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# Norepinephrine
## Overview
Norepinephrine is a potent alpha-1 adrenergic agonist and a less potent beta-1 adrenergic agonist. It causes vasoconstriction and increases systemic vascular resistance and blood pressure. It can also increase myocardial contractility.
## Primary Indications
* Severe hypotension and shock (e.g., septic shock, cardiogenic shock) refractory to fluid resuscitation.
* Cardiac arrest (as an adjunct to CPR, though epinephrine is typically first-line).
## Adult Dosing
* **Severe Hypotension/Shock:** Intravenous infusion. Initial dose: 0.01 to 0.02 mcg/kg/min. Titrate upwards to achieve target mean arterial pressure (MAP) of 65 mmHg or higher. Typical maintenance doses range from 0.01 to 0.3 mcg/kg/min. Maximum dose is generally not well-defined, but doses exceeding 1 mcg/kg/min are rarely used and require extreme caution. Dosing is highly individualized based on patient response.
## Pediatric Dosing
* **Severe Hypotension/Shock:** Intravenous infusion. Initial dose: 0.05 to 0.1 mcg/kg/min. Titrate to maintain adequate blood pressure. Usual range: 0.05 to 1 mcg/kg/min. Maximum doses can vary by protocol.
## Dose Adjustments
* No specific dose adjustments are typically required for renal or hepatic impairment, as the drug is rapidly metabolized. However, careful titration is essential in all patients.
## Contraindications
* Hypersensitivity to norepinephrine.
* Hypotension secondary to volume deficit until adequate volume resuscitation is achieved.
* In general, use with caution in patients with severe peripheral vascular disease or mesenteric ischemia due to vasoconstrictive effects.
## Adverse Effects
* **Cardiovascular:** Hypertension, reflex bradycardia, arrhythmias, peripheral ischemia (blackening of extremities), angina, decreased cardiac output at higher doses.
* **Extravasation:** Can cause severe tissue necrosis and sloughing. If extravasation occurs, discontinue infusion immediately and infiltrate the affected area with phentolamine.
* **Other:** Headache, anxiety, dizziness, tremor, dyspnea.
## Key Drug Interactions
* **Monoamine Oxidase Inhibitors (MAOIs):** Potentiates hypertensive crisis. Norepinephrine should be used with extreme caution or avoided in patients taking MAOIs within the last 14 days.
* **Tricyclic Antidepressants (TCAs):** May potentiate the pressor response.
* **Ergot Alkaloids:** Can potentiate vasoconstriction.
* **Beta-Blockers:** May cause unopposed alpha-stimulation, leading to severe hypertension.
* **Alpha-Blockers:** May antagonize the pressor effect.
* **General Anesthetics:** May increase myocardial irritability.
## Monitoring
* Continuous electrocardiogram (ECG) for arrhythmias.
* Continuous blood pressure monitoring (intra-arterial line preferred for precise titration).
* Central venous pressure (CVP) and pulmonary artery pressures (if available) to assess fluid status and cardiac function.
* Peripheral perfusion (e.g., skin temperature, capillary refill, presence of pulses).
* Urine output.
* Infusion site for signs of extravasation.
## Clinical Pearls
* Norepinephrine is typically administered via a central venous catheter to minimize the risk of peripheral extravasation and necrosis.
* It is a potent vasoactive agent; titration must be slow and guided by close hemodynamic monitoring.
* Ensure adequate volume resuscitation prior to and during norepinephrine infusion, as it can worsen end-organ perfusion in hypovolemic states.
* Dobutamine may be added to counteract the decrease in cardiac output that can occur with norepinephrine at higher doses.
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*Disclaimer: This information is intended for clinical pharmacy professionals and is not a substitute for professional medical advice. Always verify current prescribing information, including dosage, indications, contraindications, warnings, precautions, and adverse effects, with the most up-to-date product labeling and guidelines.*
