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# Norepinephrine
## Overview
Norepinephrine is a potent alpha-1 adrenergic agonist and a less potent beta-1 adrenergic agonist. It causes peripheral vasoconstriction, increasing systemic vascular resistance and blood pressure. It also has a mild positive inotropic effect.
## Primary Indications
* Treatment of severe hypotension and shock unresponsive to adequate fluid resuscitation.
* Used to increase blood pressure in patients with septic shock and other distributive shock states.
## Adult Dosing
* **Initial dose:** 0.01 to 0.02 mcg/kg/min IV infusion.
* **Titration:** Increase dose by 0.01 to 0.02 mcg/kg/min every 5 to 15 minutes as needed to achieve target mean arterial pressure (MAP) of 65 mmHg or higher.
* **Maximum dose:** Typically 0.3 mcg/kg/min IV infusion. Higher doses may be used in select cases under close monitoring, but efficacy and safety are less established.
* **Note:** Dosing is highly individualized and dependent on patient response and local protocols.
## Pediatric Dosing
* **Initial dose:** 0.05 to 0.1 mcg/kg/min IV infusion.
* **Titration:** Increase dose by 0.05 to 0.1 mcg/kg/min every 5 to 15 minutes as needed.
* **Maximum dose:** 1 to 2 mcg/kg/min IV infusion.
* **Note:** Pediatric dosing is complex and should follow established guidelines and local protocols.
## Dose Adjustments
* **No specific dose adjustments are typically required for hepatic or renal impairment.** However, extreme caution and close monitoring are necessary as these patients may have altered responses.
## Contraindications
* Hypersensitivity to norepinephrine.
* Use during general anesthesia with cyclopropane or halothane, due to risk of severe hypertension and arrhythmias.
* Hypotension due to drug overdose (e.g., phenothiazines).
## Adverse Effects
* **Cardiovascular:** Hypertensive crisis, reflex bradycardia, arrhythmias, peripheral ischemia, tissue necrosis (especially with extravasation), angina.
* **Central Nervous System:** Headache, anxiety, tremor, dizziness.
* **Respiratory:** Dyspnea.
* **Other:** Pale skin, sweating.
## Key Drug Interactions
* **Monoamine Oxidase Inhibitors (MAOIs) & Tricyclic Antidepressants (TCAs):** Potentiate pressor effects, leading to severe hypertension. Concurrent use is generally contraindicated; if necessary, reduce norepinephrine dose significantly and monitor closely.
* **Beta-adrenergic Blockers:** May cause unopposed alpha-adrenergic stimulation, leading to severe hypertension.
* **Alpha-adrenergic Blockers:** May reduce pressor effects.
* **Ergot Alkaloids:** May potentiate vasoconstrictive effects.
* **Guanethidine, Guanadrel:** May potentiate pressor effects.
## Monitoring
* **Hemodynamics:** Continuous arterial blood pressure monitoring is essential. Monitor heart rate, cardiac rhythm, and central venous pressure (CVP) or pulmonary artery catheter (PAC) data if available.
* **Urine Output:** Monitor for adequate renal perfusion.
* **Extremities:** Assess for signs of peripheral ischemia (e.g., coldness, cyanosis).
* **Infusion Site:** Monitor closely for signs of extravasation.
## Clinical Pearls
* Norepinephrine is typically administered via a central venous catheter to minimize risk of extravasation.
* If extravasation occurs, discontinue infusion immediately and infiltrate the affected area with phentolamine.
* Titrate to the lowest effective dose to achieve target MAP and minimize adverse effects.
* Consider the underlying cause of hypotension and address it concurrently with norepinephrine infusion.
* Norepinephrine has a short half-life, so continuous infusion is required.
***
**Disclaimer:** This information is intended for healthcare professionals. Always consult the official prescribing information and relevant clinical guidelines for the most current and complete drug information, including contraindications, warnings, precautions, and adverse reactions, before prescribing or administering any medication. Dosing can vary significantly based on patient-specific factors and institutional protocols.
