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# Norepinephrine (Levophed)
## Overview
- Direct-acting sympathomimetic amine; potent alpha-1 adrenergic agonist with mild beta-1 activity.
- Primary vasopressor for septic shock and other distributive shock states.
- First-line agent per Surviving Sepsis Campaign guidelines.
## Primary Indications
- Hypotension refractory to fluid resuscitation (septic, neurogenic, or vasodilatory shock).
- Acute hypotension during myocardial infarction or post-cardiotomy.
- Adjunct in cardiac arrest (per ACLS) if epinephrine is insufficient.
## Adult Dosing
- **Initial rate:** 0.05–0.1 mcg/kg/min (typical starting dose). For ease, many protocols begin at 2–4 mcg/min without weight-based dosing.
- **Titrate:** Increase by 0.05–0.2 mcg/kg/min every 5–10 minutes to target MAP ≥65 mmHg.
- **Max dose:** No absolute maximum; usual upper range 0.5–1.0 mcg/kg/min (higher doses may be used short-term if risk/benefit favorable).
- Exact dosing depends on local protocol and patient response; use weight-based dosing for consistency.
## Pediatric Dosing
- **Initial rate:** 0.05–0.1 mcg/kg/min.
- **Titrate:** Increase by 0.05–0.1 mcg/kg/min every 5–10 minutes to desired effect.
- **Max dose:** Typically 1–2 mcg/kg/min; higher doses may be used in extreme cases but increase risk of adverse effects.
- Use central venous access when possible; peripheral infusion acceptable at low concentrations with close monitoring for extravasation.
## Dose Adjustments
- **Renal impairment:** No adjustment needed.
- **Hepatic impairment:** No specific adjustment, but monitor closely due to increased sensitivity risk.
- **Elderly:** Start at lower end of dosing range; higher sensitivity to vasopressors.
## Contraindications
- Hypersensitivity to norepinephrine or sulfites (commercial formulations contain sulfite preservatives).
- Uncorrected hypovolemia (must be volume-resuscitated first).
- Mesenteric or peripheral vascular thrombosis (may worsen ischemia).
- Severe hypertension.
## Adverse Effects
- **Common:** Hypertension, tachycardia, bradycardia (reflex), arrhythmias, peripheral ischemia.
- **Serious:** Extravasation necrosis (treat with phentolamine infiltration), reduced renal/splanchnic perfusion, metabolic acidosis.
- Less common: Hyperglycemia, anxiety, headache.
## Key Drug Interactions
- **MAOIs** (linezolid, selegiline): Severe hypertensive crisis; avoid concurrent use.
- **TCAs, COMT inhibitors:** Potentiate pressor effect; use lower starting doses.
- **Beta-blockers:** Unopposed alpha-vasoconstriction → hypertension, bradycardia.
- **Ergot alkaloids:** Enhanced vasoconstriction/ischemia risk.
## Monitoring
- Continuous blood pressure (intra-arterial preferred), heart rate, ECG.
- End-organ perfusion: urine output, lactate clearance, mental status.
- Extravasation signs: Blanching, pallor, pain at peripheral IV site.
- Serum electrolytes, glucose, ABG as indicated.
## Clinical Pearls
- Mix and administer via central line if prolonged use; peripheral access is acceptable short-term in large, proximal vein.
- Never mix with alkaline solutions (e.g., sodium bicarbonate) – incompatible.
- Decrease rate gradually to avoid rebound hypotension.
- For extravasation, stop immediately, infiltrate phentolamine 5–10 mg in 10–15 mL NS (subcutaneous).
- Taper when adding alternative pressors (e.g., vasopressin) to avoid overshoot hypotension.
*This information is for educational purposes. Always verify current prescribing information from reliable sources (e.g., FDA labeling, institutional guidelines) before clinical use.*
