Vasopressin

How it’s used in anaesthesia/ICU

Refractory vasodilatory shock (esp. septic shock) as an adjunct to catecholamines
- Typical infusion: 0.01–0.03 units/min (often fixed-dose); higher doses increase ischaemic risk
- Reduces noradrenaline requirement; may improve MAP when catecholamine-resistant
Vasoplegia after cardiopulmonary bypass / post-cardiac surgery
- Often effective when SVR low with normal/high CO; consider early if on high-dose catecholamines
Cardiac arrest (historical/selected use)
- Previously used as alternative to adrenaline; not routine in current ALS algorithms
Variceal upper GI bleeding (splanchnic vasoconstriction)
- More commonly terlipressin used in UK practice; vasopressin may be used with nitrates to reduce coronary ischaemia
Pulmonary hypertension / RV failure (selected settings)
- At low doses may increase SVR with relatively less increase in PVR than catecholamines; can support coronary perfusion to RV
Endocrine replacement in vasopressin deficiency (central diabetes insipidus)
- Desmopressin is preferred for chronic therapy; vasopressin infusion sometimes used in ICU

Practical prescribing/monitoring

Haemodynamic target: raise MAP by increasing SVR; assess CO, lactate, capillary refill, urine output
- Consider echocardiography to avoid treating cardiogenic shock with pure vasoconstrictor
Monitor for ischaemia
- Digital, mesenteric, myocardial ischaemia; rising lactate, abdominal pain/distension, ECG changes
Monitor sodium/osmolality and fluid balance
- V2-mediated water retention can cause hyponatraemia; more relevant with higher doses/prolonged use

Classification and endogenous physiology

Endogenous peptide hormone (nonapeptide) synthesised in hypothalamus; stored/released from posterior pituitary
Physiological triggers: increased plasma osmolality, decreased effective circulating volume/arterial pressure, nausea, pain, stress
Acts via GPCRs: V1a (vascular), V1b/V3 (pituitary), V2 (renal collecting duct)

Mechanism of action (receptor pharmacology)

V1a (Gq): ↑IP3/DAG → ↑intracellular Ca2+ in vascular smooth muscle → vasoconstriction (↑SVR, ↑MAP)
- Also constricts splanchnic circulation → reduced portal venous pressure (basis for variceal bleeding therapy)
V2 (Gs): ↑cAMP → insertion of aquaporin-2 channels in collecting duct → water reabsorption (antidiuresis)
- Can cause dilutional hyponatraemia; may reduce urine output independent of renal perfusion changes
V1b/V3 (Gq): stimulates ACTH release (minor relevance clinically; part of stress response)
Relative catecholamine independence: effective in acidosis/hypoxia where adrenergic responsiveness may be reduced

Haemodynamic effects

Primary: ↑SVR → ↑MAP; often reduces noradrenaline dose requirement
Heart rate: may decrease via baroreflex; lacks direct β1 inotropy
Cardiac output: may fall if afterload rises or if hypovolaemic; ensure adequate preload and assess LV function
Coronary circulation: can cause coronary vasoconstriction/ischaemia, especially at higher doses or with existing CAD
Pulmonary circulation: at low doses may have less effect on PVR than catecholamines; at higher doses can increase PVR
Renal: may improve MAP and renal perfusion pressure; V2 effect reduces free water excretion (may reduce urine output)

Pharmacokinetics and preparation

Administration: IV infusion (shock/vasoplegia) or IV bolus in selected scenarios; also IM/SC/intranasal forms exist historically
Onset: rapid (minutes) with IV; offset relatively quick after stopping infusion but variable with dose and physiology
Half-life: short (order of 10–20 minutes) due to metabolism by vasopressinases and hepatic/renal clearance
Dosing (ICU shock): commonly 0.01–0.03 units/min; avoid escalating beyond usual ceiling unless specialist indication
Compatibility: check local guidance; use dedicated line where possible; avoid inadvertent bolus

Indications (exam list)

