Noradrenaline

Where it fits clinically

First-line vasopressor for vasodilatory shock (especially sepsis) to restore MAP and organ perfusion
- Titrate to MAP target (commonly ≥65 mmHg; individualise for chronic hypertension, raised ICP, etc.)
- Often combined with fluids and source control; add vasopressin/epinephrine if escalating dose
Perioperative hypotension due to vasodilation (e.g., neuraxial anaesthesia, vasoplegia after CPB, anaesthetic-induced vasodilation)
- Useful when SVR is low with preserved/adequate cardiac output
Bridge in cardiogenic shock when hypotensive (often alongside inotrope such as dobutamine) to maintain coronary perfusion pressure
- Avoid excessive afterload in severe LV failure; titrate carefully with echo/CO monitoring
Not primarily a chronotrope; if bradycardia is dominant problem consider adrenaline, ephedrine, atropine, pacing depending on context

Practical administration (ICU/anaesthesia)

Route: continuous IV infusion (preferably central venous); can start peripherally short-term with large-bore cannula and close monitoring
- If peripheral: use proximal vein, check patency frequently, avoid hand/wrist veins; have extravasation plan
Typical infusion range: ~0.02–1 microgram/kg/min (wide variation; use local protocols and clinical response)
- Start low and titrate every 1–3 min in theatre; every 5–15 min in ICU depending on stability
Bolus dosing: generally avoided due to overshoot hypertension/arrhythmia; if used, very small aliquots with invasive BP monitoring
Monitoring: invasive arterial BP strongly recommended; assess perfusion (lactate, urine output, capillary refill), rhythm, and cardiac output where relevant

Drug class and chemistry

Endogenous catecholamine; sympathomimetic amine
Predominantly direct-acting agonist at adrenergic receptors
Catechol structure → poor oral bioavailability, rapid metabolism, short duration

Receptor pharmacology

Receptor profile: strong α1 agonist; α2 agonist; modest β1 agonist; minimal β2 activity
- α1: arteriolar and venous vasoconstriction → ↑SVR and ↑venous return
- β1: ↑inotropy (and some chronotropy) but reflex bradycardia often offsets HR rise
- α2 (central/peripheral): reduces sympathetic outflow and noradrenaline release (complex net effects clinically dominated by α1 vasoconstriction when infused)
Net haemodynamic pattern: ↑MAP mainly via ↑SVR; HR often unchanged or ↓; CO variable (may ↑, unchanged, or ↓ depending on preload/afterload and myocardial function)

Physiological effects (system-by-system)

Cardiovascular: ↑SVR, ↑diastolic pressure; ↑coronary perfusion pressure; may increase myocardial oxygen demand (afterload + β1)
- Reflex vagal bradycardia common (baroreceptor-mediated)
- Arrhythmias less frequent than adrenaline but still possible, especially with hypoxia, acidosis, or high doses
Venous tone: venoconstriction can augment stressed volume and venous return; may reduce need for excessive fluid in vasodilatory shock
Respiratory: minimal bronchodilation (little β2) → not a bronchodilator
Renal/splanchnic: raises perfusion pressure but intense vasoconstriction can reduce regional blood flow; net effect depends on restoring MAP vs excessive vasoconstriction
- Aim for adequate MAP and avoid unnecessary high doses; assess lactate, gut perfusion markers, urine output
Uteroplacental: vasoconstriction may reduce uterine blood flow; use only if maternal hypotension threatens perfusion (balance risk/benefit)
Metabolic: less hyperglycaemia/lactate generation than adrenaline; still can increase lactate via improved perfusion and β effects at higher doses

Pharmacokinetics

Administration: IV infusion (not orally active)
Onset: rapid (seconds to minutes); offset: rapid after stopping (minutes)
Distribution: limited CNS penetration; does not cross BBB well
Metabolism: primarily by COMT and MAO in liver and other tissues; metabolites excreted in urine

Indications

Septic shock with persistent hypotension after adequate fluid resuscitation
Vasoplegic shock (post-CPB, anaphylactoid/vasodilatory states, drug-induced vasodilation)
Neuraxial anaesthesia-related hypotension when SVR is reduced (less common than phenylephrine in obstetrics; choice depends on HR/CO goals)
Adjunct in cardiogenic shock with hypotension to maintain perfusion pressure (often with an inotrope)

