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# Norepinephrine
## Overview
Norepinephrine is a potent vasopressor and inotropic agent that acts primarily on alpha-adrenergic receptors, causing vasoconstriction, and to a lesser extent on beta-1 adrenergic receptors, increasing heart rate and contractility. It is available as a solution for intravenous infusion.
## Primary Indications
* Treatment of severe hypotension and shock, particularly septic shock and cardiogenic shock, refractory to fluid resuscitation.
* Restoration and maintenance of blood pressure.
## Adult Dosing
* **Initial Dose:** 4 to 8 mcg/minute (0.04 to 0.08 mcg/kg/minute) intravenously via a central venous catheter.
* **Titration:** Titrate infusion rate to achieve target mean arterial pressure (MAP) of 65 mmHg or higher. Doses can be increased by 0.05 to 0.1 mcg/kg/minute every 5 to 15 minutes.
* **Maximum Dose:** Doses up to 1 mcg/kg/minute have been used in refractory shock, but higher doses are associated with increased risks. Common maximums are often dictated by local protocol.
## Pediatric Dosing
* **Initial Dose:** 0.05 to 0.1 mcg/kg/minute intravenously.
* **Titration:** Titrate to achieve target MAP (e.g., > gestational age + 2 years mmHg, or > 50 mmHg in neonates, or > 65 mmHg in older children). Doses can be increased in increments of 0.05 to 0.1 mcg/kg/minute every 10-20 minutes.
* **Maximum Dose:** 1 to 2 mcg/kg/minute, though higher doses may be used under expert guidance. Dosing is highly variable and should be guided by institutional protocols and patient response.
## Dose Adjustments
* **Renal Impairment:** No specific dose adjustment, but prolonged use may require careful monitoring.
* **Hepatic Impairment:** No specific dose adjustment, but careful monitoring is needed.
* **Elderly:** No specific dose adjustment recommended, but use with caution due to potential for increased cardiovascular effects.
## Contraindications
* Hypersensitivity to norepinephrine.
* Severe uncorrected hypotension with metabolic acidosis, hypoxemia, or hypothermia, as vasopressors may be ineffective and potentially worsen tissue perfusion.
* Use during cyclopropane and halothane anesthesia due to risk of severe hypertension and arrhythmias.
## Adverse Effects
* **Cardiovascular:** Hypertension, bradycardia (reflex), arrhythmias, chest pain, peripheral ischemia, gangrene (especially with prolonged infusions or extravasation).
* **Central Nervous System:** Headache, anxiety, dizziness, tremor.
* **Other:** Extravasation leading to tissue necrosis, decreased urine output, nausea, vomiting.
## Key Drug Interactions
* **Anesthetics (inhalational):** Increased risk of arrhythmias and severe hypertension.
* **Beta-blockers:** Can potentiate alpha-adrenergic effects, leading to severe hypertension and reflex bradycardia.
* **MAO Inhibitors:** Can cause hypertensive crisis; avoid concurrent use or within 14 days of MAOI discontinuation.
* **Tricyclic Antidepressants:** May potentiate hypertensive effects.
* **Guanadrel, Guanethidine, Reserpine:** May enhance pressor response.
* **Ergot alkaloids:** May increase pressor effects.
* **Dobutamine:** May blunt the pressor response of norepinephrine.
## Monitoring
* Continuous blood pressure monitoring (arterial line preferred).
* Heart rate and rhythm.
* Central venous pressure (CVP) or other measures of fluid status.
* Urine output.
* Signs of peripheral ischemia (e.g., skin color, temperature, capillary refill).
* Lactate levels, acid-base status.
## 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 and infiltrate the affected area with phentolamine.
* Titrate to the lowest effective dose to achieve target MAP.
* Consider adding vasopressin for refractory septic shock.
* Refrigerate and protect from light. Discard if solution is discolored or contains precipitate.
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*This information is intended for clinical use and does not replace a thorough review of the most current prescribing information or specific patient assessment. Always verify current drug information with official resources.*