Septic shock with persistent hypotension despite adequate fluid resuscitation and catecholamines
Post-cardiac surgery vasoplegic syndrome / vasodilatory shock (e.g., ACEi, CPB inflammatory response)
Variceal bleeding (less common than terlipressin in UK; vasopressin may be used with GTN to mitigate coronary ischaemia)
Central diabetes insipidus (acute ICU management; desmopressin usually preferred)
Selected peri-arrest situations (historical alternative to adrenaline; not standard ALS)

Contraindications and cautions

Caution in ischaemic heart disease, peripheral vascular disease, mesenteric ischaemia risk, severe pulmonary hypertension (dose-dependent)
Hypovolaemia: may worsen tissue perfusion by intense vasoconstriction; correct volume status first
Hyponatraemia or risk of water intoxication (prolonged V2 effect)

Adverse effects

Ischaemia: digital necrosis, mesenteric ischaemia, myocardial ischaemia; risk increases with higher doses and vasoconstrictor combinations
Skin/soft tissue: extravasation can cause local ischaemia (treat as vasopressor extravasation per local protocol)
Hyponatraemia, water retention, reduced urine output (V2-mediated)
Arrhythmias: less pro-arrhythmic than catecholamines, but myocardial ischaemia can precipitate arrhythmia
GI: abdominal cramps/diarrhoea; severe complication is mesenteric ischaemia

Comparators and related drugs

Noradrenaline: α1 vasoconstriction + some β1; vasopressin is non-adrenergic and catecholamine-sparing
Adrenaline: strong β and α effects; more tachycardia/arrhythmia and lactate rise than vasopressin
Terlipressin: prodrug with longer duration; commonly used for variceal bleeding and hepatorenal syndrome
Desmopressin (DDAVP): V2-selective; antidiuretic + increases vWF/factor VIII; used in DI and bleeding disorders

Describe the mechanism of action of vasopressin and relate this to its clinical effects in septic shock.

Structure your answer by receptors → second messengers → organ effects → bedside consequences.

V1a receptor (vascular smooth muscle): Gq → IP3/DAG → ↑Ca2+ → vasoconstriction → ↑SVR and ↑MAP
V2 receptor (collecting duct): Gs → ↑cAMP → aquaporin-2 insertion → water reabsorption (antidiuresis)
In septic shock: endogenous vasopressin levels may be inappropriately low (“relative deficiency”) and adrenergic receptors may be downregulated/desensitised; vasopressin can restore vascular tone when catecholamines are less effective
Clinical effects: raises MAP, reduces noradrenaline requirement; but can reduce CO if hypovolaemic or LV dysfunction and can cause ischaemic complications

Compare vasopressin with noradrenaline as vasopressors in vasodilatory shock.

Aim for: receptor profile, haemodynamics, adverse effects, and when you would choose one over the other.

Noradrenaline: α1 (vasoconstriction) + β1 (inotropy/chronotropy) → ↑SVR with some ↑CO; more tachycardia/arrhythmia than vasopressin
Vasopressin: V1a vasoconstriction without β1 stimulation → less tachycardia but greater risk of regional ischaemia at higher doses
Use: noradrenaline is first-line in septic shock; vasopressin is typically added when noradrenaline dose is escalating or vasoplegia suspected (e.g., post-CPB)
Monitoring differences: with vasopressin pay particular attention to digital/mesenteric perfusion and sodium/water balance

A post-cardiac surgery patient has vasoplegia: MAP 50 mmHg, high cardiac output, low SVR, on high-dose noradrenaline. How would you use vasopressin and what are the risks?

This is a classic scenario for vasopressin in FRCA vivas: define vasoplegia, justify choice, give dose, monitoring, complications.

Rationale: vasoplegic syndrome (low SVR, normal/high CO) often responds to non-adrenergic vasoconstrictors; vasopressin can restore vascular tone and reduce catecholamine dose
Dose: start infusion 0.01–0.03 units/min (local protocol); avoid large boluses and avoid excessive dose escalation
Prerequisites: ensure adequate preload; exclude tamponade/bleeding; assess LV function (echo) because pure vasoconstriction can reduce CO
Risks: digital/mesenteric/coronary ischaemia, reduced CO, hyponatraemia/water retention, extravasation injury

Explain why vasopressin may be effective when catecholamines are not (e.g., severe acidosis or septic shock).

