Adrenaline

Adrenaline is the endogenous catecholamine with alpha and beta adrenergic agonist activity. It is the first line drug for anaphylaxis, a core drug in cardiac arrest, a second line vasopressor and inotrope in shock, a nebulised treatment for croup and an additive to local anaesthetic. The commonest and most dangerous error is confusing the 1 mg/mL and 0.1 mg/mL strengths.

Classification. Catecholamine; non-selective adrenergic agonist.

Mechanism. Alpha 1 stimulation causes vasoconstriction, reduces mucosal oedema and raises blood pressure. Beta 1 stimulation raises heart rate and contractility. Beta 2 stimulation causes bronchodilation and vasodilation in muscle. Low dose infusions favour beta effects; high doses favour alpha effects. It also stops mast cell mediator release.

Pharmacodynamics. IV onset within seconds; IM onset 3 to 5 minutes (faster at the thigh than the deltoid); duration 5 to 10 minutes IV. Causes hyperglycaemia, hypokalaemia, raised lactate and tachyarrhythmia.

Pharmacokinetics. Inactive orally. Metabolised by monoamine oxidase and catechol O methyltransferase; half life about 2 minutes. Crosses the placenta, not the blood brain barrier meaningfully.

Anaphylaxis, IM (first line). Use the 1 mg/mL (1 in 1000) solution into the mid anterolateral thigh. Repeat after 5 minutes if there is no improvement.

• Adult and child over 12 years: 0.5 mg (0.5 mL).

• 6 to 12 years: 0.3 mg (0.3 mL).

• 6 months to 6 years: 0.15 mg (0.15 mL).

• Under 6 months: 0.1 to 0.15 mg (about 0.01 mg/kg).

• Autoinjectors contain 0.15 mg, 0.3 mg or 0.5 mg.

• Refractory anaphylaxis, specialist: IV infusion 0.05 to 0.1 micrograms/kg/min, titrated to blood pressure and airway, with continuous monitoring. Give IV fluids and treat reversible factors.

Cardiac arrest, adult. 1 mg IV or intraosseous, using the 0.1 mg/mL (1 in 10 000) solution, flushed with 20 mL, repeated every 3 to 5 minutes. Give as soon as possible in non-shockable rhythms; in shockable rhythms give after the third shock.

Cardiac arrest, child. 0.01 mg/kg (0.1 mL/kg of 0.1 mg/mL) IV or intraosseous, maximum 1 mg, repeated every 3 to 5 minutes.

Shock, adult (second line vasopressor or inotrope). Infusion starting at 0.05 to 0.1 micrograms/kg/min (or 2 to 5 micrograms/minute), titrated every 5 minutes; usual range 0.05 to 0.5 micrograms/kg/min; maximum set by local practice, rarely over 1 microgram/kg/min.

Symptomatic bradycardia not responding to atropine, adult. Infusion 2 to 10 micrograms/minute titrated to heart rate, while arranging pacing.

Croup, child. Nebulised adrenaline 400 micrograms/kg (0.4 mg/kg) in 3 to 5 mL 0.9% sodium chloride, maximum 5 mg, with dexamethasone; observe at least 2 to 4 hours because effect lasts 1 to 2 hours.

Severe asthma not responding to nebulised beta agonists, adult. IM 0.3 to 0.5 mg, specialist use only.

Local anaesthetic additive. Adrenaline 5 micrograms/mL (1 in 200 000) prolongs block and reduces absorption. Avoid in end arterial sites (fingers, toes, penis, ear lobe).

Contraindications. None absolute in anaphylaxis or cardiac arrest. In other settings use with caution in severe hypertension, tachyarrhythmia, phaeochromocytoma, closed angle glaucoma, uncorrected hypovolaemia.

Warnings. Arrhythmias, myocardial ischaemia, hypertension and intracranial haemorrhage. Tissue necrosis on extravasation. Lactic acidosis and hyperglycaemia (a type A lactate rise) on infusion. Contains sulphite in some products.

Adverse effects. Anxiety, tremor, palpitations, tachycardia, pallor, headache, nausea, hypokalaemia, hyperglycaemia.

Interactions.

• Non-selective beta blockers: severe hypertension with reflex bradycardia, and resistance to adrenaline in anaphylaxis; give glucagon 1 to 5 mg IV over 5 minutes then 5 to 15 micrograms/minute.

• Monoamine oxidase inhibitors, tricyclic antidepressants, linezolid: exaggerated pressor response.

• Halogenated anaesthetics and digoxin: arrhythmia.

• Alpha blockers reduce the pressor effect.

Special groups.

• Pregnancy: do not withhold in anaphylaxis or arrest; place the patient in left lateral tilt.

• Breastfeeding: compatible.

• Children: dose by weight or age band.

• Older adults: same IM dose in anaphylaxis; watch cardiac ischaemia.

• Kidney and liver impairment: no adjustment.

Extravasation. Infiltrate phentolamine 5 to 10 mg in 10 mL 0.9% sodium chloride; stop the infusion and elevate the limb.

Formulations. 1 mg/mL (1 in 1000), 0.1 mg/mL (1 in 10 000) prefilled syringes, and autoinjectors.

Preparation of infusion. For example 1 mg in 100 mL 0.9% sodium chloride or 5% glucose (10 micrograms/mL) for peripheral use, or a more concentrated central line preparation set by local practice; always label concentration clearly. Adrenaline is incompatible with sodium bicarbonate.

Route. IM into the thigh for anaphylaxis; IV or intraosseous for arrest; infusion preferably through a central line; avoid subcutaneous use in shock.

Baseline. Airway, breathing, pulse, blood pressure, ECG, glucose, potassium, lactate.

Monitoring. Continuous ECG, oxygen saturation, blood pressure every 1 to 5 minutes during infusion; serum potassium, glucose and lactate every 2 to 4 hours; infusion site. After anaphylaxis, observe for at least 6 hours, up to 12 to 24 hours for severe or biphasic risk, and give a prescribed autoinjector with training.

Stopping. Wean the infusion in steps; do not stop abruptly in shock.

Common prescribing errors. Giving 1 mg/mL IV as a bolus in a non-arrest patient; confusing the two strengths; under dosing or delaying IM adrenaline in anaphylaxis; giving it subcutaneously or into the buttock; withholding it because the patient takes a beta blocker.