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 &amp, 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

Test yourself…

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