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# Norepinephrine
## Overview
Norepinephrine is a potent alpha-1 adrenergic agonist and a weaker beta-1 adrenergic agonist. It causes peripheral vasoconstriction, increasing systemic vascular resistance and blood pressure. It also has some inotropic and chronotropic effects on the heart.
## Primary Indications
* Management of severe hypotension and shock unresponsive to adequate fluid resuscitation, including septic shock and cardiogenic shock.
## Adult Dosing
* **Initial Infusion:** 0.01 to 0.1 mcg/kg/min.
* **Titration:** Titrate infusion rate upwards to achieve target mean arterial pressure (MAP) of 65 mmHg or higher, or to reverse hypotension.
* **Maximum Dose:** Doses may be increased up to 1 mcg/kg/min or higher based on clinical response and institutional protocols. Higher doses are associated with increased risk of adverse events.
## Pediatric Dosing
* **Initial Infusion:** 0.05 to 0.1 mcg/kg/min.
* **Titration:** Titrate infusion rate upwards to achieve target MAP greater than or equal to the patient's age in years plus 2 mmHg (MAP > [age in years + 2] mmHg), or to reverse hypotension.
* **Maximum Dose:** Doses may be increased up to 2 mcg/kg/min or higher based on clinical response and institutional protocols.
## Dose Adjustments
* No specific dose adjustments are required for hepatic or renal impairment. However, close monitoring is essential as these patients may have altered pharmacokinetics.
## Contraindications
* Hypersensitivity to norepinephrine.
* Hypotension secondary to drug-induced shock (e.g., phenothiazines) unless used as an adjunct to restore blood pressure.
* Use during cyclopropane or halogenated hydrocarbon anesthesia is relative contraindication due to risk of severe arrhythmias.
## Adverse Effects
* **Cardiovascular:** Arrhythmias (including tachycardia, bradycardia, ventricular fibrillation), hypertension, peripheral ischemia, limb necrosis, angina, palpitations.
* **Central Nervous System:** Headache, anxiety, dizziness, tremor.
* **Other:** Dyspnea, extravasation leading to tissue necrosis (antidote: phentolamine).
## Key Drug Interactions
* **Monoamine Oxidase Inhibitors (MAOIs):** Can potentiate the pressor response; avoid concurrent use or use with extreme caution and reduced doses.
* **Tricyclic Antidepressants (TCAs) and Guanadrel/Guanethidine:** May potentiate the pressor effect; use with caution.
* **Alpha and Beta Blockers:** May antagonize or unpredictably alter the effects.
* **Ergot Alkaloids:** May potentiate the pressor effect.
* **Oxytocic Agents:** May cause severe persistent hypertension.
## Monitoring
* **Hemodynamics:** Continuous ECG monitoring for arrhythmias, frequent blood pressure monitoring (arterial line preferred for continuous data), central venous pressure, and pulmonary artery pressures if indicated.
* **Tissue Perfusion:** Monitor peripheral circulation, urine output, and mental status.
* **Infusion Site:** Closely monitor for signs of extravasation.
* **Electrolytes and Acid-Base Balance:** Monitor for potential imbalances.
## Clinical Pearls
* Norepinephrine should be administered via a central venous catheter to minimize the risk of extravasation and tissue necrosis.
* If extravasation occurs, discontinue the infusion immediately and infiltrate the affected area with phentolamine.
* Norepinephrine has a short half-life, allowing for rapid titration but also requiring continuous infusion.
* Consider concurrent use of other vasopressors or inotropes based on the underlying cause of shock and hemodynamic response.
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**Disclaimer:** This information is intended for clinical use and is not a substitute for professional medical advice. Always consult the current prescribing information and relevant guidelines before administering any medication. Dosing can vary significantly based on patient-specific factors and local protocols.
