norepinephrine

Potent alpha-1 vasoconstrictor with modest beta-1 inotropy. First-line for septic, cardiogenic, hypovolaemic (bridge), obstructive, and neurogenic shock. Raises MAP without the arrhythmia burden of dopamine or the metabolic cost of epinephrine.

mechanism

Alpha-1 +++ → arterial and venous smooth muscle constriction → ↑SVR, ↑venous return
Beta-1 ++ → modest ↑contractility, minimal ↑HR (reflex bradycardia from alpha-1 largely cancels beta-1 chronotropy → HR usually stays flat or falls)
Negligible beta-2 → no vasodilation, no bronchodilation, no significant lactate generation

Net haemodynamics: ↑↑SVR, ↑MAP, ↔/↑CO, ↔HR

dosing

setting	dose
usual range	0.01–0.5 mcg/kg/min (≈2–40 mcg/min)
refractory shock	no true ceiling; >0.5 mcg/kg/min = high dose, >1 mcg/kg/min = refractory — add a second agent rather than climbing alone
add vasopressin at	≈0.25–0.5 mcg/kg/min (SSC 2021)
HRS-AKI	0.5–3 mg/hr (8–50 mcg/min), titrated to raise MAP by 10–15 mmHg or MAP >65
typical bag	4 mg / 250 mL = 16 mcg/mL (check local concentration)

PK: onset 1–2 min · half-life <5 min (rapid titration) · metabolised by MAO and COMT · no renal or hepatic dose adjustment
Base vs bitartrate salt: 2 mg bitartrate = 1 mg base — some jurisdictions and papers report one, some the other

key points

Start peripherally rather than delay — large proximal vein (upper arm/AC, never hand or foot), ≥20G, hourly checks. Get central access when convenient, not before starting
Wean norepinephrine before vasopressin — stopping vasopressin first causes more rebound hypotension
Rising requirement despite adequate dose → look for a missed diagnosis (bleeding, source control failure, tamponade, adrenal insufficiency, hypocalcaemia, acidaemia), not just a higher infusion rate
First-line in Canada for HRS-AKI, where terlipressin requires Special Access Programme

extravasation

Stop the infusion, leave the cannula in, aspirate, then infiltrate phentolamine 5–10 mg in 10 mL NS locally. Alternatives: topical nitroglycerin 2% paste, terbutaline infiltration. Elevate the limb.

pressors on an empty tank

Clamping down on hypovolaemia generates a number, not perfusion. Optimise preload in parallel. No absolute contraindications in shock — relative caution in severe aortic stenosis, untreated tachyarrhythmia, and mesenteric ischaemia.

adverse effects

Digital / mesenteric ischaemia — high dose or pre-existing vascular disease
Reflex bradycardia — usually benign, occasionally marked
Hyperglycaemia — mild, alpha-mediated ↓insulin release
Extravasation → tissue necrosis (see above)

evidence

SOAP II (2010) — vs dopamine: no overall mortality difference but half the arrhythmias and lower mortality in the cardiogenic shock subgroup. Why dopamine fell out of use
Levy, JACC. 2018 — vs epinephrine in cardiogenic shock: epi associated with more refractory shock, higher lactate, signal toward ~3x mortality → norepinephrine preferred
CENSER (2019) — early low-dose norepinephrine in sepsis improved shock control at 6 h without mortality difference
HRS-AKI — meta-analysis data suggest non-inferior to terlipressin for HRS reversal, with fewer treatment discontinuations