Adrenaline

Where you use it (anaesthesia/ICU/ED)

Cardiac arrest (ALS): VF/pVT after 3rd shock; asystole/PEA immediately; then every 3–5 min
- Standard adult dose: 1 mg IV/IO (10 mL of 1:10,000) per cycle
- Paediatric: 10 micrograms/kg IV/IO (0.1 mL/kg of 1:10,000)
Anaphylaxis: first-line vasopressor/bronchodilator
- IM (adult): 500 micrograms (0.5 mL of 1:1000) into anterolateral thigh; repeat every 5 min if needed
- IV titration (experienced clinician): 10–50 micrograms boluses; consider infusion if refractory
Peri-arrest hypotension/vasoplegia (e.g., post-induction, septic vasodilation) as bolus or infusion
- Bolus: commonly 10–100 micrograms IV titrated to effect (context-dependent)
- Infusion: often 0.02–0.2 micrograms/kg/min (titrate; higher doses sometimes required in shock)
Adjunct to local anaesthetic (LA) to reduce systemic absorption and prolong block; marker of intravascular injection
- Typical concentration: 1:200,000 (5 micrograms/mL) or 1:100,000 (10 micrograms/mL)
- Caution in end-artery areas and in patients with severe cardiac disease; avoid in IV regional anaesthesia (Bier’s) in many protocols
Severe asthma/bronchospasm (rarely first-line in anaesthesia; consider in life-threatening bronchospasm, especially with anaphylaxis)
Post-cardiac surgery/low cardiac output states: inotrope + vasopressor effect

How it behaves clinically (dose-dependent haemodynamics)

Low dose: β effects predominate → ↑HR, ↑contractility, bronchodilation; β2 vasodilation may ↓SVR/diastolic BP
Higher dose: α1 vasoconstriction predominates → ↑SVR, ↑diastolic BP, ↑coronary perfusion pressure; reflex effects may blunt tachycardia
Net effect: ↑MAP (dose dependent), ↑CO (via β1), variable change in SVR; ↑myocardial O2 demand and arrhythmia risk

Practical prescribing & preparation (common UK concentrations)

1:1000 = 1 mg/mL (used for IM anaphylaxis; also topical use)
1:10,000 = 0.1 mg/mL = 100 micrograms/mL (used for IV arrest dosing; also for cautious IV boluses when diluted)
Infusion example: 4 mg in 50 mL = 80 micrograms/mL (check local policy; label clearly)
- At 5 mL/h delivers 400 micrograms/h ≈ 6.7 micrograms/min
Central line preferred for infusions; if peripheral, use a large vein, close monitoring, and plan for early central access

Class, structure, and receptor pharmacology

Endogenous catecholamine; direct-acting sympathomimetic
Receptor activity: α1, α2, β1, β2 agonist (dose-dependent predominance)
- β1: ↑inotropy, ↑chronotropy, ↑dromotropy; ↑automaticity (arrhythmogenic)
- β2: bronchodilation; vasodilation in skeletal muscle; drives intracellular K+ shift (↓K+); ↑glycogenolysis
- α1: vasoconstriction (skin/splanchnic), ↑SVR, ↑diastolic BP; reduces mucosal oedema (upper airway)
- α2: presynaptic inhibition of noradrenaline release (less clinically prominent at typical doses)
Second messenger systems: α1 (Gq → ↑IP3/DAG), α2 (Gi → ↓cAMP), β (Gs → ↑cAMP)

Pharmacokinetics

Routes: IV/IO (immediate), IM (rapid), SC (slower due to vasoconstriction), inhaled/nebulised/topical (local effect), endotracheal (historical/less favoured)
Onset/offset: very rapid onset IV; short duration due to redistribution and metabolism
Metabolism: COMT and MAO (liver, kidney, other tissues); metabolites include metanephrine and VMA (urinary)
Elimination: renal (metabolites); plasma half-life is short (minutes)

Pharmacodynamics and organ effects

Cardiovascular: ↑CO (β1), ↑SVR at higher doses (α1), ↑coronary perfusion pressure (key in CPR), ↑myocardial O2 consumption
Respiratory: bronchodilation (β2); reduces mucosal oedema (α1) e.g. upper airway swelling
Metabolic: hyperglycaemia (glycogenolysis/gluconeogenesis), lactic acidosis (β2-mediated glycolysis), hypokalaemia (β2 intracellular shift)
Renal/splanchnic: reduced flow due to α-mediated vasoconstriction; may worsen gut/renal perfusion at high doses
CNS: does not significantly cross BBB; central effects limited

