vasopressin
Contents
Non-adrenergic V1 vasoconstrictor. Standard first add-on to norepinephrine in septic shock, added at norepi ≈0.25–0.5 mcg/kg/min. Keeps working in severe acidaemia when catecholamine receptors are desensitised, doesn’t cause tachyarrhythmia, and doesn’t undergo tachyphylaxis. Run at a fixed dose — it is not titrated.
mechanism
- V1 receptor (vascular smooth muscle) → contraction via phospholipase C/IP3, an entirely non-adrenergic pathway → ↑SVR, ↑MAP
- V2 receptor (renal collecting duct) → aquaporin insertion → water reabsorption. Minimal at pressor doses
- Also restores catecholamine sensitivity and inhibits K-ATP channels/iNOS pathways implicated in vasoplegia
- Endogenous vasopressin stores deplete early in septic shock — low-dose infusion is physiological replacement, not pharmacological dosing
Net haemodynamics: ↑↑SVR, ↑MAP, ↔/↓CO, ↔/↓HR. No inotropy.
Vasopressin raises SVR without raising PVR (and may cause pulmonary vasodilation via NO at low doses) → preferred second agent in RV failure and pulmonary hypertension. The opposite of phenylephrine.
dosing
| setting | dose |
|---|---|
| septic shock | fixed 0.03 U/min (some units 0.04 U/min; ≈1.8–2.4 U/hr) |
| range studied | 0.01–0.04 U/min; doses >0.04 U/min → sharply ↑ischaemia risk |
| post-CPB vasoplegia | 0.03–0.04 U/min |
| cardiac arrest | removed from ACLS — no benefit over epinephrine alone |
- PK: onset 5–15 min · half-life 10–20 min (much longer than catecholamines) · metabolised by vasopressinases (liver/kidney)
- Do not titrate up and down like a catecholamine — the longer half-life means you chase your tail, and the dose–ischaemia relationship is steep
key points
- Acidaemia — remains effective at pH <7.15, where alpha-receptors are desensitised. If norepinephrine has “stopped working” in a profoundly acidaemic patient, this is the drug to add (while fixing the acidosis)
- No tachyphylaxis — unlike catecholamines, efficacy doesn’t fade over days
- Wean it LAST — multiple retrospective studies show more rebound hypotension when vasopressin is discontinued before norepinephrine. Wean norepi first, then taper vasopressin
- Doesn’t increase HR — useful in shock with concurrent AF/RVR
- Reduced CO in patients with poor LV function — no inotropy to offset afterload rise. Pair with an inotrope if EF is poor
adverse effects
Digital, mesenteric (gut), and coronary ischaemia — the dominant safety concern, dose-related. Caution in known CAD, mesenteric ischaemia, Raynaud’s, severe PVD. Skin necrosis at high doses, even without extravasation.
- Hyponatraemia (V2 effect) — uncommon at 0.03 U/min but worth watching; avoid in patients with or at risk of raised ICP
- ↓CO — see key points above
evidence
- VASST (2008) — vasopressin + norepi vs norepi alone: no overall mortality difference, but signal of benefit in less severe shock (norepi <15 mcg/min). Established the catecholamine-sparing role
- VANISH (2016) — vasopressin as first-line vs norepi: no difference in kidney-failure-free days, but less RRT in the vasopressin arm
- Meta-analyses — consistent reduction in norepinephrine requirement and atrial fibrillation; mortality effect neutral to modestly favourable
- Timing — observational data favour earlier addition (at lower norepinephrine doses); waiting until shock is refractory reduces the chance of response