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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, which increases systemic vascular resistance and 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).
* Restoration and maintenance of blood pressure during cardiac arrest.
## Adult Dosing
* **Hypotension/Shock:** Typically initiated at 0.01 to 0.02 mcg/kg/min, titrated upwards based on hemodynamic response. Usual maintenance doses range from 0.01 to 0.3 mcg/kg/min. Doses up to 1 mcg/kg/min have been used in severe cases. Titration should be guided by mean arterial pressure (MAP) targets, often aiming for MAP > 65 mmHg.
* **Cardiac Arrest:** 0.01 mg (10 mcg) IV/IO push every 3-5 minutes as needed.
## Pediatric Dosing
* **Hypotension/Shock:** Typically initiated at 0.05 to 0.1 mcg/kg/min, titrated upwards based on hemodynamic response. Usual maintenance doses range from 0.05 to 1 mcg/kg/min. Pediatric resuscitation guidelines may recommend starting at 0.1 mcg/kg/min.
* **Cardiac Arrest:** 0.01 mg/kg (10 mcg/kg) IV/IO push, maximum 1 mg. May repeat every 3-5 minutes.
## Dose Adjustments
No specific dose adjustments are typically required for renal or hepatic impairment, but these patients may have altered hemodynamic responses requiring closer monitoring and titration.
## Contraindications
* Hypersensitivity to norepinephrine.
* Hypotensive patients with mechanical obstruction of cardiac filling or ejection (e.g., cardiac tamponade, severe aortic stenosis).
## Adverse Effects
* **Cardiovascular:** Hypertension, bradycardia (reflex), tachycardia, arrhythmias, peripheral ischemia, vasoconstriction (potentially leading to limb ischemia, digital ischemia), myocardial infarction, extravasation leading to tissue necrosis.
* **Other:** Headache, anxiety, dizziness, tremor, nausea, vomiting, difficulty breathing, decreased urine output.
## Key Drug Interactions
* **Monoamine Oxidase Inhibitors (MAOIs):** Potentiates the hypertensive effects; concurrent use is generally contraindicated. If concurrent use is necessary, extreme caution and dose reduction of norepinephrine are advised.
* **Tricyclic Antidepressants (TCAs):** May potentiate the pressor response; use with caution.
* **General Anesthetics:** Can increase the risk of arrhythmias.
* **Beta-blockers:** May cause unopposed alpha-stimulation, leading to severe hypertension.
* **Alpha-blockers:** May attenuate the pressor effect.
* **Dopamine:** May decrease the pressor effect of norepinephrine.
## Monitoring
* Continuous electrocardiogram (ECG).
* Continuous blood pressure monitoring (arterial line preferred for titratable infusions).
* Central venous pressure (CVP).
* Urine output.
* Peripheral perfusion (skin temperature, color, capillary refill).
* Lactate levels.
* Heart rate and rhythm.
## Clinical Pearls
* Norepinephrine is typically administered via a central venous catheter to minimize the risk of extravasation and tissue necrosis.
* If extravasation occurs, stop the infusion immediately and infiltrate the affected area with phentolamine.
* Titrate norepinephrine to achieve the target MAP and ensure adequate organ perfusion, rather than relying solely on a fixed dose.
* Norepinephrine is often considered a first-line agent for septic shock.
* Monitor for signs of limb ischemia, especially with prolonged or high-dose infusions.
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*This information is intended for healthcare professionals. Always consult the official prescribing information and relevant clinical guidelines for the most up-to-date and comprehensive details.*