Indications and dosing (core numbers to know)

Cardiac arrest (adult): 1 mg IV/IO every 3–5 min
Anaphylaxis (adult): IM 500 micrograms; IV bolus 10–50 micrograms titrated; infusion if refractory
Infusion (shock/vasoplegia): commonly 0.02–0.2 micrograms/kg/min; titrate to MAP/perfusion; anticipate tachyarrhythmias
With LA: 1:200,000 (5 micrograms/mL) or 1:100,000 (10 micrograms/mL) depending on technique and local policy
Nebulised/topical for airway oedema/stridor (institution-specific): used for vasoconstriction and reduced oedema

Adverse effects

Tachycardia, hypertension, myocardial ischaemia/infarction (especially with coronary disease), arrhythmias (SVT, VT, VF)
Pulmonary oedema (afterload increase, myocardial dysfunction, fluid shifts) particularly with high doses
Peripheral/ischaemic complications: extravasation → local vasoconstriction and tissue necrosis
- Treat: stop infusion, aspirate via cannula if possible, elevate, warm compress; infiltrate phentolamine (α-blocker) per local protocol
Metabolic: hyperglycaemia, hypokalaemia, raised lactate
Tremor/anxiety (more with systemic β stimulation, especially in awake patients)

Contraindications and cautions (contextual)

No absolute contraindication in life-threatening anaphylaxis or cardiac arrest
Caution: ischaemic heart disease, severe hypertension, tachyarrhythmias, hypertrophic obstructive cardiomyopathy (may worsen obstruction via inotropy/tachycardia)
Local infiltration caution: end-artery sites (digits, penis, pinna, nose tip) and compromised peripheral circulation (traditional teaching; practice varies and depends on concentration/technique)

Drug interactions (viva-friendly)

β-blockers (especially non-selective): unopposed α vasoconstriction → severe hypertension/bradycardia; reduced bronchodilation
Volatile agents (esp. halothane historically): increased myocardial irritability → arrhythmias; modern agents still warrant caution with high catecholamine levels
MAO inhibitors/COMT inhibitors: potentiation/prolonged effect (less dramatic than indirect sympathomimetics but relevant)
Tricyclic antidepressants and cocaine: potentiate catecholamine effects (reuptake inhibition) → hypertension/arrhythmias
α-blockers: reduce pressor response; may accentuate β effects (tachycardia)

Special topics often examined

Adrenaline in CPR: improves ROSC via α1-mediated ↑aortic diastolic pressure and ↑coronary perfusion pressure; may worsen post-ROSC myocardial dysfunction/arrhythmias and microcirculatory flow
Adrenaline and lactate: β2 stimulation increases glycolysis and lactate production; rising lactate on adrenaline does not always mean worsening tissue hypoxia
Adrenaline test dose with epidural: intravascular injection may cause HR rise; unreliable under GA, β-blockade, labour, or with high sympathetic tone

Describe the mechanism of action of adrenaline and explain its dose-dependent cardiovascular effects.

Structure your answer: receptors → second messengers → haemodynamic changes at low vs high dose.

Agonist at α1, α2, β1, β2 receptors; relative effect depends on dose and background sympathetic tone
β1 (Gs → ↑cAMP): ↑inotropy/chronotropy/dromotropy → ↑CO; ↑automaticity → arrhythmias
β2 (Gs → ↑cAMP): bronchodilation; skeletal muscle vasodilation → may ↓SVR/diastolic BP at low dose
α1 (Gq → ↑IP3/DAG): vasoconstriction → ↑SVR and ↑diastolic BP; improves coronary perfusion pressure
Low dose: β effects dominate → tachycardia/inotropy with possible fall in SVR; high dose: α1 dominates → pressor effect

What are the standard concentrations of adrenaline used in UK practice and what are they used for?

1:1000 = 1 mg/mL: IM anaphylaxis (adult 0.5 mL = 500 micrograms); also topical use
1:10,000 = 0.1 mg/mL (100 micrograms/mL): IV/IO cardiac arrest dosing (1 mg = 10 mL); also cautious IV titration when appropriately diluted
LA mixtures: commonly 1:200,000 (5 micrograms/mL) or 1:100,000 (10 micrograms/mL)

Outline the management of anaphylaxis and where adrenaline fits in (include doses and routes).

Expect to be asked for immediate actions + exact adrenaline dosing.

