Why this drug is interesting

Adrenaline is the drug with the strongest claim to be indispensable in emergency medicine. In anaphylaxis it is the only intervention that reverses the pathophysiology, and delay in giving it is the single factor most consistently associated with death. In cardiac arrest it is in every algorithm in the world.

It is also the drug most consistently associated with route and concentration errors. The 1:1000 and 1:10,000 preparations sit in the same resus room. The intramuscular dose and the intravenous dose differ by an order of magnitude. Intravenous boluses in anaphylaxis are explicitly not recommended in UK guidance, and yet remain a recurring source of harm.

Pharmacology

Mechanism

Adrenaline is a non-selective agonist at α and β adrenoceptors, and in anaphylaxis every one of those actions is therapeutic:

Receptor	Action	Why it matters in anaphylaxis
α₁	Vasoconstriction	Reverses vasodilatation and capillary leak; reduces mucosal oedema, including laryngeal
β₁	Positive inotropy and chronotropy	Supports cardiac output against distributive shock
β₂	Bronchodilatation; mast cell and basophil stabilisation	Relieves bronchospasm and reduces further mediator release

That last action is the reason adrenaline is not simply an inotrope with bronchodilator side effects — it interrupts ongoing mediator release, which is why early administration changes the trajectory of the reaction rather than only supporting the patient through it.

Kinetics

Onset, IM: Rapid; peak plasma concentration within about 10 minutes from the thigh
Onset, IV: Within seconds
Half-life: 2–3 minutes — metabolised by COMT and MAO
Implication: Effects are short-lived: repeat dosing or an infusion is required for sustained effect

Anaphylaxis

Intramuscular dosing — RCUK

Use adrenaline at 1 mg/mL (1:1000) concentration, injected at the anterolateral aspect of the middle third of the thigh.³

RCUK anaphylaxis IM adrenaline doses
Age	Dose	Volume of 1:1000
Adult and child over 12 years	500 micrograms	0.5 mL
Child 6–12 years	300 micrograms	0.3 mL
Child 6 months to 6 years	150 micrograms	0.15 mL
Child under 6 months	100–150 micrograms	0.1–0.15 mL

If there is no response

Repeat IM adrenaline after 5 minutes
Give an IV fluid bolus — adult 500–1000 mL, child 10 mL/kg, using a glucose-free crystalloid such as Hartmann's
Position the patient supine with legs raised; if pregnant, lie on the left side; if breathing is difficult, sitting up may help

Refractory anaphylaxis

Defined as respiratory and/or cardiovascular symptoms persisting despite two appropriate doses of IM adrenaline. At that point, confirm the resuscitation team or ambulance has been called and follow the refractory algorithm.⁴

Still refractory

Consider a second vasopressor alongside the adrenaline infusion — noradrenaline, vasopressin or metaraminol
In patients on beta-blockers, consider glucagon — see also Bisoprolol
Airway: partial upper airway obstruction or stridor — nebulised adrenaline; follow the difficult airway algorithm if needed
Breathing: nebulised salbutamol and ipratropium with oxygen; consider IV salbutamol or aminophylline; oxygenation matters more than intubation
Consider extracorporeal life support
Take mast cell tryptase, give high-flow oxygen, titrate to SpO₂ 94–98%

Cardiac arrest

RCUK 2025 adult ALS algorithm⁵
Rhythm	When to give adrenaline	Then
Non-shockable — PEA / asystole	Immediately, as soon as IV or IO access is obtained	Every 3–5 minutes
Shockable — VF / pulseless VT	After the 3rd shock	Every 3–5 minutes

The dose is 1 mg IV or IO — 10 mL of 1:10,000, or 1 mL of 1:1000 diluted. Amiodarone is also given after the third shock in shockable rhythms; see Amiodarone and Lidocaine.

Adrenaline in bradycardia

The RCUK 2025 bradyarrhythmia algorithm includes adrenaline 2–10 micrograms/minute IV among the interim measures where atropine has been unsatisfactory, alongside isoprenaline 5 micrograms/minute and transcutaneous pacing.⁶ See Atropine.

