Norepinephrine & Vasopressin

Septic shock protocol names norepinephrine as the first-line vasopressor — but when the MAP still won't budge, vasopressin gets added through an entirely different mechanism. Knowing which does what changes your priorities at the bedside.

Norepinephrine is a potent alpha-1 agonist with mild beta-1 activity, producing strong arterial vasoconstriction and a modest increase in cardiac contractility. It is the first-line vasopressor in septic shock, titrated to maintain a MAP ≥ 65 mmHg. It must run through a central line (or a designated large-bore peripheral for short durations per protocol) because extravasation causes severe tissue necrosis. Vasopressin (antidiuretic hormone, ADH) works through V1 receptors on vascular smooth muscle — completely independent of adrenergic pathways. This matters because in prolonged shock, adrenergic receptors downregulate and catecholamine vasopressors lose effectiveness. Vasopressin bypasses that problem. It is typically added as a fixed-rate infusion (up to 0.03 units/min; some protocols allow up to 0.04 units/min) alongside norepinephrine, not titrated up and down like norepinephrine. Together they target two different receptor systems, producing additive vasoconstriction and often allowing norepinephrine doses to be reduced.

Key Distinctions

Norepinephrine is titrated to MAP; vasopressin runs at a fixed rate — students confuse these dosing strategies. Norepinephrine acts on adrenergic receptors; vasopressin acts on V1 receptors — they are not interchangeable mechanisms. Don't confuse vasopressin the vasopressor (low fixed dose) with desmopressin used for diabetes insipidus — different indication, different dose range.

Clinical Pearl

Norepi you titrate, vasopressin you set and forget. If adrenergic receptors stop listening, vasopressin speaks a different language.