Please check your internet connection and try again.
# Norepinephrine
## Overview
Norepinephrine is a potent alpha-adrenergic agonist with some beta-adrenergic activity. It acts primarily as a vasoconstrictor, increasing peripheral vascular resistance and thus blood pressure. It also has a mild positive inotropic effect on the heart.
## Primary Indications
* Treatment of hypotension and shock (e.g., septic shock, cardiogenic shock, distributive shock).
* Restoration of blood pressure in patients with severe hypotension and shock.
## Adult Dosing
* **Initial dose:** Typically 2 to 10 mcg/minute via continuous intravenous infusion.
* **Titration:** Titrate dose to achieve target mean arterial pressure (MAP) of 65 mmHg or higher. Doses can be increased up to 30 mcg/minute or higher in refractory cases, depending on patient response and local protocol.
* **Dilution:** Usually diluted to a concentration of 40 mcg/mL (e.g., 4 mg in 100 mL of D5W or NS).
## Pediatric Dosing
* **Initial dose:** 0.05 to 0.1 mcg/kg/minute via continuous intravenous infusion.
* **Titration:** Titrate dose to achieve target MAP based on age (e.g., MAP > gestational age + 2 in neonates, or MAP > 50 mmHg in older children). Doses can be increased up to 1 mcg/kg/minute or higher, depending on patient response and local protocol.
* **Dilution:** Common concentrations include 20 mcg/mL (e.g., 1 mg in 50 mL) or 40 mcg/mL (e.g., 2 mg in 50 mL).
## Dose Adjustments
* No specific dose adjustments are routinely required for hepatic or renal impairment, as norepinephrine is metabolized in the liver and excreted by the kidneys, but its rapid action and IV administration typically bypass the need for dose reduction in these populations unless severe dysfunction significantly impacts drug clearance. Close monitoring of response is crucial.
## Contraindications
* Hypersensitivity to norepinephrine.
* Hypotensive anesthesia, especially with the use of cyclopropane or halothane (due to risk of severe hypertension and arrhythmias).
* Should not be used during inhalation anesthesia unless it is the only alternative.
## Adverse Effects
* **Cardiovascular:** Hypertension, bradycardia (reflex), tachycardia, arrhythmias, peripheral ischemia, venous thrombosis, extravasation (leading to tissue necrosis).
* **Central Nervous System:** Headache, anxiety, dizziness, tremor.
* **Respiratory:** Dyspnea.
* **Other:** Piloerection, sweating, nausea, vomiting.
## Key Drug Interactions
* **Monoamine Oxidase Inhibitors (MAOIs) & Tricyclic Antidepressants (TCAs) & Atomoxetine:** Can potentiate the pressor effect of norepinephrine, leading to severe, prolonged hypertension. Avoid concurrent use; if necessary, use with extreme caution and reduced doses.
* **Alpha-adrenergic Blockers (e.g., Prazosin, Phentolamine):** May reduce the pressor effect of norepinephrine.
* **Beta-adrenergic Blockers:** May antagonize the beta-mediated effects of norepinephrine, potentially leaving unopposed alpha-mediated vasoconstriction.
* **Vasopressin & Angiotensin II:** Additive pressor effects.
* **Dobutamine & Other Beta-agonists:** May cause additive effects on heart rate and cardiac output; caution is advised.
## Monitoring
* **Hemodynamic parameters:** Continuous blood pressure monitoring (arterial line preferred), heart rate, central venous pressure (CVP), pulmonary artery pressures (if available).
* **Urine output:** Monitor for adequate renal perfusion.
* **Peripheral circulation:** Assess for signs of ischemia, especially in extremities, nose, and ears.
* **Infusion site:** Regularly inspect for signs of extravasation.
* **Electrolytes and acid-base balance:** Particularly in critically ill patients.
## Clinical Pearls
* Norepinephrine is a potent vasoconstrictor and should be administered via a central venous catheter when possible to minimize risk of extravasation.
* If extravasation occurs, stop the infusion immediately. Treatment with phentolamine (an alpha-blocker) injected subcutaneously into the affected area may help to prevent tissue necrosis.
* Norepinephrine has a short half-life, so continuous infusion is required to maintain therapeutic effects. Rapid tapering can lead to a sudden drop in blood pressure.
* The choice of diluent (D5W vs. NS) is controversial; D5W is often preferred to reduce the risk of hyponatremia, but norepinephrine is reported to be unstable in D5W over longer periods. Many institutions use NS.
* In patients receiving concurrent MAOIs or TCAs, a significantly lower starting dose of norepinephrine is recommended.
***
*Disclaimer: This information is intended for healthcare professionals. Always verify current prescribing information with the official product monograph or trusted drug reference databases, as dosing and safety guidelines can change.*
