Etomidate

• Drug Class: Non-barbiturate hypnotic; IV anesthetic induction agent
• Core Uses: Rapid-onset IV hypnotic used primarily for induction of anesthesia and procedural sedation, especially in hemodynamically unstable patients because it tends to preserve blood pressure and cardiac output compared with many alternatives
• Mechanism: Potentiates GABA-A receptor activity (and at higher doses directly activates the receptor), increasing chloride conductance and producing hypnosis and amnesia without significant intrinsic analgesia
• Typical Adult Induction Dose: 0.2–0.3 mg/kg IV (ideal body weight) given over 30–60 seconds. In very unstable or elderly patients, 0.1–0.2 mg/kg may be sufficient; higher doses (up to ~0.4 mg/kg) deepen hypnosis but increase risk of hypotension and myoclonus
• Onset: Loss of consciousness usually within 30–60 seconds after IV bolus, with duration of a single induction dose around 5–10 minutes due to rapid redistribution. Elimination half-life is ~2–5 hours
• Hemodynamic Profile: Relatively stable systemic blood pressure and heart rate at standard doses, with minimal myocardial depression and little histamine release; modest reductions in SVR and BP can still occur, especially in hypovolemic or septic patients
• Key Adverse Effect: Adrenal suppression via inhibition of 11β-hydroxylase, leading to decreased cortisol and aldosterone synthesis. A single induction dose measurably suppresses cortisol production for 6–24 hours; clinical impact of a one-time dose is debated but likely small in most patients, while prolonged infusions are generally avoided
• Other Adverse Effects: Injection-site pain, myoclonus (common), nausea/vomiting, respiratory depression/apnea, and (rarely) seizures. Etomidate has no analgesic properties—co-administration of opioids is needed for painful procedures
• Critical Consideration: Use with caution in septic shock or critical illness where adrenal function is a concern; many centers still use etomidate for RSI in unstable patients but avoid continuous infusions or repeated dosing

• Generic Name: Etomidate
• Brand Names: Amidate (U.S.), various generics—availability institution- and region-specific

Non-barbiturate hypnotic; IV anesthetic induction agent

Mechanism of Action:

• Etomidate is an imidazole-derived hypnotic that acts primarily as a positive allosteric modulator of the GABA-A receptor, enhancing the inhibitory effects of GABA in the CNS
• At higher concentrations, etomidate can directly activate GABA-A receptors even in the absence of GABA, further increasing chloride influx and neuronal hyperpolarization
• The net effect is rapid onset of hypnosis, amnesia, and sedation with relatively limited cardiovascular depression compared to agents like propofol or thiopental
• Etomidate does not provide significant analgesia; pain pathways are not directly blocked, so additional analgesics (e.g., opioids, ketamine) are required for painful stimuli
• Etomidate inhibits 11β-hydroxylase and possibly 17α-hydroxylase in the adrenal cortex, reducing conversion of 11-deoxycortisol to cortisol and contributing to adrenal suppression after even a single bolus

Pharmacokinetics (IV):

• Formulation: Supplied as a 2 mg/mL solution in 35% propylene glycol for IV injection
• Onset: Hypnosis typically occurs within 30–60 seconds after intravenous bolus administration
• Duration: A single induction dose produces 3–10 minutes of hypnosis due to rapid redistribution from the brain to peripheral tissues
• Distribution: Highly lipophilic with rapid distribution; volume of distribution is approximately 2–4.5 L/kg
• Protein Binding: About 75% plasma protein bound (mainly to albumin)
• Metabolism: Primarily hepatic via ester hydrolysis to inactive metabolites; some metabolism also occurs via plasma esterases
• Elimination: Metabolites are excreted mainly in the urine (75–80%) and bile; elimination half-life is roughly 2–5 hours in adults
• Special Populations: Elderly, cirrhotic, or critically ill patients may show reduced clearance and prolonged effect; dose reductions are recommended

• Induction of general anesthesia in the operating room, ED, or ICU, especially in hemodynamically unstable or trauma patients where minimizing hypotension is a priority
• Rapid sequence intubation (RSI) in the ED/ICU as the induction agent, often paired with a neuromuscular blocker (e.g., succinylcholine or rocuronium)
• Short procedural sedation (e.g., cardioversion, joint reduction) when rapid onset and short duration are desired and hemodynamic stability is important (institutional and credentialing dependent)
• Induction for cardioversion in patients with limited cardiac reserve when other agents pose a higher risk of hypotension (with appropriate monitoring and airway management)
• Severe trauma with hemodynamic instability requiring emergent airway control
• Septic shock or distributive shock where providers wish to limit additional hypotension during induction (controversial due to adrenal suppression concerns)
• Cardiogenic shock and severe valvular disease when more profound hypotension during induction would be poorly tolerated
• Status epilepticus requiring intubation and sedation (often in combination with other agents and per neurologic ICU protocols)

