Etomidate: English spelling of the imidazole hypnotic etomidat
Etomidate is the English spelling of the substance etomidat, a short-acting intravenous hypnotic from the imidazole class. Introduced in 1972, etomidate has established itself for anaesthesia induction in haemodynamically unstable patients, since it shows remarkable haemodynamic stability compared with propofol or thiopental. Internationally the spelling etomidate is common; in Germany etomidat.
Characteristic is the selective inhibition of cortisol synthesis in the adrenal cortex through inhibition of 11 beta hydroxylase. From this comes the important safety aspect that etomidate is unsuitable for continuous infusion to sedate critically ill patients, since prolonged use leads to clinically relevant adrenal suppression.
Mechanism of action
Etomidate enhances the action of GABA at the GABA A receptor, a ligand-gated chloride channel in the CNS. Through a specific binding site, the affinity of GABA for the receptor is increased and the chloride channel stays open longer. This produces marked neuronal hyperpolarisation with rapid loss of consciousness and deep sedation.
Compared with propofol or thiopental, etomidate has barely any effect on blood pressure and cardiac contractility, which explains the haemodynamic stability at induction.
Inhibition of 11 beta hydroxylase in the adrenal cortex causes dose-dependent suppression of cortisol and aldosterone synthesis. This effect appears even after a single dose and can persist up to 24 hours. With repeated use or continuous infusion the effect is amplified.
Indications
- Anaesthesia induction: especially in cardiovascularly unstable patients, polytrauma, sepsis
- Emergency medicine: rapid sequence induction in critically ill patients
- Short diagnostic and therapeutic procedures: cardioversion, fracture reduction, endoscopic interventions
- Off-label diagnostic: etomidate test in endocrinology to assess cortisol suppression
Etomidate is not suitable for continuous sedation of critically ill patients in intensive care, since cortisol inhibition is associated with mortality.
Dosing and administration
Adults, anaesthesia induction: 0.2 to 0.3 mg per kg body weight intravenously as a bolus over 15 to 30 seconds.
Children from 6 months: 0.2 to 0.3 mg per kg, individually adjusted.
Onset 30 to 60 seconds, duration 5 to 10 minutes. Due to short duration, maintenance therapy is usually combined with other hypnotics or volatile anaesthetics.
Use: always in a clinically equipped setting with monitoring of breathing, circulation and oxygen saturation. Ventilation, intubation readiness and emergency drugs must be available.
Side effects
Very common: pain or burning at the injection site, myoclonus (involuntary muscle twitches, especially at induction), postoperative nausea and vomiting.
Common: brief phase of clouded consciousness, cough, hiccup, mild respiratory depression.
Uncommon: allergic reactions, tachycardia or bradycardia, rarely marked hypotension, apnoea.
Rare and very rare: acute adrenal insufficiency especially in critically ill or after repeated use, anaphylactic reactions, seizures, porphyria exacerbation.
Important safety points:
- Cortisol suppression for up to 24 hours after a single dose, clinically relevant in critically ill patients
- Myoclonus can be misinterpreted but occurs commonly without sufficient premedication; consider opioid or benzodiazepine
- Postoperative nausea and vomiting more common than with propofol
- Lipid emulsion (etomidate-Lipuro) reduces injection-site pain
Interactions
- Other sedatives, hypnotics, opioids: additive effect, dose adjustment
- Antihypertensives: additive blood pressure lowering
- CYP3A4 inhibitors: theoretically raised levels, rarely relevant with single use
- Glucocorticoids: with cortisol suppression by etomidate, substitution may be needed
Special considerations
Pregnancy: data limited. With urgent indication, e.g. emergency anaesthesia, acceptable.
Breastfeeding: resuming breastfeeding after short sedation is usually possible.
Contraindications: known hypersensitivity, sepsis (relatively contraindicated due to cortisol suppression), acute porphyria, severe adrenal insufficiency.
Sepsis and critically ill: cortisol suppression can negatively affect the clinical course. Studies show association between etomidate induction and increased mortality in sepsis. Steroid substitution after use is discussed in some guidelines.
Alternative substances: ketamine, a hypnotic with sympathomimetic effect, can be a useful alternative in critically ill patients, especially with hypotension.
Patient communication: after short sedation, patients can experience mild nausea or confusion. Counselling before the procedure and a companion home after outpatient procedures are sensible.
Related substances
- Propofol, another intravenous hypnotic
- Thiopental, classic barbiturate for induction
- Sevoflurane, volatile anaesthetic for maintenance
- Remifentanil, short-acting opioid in anaesthesia
Frequently asked questions
Etomidate or etomidat?
Etomidate English, etomidat German. Identical substance.
Why so little effect on blood pressure?
Unlike propofol or thiopental, etomidate has only minimal negative inotropic and cardiodepressant effects. This haemodynamic stability makes it the first choice in cardiovascularly unstable patients in emergency medicine and in polymorbid patients.
Why no continuous infusion for sedation?
Etomidate inhibits cortisol synthesis in the adrenal cortex. With a single dose this inhibition is transient and usually clinically unproblematic. With continuous use over hours to days, however, relevant adrenal insufficiency develops, associated with increased mortality in critically ill patients. Etomidate is therefore used only for induction, not for maintenance.
What are myoclonus events under etomidate?
Involuntary muscle twitches, especially at the start of sedation, can occur in half of patients. They are usually harmless and pass quickly. Premedication with an opioid or benzodiazepine markedly reduces their frequency.
Sources
- BfArM Federal Institute for Drugs and Medical Devices
- EMA European Medicines Agency
- AWMF guidelines anaesthesia and emergency medicine
- Gelbe Liste etomidat monograph
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