CLASS
Sympathomimetic
PRESENTATION
Clear, colourless solution in a brown vial.
Formulations
- 1ml vial; 1mg, 1mg/ml (1:1000)
- 10ml vial; 1mg, 100mcg/ml (1:10,000)
INDICATIONS & DOSING
Cardiac arrest
- Adult; 1mg IV/IO
- Paediatric; 10mcg/kg IV/IO
- Neonate <34/40 or <2kg; 50mcg IV/IO
- Neonate >34/40; 100mcg IV/IO
Shock
- Adult; 25mcg-1mg IV bolus
- Paediatric; 0.5-10mcg/kg IV bolus
- Adult/paediatric infusion; 0-1mcg/kg/min IV
Anaphylaxis (ANZAAG guideline)
- Adult IM; 500mcg IM
- Adult IV; class II anaphylaxis 20mcg IV, class III anaphylaxis 100-200mcg IV
- Paediatric IM; <6 years 150mcg IM, 6-12 years 300mcg IM (or 10mcg/kg IM)
- Paediatric IV; class II anaphylaxis 2mcg/kg IV, class III anaphylaxis 4-10mcg IV
Bronchospasm, airway oedema
- Adult neb; 5mg/5ml, nebulised
- Paediatric neb; 0.5ml/kg of 1:1000, maximum 5ml, diluted to 5ml with N/saline, nebulised
- Adult/paediatric infusion; 0-1mcg/kg/min IV
Regional anaesthesia additive
- 5mcg/ml (1:200,000); dilute 100mcg (1ml of 1:10 000) up to 20ml of local anaesthetic solution
- Maximum dose 2-4mcg/kg
PRACTICALITIES
Administration
- Boluses; avoid unless clinically peri-arrest/cardiac arrest, start low (~25mcg) and double dose until clinical effect
- Infusion; mixed with N/saline or 5% dextrose, using a dilution of 3mg in 50ml (60mcg/ml) allows the simplicity of 1ml/hr = 1mcg/min
Incompatibilities
- Incompatible with alkaline solutions including sodium bicarbonate
Practice tips
- Consider intramuscular injection as a first-line route in anaphylaxis if not familiar with intravenous use
- Administration through a large peripheral vein is acceptable in the short-term if warranted; use a dilute concentration, watch for extravasation
PHARMACOKINETICS
Onset
- IV/IO/neb; rapid onset <1 minute
- IM (lateral thigh); 3-5 minutes
- ETT; de-emphasised due to unreliable and prolonged absorption
Duration of action
- IV/IO/neb; duration 5-10 minutes
- IM; depot store prolongs action
Metabolism
Half-life 2-3 minutes due to rapid metabolism. Majority metabolised in the liver by catechol-O-methyl transferase to met adrenaline and vanillylmandelic acid. Metabolism by a lesser extent by monoamine oxidase after uptake in adrenergic neurones. Metabolised to inactive products
Elimination
Predominantly renal excretion
MECHANISM
Direct agonism of alpha and beta sympathetic adrenoreceptors
DESIRED CLINICAL EFFECTS
Airway
- Reduces airway mucosal oedema in nebulised form
Respiratory
- Potent bronchodilation
Cardiovascular
- Beta-adrenergic agonism (lower dose range); increased cardiac output via increased chronotropy, inotropy, lusitropy, dromotropy, increased coronary blood flow
- Alpha-adrenergic agonism (higher dose range); systemic vasoconstriction, increased systemic vascular resistance and systolic > diastolic blood pressure
Neurological
- Cerebral blood flow preserved
OTHER CLINICAL EFFECTS, ADVERSE EFFECTS & TOXICITIES
Respiratory
- Increases bronchial secretions
- Increases respiratory rate and tidal volume marginally
Cardiovascular
- Increased myocardial work and oxygen consumption; myocardial ischaemia
- Arrhythmogenicity; cardiac arrhythmias
- Beta-adrenergic agonism (lower dose range); diastolic pressure may fall due to skeletal muscle vasodilatation
- Increases pulmonary vascular resistance, acute pulmonary oedema
Neurological
- Hypertensive cerebral haemorrhage
- Tremors, anxiety
Renal & electrolytes
- Decreases renal blood flow, GFR largely unaltered
- Increases sodium reabsorption directly and via stimulation of renin secretion
- Hypokalaemia due to cellular potassium influx
Gastrointestinal
- Decreases gastrointestinal tone and secretions
- Decreases splanchnic blood flow
Endocrine
- Decreases insulin secretion
- Increases glucagon secretion, glycogenolysis, gluconeogenesis, hyperglycaemia
- Increases lipolysis
- Increases plasma renin activation, aldosterone secretion and sodium retention
- Increases basal metabolic rate
- Increases plasma lactate, metabolic acidaemia
Haematological
- Increases platelet adhesiveness and factor V activity
Other
- Extravasation, tissue ischaemia and necrosis
Antidote
- Use direct-acting vasodilators or alpha-1 antagonists, non-cardioselective beta-blockers may worsen hypertension due to beta-2 blockade
CONSIDERATIONS
Precautions
- Ischaemic heart disease
- Hypertension, tachycardia
- Tachyarrhythmia
Obstetric
ADEC category C
Drug interactions
- Beta-blockade; resistance to beta-1 cardiac effects, resistance to beta-2 effects may potentiate hypertensive response
- MAO-inhibitors, tricyclic antidepressants; potentiates vasopressor action, adrenergic crisis
REFERENCES
Drug information has been compiled from multiple sources including
- Drugs in Anaesthesia and Intensive Care (Scarth & Smith)
- Micromedex (IBM)
- BJA Education (Oxford Academic)
- Pharmacology for Anaesthesia and Intensive Care (Cambridge)
- Australian Prescriber (NPS MedicineWise)
- Clinical experience of authors