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# Norepinephrine
## Overview
Norepinephrine is a vasopressor and inotrope that acts primarily on alpha-1 adrenergic receptors, causing vasoconstriction and an increase in peripheral vascular resistance and blood pressure. It also has some beta-1 adrenergic receptor activity, which can increase heart rate and contractility.
## Primary Indications
* Severe hypotension and shock, particularly in the setting of distributive shock (e.g., septic shock, neurogenic shock).
* Cardiogenic shock (adjunct therapy).
## Adult Dosing
* **Loading Dose:** Not typically used.
* **Infusion:** Start at 0.01 to 0.02 mcg/kg/min. Titrate to achieve target mean arterial pressure (MAP) of 65 mmHg or higher.
* **Maximum Dose:** Generally considered to be 0.1 mcg/kg/min, though higher doses may be used in refractory shock under expert guidance.
## Pediatric Dosing
* **Loading Dose:** Not typically used.
* **Infusion:** Start at 0.05 to 0.1 mcg/kg/min. Titrate to achieve target MAP equal to or greater than the gestational age plus 10 mmHg, or 50 mmHg in older children.
* **Maximum Dose:** Generally considered to be 0.4 mcg/kg/min, though higher doses may be used in refractory shock under expert guidance.
## Dose Adjustments
* No specific dose adjustments are required for renal or hepatic impairment, as the drug is metabolized locally.
## Contraindications
* Hypersensitivity to norepinephrine.
* Use during cyclopropane and halogenated hydrocarbon anesthesia (risk of severe hypertension and arrhythmias).
* Hypotension due to hypovolemia (must be corrected with volume resuscitation first).
## Adverse Effects
* **Cardiovascular:** Arrhythmias, bradycardia (reflex), hypertension, peripheral ischemia, myocardial infarction, palpitations, tachycardia.
* **Central Nervous System:** Anxiety, headache, dizziness, insomnia, tremor.
* **Other:** Extravasation (leading to tissue necrosis), respiratory distress, sweating.
## Key Drug Interactions
* **Anesthetics (volatile):** Increased risk of arrhythmias.
* **Beta-blockers:** May antagonize the effects of norepinephrine on beta-1 receptors, potentially leading to unopposed alpha-1 mediated vasoconstriction and severe hypertension.
* **MAO inhibitors and Tricyclic Antidepressants:** May potentiate the pressor response to norepinephrine. Monitor blood pressure closely.
* **Ergot alkaloids and Oxytocin:** May cause severe, persistent hypertension.
* **Guanethidine and similar adrenergic neuron blocking agents:** May reduce the pressor response to norepinephrine.
## Monitoring
* **Hemodynamics:** Continuous ECG and blood pressure monitoring are essential. Monitor heart rate, MAP, cardiac output (if available), and central venous pressure.
* **Perfusion:** Assess peripheral perfusion, urine output, mental status, and lactate levels.
* **Infusion Site:** Regularly inspect the IV site for signs of extravasation.
## Clinical Pearls
* Norepinephrine is a first-line agent for septic shock.
* Always ensure adequate intravascular volume resuscitation *before* initiating norepinephrine.
* Administer via a central venous catheter to minimize the risk of extravasation and tissue necrosis. If a peripheral line must be used, it should be a large bore catheter in a major vein, and the site must be monitored meticulously.
* If extravasation occurs, stop the infusion and infiltrate the area with phentolamine (an alpha-adrenergic blocker).
* Norepinephrine has a short half-life; effects diminish rapidly after discontinuing infusion. Gradual tapering is generally recommended to avoid rebound hypotension.
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*This information is intended for healthcare professionals. Always consult the most current prescribing information and relevant clinical guidelines for complete details and to ensure patient safety.*
