FRCA Notes


Etomidate


  • Etomidate is a carboxylated imidazole ester derivative
  • Its use in the UK has largely ceased due to undesirable pharmacodynamic properties (BJA, 2025)
  • Induction of anaesthesia with a dose of 0.3mg/kg
  • Maintenance of anaesthesia via infusion, although this is associated with an increased mortality in ICU patients
  • Treatment of Cushing's disease

  • Only the R(+) enantiomer exhibits anaesthetic properties; the S(-) ennatiomer is 10x less potent
  • It presents as:
    • 20mg of R-etomidate in 10ml of 35% propylene glycol
    • ± as a lipid emulsion to reduce pain on injection

  • This gives a 0.2% solution with a pKa of 4.1

  • Weak base
  • Highly lipid soluble
  • Molecular weight of 342.36g/mol

Absorption

  • Onset within 60s and peak effect at 1 minute

Distribution

  • 75% protein bound
  • Volume of distribution 3 L/kg

Metabolism

  • Hepatic metabolism with a hepatic extraction ratio of 0.5
    • Non-specific hepatic esterases
    • Hydrolysed to ethyl-alcohol and carboxylic acid metabolites
  • Action terminated mostly by rapid distribution into the tissues

Excretion

  • Elimination half life 3 - 5hrs
  • Mostly renally (85%) excreted, although some is excreted in bile (13%)
  • Clearance is reduced in presence of 67% N2O

Respiratory

  • Minimal respiratory depression with transient coughing/hiccoughs
  • Slight depression of ventilatory response to CO2

Cardiovascular

  • Very stable cardiovascular profile
  • Doesn't suppress the baroreceptor reflex or sympathetic nervous system, which leaves myocardial oxygen supply/consumption, contractility and BP unchanged
  • Slight reduction in PVR

Neurological

  • Produces hypnosis via action on β2 and β3 subunits of the GABAA receptor
  • Does not produce analgesia
  • Reduces CBF, CMRO2
  • Reduces IOP at induction dose

  • Excitatory phenomena
    • Causes excitatory/myoclonic movements and hypertonus that is not epileptiform
    • Myoclonus occurs in up to a third of patients
    • 20% demonstrate generalised epileptiform activity on EEG associated with δ-wave activity and grand mal seizure

Gastrointestinal

  • Is emetogenic, increasing rate of N&V
  • May precipitate porphyric crisis

Metabolic

  • Dose-dependent, reversible inhibition of 11-β-hydroxylase causes reduced adrenocortical function
  • Causes reduced cortisol and aldosterone synthesis for 24hrs post-administration
  • It increases mortality when used as an infusion to sedate septic patients on ICU
  • I.e. the situation in which it has the best CV profile are those in which the consequences of steroid inhibition are most detrimental

Haematological

  • Anti-platelet activity
  • May cause venous thrombosis

Other

  • Pain on injection (25-50%) reduced by use of lidocaine or lipuro formations