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# Norepinephrine
## Overview
Norepinephrine is a potent alpha-1 adrenergic agonist and a weaker beta-1 adrenergic agonist. It causes vasoconstriction, which increases systemic vascular resistance and blood pressure. It also has a positive inotropic effect on the heart. It is administered as a continuous intravenous infusion.
## Primary Indications
* Treatment of hypotension in the setting of septic shock and other distributive shock states.
* To restore and maintain adequate blood pressure in patients with severe hypotension unresponsive to fluid resuscitation.
## Adult Dosing
* **Initial dose:** 0.01 to 0.02 mcg/kg/min IV.
* **Titration:** Titrate infusion rate to achieve target mean arterial pressure (MAP) of 65 mmHg or higher. Doses may be increased in increments of 0.01 to 0.05 mcg/kg/min every 5-15 minutes as needed.
* **Maximum dose:** Typically not to exceed 0.1 to 2 mcg/kg/min, though higher doses have been used in refractory shock. Dosing is highly individualized based on patient response and institutional protocols.
## Pediatric Dosing
* **Initial dose:** 0.05 to 0.1 mcg/kg/min IV.
* **Titration:** Titrate infusion rate to achieve target MAP greater than or equal to the patient's post-conceptional age plus 5 years, or a minimum MAP of 50 mmHg. Doses may be increased in increments of 0.05 to 0.2 mcg/kg/min every 5-15 minutes.
* **Maximum dose:** Typically not to exceed 1-2 mcg/kg/min, but higher doses may be necessary. Pediatric dosing is highly dependent on institutional protocols and patient condition.
## Dose Adjustments
* **Renal impairment:** No specific dose adjustment is generally recommended, but caution and close monitoring are advised due to potential for accumulation.
* **Hepatic impairment:** No specific dose adjustment is generally recommended, but caution and close monitoring are advised.
## Contraindications
* Hypersensitivity to norepinephrine.
* Use during cyclopropane or halogenated hydrocarbon anesthesia (risk of severe hypertension and arrhythmias).
## Adverse Effects
* **Common:** Hypertension, reflex bradycardia, peripheral ischemia, decreased cardiac output, headache, anxiety, dizziness, tremor, extravasation leading to tissue necrosis.
* **Serious:** Arrhythmias, angina, pulmonary edema, severe hypertension.
## Key Drug Interactions
* **Monoamine oxidase inhibitors (MAOIs):** Potentiates the pressor response, potentially leading to hypertensive crisis. Avoid concurrent use or use with extreme caution if unavoidable.
* **Tricyclic antidepressants (TCAs):** Potentiates the pressor response. Use with caution.
* **Guanethidine, bethanidine:** May block the uptake of norepinephrine, reducing its effectiveness.
* **Oxytocic agents:** May potentiate the hypertensive effect.
* **Beta-adrenergic blockers:** May unopposed alpha-adrenergic effects, leading to severe hypertension.
## Monitoring
* Continuous electrocardiogram (ECG) for arrhythmias.
* Continuous blood pressure monitoring (intra-arterial preferred).
* Central venous pressure and pulmonary artery pressures if available.
* Urine output.
* Peripheral perfusion (e.g., skin color, temperature, capillary refill).
* Mental status.
* Infusion site for signs of extravasation.
## Clinical Pearls
* Norepinephrine should be administered via a central venous catheter to minimize the risk of extravasation and tissue necrosis.
* If extravasation occurs, stop the infusion immediately. Administer phentolamine (intradermal or subcutaneous) to the affected area to antagonize alpha-receptor-mediated vasoconstriction.
* Ensure adequate intravascular volume resuscitation before initiating norepinephrine, as it is less effective in hypovolemic states.
* Titrate to the lowest effective dose to achieve the target MAP.
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*Disclaimer: This information is intended for clinical decision support and does not replace independent clinical judgment. Always verify current prescribing information and consult relevant guidelines before making therapeutic decisions.*
