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# Norepinephrine
## Overview
Norepinephrine is a potent alpha-1 adrenergic agonist and a weaker beta-1 adrenergic agonist. It primarily causes vasoconstriction, leading to increased systemic vascular resistance and blood pressure.
## Primary Indications
* Severe hypotension and shock (e.g., septic shock, neurogenic shock) unresponsive to fluid resuscitation.
## Adult Dosing
* **Intravenous infusion:** Typically initiated at 0.01 to 0.05 mcg/kg/min.
* **Titration:** Gradually increased based on hemodynamic response (mean arterial pressure [MAP] goals, usually target >65 mmHg).
* **Maximum dose:** Often cited as 0.1 to 1 mcg/kg/min, but doses up to 2 mcg/kg/min or higher may be used in refractory shock under close monitoring. Exact maximum dose may vary by local protocol.
## Pediatric Dosing
* **Intravenous infusion:** Typically initiated at 0.05 to 0.1 mcg/kg/min.
* **Titration:** Gradually increased based on hemodynamic response.
* **Maximum dose:** Commonly up to 1 mcg/kg/min, but doses up to 2 mcg/kg/min may be used. Specific dosing and titration parameters are often guided by institutional protocols.
## Dose Adjustments
* No specific dose adjustments are typically required for renal or hepatic impairment due to its parenteral route and metabolism. Dosing is primarily driven by patient response.
## Contraindications
* Hypersensitivity to norepinephrine.
* Hypotensive patients with mechanical obstruction to cardiac outflow (e.g., severe aortic stenosis).
* Usually avoided in patients with mesenteric or peripheral vascular thrombosis due to risk of exacerbation.
## Adverse Effects
* **Cardiovascular:** Hypertension, bradycardia (reflex), arrhythmias, peripheral ischemia, extravasation leading to tissue necrosis.
* **Other:** Anxiety, headache, dizziness, tremor.
## Key Drug Interactions
* **MAO inhibitors and tricyclic antidepressants:** May potentiate the pressor effects of norepinephrine; concurrent use requires extreme caution and may necessitate dose reduction of norepinephrine.
* **Beta-blockers:** May unopposed alpha-agonism, leading to severe hypertension.
* **General anesthetics:** May increase myocardial irritability and risk of arrhythmias.
## Monitoring
* Continuous hemodynamic monitoring: blood pressure (arterial line preferred), heart rate.
* Central venous pressure, pulmonary artery pressures, cardiac output (if available).
* Urine output.
* Signs of peripheral perfusion (e.g., skin color, temperature, capillary refill).
* Infusion site for signs of extravasation.
## Clinical Pearls
* Administer via a central venous catheter to minimize risk of peripheral vasoconstriction and extravasation.
* If extravasation occurs, discontinue infusion immediately and infiltrate the area with phentolamine.
* Titrate to achieve target MAP, not just to normalize blood pressure, considering individual patient's autoregulation.
* Sudden discontinuation can lead to abrupt hypotension; gradual tapering is recommended if possible.
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**Disclaimer:** This information is intended for healthcare professionals. Always consult the most current prescribing information and institutional protocols before administering any medication.