Contraindications and cautions

No absolute contraindication in life-threatening shock; relative cautions relate to excessive vasoconstriction and arrhythmia risk
Caution: severe peripheral vascular disease, mesenteric ischaemia risk, uncontrolled hypertension, severe LV failure (afterload sensitivity)
Correct contributing factors: hypovolaemia, hypoxia, acidosis, hypocalcaemia; these reduce efficacy and increase adverse effects

Adverse effects

Excessive vasoconstriction: digital/ischaemic complications, skin necrosis, mesenteric ischaemia (dose and duration related)
Cardiac: bradycardia (reflex), tachyarrhythmias (less than adrenaline), myocardial ischaemia (↑afterload/oxygen demand)
Extravasation: severe local vasoconstriction → tissue ischaemia/necrosis
- Management: stop infusion, aspirate via cannula, leave cannula in situ, infiltrate with phentolamine if available; consider topical nitroglycerin and surgical/plastics review

Important interactions

MAO inhibitors: markedly potentiated effect → hypertensive crisis risk
Tricyclic antidepressants/SNRIs: potentiation via reduced reuptake → exaggerated pressor response
Non-selective β-blockers: unopposed α effects → severe hypertension and reflex bradycardia; β1 inotropy blunted
Volatile anaesthetics (esp halothane historically): increased arrhythmogenicity with catecholamines
α-blockers (e.g., phentolamine): antagonise pressor effect

Preparation and dosing (UK practice-oriented)

Common ICU syringe: noradrenaline 4 mg in 50 mL (80 micrograms/mL) or 8 mg in 50 mL (160 micrograms/mL) — check local standard
- Use a dedicated line/port where possible; label clearly; use smart pump/drug library
Titration: aim for the lowest dose achieving perfusion goals; reassess volume status and cardiac function frequently
Weaning: reduce gradually while ensuring MAP and perfusion maintained; address underlying vasodilation (sepsis control, stop vasodilators, treat adrenal insufficiency if suspected)

Comparisons (high-yield)

Noradrenaline vs phenylephrine: both increase SVR; noradrenaline has β1 activity → less reduction in stroke volume/CO in some patients; phenylephrine more likely to cause reflex bradycardia and reduced CO
Noradrenaline vs adrenaline: adrenaline has strong β1 and β2 (plus α at higher doses) → more tachycardia, arrhythmia, lactate; noradrenaline more 'pure' vasopressor
Noradrenaline vs dopamine: dopamine more arrhythmogenic and endocrine effects; noradrenaline preferred in septic shock

Describe the receptor actions of noradrenaline and the expected haemodynamic effects.

A common viva stem is to link receptor profile to BP/HR/CO changes and explain why HR may fall.

Strong α1 agonism → arteriolar + venous vasoconstriction → ↑SVR and ↑MAP
Modest β1 agonism → ↑contractility (± ↑HR)
Minimal β2 → little vasodilation/bronchodilation
Baroreceptor-mediated reflex → vagal bradycardia, so HR often unchanged or reduced despite β1
CO response is variable: may rise (improved preload/perfusion), remain stable, or fall (excess afterload, bradycardia, LV dysfunction)

You start noradrenaline in septic shock. What endpoints do you use to judge adequacy and safety?

Examiners look for perfusion-based targets beyond a single MAP number.

Primary: MAP target (often ≥65 mmHg; individualise for chronic HTN/raised ICP)
Perfusion: urine output, mental state, skin temperature/capillary refill, peripheral mottling
Biochemistry: lactate trend, acid–base status
Haemodynamics: HR/rhythm, echo/CO monitoring if available; assess volume responsiveness to avoid under-resuscitation
Safety: signs of excessive vasoconstriction (cool peripheries, digital ischaemia), myocardial ischaemia, arrhythmias

Why can noradrenaline cause bradycardia, and when is that clinically important?

This is frequently examined because it distinguishes noradrenaline from adrenaline and ephedrine.

