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# Norepinephrine
## Overview
Norepinephrine is a potent vasopressor and inotropic agent. It acts primarily on alpha-1 adrenergic receptors, causing vasoconstriction and increasing systemic vascular resistance. It also has some beta-1 adrenergic receptor activity, which can increase heart rate and contractility, though this effect is less pronounced than its alpha-1 effects.
## Primary Indications
* Severe hypotension and shock (e.g., septic shock, cardiogenic shock) refractory to fluid resuscitation.
## Adult Dosing
* **Usual dose:** 0.01 to 0.3 mcg/kg/minute intravenously.
* **Initiation:** Typically started at 0.01 to 0.05 mcg/kg/minute and titrated up to achieve the desired hemodynamic effect (e.g., mean arterial pressure [MAP] ≥ 65 mmHg).
* **Maximum dose:** Doses higher than 0.3 mcg/kg/minute are generally not recommended due to increased risk of adverse effects, but may be used in select, refractory cases under close monitoring. Exact maximums may depend on local protocols.
## Pediatric Dosing
* **Usual dose:** 0.05 to 1 mcg/kg/minute intravenously.
* **Initiation:** Typically started at 0.05 to 0.1 mcg/kg/minute and titrated.
* **Maximum dose:** Doses up to 2 mcg/kg/minute may be used in severe cases, but higher doses are associated with increased risk. Dosing is highly individualized and guided by response; specific maximums may depend on local protocols and patient factors.
## Dose Adjustments
* **Renal Impairment:** No specific dose adjustment is usually necessary, but careful monitoring is crucial as clearance may be reduced.
* **Hepatic Impairment:** No specific dose adjustment is usually necessary, but careful monitoring is crucial.
## Contraindications
* Hypersensitivity to norepinephrine.
* Severe uncontrolled hypertension.
* Use with volatile inhalation anesthetics (relative contraindication due to increased risk of arrhythmias).
## Adverse Effects
* **Cardiovascular:** Hypertension, bradycardia (reflex), arrhythmias, peripheral ischemia, myocardial ischemia, extravasation leading to tissue necrosis.
* **Central Nervous System:** Headache, anxiety, dizziness.
* **Respiratory:** Dyspnea.
* **Other:** Decreased blood flow to splanchnic circulation, kidneys, and extremities.
## Key Drug Interactions
* **Monoamine Oxidase Inhibitors (MAOIs):** Potentiated hypertensive crisis; avoid concurrent use. If unavoidable, administer extreme caution and reduced doses.
* **Tricyclic Antidepressants (TCAs):** Potentiated hypertensive response; avoid concurrent use. If unavoidable, administer extreme caution and reduced doses.
* **Beta-Adrenergic Blockers:** May blunt the desired pressor effect or unmask unopposed alpha-stimulation, leading to severe hypertension.
* **Ergot Alkaloids:** Increased risk of severe hypertension and peripheral ischemia.
* **Oxytocic Agents:** May cause severe persistent hypertension.
## Monitoring
* Continuous electrocardiogram (ECG).
* Continuous blood pressure monitoring (arterial line preferred).
* Central venous pressure (CVP) or pulmonary artery catheter (PAC) if indicated.
* Urine output.
* Peripheral circulation (e.g., skin temperature, color, capillary refill).
* Mental status.
* Lactate levels.
## Clinical Pearls
* **Extravasation:** Norepinephrine is a potent vasoconstrictor and can cause severe tissue necrosis if it infiltrates surrounding tissues. Monitor the IV infusion site closely. If extravasation occurs, stop the infusion and administer phentolamine (intradermal or subcutaneous injection) to the affected area promptly.
* **Infusion Rate:** Titrate slowly to achieve the target MAP and titrate down as patient's hemodynamic status improves.
* **Dilution:** Norepinephrine is typically diluted in dextrose or saline solutions to a concentration of 16 mcg/mL (e.g., 4 mg in 250 mL) or 32 mcg/mL (e.g., 8 mg in 250 mL) for adult infusions, and often lower concentrations for pediatric infusions. Specific dilution protocols vary by institution.
* **Underlying Cause:** Always address the underlying cause of hypotension in addition to using vasopressors.
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*Disclaimer: This information is intended for clinical use and is not a substitute for professional medical advice. Always consult the most current prescribing information or a qualified healthcare provider for diagnosis and treatment.*
