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# Norepinephrine
## Overview
A potent endogenous catecholamine with primary alpha-1 adrenergic agonist activity (vasoconstriction) and moderate beta-1 adrenergic activity (inotropism). It is the first-line vasopressor for septic shock.
## Primary Indications
* Septic shock (first-line).
* Distributive shock (after fluid resuscitation).
* Hypotension refractory to fluid resuscitation.
## Adult Dosing
* **Initial:** 0.01–0.05 mcg/kg/min or 5–10 mcg/min continuous IV infusion.
* **Titration:** Titrate to clinical goal (usually MAP ≥65 mmHg). Usual maintenance range is 0.05–0.5 mcg/kg/min.
* **Maximum:** No standard hard maximum defined; doses exceeding 1–3 mcg/kg/min are associated with significant mortality and severe ischemia risks.
## Pediatric Dosing
* **Continuous Infusion:** Start at 0.05–0.1 mcg/kg/min.
* **Titration:** Titrate by 0.05–0.1 mcg/kg/min increments to achieve target perfusion goals.
* **Range:** 0.05–2 mcg/kg/min.
## Dose Adjustments
* **Renal/Hepatic Impairment:** No formal dose adjustments required; however, caution is advised as clearance may be altered in multiorgan failure.
* **Local Protocol:** Exact titration parameters and concentration limits vary widely by institution (typically 4 mg/250 mL or 8 mg/250 mL). Always verify hospital-specific concentrations and central line requirements.
## Contraindications
* Hypersensitivity to norepinephrine or sulfite-containing products.
* Hypotension due to uncorrected blood volume deficit (relative contraindication; intravascular volume MUST be addressed).
## Adverse Effects
* **Cardiovascular:** Tachycardia, arrhythmias, hypertension, myocardial ischemia/infarction.
* **Peripheral:** Digital ischemia, limb gangrene (due to profound vasoconstriction).
* **Metabolic:** Hyperglycemia, lactic acidosis (at high doses).
* **Extravasation:** Tissue necrosis at the injection site (risk of skin sloughing).
## Key Drug Interactions
* **MAO Inhibitors / TCAs:** May significantly potentiate pressor effects.
* **Beta-blockers:** May result in unopposed alpha-adrenergic stimulation, leading to severe hypertension and reflex bradycardia.
* **General Anesthetics (Halogenated):** May sensitize the myocardium to arrhythmias.
## Monitoring
* **Continuous:** Blood pressure (preferably arterial line), heart rate, and rhythm (ECG).
* **Perfusion:** Pulse oximetry, capillary refill, urine output, and serum lactate levels.
* **IV Site:** Frequent monitoring for infiltration or extravasation.
* **Peripheral Perfusion:** Monitor hands and feet for mottling or cold skin.
## Clinical Pearls
* **Central Access:** Must be administered via a large-bore central venous catheter whenever possible to mitigate the risk of extravasation and necrosis. Peripheral administration is only acceptable in emergencies via a large-bore peripheral IV for a short duration with extreme diligence.
* **Extravasation Rescue:** If extravasation occurs, discontinue infusion and consider local infiltration with **phentolamine** (alpha-antagonist) per institutional protocol.
* **Weaning:** Wean gradually once hemodynamic stability is achieved to avoid profound rebound hypotension.
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*Disclaimer: This information is for educational purposes and does not replace professional clinical judgment. Always verify dosages, contraindications, and administration requirements against the latest institutional protocols and the official manufacturer's prescribing information before administration.*