The concentration problem

1:1000 and 1:10,000 — know both, every time

Preparation	Concentration	Typical use
1:1000	1 mg in 1 mL (1 mg/mL)	Intramuscular anaphylaxis; nebulised; source for infusions
1:10,000	1 mg in 10 mL (100 µg/mL)	Intravenous in cardiac arrest

The ratio notation is itself a hazard — it expresses grams per millilitres of solution, which is not how any other drug in the department is labelled, and it is not intuitive under stress. Say and document micrograms and millilitres, not ratios, and confirm the ampoule out loud before giving it.

Auto-injectors add a further layer: device strengths differ, patients may carry more than one, and prescribing and expiry are frequent problems. Every patient treated for anaphylaxis needs an auto-injector, training in its use, and referral to allergy services — that follow-up is part of the treatment, not an administrative afterthought.

Adverse effects and cautions

Adverse effects

Tachycardia, palpitations, tremor, anxiety — near-universal and usually benign at IM doses
Hypertension — a sharply rising blood pressure during an infusion indicates overdose
Myocardial ischaemia and arrhythmia — the concern in older patients and those with coronary disease
Headache, pallor, nausea
Extravasation injury from infusions — tissue necrosis; another reason for a dedicated line
Hyperglycaemia and lactataemia

Interactions

Beta-blockers — may blunt the response to adrenaline and produce unopposed α effects; consider glucagon in refractory anaphylaxis
Tricyclic antidepressants and MAO inhibitors — potentiate the pressor response
Volatile anaesthetic agents — sensitise the myocardium to catecholamine-induced arrhythmia

Critical appraisal

PARAMEDIC-2

This is the trial that should shape how adrenaline in cardiac arrest is taught. 8,014 patients with out-of-hospital cardiac arrest were randomised to adrenaline or placebo.⁷

Adrenaline produced a small increase in 30-day survival
There was no significant difference in favourable neurological outcome
More survivors in the adrenaline group had severe neurological impairment

Wider points

The anaphylaxis evidence base is observational, and rightly so. There is no randomised trial of adrenaline versus placebo in anaphylaxis and there never will be. The evidence is mechanistic and epidemiological — and consistent: delayed administration is associated with fatal outcome. This is a case where demanding randomised evidence would be a category error.
Under-treatment remains commoner than over-treatment in anaphylaxis. Hesitation over cardiac risk, uncertainty about the diagnosis, and reaching for antihistamines and steroids first all delay the only drug that works. Steroids in particular no longer feature as a routine first-line measure in current guidance.
The intravenous bolus problem is a systems failure, not a knowledge gap. Clinicians who know the IM dose still give IV boluses in extremis. The mitigation is having a written infusion recipe and a dedicated line available before it is needed.
The optimal arrest dose and interval are not well established. The 1 mg every 3–5 minutes regimen is conventional rather than derived from dose-finding work, and whether a lower dose or different interval would preserve the survival benefit while reducing neurological harm is genuinely unknown.

References

1
Adrenaline (epinephrine) injection — Summary of Product Characteristics. Consult the preparation stocked locally via the electronic Medicines Compendium.
2
Adrenaline/epinephrine — dosing and safety monograph. BNF, NICE. bnf.nice.org.uk
3
Resuscitation Council UK. Anaphylaxis algorithm, 2021. resus.org.uk — mirrored at lifesupport.resusdoc.uk. Source of the IM dose table, injection site and repeat interval. Verified 20 Aug 2026.
4
Resuscitation Council UK. Refractory anaphylaxis algorithm, 2021. resus.org.uk. Source of the peripheral low-dose infusion recipe, the statement that IV boluses are not recommended, fluid volumes and second-vasopressor guidance.
5
Resuscitation Council UK. Adult advanced life support algorithm, 2025. resus.org.uk. Adrenaline immediately in non-shockable rhythms; after the 3rd shock in shockable rhythms; then every 3–5 minutes.
6
Resuscitation Council UK. Adult bradyarrhythmia algorithm, 2025. resus.org.uk. Adrenaline 2–10 micrograms/minute IV among interim measures.
7
Perkins GD, Ji C, Deakin CD, et al. A randomized trial of epinephrine in out-of-hospital cardiac arrest (PARAMEDIC-2). N Engl J Med 2018;379(8):711–21.
8
NICE NG253. Anaphylaxis: assessment and referral after emergency treatment. National Institute for Health and Care Excellence.

Adrenaline

At a glance