Available Forms:

• IV Solution: 2 mg/mL etomidate in 35% propylene glycol, supplied in single-use vials (e.g., 10 mL vial containing 20 mg)
• Alternative Formulations: Some markets may have lipid-based formulations with different excipients; check product-specific labeling
• Route: No oral or IM formulations are used clinically; etomidate is delivered intravenously for induction/sedation

Standard Dosing – IV Etomidate (Always Follow Local Protocols and Anesthesia/Airway Guidelines):

Contraindications:

• Known hypersensitivity to etomidate or formulation excipients
• Use for prolonged sedation or continuous infusion in critically ill patients (due to adrenal suppression)

Major Precautions:

• Sepsis and septic shock: Etomidate-induced adrenal suppression is more concerning; some guidelines suggest considering alternative agents in septic shock, particularly where other hemodynamically acceptable options exist
• Adrenal insufficiency or patients on chronic steroids: Further suppression of cortisol synthesis may worsen hemodynamics; stress-dose steroids may be considered in consultation with critical care/endocrinology
• Elderly, frail, and hemodynamically unstable patients: Use reduced doses (0.1–0.2 mg/kg) and be prepared with vasopressors and volume resuscitation
• History of myoclonus, seizure disorders, or conditions where myoclonic movements are problematic: (e.g., open globe injury, elevated ICP)—premedication with a small benzodiazepine or opioid may reduce myoclonus
• Porphyria: Older literature raised concerns about use in porphyric patients; etomidate is generally considered safer than barbiturates but caution is still advised

Common:

• Injection-site pain or burning (due to propylene glycol formulation)
• Myoclonus (transient, involuntary muscle jerks) in up to 30–60% of patients without premedication
• Nausea and vomiting during recovery
• Mild transient respiratory depression or apnea, especially when combined with other sedatives or in high doses

Serious:

• Adrenal suppression: With decreased cortisol and aldosterone production, potentially contributing to hypotension and shock in critically ill patients, particularly with repeated dosing or infusion
• Hemodynamic instability (hypotension): In hypovolemic, septic, or very frail patients despite overall favorable profile
• Laryngospasm, bronchospasm, or airway obstruction: Rare but possible, particularly in reactive airways
• Seizure-like activity or prolonged myoclonus: Rare
• Anaphylaxis or severe hypersensitivity: Rare

• Pediatrics: 0.2–0.3 mg/kg IV (max 20 mg); use with caution in sepsis/critical illness; requires specialist guidance
• Pregnancy: Limited data; use only when benefit outweighs risk; can cross placenta
• Older Adults: Increased sensitivity; use reduced doses (0.1–0.2 mg/kg) and slower administration
• Hepatic Impairment: Reduced clearance and prolonged effect; use lower doses with careful titration
• Critically Ill: Reduced clearance; consider dose reduction and monitor closely for hemodynamic changes

• Continuous ECG, blood pressure (NIBP q2–3 min or arterial line), and pulse oximetry: During and after administration
• Capnography: When used for procedural sedation or induction, particularly once the airway is instrumented or if spontaneous ventilation is preserved
• Level of consciousness and depth of sedation: Especially if used without paralytics
• Hemodynamic response (MAP, HR): Before and after induction; be prepared to treat hypotension with fluids and vasopressors
• Adrenal function monitoring: In septic or high-risk patients where adrenal suppression is a concern, monitor for refractory hypotension post-intubation and consider evaluation for adrenal insufficiency if clinically indicated

• 1. Andresen, E. K., & Sair, H. I. (2024). Etomidate. In StatPearls [Internet]. StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK535364/
• 2. Miner, J. R., Heegaard, W., & Plummer, D. (2002). Endotracheal intubation in the emergency department: A comparison of etomidate and midazolam. Academic Emergency Medicine, 9(9), 972–980. https://doi.org/10.1197/aemj.9.9.972
• 3. Hsu, C. H., & Fu, Y. C. (2021). Etomidate for rapid sequence intubation in the emergency department: Friend or foe of the adrenal gland? Journal of Clinical Medicine, 10(3), 497. https://doi.org/10.3390/jcm10030497
• 4. den Brinker, M., et al. (2008). Adrenal insufficiency in shock: Etomidate versus alternative induction agents. Intensive Care Medicine, 34(2), 238–243. https://doi.org/10.1007/s00134-007-0886-0
• 5. DrugBank Online. (2024). Etomidate (DB00292). DrugBank. https://go.drugbank.com/drugs/DB00292