and hormone. It primarily causes vasoconstriction through alpha-1 adrenergic receptor stimulation, increasing peripheral vascular resistance and blood pressure. It also has some beta-1 adrenergic effects, increasing heart rate and contractility, though these are less pronounced than its alpha-1 effects. ## Primary Indications * Treatment of severe hypotension and shock, particularly distributive shock (e.g., septic shock, neurogenic shock). * Adjunct in cardiopulmonary arrest resuscitation. ## Adult Dosing * **Hypotension/Shock:** Typically initiated as a continuous intravenous infusion. * Starting dose: 0.01 to 0.02 mcg/kg/min. * Titration: Increase dose gradually in increments of 0.01 to 0.02 mcg/kg/min every 5-10 minutes to achieve desired blood pressure (e.g., mean arterial pressure [MAP] of 65 mmHg or higher). * Maximum dose: Generally not to exceed 0.2 to 1 mcg/kg/min, though higher doses may be used under extreme circumstances and close monitoring. Specific maximums depend on local protocols and patient response. * **Cardiopulmonary Arrest:** Not a first-line agent, but may be considered in specific refractory shock states during resuscitation. Dosing and use are guided by advanced cardiac life support (ACLS) protocols and local resuscitation guidelines. ## Pediatric Dosing * **Hypotension/Shock:** * Starting dose: 0.05 to 0.1 mcg/kg/min. * Titration: Increase dose as needed to achieve target MAP (e.g., greater than gestational age + 2 years = 50 mmHg; greater than 10 years = 70 mmHg). * Maximum dose: Doses up to 1 mcg/kg/min have been reported. Precise dosing and maximums are often guided by institutional protocols and expert consensus. * **Cardiopulmonary Arrest:** Dosing and use are guided by pediatric advanced life support (PALS) protocols and local resuscitation guidelines. ## Dose Adjustments No dose adjustments are typically required for hepatic or renal impairment, as norepinephrine is rapidly metabolized and cleared. However, severe dysfunction may necessitate closer monitoring of response and potential for accumulation. ## Contraindications * Hypersensitivity to norepinephrine. * Hypotensive patients with mechanical obstruction of cardiac output (e.g., aortic stenosis, pulmonary embolism). * During general anesthesia with cyclopropane or halothane (risk of severe hypertension and arrhythmias). ## Adverse Effects Common adverse effects include: * Hypertension * Bradycardia (reflex) * Peripheral ischemia and tissue necrosis (especially with extravasation) * Arrhythmias (tachycardia, palpitations) * Headache * Anxiety, nervousness * Extremity pain * Reduced blood flow to splanchnic, renal, and muscular organs. ## Key Drug Interactions * **Monoamine Oxidase Inhibitors (MAOIs):** Can potentiate pressor response, leading to hypertensive crisis. Use with extreme caution or avoid. * **Tricyclic Antidepressants (TCAs):** May potentiate the pressor response. * **Beta-adrenergic Blockers:** May blunt beta-1 effects (positive inotropy/chronotropy) while unopposed alpha-1 stimulation can lead to severe hypertension. * **Alpha-adrenergic Blockers:** May decrease pressor effect. * **Ergot Alkaloids, Oxytocin:** Can cause severe hypertension. * **Anesthetics (e.g., Halothane, Cyclopropane):** Increased risk of arrhythmias. ## Monitoring * **Hemodynamics:** Continuous electrocardiogram (ECG), blood pressure (arterial line preferred), central venous pressure (CVP), pulmonary artery pressures (if available). * **Infusion Site:** Closely monitor for signs of extravasation (pallor, coolness, pain) and implement immediate management (e.g., phentolamine). * **Urine Output:** Monitor for adequate renal perfusion. * **Lactate Levels:** Assess tissue perfusion. * **Cardiac Output:** If available. ## Clinical Pearls * Norepinephrine is a potent vasoconstrictor and should be administered via a central venous catheter to minimize risk of extravasation and tissue necrosis. * An extravasation should be treated immediately with local infiltration of phentolamine. * Titrate to the lowest effective dose to achieve target hemodynamic goals. * Norepinephrine is often a vasopressor of choice in septic shock due to its balanced alpha and beta effects and relative ease of titration. * The concentration of the prepared infusion should be standardized across the institution to reduce the risk of medication errors. **Disclaimer:** This information is intended for healthcare professionals and does not replace a thorough review of the full prescribing information or institutional protocols. Always verify current drug information and dosing guidelines with official sources before prescribing or administering any medication.