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# Norepinephrine
## Overview
Norepinephrine is a potent vasopressor and inotropic agent that acts primarily via alpha-1 adrenergic receptors, causing vasoconstriction, and to a lesser extent via beta-1 adrenergic receptors, increasing heart rate and contractility.
## Primary Indications
* Treatment of severe hypotension unresponsive to fluid resuscitation.
* Shock, including septic shock and cardiogenic shock.
## Adult Dosing
* **Starting Dose:** 0.01 to 0.02 mcg/kg/min IV infusion.
* **Titration:** Increase dose in increments of 0.005 to 0.01 mcg/kg/min every 5-15 minutes to achieve target mean arterial pressure (MAP) of 65 mmHg or higher.
* **Maximum Dose:** Typically 0.1 mcg/kg/min, but higher doses may be used in select cases under close monitoring. The precise maximum dose can vary based on institutional protocol and patient response.
## Pediatric Dosing
* **Starting Dose:** 0.05 to 0.1 mcg/kg/min IV infusion.
* **Titration:** Increase dose in increments of 0.05 to 0.1 mcg/kg/min every 5-15 minutes to achieve target MAP based on age (e.g., 2 mmHg above baseline or age in years + 60 mmHg for infants and children).
* **Maximum Dose:** Typically 1-2 mcg/kg/min, but may be higher in specific situations. Dosing often follows institutional protocols.
## Dose Adjustments
* **Renal Impairment:** No specific dose adjustment is typically recommended, but caution and close monitoring are advised due to potential accumulation.
* **Hepatic Impairment:** No specific dose adjustment is typically recommended, but caution and close monitoring are advised.
## Contraindications
* Hypersensitivity to norepinephrine.
* In patients with profound hypovolemia without adequate fluid replacement.
* Use with volatile inhalation anesthetics or cyclopropane due to potential for severe arrhythmias.
## Adverse Effects
* **Common:** Hypertension, bradycardia (reflex), peripheral ischemia, headache, anxiety, tremor.
* **Serious:** Extravasation leading to tissue necrosis, arrhythmias, acute heart failure, pulmonary edema, rebound hypotension upon withdrawal.
## Key Drug Interactions
* **Monoamine Oxidase Inhibitors (MAOIs):** Potentiates the pressor effect; concurrent use is generally contraindicated. If unavoidable, a significantly reduced dose is required.
* **Tricyclic Antidepressants (TCAs):** May potentiate the pressor effect; concurrent use requires caution and potential dose reduction.
* **Beta-blockers:** Can antagonize the beta-1 effects, potentially leading to unopposed alpha-1 stimulation and severe hypertension.
* **Alpha-blockers:** May antagonize alpha-1 effects, reducing efficacy.
* **Ergot alkaloids, oxytocics:** May cause severe, persistent hypertension.
## Monitoring
* Continuous blood pressure monitoring (arterial line preferred).
* Heart rate and rhythm.
* Central venous pressure (CVP) and/or pulmonary artery pressures if available.
* Urine output.
* Signs of peripheral perfusion (skin temperature, color, capillary refill).
* Infusion site for signs of extravasation.
## Clinical Pearls
* Norepinephrine is typically administered via a central venous catheter to minimize the risk of extravasation and tissue necrosis.
* If extravasation occurs, stop the infusion and administer phentolamine locally to counteract the vasoconstriction.
* Rapid withdrawal can lead to significant hypotension; taper the infusion gradually.
* Consider concurrent use of beta-blockers for excessive tachycardia or arrhythmias.
* Norepinephrine is light-sensitive and solutions should be protected from light.
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*Disclaimer: This information is intended for healthcare professionals and is not a substitute for professional medical advice. Always consult the most current prescribing information and institutional guidelines for the drug you are prescribing.*
