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EPISODE · Aug 27, 2026 · 23 MIN

CC Pharm | Norepinephrine

from STAT Stitch Deep Dive Podcast Beyond The Bedside

Norepinephrine (Levophed) 80/20 Summary Action & MOA: Direct α-agonist causing potent vasoconstriction. Modest β1​ activity triggers cardiac stimulation at lower doses; vasoconstriction dominates at higher doses. Elevated SVR triggers reflex vagal bradycardia (slowing HR). Coronary flow increases without raising myocardial oxygen demand. Uses: First-line for septic shock, sepsis, acute hypotension, cardiogenic shock. Alternative in hepatorenal syndrome (with albumin). Complications: Tissue necrosis (extravasation), bradycardia, lactic acidosis, pulmonary edema, hypertension, and local hypoxia. Administration & Dilution: Dilution: Standard: 4mg in 1,000mL. Preferred: D5W/D5NS (dextrose protects against oxidation). Saline alone stable up to 16mcg/mL, though FDA discourages. Adult standard: 16, 32, 128mcg/mL. Incompatibility: Do not mix with alkaline solutions (e.g., bicarb). Reject if pinkish/discolored or has precipitate. Route: Large vein infusion; transition to central line ASAP. Avoid leg veins in elderly. Monitoring: BP every 2 mins initially, then every 5 mins. Check site frequently for free flow/extravasation. Weaning: Reduce rate gradually; avoid abrupt withdrawal to prevent rebound hypotension. Extravasation Antidote: Infiltrate ASAP (within 12h) with phentolamine 5-10mg in 10-15mL NS. Pharmacokinetics: Onset <30s; steady-state 5 mins; duration <10 mins. Half-life ~2.4 mins; metabolized by COMT/MAO. Why Choose It? Preferred in septic shock; raises MAP/SVR with less tachycardia than dopamine, sparing oxygen demand. Final 80/20 Review The 20% to Absolutely Know: Hypovolemia First: Correct fluid deficit before starting norepinephrine. Central Line Priority: Transition to central line ASAP to mitigate necrosis risk. Phentolamine for Extravasation: Immediate local infiltration reverses ischemia. Dextrose Over Saline: Dextrose-containing diluents prevent oxidation. Incompatible with Bicarb: Inactivated in alkaline solutions. If I Remember Nothing Else: Norepinephrine is the first-line vasopressor for septic shock. With a <30s onset and 2.4m half-life, it requires continuous infusion, BP checks every 2–5 mins, and gradual weaning. Monitor the IV site continuously; treat extravasation with immediate phentolamine infiltration to prevent necrosis.

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