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# Norepinephrine
## Overview
Norepinephrine (Levophed) is a potent alpha-1 adrenergic agonist and a weaker beta-1 adrenergic agonist. It increases systemic vascular resistance and blood pressure.
## Primary Indications
* Management of severe hypotension unresponsive to adequate fluid resuscitation.
* Cardiogenic shock.
* Septic shock.
## Adult Dosing
* **Initial:** 0.01 to 0.02 mcg/kg/min intravenously.
* **Titration:** Increase by 0.005 to 0.01 mcg/kg/min every 5-15 minutes as needed to maintain target blood pressure.
* **Maximum:** Typically not to exceed 0.1 to 0.3 mcg/kg/min, but may be higher in refractory shock under close monitoring and expert guidance. Target mean arterial pressure (MAP) is often 65 mmHg.
## Pediatric Dosing
* **Initial:** 0.05 to 0.1 mcg/kg/min intravenously.
* **Titration:** Increase by 0.05 to 0.1 mcg/kg/min every 5-15 minutes as needed.
* **Maximum:** Typically not to exceed 1 to 2 mcg/kg/min, but may be higher in refractory shock under close monitoring and expert guidance. Target MAP or systolic blood pressure varies by age and clinical scenario; often target MAP ≥ 40 mmHg or systolic BP ≥ 70 mmHg.
## Dose Adjustments
* **Renal/Hepatic Impairment:** No specific dose adjustments are typically recommended due to its use in critical illness and short half-life. However, caution and closer monitoring are advised as hepatic metabolism can be affected in severe liver dysfunction.
## Contraindications
* Hypersensitivity to norepinephrine.
* Concurrent use with cyclopropane or halogenated hydrocarbon anesthetics (risk of severe hypertension and arrhythmias).
* Hypotension due to volume deficit (must be corrected first).
## Adverse Effects
* **Cardiovascular:** Arrhythmias (including ventricular), bradycardia, hypertension, peripheral ischemia, vasoconstriction leading to organ hypoperfusion (e.g., mesenteric, renal), angina, headache.
* **Local:** Extravasation can cause severe tissue necrosis; antidote is phentolamine.
* **Other:** Anxiety, dizziness, shortness of breath.
## Key Drug Interactions
* **General Anesthetics (e.g., halothane, sevoflurane):** Increased risk of arrhythmias and severe hypertension.
* **Beta-blockers:** May potentiate unopposed alpha-adrenergic effects, leading to severe hypertension.
* **MAO Inhibitors & Tricyclic Antidepressants:** Can prolong and intensify the pressor response. Avoid concurrent use.
* **Ergot Alkaloids:** Potentiated pressor effect.
* **Oxytocic Drugs:** May cause severe, persistent hypertension.
* **Guanethidine:** May inhibit reuptake, potentiating pressor effects.
## Monitoring
* Continuous arterial blood pressure monitoring is essential.
* Central venous pressure (CVP) or pulmonary artery catheter (PAC) for fluid status and cardiac output assessment.
* Urine output.
* Peripheral perfusion (e.g., skin temperature, capillary refill).
* Cardiac rhythm.
* Blood glucose levels (hyperglycemic effects).
* Lactate levels.
## Clinical Pearls
* Norepinephrine is a potent vasoconstrictor and must be administered via a central line to minimize risk of extravasation and tissue necrosis.
* Adequate volume resuscitation is paramount before initiating norepinephrine. It should not be used as a primary therapy for hypovolemic shock.
* Titrate to the lowest effective dose to achieve target MAP while minimizing peripheral vasoconstriction and organ hypoperfusion.
* If extravasation occurs, discontinue the infusion immediately, do not flush the line, and administer phentolamine diluted in saline infiltrated into the affected area.
* The risk of arrhythmias increases with higher doses.
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*Disclaimer: This information is intended for healthcare professionals. It is essential to consult the most current prescribing information and institutional protocols for definitive patient care decisions. Dosing and guidelines can vary.*
