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# Norepinephrine
## Overview
Norepinephrine is a potent vasopressor and inotrope that acts primarily on alpha-1 adrenergic receptors, causing vasoconstriction, and to a lesser extent on beta-1 adrenergic receptors, increasing heart rate and contractility. It is used to raise blood pressure in hypotensive states.
## Primary Indications
* Severe hypotension, particularly when unresponsive to fluid resuscitation.
* Septic shock.
* Cardiogenic shock.
## Adult Dosing
* **Initial Infusion:** Typically starts at 0.01 to 0.05 mcg/kg/min.
* **Titration:** Increase dose in increments of 0.01 to 0.05 mcg/kg/min every 5-15 minutes as needed to achieve target mean arterial pressure (MAP), often target MAP $\ge$ 65 mmHg.
* **Maximum Dose:** Doses up to 0.5 mcg/kg/min may be required in some patients. Higher doses are sometimes used but are associated with increased risk.
## Pediatric Dosing
Dosing is highly individualized and often guided by local protocols.
* **Initial Infusion:** Typically 0.05 to 0.1 mcg/kg/min.
* **Titration:** Increase dose in increments of 0.05 to 0.1 mcg/kg/min every 5-15 minutes as needed.
* **Maximum Dose:** May range from 0.2 to 2 mcg/kg/min depending on clinical context and response.
## Dose Adjustments
No specific dose adjustments are typically required for renal or hepatic impairment, as the drug is primarily metabolized in the liver and kidneys. However, prolonged use may necessitate caution in patients with compromised organ function.
## Contraindications
* Hypersensitivity to norepinephrine.
* Severe hypotension with hypoperfusion and metabolic acidosis, particularly if unresponsive to fluid resuscitation (relative contraindication; risk-benefit assessment required).
* Use during inhalation anesthesia is generally avoided due to risk of severe arrhythmias.
## Adverse Effects
* **Cardiovascular:** Arrhythmias (bradycardia, tachycardia, ventricular arrhythmias), hypertension, peripheral ischemia, decreased cardiac output (at higher doses due to increased afterload).
* **Local:** Extravasation leading to tissue necrosis and sloughing.
* **Other:** Headache, anxiety, tremor, dyspnea, reduced blood flow to vital organs (renal, splanchnic).
## Key Drug Interactions
* **MAO Inhibitors & Tricyclic Antidepressants:** Can potentiate pressor effects; discontinue MAOIs at least 14 days prior to norepinephrine administration.
* **Beta-Blockers:** May blunt the beta-1 effects (inotropy) of norepinephrine, potentially leading to unopposed alpha-stimulation and severe hypertension.
* **Alpha-Blockers:** May antagonize the alpha-1 vasoconstrictive effects.
* **Anesthetic Agents:** Can increase myocardial irritability and risk of arrhythmias.
* **Vasodilators:** May require increased doses of norepinephrine to overcome their vasodilatory effects.
## Monitoring
* **Hemodynamics:** Continuous ECG, frequent blood pressure monitoring (intra-arterial preferred for accurate MAP).
* **Perfusion:** Urine output, capillary refill, mental status, lactate levels.
* **Infusion Site:** Regular checks for signs of extravasation.
* **Laboratory:** Serum electrolytes, acid-base status.
## Clinical Pearls
* Norepinephrine is a potent vasoconstrictor and should be administered via a central venous catheter whenever possible to minimize the risk of extravasation and tissue necrosis.
* If extravasation occurs, stop the infusion and infiltrate the area with phentolamine (an alpha-adrenergic blocker).
* Titrate to the lowest effective dose that achieves the hemodynamic target.
* Beware of potential for rebound hypotension upon abrupt discontinuation. Taper slowly.
* Use with caution in patients with peripheral vascular disease, diabetes, or pulmonary hypertension.
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*This information is intended for healthcare professionals. Always consult the most current prescribing information and institutional protocols.*
