Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution, Intravenous:
Amidate: 2 mg/mL (10 mL, 20 mL) [contains propylene glycol]
Generic: 2 mg/mL (10 mL, 20 mL)
Solution, Intravenous [preservative free]:
Generic: 2 mg/mL (10 mL [DSC], 20 mL [DSC])
Pharmacology
Mechanism of Action
Ultra-short-acting nonbarbiturate general anesthetic (benzylimidazole) used for rapid induction of anesthesia with minimal cardiovascular effects; produces EEG burst suppression at high doses.
Pharmacokinetics/Pharmacodynamics
Distribution
Vd: 2 to 4.5 L/kg
Metabolism
Hepatic and plasma esterases
Excretion
Urine ~ 75% (80% as metabolite; 2% as unchanged drug)
Onset of Action
30 to 60 seconds; Peak effect: 1 minute
Time to Peak
Serum: 7 minutes
Duration of Action
Dose dependent: 2 to 3 minutes (0.15 mg/kg dose); 3 to 5 minutes (0.3 mg/kg dose); rapid recovery is due to rapid redistribution
Half-Life Elimination
Terminal: 2.6 to 3.5 hours
Protein Binding
76%; decreased protein binding resulting in an increased percentage of “free” etomidate in patients with renal failure or hepatic cirrhosis
Use in Specific Populations
Special Populations: Hepatic Function Impairment
Vd and elimination half-life increase 2-fold in patients with cirrhosis compared with healthy subjects.
Special Populations: Elderly
Vd, total clearance, and plasma protein binding are decreased in elderly patients.
Use: Labeled Indications
General anesthesia: Induction of general anesthesia; as a supplement to subpotent anesthetic agents during maintenance of anesthesia for short operative procedures (eg, dilation and curettage, cervical conization).
Use: Off Label
Cushing syndromeyes
Based on the Endocrine Society’s Clinical Practice Guidelines for Treatment of Cushing’ Syndrome, etomidate, given for severe hypercortisolism in critically ill patients with Cushing syndrome, is an effective and recommended agent in patients who are not immediate surgical candidates and cannot take oral medications.
Procedural sedationbyes
In a randomized, nonblinded, prospective trial, etomidate, although it appeared equally safe for procedural sedation in the emergency department, had lower procedural success compared to propofol in adults undergoing procedural sedation. Notably, etomidate induced myoclonus in 20% of patients compared to 1.8% of patients receiving propofol Miner 2007. A retrospective study for procedural sedation found that the use of etomidate was effective in 93% of subjects in the emergency department (ED) with few adverse events although many adverse events (eg, myoclonus) may not be well documented in the ED Vinson 2002. Additional trials may be necessary to further define the role of etomidate in procedural sedation.
Based on the American College of Emergency Physicians (ACEP) clinical policy for procedural sedation and analgesia in the ED, etomidate may be safely administered to adults for procedural sedation and analgesia in the ED.
Contraindications
Hypersensitivity to etomidate or any component of the formulation
Dosage and Administration
Dosing: Adult
General anesthesia: IV: Initial: 0.3 mg/kg (range: 0.2 to 0.6 mg/kg) over 30 to 60 seconds for induction of anesthesia.
Supplementation to subpotent anesthetic agents: IV: Administer smaller increments during short operative procedures to supplement subpotent anesthetic agents, such as nitrous oxide; individualize dosage (usually smaller than the original induction dose).
Cushing syndrome (off-label use): IV: Initial: 0.04 to 0.05 mg/kg/hour (usually equates to ~2.5 to 3 mg/hour). Titrate to serum cortisol of 18 to 29 mcg/dL (500 to 800 nmol/L) in a physiologically stressed patient or 5.5 to 11 mcg/dL (150 to 300 nmol/L) in a non-physiologically stressed patient. For complete blockade, titrate infusion rate to achieve a cortisol level <5.5 mcg/dL (<150 nmol/L). Hydrocortisone IV is required if complete blockade desired rather than partial blockade (‘block and replace’) (Preda 2012). Note: Studies have not reported sedation at these etomidate doses; however, patients should be managed in an intensive care unit with sedation scoring every 2 hours initially for the first 24 hours, then every 12 hours. Cortisol levels should be measured every 4 to 6 hours (ES [Nieman 2015]; Preda 2012).
Procedural sedation (off-label use): IV: Initial: 0.1 to 0.2 mg/kg, followed by 0.05 mg/kg every 3 to 5 minutes as needed (Bahn, 2005; Miner, 2007; Vinson, 2002)
Dosing: Geriatric
Refer to adult dosing; reduced doses may be required.
Dosing: Pediatric
Anesthesia, induction:
Infants: Very limited data available: IV: 0.2 to 0.3 mg/kg/dose as a single dose; dosing based on a prospective, observational trial and two pharmacokinetic studies (Kay 1976; Lin 2012; Su 2015)
Children <10 years: Limited data available: IV: 0.2 to 0.3 mg/kg/dose as a single dose (Coté 2013; Du 2015; Kay 1976)
Children ≥10 years and Adolescents: Usual dose: IV: 0.3 mg/kg/dose as a single dose; range: 0.2 to 0.6 mg/kg/dose
Procedural sedation: Limited data available; dosing variable: Infants ≥6 months, Children, and Adolescents: IV: Usual initial dose: 0.2 mg/kg/dose prior to procedure (reported range: 0.1 to 0.4 mg/kg/dose); repeat doses may be needed depending on patient response and duration of the procedure; repeat doses vary in the literature and range from 0.1 to 0.2 mg/kg/dose; reported total dose ranged from 0.3 to 0.6 mg/kg/procedure; dosing based on several prospective and retrospective studies primarily in the ED setting; procedures included orthopedic reductions and sedation for CT scans (Baxter 2007; Dickinson 2001; Di Liddo 2006; Lee-Jayaram 2010; Kienstra 2004; Mandt 2012). Note: Etomidate does not have analgesic properties; additional therapy (eg, fentanyl) may be needed for painful procedures (ACEP [Godwin 2014]).