Mechanism: α1-mediated rise in MAP → baroreceptor activation → increased vagal tone → reflex bradycardia
Importance: in patients with fixed stroke volume (e.g., severe AS) bradycardia may be tolerated; in others it may reduce CO if stroke volume cannot compensate
If bradycardia with hypotension persists: consider reducing dose, correcting hypovolaemia, adding/increasing inotrope, or using an agent with more chronotropy (e.g., adrenaline) depending on scenario

Compare noradrenaline with phenylephrine for treating hypotension under anaesthesia.

A common FRCA comparison: receptor selectivity and effect on CO/HR.

Phenylephrine: pure α1 → ↑SVR with more reflex bradycardia; can reduce CO (especially if preload limited)
Noradrenaline: α1 + some β1 → ↑SVR with better preservation of contractility; HR often unchanged/↓
Choice depends on physiology: low SVR with adequate CO may suit either; if CO is marginal, noradrenaline may be preferable to avoid CO drop
Both require careful titration and ideally invasive BP monitoring if ongoing infusion

Explain how noradrenaline can improve venous return and why that matters in shock.

This tests understanding of venous capacitance and stressed volume.

Noradrenaline causes venoconstriction (α1) → reduces venous capacitance → increases stressed volume and mean systemic filling pressure
This can augment venous return and support CO, partly substituting for fluid in vasodilatory shock
However, excessive afterload can still reduce CO in LV dysfunction; reassess with echo/CO monitoring

What are the key adverse effects of noradrenaline and how do you mitigate them?

Expect to cover ischaemia, arrhythmias, and extravasation.

Excess vasoconstriction → peripheral/digital ischaemia, skin necrosis, mesenteric ischaemia
- Mitigation: use lowest effective dose, ensure adequate volume status, monitor limbs/perfusion, consider adding vasopressin to reduce catecholamine requirement
Cardiac: bradycardia, myocardial ischaemia, arrhythmias
- Mitigation: correct hypoxia/acidosis/electrolytes, treat pain/agitation, avoid excessive MAP targets
Extravasation injury
- Mitigation: central line where possible; if peripheral, use proximal large vein and frequent checks; have phentolamine protocol

How is noradrenaline metabolised and what is the relevance of MAO inhibitors and TCAs?

This links catecholamine metabolism to drug interactions.

Metabolised by COMT and MAO in liver and extrahepatic tissues; inactive metabolites excreted in urine
MAO inhibitors → reduced breakdown → potentiated pressor response and hypertensive crisis risk
TCAs/SNRIs inhibit reuptake → increased synaptic catecholamine → exaggerated response

A patient on noradrenaline has rising lactate. How do you interpret this and what actions do you take?

This tests nuance: lactate is not always ‘worsening shock’ and noradrenaline can both help and harm regional perfusion.

Interpretation: rising lactate may reflect ongoing hypoperfusion, impaired clearance, increased production from stress/β effects, or regional ischaemia from excessive vasoconstriction
Actions: reassess haemodynamics (MAP, CO), volume status, Hb/oxygenation, source control; review dose and MAP target (avoid over-vasoconstriction)
Look for red flags: abdominal pain/distension, worsening acidosis, mottled/cold peripheries → consider mesenteric/peripheral ischaemia and reduce catecholamine burden/add alternative agents

Describe safe peripheral administration of noradrenaline and management of extravasation.

Frequently examined as a patient safety/critical incident scenario.

Peripheral use: acceptable short-term while obtaining central access if haemodynamically unstable
Technique: large-bore cannula in a proximal vein (e.g., forearm/ACF), avoid hand/wrist, secure well, check patency and site frequently, use lowest concentration feasible
Extravasation management: stop infusion, leave cannula in situ, aspirate, elevate limb; infiltrate phentolamine around site if available; consider topical GTN; urgent plastics/surgical review if threatened tissue

In cardiogenic shock, when might noradrenaline be preferred to adrenaline or dopamine?

Assesses understanding of arrhythmia risk and balancing perfusion pressure with inotropy.

When hypotension is prominent and coronary perfusion needs support, noradrenaline provides reliable vasopressor effect with less tachyarrhythmia than adrenaline/dopamine
Often paired with an inotrope (e.g., dobutamine) if CO is low, rather than escalating catecholamine with more β effects
Avoid excessive afterload in severe LV failure; use echo/CO monitoring to titrate