Examiners want you to link receptor pharmacology to pathophysiology.

Adrenergic receptor responsiveness can be reduced in sepsis and acidosis (downregulation/desensitisation, altered signal transduction)
Vasopressin acts via V1a (Gq) rather than α/β receptors, so can still produce vasoconstriction when catecholamine effect is blunted
Sepsis may feature a relative vasopressin deficiency over time, supporting rationale for supplementation

What are the key adverse effects of vasopressin and how would you detect them early in ICU?

Give system-based adverse effects and practical bedside markers.

Ischaemia: digital mottling/necrosis, abdominal pain/distension or rising lactate (mesenteric), ECG/troponin changes (coronary)
Renal/water: falling sodium, reduced free water clearance, decreasing urine output not necessarily reflecting worsening renal perfusion
Haemodynamic: excessive afterload → reduced CO; detect with echo, ScvO2 trends, lactate, peripheral perfusion
Local: extravasation causing skin ischaemia; ensure central access where possible and frequent line checks

Discuss the use of vasopressin in variceal bleeding and why nitrates may be co-prescribed.

This often appears as a pharmacology viva: portal pressure, splanchnic vasoconstriction, and coronary risk.

V1a-mediated splanchnic vasoconstriction reduces portal venous inflow and portal pressure → helps control variceal bleeding
Major limitation: systemic vasoconstriction including coronary vasoconstriction → myocardial ischaemia risk
Nitrates (e.g., GTN) may be used to reduce coronary vasoconstriction/ischaemia risk while maintaining portal pressure reduction
In UK practice, terlipressin is more commonly used due to longer action and established protocols

Outline the receptor subtypes for vasopressin and give one clinically relevant effect for each.

V1a (vascular): vasoconstriction → ↑SVR/↑MAP; splanchnic vasoconstriction → ↓portal pressure
V2 (renal collecting duct): antidiuresis via aquaporin-2 → water retention, risk of hyponatraemia
V1b/V3 (pituitary): ↑ACTH release (stress response; limited direct therapeutic use in anaesthesia)

A patient on vasopressin develops falling sodium and low urine output. Explain the mechanism and your response.

This tests V2 physiology and safe ICU practice.

Mechanism: V2 activation → aquaporin-2 insertion → free water retention → dilutional hyponatraemia; urine output may fall due to antidiuresis
Assess: volume status, serum/urine osmolality, other causes (SIADH, excess hypotonic fluids), and overall perfusion/renal function
Response: review need for vasopressin dose/duration, restrict free water/hypotonic fluids, consider alternative vasopressor strategy if appropriate; correct sodium cautiously per hyponatraemia guidelines

Why can vasopressin reduce the dose requirement of noradrenaline in septic shock?

Provides additional vasoconstrictor pathway (V1a) independent of adrenergic receptors
Addresses relative vasopressin deficiency seen in prolonged septic shock
Restores vascular tone and MAP, allowing down-titration of catecholamines and potentially reducing catecholamine-related adverse effects

Give a structured approach to starting vasopressin in septic shock in ICU.

Think: confirm diagnosis, optimise basics, start drug safely, monitor response and harm.

Confirm vasodilatory shock: hypotension with low SVR features; exclude/ treat hypovolaemia, bleeding, cardiogenic shock, obstructive causes
Optimise: source control, antibiotics, fluids guided by dynamic assessment, first-line noradrenaline to target MAP (often 65 mmHg, individualise)
Add vasopressin: start 0.01–0.03 units/min as adjunct when noradrenaline requirement is rising; avoid bolus dosing
Monitor: MAP, CO/echo, lactate, peripheral perfusion, ECG; check sodium and fluid balance; watch for digital/mesenteric ischaemia
Weaning: once vasoplegia resolves and catecholamine dose falls, wean carefully to avoid rebound hypotension