Rapid sequence intubation (RSI): Limited data available: Infants, Children, and Adolescents: IV, Intraosseous: 0.2 to 0.4 mg/kg/dose as a single dose; maximum dose: 20 mg/dose (AHA [Hazinski 2015]; Hegenbarth 2008). Note: Not recommended for patients in septic shock due to an association between transient adrenocortical suppression and increased mortality rate (den Brinker 2008; PALS [Kleinman 2010]).
Administration
IV: Administer IV push over 30 to 60 seconds. Solution is highly irritating; avoid administration into small vessels; in some cases, preadministration of lidocaine may be considered.
Storage
Store at 20°C to 25°C (68°F to 77°F).
Drug Interactions
Fexinidazole [INT]: May increase the serum concentration of Products Containing Propylene Glycol. Avoid combination
MetroNIDAZOLE (Systemic): May enhance the adverse/toxic effect of Products Containing Propylene Glycol. A disulfiram-like reaction may occur. Avoid combination
Adverse Reactions
>10%:
Central nervous system: Myoclonus (33%)
Endocrine & metabolic: Adrenal suppression
Gastrointestinal: Nausea, vomiting (on emergence from anesthesia)
Local: Pain at injection site (30% to 80%)
Neuromuscular & skeletal: Musculoskeletal disease (transient skeletal movements)
Ophthalmic: Nystagmus
1% to 10%: Gastrointestinal: Hiccups
<1%, postmarketing, and/or case reports: Apnea, bradycardia, cardiac arrhythmia, decreased cortisol (decreased cortisol synthesis), hypertension, hyperventilation, hypotension, hypoventilation, laryngospasm, muscle spasm (masseter; Bozeman 2002), tachycardia
Warnings/Precautions
Concerns related to adverse effects:
- Adrenal steroid production: Etomidate inhibits 11-B-hydroxylase, an enzyme important in adrenal steroid production. A single induction dose blocks the normal stress-induced increase in adrenal cortisol production for 6 to 8 hours, up to 24 hours in elderly and debilitated patients. Continuous infusion of etomidate for sedation in the ICU may increase mortality because patients may not be able to respond to stress. Administration by continuous infusion is not recommended by the manufacturer. No increase in mortality has been identified with a single dose for induction of anesthesia (McPhee 2013).
Disease-related concerns:
- Heart failure: In a scientific statement from the American Heart Association, etomidate has been determined to be an agent that may exacerbate underlying myocardial dysfunction (magnitude: moderate) (AHA [Page 2016]).
- Renal impairment: Risk of toxicity is greater in patients with renal impairment; use with caution and monitor renal function.
Special populations:
- Elderly: May induce cardiac depression in elderly patients, especially those with hypertension; may require lower doses.
- Pediatric neurotoxicity: In pediatric and neonatal patients <3 years and patients in third trimester of pregnancy (ie, times of rapid brain growth and synaptogenesis), the repeated or lengthy exposure to sedatives or anesthetics during surgery/procedures may have detrimental effects on child or fetal brain development and may contribute to various cognitive and behavioral problems. Epidemiological studies in humans have reported various cognitive and behavioral problems, including neurodevelopmental delay (and related diagnoses), learning disabilities, and ADHD. Human clinical data suggest that single, relatively short exposures are not likely to have similar negative effects. No specific anesthetic/sedative has been found to be safer. For elective procedures, risks versus benefits should be evaluated and discussed with parents/caregivers/patients; critical surgeries should not be delayed (FDA 2016).
Other warnings/precautions:
- Appropriate use: When considering use, weigh etomidate hemodynamic properties against the high frequency of transient skeletal muscle movements.
- Experienced personnel: According to the manufacturer, etomidate should only be administered by experienced personnel trained in the administration of general anesthetics and in the management of complications encountered during the conduct of general anesthesia. Consult local regulations and individual institutional policies and procedures.
Monitoring Parameters
Cardiac monitoring; blood pressure; renal function (in renal impairment)
Pregnancy
Pregnancy Considerations
Etomidate crosses the placenta (Esener 1992; Gregory 1991).
Based on animal data, repeated or prolonged use of general anesthetic and sedation medications that block N-methyl-D-aspartate receptors and/or potentiate GABA activity may affect brain development. Evaluate benefits and potential risks of fetal exposure to etomidate when duration of surgery is expected to be >3 hours (Olutoye 2018).
Use of etomidate for induction of anesthesia prior to cesarean delivery has been described (Downing 1979; Houlton 1978; Regaert 1984). However, other agents are more commonly used (ACOG 209 2019).
The ACOG recommends that pregnant women should not be denied medically necessary surgery, regardless of trimester. If the procedure is elective, it should be delayed until after delivery (ACOG 775 2019).
Patient Education
What is this drug used for?
- It is used to put you to sleep for surgery.
- It may be given to you for other reasons. Talk with the doctor.
Frequently reported side effects of this drug
- Fatigue
- Nausea
- Vomiting
- Twitching
- Injection site pain
Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:
- Severe dizziness
- Passing out
- Vision changes
- Trouble breathing
- Slow breathing
- Shallow breathing
- Fast heartbeat
- Slow heartbeat
- Abnormal heartbeat
- Involuntary eye movements
- Stiff muscles
- Abnormal movements
- Severe headache
- Injection site irritation
- Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.
Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.
Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.
