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# Norepinephrine
## Overview
Norepinephrine is a sympathomimetic amine that acts as a potent alpha-adrenergic agonist, causing vasoconstriction, and a weaker beta-adrenergic agonist, causing increased heart rate and contractility. It is primarily used to increase blood pressure in hypotensive states.
## Primary Indications
* Severe Hypotension: Primarily in shock (e.g., septic shock, cardiogenic shock) to restore and maintain adequate blood pressure.
## Adult Dosing
* **Initial Bolus:** Not typically given as a bolus.
* **Continuous Infusion:**
* **Starting Dose:** 0.01 to 0.02 mcg/kg/minute.
* **Titration:** Titrate up to achieve the desired systolic blood pressure (often target SBP of 90-100 mmHg or Mean Arterial Pressure (MAP) of 65-75 mmHg) or adequate tissue perfusion. Doses can be increased every 5-15 minutes.
* **Maximum Dose:** Typically up to 0.1 mcg/kg/minute, but higher doses (up to 1 mcg/kg/minute or more) may be used in refractory hypotension under expert guidance.
## Pediatric Dosing
* **Continuous Infusion:**
* **Starting Dose:** 0.05 to 0.1 mcg/kg/minute.
* **Titration:** Titrate to achieve target SBP or adequate end-organ perfusion. Doses can be increased every 5-15 minutes.
* **Maximum Dose:** Typically up to 1 mcg/kg/minute. Doses higher than 1 mcg/kg/minute may be used in refractory shock under close monitoring.
## Dose Adjustments
* **Renal Impairment:** No specific dose adjustment. Use with caution and monitor closely.
* **Hepatic Impairment:** No specific dose adjustment. Use with caution and monitor closely.
## Contraindications
* Hypersensitivity to norepinephrine.
* Hypotension due to pure vasodilatory states (e.g., hypovolemia) without adequate volume resuscitation.
* Use during cyclopropane or halogenated hydrocarbon anesthesia (risk of severe arrhythmias).
## Adverse Effects
* **Cardiovascular:** Hypertensive crisis, reflex bradycardia, arrhythmias (tachycardia, bradycardia, ventricular extrasystoles), peripheral ischemia, necrosis at infusion site (extravasation), reduced blood flow to vital organs (e.g., kidneys, gut) at high doses.
* **Other:** Headache, anxiety, dizziness, dyspnea, nausea, vomiting.
## Key Drug Interactions
* **MAO Inhibitors & Tricyclic Antidepressants (TCAs):** Potentiate the pressor effects of norepinephrine, leading to hypertensive crisis. Discontinue MAOIs at least 14 days prior to norepinephrine initiation.
* **Anesthetics (e.g., halothane, enflurane):** Increased risk of arrhythmias.
* **Beta-blockers:** May blunt the desired beta-1 effects, leaving unopposed alpha-stimulation leading to severe peripheral vasoconstriction and hypertension.
* **Alpha-blockers:** May antagonize the pressor effects.
* **Oxytocics:** May cause severe hypertension.
* **Ergot alkaloids, Guanethidine, Methyl-dopa:** Potentiate pressor effects.
## Monitoring
* **Hemodynamics:** Continuous ECG, arterial blood pressure (invasive preferred for titration), central venous pressure, heart rate, cardiac output (if available).
* **Perfusion Status:** Urine output, mental status, skin temperature and color, lactate levels.
* **Infusion Site:** For signs of extravasation (pallor, blanching, edema, pain), especially if peripheral IV.
## Clinical Pearls
* Norepinephrine is a potent vasoconstrictor and should be administered via a central venous catheter to minimize the risk of extravasation and tissue necrosis.
* If extravasation occurs, stop the infusion and infiltrate the area with phentolamine (an alpha-adrenergic blocker).
* Titrate to a hemodynamic endpoint (e.g., MAP, SBP, urine output) rather than a fixed dose.
* Ensure adequate volume resuscitation is achieved before or concurrently with norepinephrine initiation, as it is not a substitute for fluid therapy.
* Consider the underlying cause of hypotension.
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*This information is intended for healthcare professionals. Always consult the current prescribing information and institutional protocols for complete details and guidance.*
