Induction agent
Etomidate (Amidate)
Also called Amidate
Indications
- RSI and induction of general anesthesia, chosen for hemodynamic stability
- Supplementing weaker anesthetics such as nitrous oxide in short procedures (label)
- Brief procedural sedation such as cardioversion (off-label)
- Low-dose infusion to lower cortisol in severe Cushing syndrome (off-label)
Dosing
| Where | Dose |
|---|---|
| Airway and RSI | Etomidate: 0.3 mg/kg (adrenal suppression after one dose is small but real) |
On the quick cards
Mechanism of action
Etomidate is a positive allosteric modulator of GABA-A receptors that contain β2 or β3 subunits. It binds two transmembrane pockets at the β–α interfaces, just below the GABA sites; asparagine 265 on β2 and β3 makes them sensitive, so β1-containing receptors barely respond. It increases GABA affinity and prolongs chloride current, and at higher concentrations opens the channel directly. The R-(+) enantiomer is 10–20 times more potent than S-(−).
Pharmacology
- CNS: hypnosis within a minute with no analgesia; lowers cerebral O₂ use, blood flow and ICP while MAP holds; myoclonus is subcortical, not seizure activity
- Cardiovascular: the most neutral induction drug, with little change in heart rate, BP, contractility or sympathetic tone; it does not blunt the pressor response to laryngoscopy
- Respiratory: less depression than propofol; brief apnea possible; slight PaCO₂ rise (label)
- Endocrine: blocks adrenal 11β-hydroxylase, lowering cortisol and aldosterone for 6–8 h after one dose (label), longer in critical illness
Pharmacokinetics
| Onset | Within 1 min IV (label) |
|---|---|
| Duration | 3–5 min after 0.3 mg/kg (label), ended by redistribution |
| Half-life | About 75 min after the first 30 min (label); terminal 2–5 h |
| Distribution | Hydrophobic: fast brain uptake, then redistribution to muscle and fat |
| Protein binding | About 75% (albumin); more free drug with low albumin, cirrhosis, uremia and age |
| Metabolism | Liver and plasma esterases hydrolyze the ester to an inactive carboxylic acid |
| Clearance | High, 15–20 mL/kg/min |
| Elimination | About 75% in urine within a day (label), as the inactive acid |
| Adrenal recovery | 6–8 h (label); in critically ill adults 80% were still suppressed at 12 h and few at 48 h (Vinclair 2008) |
Chemistry
- R-(+)-ethyl 1-(1-phenylethyl)-1H-imidazole-5-carboxylate: a carboxylated imidazole, sold as the single R-isomer
- pKa 4.2: un-ionized and very hydrophobic at body pH, so it needs a solubilizing vehicle
- Amidate is 2 mg/mL in 35% propylene glycol, pH 6.0; the hyperosmolar vehicle causes injection pain (about 20%) and thrombophlebitis. A lipid emulsion sold outside the US hurts less
- The imidazole nitrogen binds the heme iron of 11β-hydroxylase (CYP11B1), blocking 11-deoxycortisol's conversion to cortisol at nanomolar levels, far below hypnotic concentrations
Adverse effects and cautions
In the one-pagers
- Airway and RSIRSI drugs: Etomidate: 0.3 mg/kg: Under 1 min: Myoclonus; cortisol suppressed 6–8 h
- Pulmonary EmbolismSupporting the failing RV: Intubation can trigger arrest: induction drops SVR, positive pressure cuts venous return, apnea raises CO₂ and PVR. If unavoidable: norepinephrine running, expert operator, preoxygenate, reduced-dose etomidate or ketamine, VT 6 mL/kg, plateau <30, low PEEP, ECMO team aware.
- Right Heart Failure and Pulmonary HypertensionIntubation and home prostacyclin: Etomidate or reduced-dose ketamine; avoid propofol boluses; keep apnea short.
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In the algorithms
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Sources
- FDA label: Amidate (2022)
- Forman 2011 (review)
- Vinclair 2008
- SCCM 2023 RSI guideline
For education and exam preparation only. Follow your institution’s protocols. Typical adult values for study. Follow the order, the label and your institution's protocols.