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# Norepinephrine
## Overview
Norepinephrine is a potent vasopressor and inotropic agent that stimulates alpha- and beta-adrenergic receptors. It increases systemic vascular resistance and myocardial contractility, leading to increased blood pressure and cardiac output.
## Primary Indications
* Treatment of septic shock and other distributive shock states to restore and maintain blood pressure.
* Cardiogenic shock (often as an adjunct).
## Adult Dosing
* **Dosing is highly individualized and guided by hemodynamic response.**
* **Initial infusion rate:** Typically starts at 0.01 to 0.02 mcg/kg/min.
* **Titration:** Increase dose incrementally every few minutes based on blood pressure response.
* **Maximum dose:** Often cited as 1 to 2 mcg/kg/min, but doses up to 10 mcg/kg/min or higher may be used in refractory shock under close monitoring.
## Pediatric Dosing
* **Dosing is highly individualized and guided by hemodynamic response, often per institutional protocol.**
* **Initial infusion rate:** Typically starts at 0.05 to 0.1 mcg/kg/min.
* **Titration:** Increase dose incrementally based on blood pressure response.
* **Maximum dose:** Varies, often up to 2 mcg/kg/min, but higher doses may be used in refractory shock.
## Dose Adjustments
* **Renal Impairment:** No specific dose adjustment is typically required; however, close monitoring of response is crucial as clearance may be reduced.
* **Hepatic Impairment:** No specific dose adjustment is typically required; however, close monitoring of response is crucial.
## Contraindications
* Hypersensitivity to norepinephrine.
* Hypotension during anesthesia, except as needed to support blood pressure during pharmacologic shock (e.g., with certain anesthetic agents).
* **Relative contraindication:** Patients with anuria or profound hypovolemia who have not been adequately volume resuscitated.
## Adverse Effects
* **Cardiovascular:** Arrhythmias (tachycardia, bradycardia, ventricular), hypertension, peripheral ischemia/necrosis (especially with extravasation), angina, decreased cardiac output at higher doses.
* **Central Nervous System:** Headache, anxiety, dizziness, tremor.
* **Respiratory:** Dyspnea.
* **Metabolic:** Hyperglycemia.
## Key Drug Interactions
* **Monoamine Oxidase Inhibitors (MAOIs):** Potentiates the pressor response; requires significant dose reduction of norepinephrine if used concurrently or within 14 days of MAOI discontinuation.
* **Tricyclic Antidepressants (TCAs):** May potentiate the pressor response; requires dose reduction of norepinephrine.
* **Anesthetic agents (e.g., cyclopropane, halothane):** May increase myocardial irritability and risk of arrhythmias.
* **Beta-adrenergic blockers:** May cause unopposed alpha-stimulation, leading to severe hypertension.
* **Alpha-adrenergic blockers:** May attenuate the pressor effect.
## Monitoring
* **Hemodynamics:** Continuous blood pressure (intra-arterial preferred), heart rate, cardiac output (if available).
* **Urine output:** To assess renal perfusion.
* **Lactate levels:** To assess tissue perfusion.
* **Central venous pressure (CVP) and pulmonary artery pressures (PAP):** May be monitored in critically ill patients.
* **Extremity perfusion:** Assess for signs of ischemia.
## Clinical Pearls
* Administer via a central venous catheter to minimize risk of extravasation and local tissue necrosis. If peripheral administration is necessary, use a large vein, monitor closely, and discontinue immediately if signs of extravasation occur.
* Have phentolamine readily available for treatment of extravasation.
* Always ensure adequate volume resuscitation before or concurrently with norepinephrine initiation.
* Norepinephrine should be titrated to the lowest dose that achieves the desired hemodynamic effect (e.g., MAP of 65 mmHg or target based on patient condition).
* Continuous infusion is required; do not stop abruptly. Taper off gradually.
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**Disclaimer:** This information is intended for clinical pharmacy professionals. It is essential to consult the most current prescribing information and relevant clinical guidelines for definitive patient care decisions. Dosing and recommendations may vary based on institutional protocols and individual patient factors.
