CLASS
Beta agonist
PRESENTATION
White powder aerosolised by a blue Metered Dose Inhaler (MDI).
Clear, colourless solution, clear vial.
Formulations
- MDI; 200 doses, 100mcg/dose
- 2.5ml nebule solution; 2.5mg, 1mg/ml
- 2.5ml nebule solution; 5mg, 2mg/ml
- 1ml vial; 500mcg, 500mcg/ml
- 5ml vial; 5mg, 1mg/ml
INDICATIONS & DOSING
Bronchospasm (of any cause), prevention & management
- Adult MDI; 12 puffs
- Adult nebuliser; 5mg or continuous max 10-20mg/hr
- Adult IV; 250-500mcg IV
- Paediatric MDI; <6 years 6 puffs, >6 years 12 puffs
- Paediatric nebuliser; <25kg 2.5mg, >25kg 5mg, or continuous max 10-15mg/hr
- Paediatric IV; 3-10mcg/kg IV
- Adult/paediatric infusion; 5-10mcg/kg/min IV for the first hour, followed by 0.5-2mcg/kg/min IV
Hyperkalaemia
- Adult/paediatric nebuliser; 2.5-5mg or continuous at 10-15mg/hr
- Adult/paediatric infusion; 5-10mcg/kg/min IV for the first hour, followed by 0.5-2mcg/kg/min IV
Tocolysis (second-line therapy)
- Infusion; 10mcg/min IV, increase by 5mcg IV every 30 minutes, maximum 30mcg/min
PRACTICALITIES
Administration
- Shake MDI prior to use
- MDI doses should be delivered via a spacer if possible
- MDI dose can be delivered in-circuit to the ventilated patient via a purpose-made MDI connector, time with inspiration
- Infusion; 5mg ampoule mixed with N/Saline or 5% dextrose to 100mL (50mcg/ml)
Practice tips
- The preferred route of administration in treating bronchospasm is dependent on availability of route, clinical urgency, and response
- Inhaled therapy preferred for initial management
- Reserve intravenous therapy for cases of severe bronchospasm due to higher incidence of severe side-effects and less-well established efficacy
- Always co-administer salbutamol with oxygen due to possible precipitation of hypoxaemia due to worsening of pulmonary VQ matching
PHARMACOKINETICS
Onset
- Bronchodilation; 1-3 minutes IV, 2-5 minutes neb
- Potassium shift; ~30 minutes
- Tocolysis; 15 minutes
Duration of action
- Bronchodilation; 10-20 minutes IV, 15-60 minutes neb
- Potassium shift; up to 2 hours
- Tocolysis; may delay delivery for up to 48hrs
Metabolism
Majority hepatic metabolism, to salbutamol 4-O-sulfate
Elimination
Mixed renal and biliary elimination
MECHANISM
Direct agonism of beta sympathetic adrenoreceptors. Higher affinity for beta-2 than beta-1 receptors, with minimal beta-1 activity in the lower dose range.
DESIRED CLINICAL EFFECTS
Respiratory
- Bronchodilation due to bronchial smooth muscle relaxation, increasing expiratory gas flow
Renal & electrolytes
- Reduction in potassium level of ~1mmol/L due to beta-2 mediated increased Na/K/ATPase pump activity causing an intracellular shift of potassium
Obstetric
- Tocolysis secondary to uterine smooth muscle relaxation
OTHER CLINICAL EFFECTS, ADVERSE EFFECTS & TOXICITIES
Respiratory
- Hypoxaemia due to an impairment of hypoxic pulmonary vasoconstriction, increasing pulmonary VQ mismatch and shunt
Cardiovascular
- Hypotension, a fall in diastolic blood pressure of 10-20mmHg due to beta-2 mediated peripheral vasodilatation (lower dose range)
- Tachycardia and raised cardiac output, precipitation of myocardial ischaemia, due to beta-1 mediated chronotropy and inotropy (higher dose range)
- Arrhythmogenicity, particularly in the presence of hypokalaemia
Neurological
- Anxiety, tremor, diaphoresis
Renal & electrolytes
- Hypokalaemia (mechanism as above)
- Lactic acidosis (higher dose range)
Endocrine
- Hyperglycaemia, ketosis, raised plasma fatty acid concentration and stimulation of insulin secretion due to stimulation of glycolysis/gluconeogenesis, ketosis, lipolysis
Obstetric
- Foetal tachycardia following placental drug transfer
CONSIDERATIONS
Precautions
- Hypertension/tachycardia
- Hypokalaemia
- Hyperglycaemia
- Lactic acidosis
Obstetric
ADEC category A
Drug interactions
Adrenaline; additive clinical effects, may precipitate adverse cardiovascular effects, hypokalaemia
- Non-depolarising neuromuscular blockers; potentiates neuromuscular blockade
- MAO inhibitors, tricyclic antidepressants; may result in exaggerated hypertensive response
- Digoxin; salbutamol reduces digoxin serum concentration
- Non-selective beta-blockers; antagonise effects of salbutamol
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)