Etomidate

Etomidate is an imidazole intravenous hypnotic with minimal cardiovascular and respiratory depression. It is used for induction in haemodynamically unstable patients and for rapid sequence intubation. Its main drawbacks are myoclonus, pain on injection, nausea, and suppression of adrenal cortisol synthesis lasting up to 24 hours after a single dose.

Class. Intravenous general anaesthetic (imidazole).

Mechanism. Positive modulation of GABA-A receptors at the beta-2 and beta-3 subunits. It inhibits 11-beta-hydroxylase, blocking cortisol and aldosterone synthesis.

Pharmacokinetics. Onset 30 to 60 seconds, duration 3 to 5 minutes (longer with repeated dosing). Protein binding about 75%. Large volume of distribution. Elimination half-life 3 to 5 hours. Hydrolysed by hepatic and plasma esterases to inactive metabolites, mainly renal excretion.

Indications are induction of general anaesthesia and rapid sequence induction, especially in hypovolaemia, cardiac disease or haemodynamic instability.

Adults

• Induction: 0.2 to 0.3 mg/kg intravenously over 15 to 30 seconds. Rapid sequence induction: 0.3 mg/kg.
• Older adults, shock, severe sepsis: 0.1 to 0.2 mg/kg.
• No loading dose beyond induction; avoid infusion because adrenal suppression accumulates.
• Pretreat with a short-acting opioid (fentanyl 1 to 2 micrograms/kg) or a benzodiazepine to reduce myoclonus.

Children

• Over 10 years: 0.3 mg/kg intravenously.
• Some labels allow use from 6 months (0.15 to 0.3 mg/kg); others do not support use under 10 years.
• Avoid in children with suspected adrenal insufficiency.

Contraindications. Hypersensitivity; adrenocortical insufficiency (relative; depends on clinical state); use as an infusion for sedation; absent airway skills.

Boxed-warning-level risks. None formally labelled. Adrenocortical suppression for up to 24 hours (and prolonged with infusions); possible increase in mortality in septic shock is contested.

Adverse effects. Common: pain on injection (propylene glycol vehicle), myoclonus, nausea, vomiting, hiccups. Serious: adrenal suppression with hypotension in stressed patients, apnoea (less than other agents), thrombophlebitis, seizures in patients with epilepsy, anaphylaxis (rare).

Interactions. Opioids and benzodiazepines reduce myoclonus and add sedation. Antiepileptic drugs interact variably. Corticosteroids are used to counter adrenal suppression. Volatile agents prolong effect.

Common prescribing errors. Using as a continuous infusion; failing to consider hydrocortisone in a patient with septic shock or known adrenal insufficiency; ignoring myoclonus in a patient with open eye injury; giving without a plan for ventilation.

Special groups

• Pregnancy: acceptable for caesarean section induction; neonatal adrenal suppression is brief.
• Breastfeeding: compatible after recovery.
• Older adults: reduce dose by 30 to 50%.
• Kidney impairment: no adjustment.
• Liver impairment: reduce dose in severe cirrhosis; clearance is esterase-based.
• Regional: availability varies; where unavailable, ketamine or reduced-dose propofol is used.

Formulations. Injection 2 mg/mL in propylene glycol or lipid emulsion vehicles.

Administration. Inject into a large vein over 15 to 30 seconds. Lipid-emulsion formulations cause less pain.

Baseline. Airway assessment, blood pressure, adrenal history (steroid use, adrenal disease), sepsis status, seizure history and pregnancy.

Monitoring. Continuous electrocardiogram, blood pressure, oxygen saturation and capnography. After induction in sepsis, watch for hypotension suggestive of adrenal insufficiency.

Therapeutic drug monitoring. Not used.

Dose reduction and stopping thresholds. Do not repeat doses within a short interval or use as an infusion. Reduce the dose in older adults and shock.

Referral and escalation. Refractory hypotension after induction in sepsis or steroid-dependent patients: consider hydrocortisone 100 mg intravenously. Severe myoclonus or seizures need a benzodiazepine.