Immediate: call for help, stop trigger, high-flow O2, lie flat with legs elevated, secure airway, IV access, monitor
Adrenaline first-line: IM 500 micrograms (0.5 mL of 1:1000) into anterolateral thigh; repeat every 5 min if needed
If severe/refractory or peri-arrest and experienced clinician: IV adrenaline 10–50 micrograms boluses titrated; consider infusion
Fluids: rapid crystalloid boluses (vasodilation/capillary leak); adjuncts: antihistamine, corticosteroid, bronchodilators; consider glucagon if on β-blocker and refractory

Why is adrenaline used in cardiac arrest? Describe the physiological rationale and potential downsides.

Key benefit: α1 vasoconstriction → ↑aortic diastolic pressure → ↑coronary perfusion pressure → improved chance of ROSC
Also increases cerebral perfusion pressure via ↑MAP (macro-circulatory effect)
Downsides: β1-mediated tachyarrhythmias and ↑myocardial O2 demand; may worsen post-ROSC myocardial dysfunction; potential microcirculatory impairment from intense vasoconstriction

A patient becomes profoundly hypotensive immediately after induction. How would you use adrenaline safely?

Treat reversible causes: depth of anaesthesia, hypovolaemia, anaphylaxis, tension pneumothorax, tamponade, arrhythmia
If peri-arrest hypotension: give small IV boluses of adrenaline titrated (e.g., 10–20 micrograms initially; escalate as needed) while supporting airway/ventilation and giving fluids
If ongoing requirement: start infusion (e.g., 0.02–0.2 micrograms/kg/min) via pump; aim MAP/perfusion endpoints; consider arterial line
Avoid dosing errors: confirm concentration (1:10,000 vs 1:1000), label syringes, use standard dilution

Explain why adrenaline can cause a rise in lactate and how you interpret lactate trends in a patient on an adrenaline infusion.

β2 stimulation increases glycolysis and Na+/K+ ATPase activity → increased pyruvate generation and lactate production even with adequate oxygen delivery
Therefore lactate may rise after starting adrenaline without indicating worsening tissue hypoxia; interpret alongside perfusion, acid–base status, ScvO2, urine output, and clinical trajectory
Persistent or rising lactate with worsening acidosis/hypoperfusion still concerning for shock progression or inadequate resuscitation

What are the important adverse effects of adrenaline and how would you manage extravasation injury?

Adverse effects: tachyarrhythmias, hypertension, myocardial ischaemia, pulmonary oedema, hyperglycaemia, hypokalaemia, lactic acidosis, peripheral ischaemia
Extravasation: stop infusion, leave cannula in situ to aspirate, elevate limb, warm compress; infiltrate phentolamine around site per local protocol; seek plastics advice if severe

Compare adrenaline with noradrenaline as vasopressors in shock.

Adrenaline: mixed α and β → vasopressor + inotrope; more tachycardia/arrhythmias; more lactate rise; useful when low CO plus vasodilation
Noradrenaline: predominantly α1 with some β1 → strong vasopressor with less tachycardia; often first-line in septic shock for MAP support
Choice depends on phenotype (vasoplegia vs cardiogenic component), heart rate/rhythm, and response to fluids/inotropes

What interactions are clinically important with adrenaline (include β-blockers, TCAs, cocaine, and volatile agents)?

Non-selective β-blockers: reduced β2 bronchodilation and β1 effects; unopposed α → severe hypertension and reflex bradycardia; refractory anaphylaxis may require glucagon
TCAs/cocaine: inhibit reuptake → potentiated pressor/arrhythmogenic effects
Volatile anaesthetics: increase myocardial sensitivity to catecholamines (halothane classic); caution with high doses and arrhythmia-prone patients
MAO inhibitors/COMT inhibitors: can prolong/potentiate catecholamine effects (clinical relevance varies)

Why is adrenaline added to local anaesthetic solutions? Give benefits and risks.

Benefits: α1 vasoconstriction → reduced systemic absorption (lower peak plasma LA), prolonged duration, improved field haemostasis; may act as marker of intravascular injection (tachycardia)
Risks: tachycardia, hypertension, arrhythmias; local ischaemia in vulnerable tissues; reduced uteroplacental blood flow theoretically with high doses; unreliable test dose under GA/β-blockade

In anaphylaxis under general anaesthesia, what features make diagnosis difficult and how does that affect adrenaline use?

Cutaneous signs may be absent/delayed; bronchospasm may mimic light anaesthesia; hypotension may be attributed to induction/bleeding
If suspected with cardiovascular compromise: treat early with adrenaline (titrated IV boluses) rather than waiting for confirmatory signs; send tryptase samples per protocol