Version May 2024
Cushing syndrome (off-label use): 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 (Ref). Optimal regimen and doses have not been identified; refer to institutional protocols.
IV: Initial: 3 to 5 mg loading dose, followed by 0.02 to 0.05 mg/kg/hour continuous IV infusion (usually equates to 1.5 to 4 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 nonphysiologically 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’) (Ref).
General anesthesia: IV: Initial: 0.3 mg/kg over 30 to 60 seconds for induction of anesthesia; usual dosage range: 0.2 to 0.6 mg/kg.
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 (Ref).
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).
There are no dosage adjustments provided in the manufacturer's labeling; use with caution, risk of toxicity is greater in patients with renal impairment.
There are no dosage adjustments provided in the manufacturer's labeling.
The recommendations for dosing in patients with obesity are based upon the best available evidence and clinical expertise. Senior Editorial Team: Jeffrey F. Barletta, PharmD, FCCM; Manjunath P. Pai, PharmD, FCP; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC.
Class 1 and 2 obesity (BMI 30 to 39 kg/m2): IV: Use actual body weight for weight-based dose calculations (Ref). Refer to adult dosing for indication-specific doses.
Class 3 obesity (BMI ≥ 40 kg/m2): IV: Use adjusted body weight for weight-based dose calculations (Ref). Refer to adult dosing for indication-specific doses.
Rationale for recommendations: Etomidate has a large Vd (2.5 to 4.5 L/kg) with peak anesthetic effects occurring within minutes and a rapid loss of effect related to redistribution (Ref). In 1 study evaluating patients with a BMI ≥40 kg/m2, the total dose required to achieve sedation was similar between the observed dose and ideal body weight predicted dose or adjusted body weight predicted dose. The adjusted body weight predicted dose was slightly higher than the observed dose (26.8 vs 21.7 mg) (Ref). Given that the risk of underdosing (eg, awake while paralyzed) outweighs the risk of toxicity, use actual body weight in patients with a BMI 30 to 39 kg/m2 and consider adjusted body weight in patients with a BMI ≥40 kg/m2 (Ref).
Refer to adult dosing; reduced doses may be required.
(For additional information see "Etomidate: Pediatric drug information")
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 (Ref).
Children <10 years: Limited data available: IV: 0.2 to 0.3 mg/kg/dose as a single dose (Ref).
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 to 0.3 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 maximum total dose ranged from 0.3 to 0.6 mg/kg per procedure (Ref). Note: Etomidate does not have analgesic properties; additional therapy (eg, fentanyl) may be needed for painful procedures (Ref).
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 (Ref). Note: Not recommended for patients in septic shock due to an association between transient adrenocortical suppression and increased mortality rate (Ref).
There are no dosage adjustments provided in the manufacturer's labeling; use with caution, risk of toxicity is greater in patients with renal impairment.
There are no dosage adjustments provided in the manufacturer's labeling.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>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
Hypersensitivity to etomidate or any component of the formulation
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:
• Older adult: 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.
Adrenal suppression has been documented with etomidate use, even after a single dose. Cortisol concentrations decrease quickly after the induction dose, lasting up to 8 hours in healthy adults and up to 24 hours in pediatric surgical patients; however, 2 prospective pediatric studies have reported no adverse clinical outcomes due to the adrenal suppression (Du 2015; Gu 2015). However, a retrospective study of pediatric patients admitted for meningococcal sepsis found patients receiving a single etomidate dose for rapid sequence intubation (n=23) had significantly decreased cortisol concentrations for at least 24 hours, and higher ACTH and 11-deoxycortisol concentrations compared to those who did not receive etomidate. In this study, 8 patients died due to hemodynamic failure, 7 of whom had received etomidate. While the role of etomidate on mortality is unclear in these cases, weigh the risk versus benefit prior to use and if use deemed necessary use with caution (den Brinker 2008). Etomidate use is not recommended in pediatric patients with sepsis or septic shock (Brierley 2009; Dellinger 2013; PALS [Kleinman 2010]).
In pediatric and neonatal patients <3 years of age 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 the child's or fetus’ brain development and may contribute to various cognitive and behavioral problems; the FDA is requiring warnings be included in the manufacturer's labeling for all general anesthetic/sedative drugs. Multiple animal species studies have shown adverse effects on brain maturation; in juvenile animals, drugs that potentiate GABA activity and/or block NMDA receptors for >3 hours demonstrated widespread neuronal and oligodendrocyte cell loss along with alteration in synaptic morphology and neurogenesis. Epidemiological studies in humans have reported various cognitive and behavioral problems including neurodevelopmental delay (and related diagnoses), learning disabilities, and attention-deficit/hyperactivity disorder. Human clinical data suggest that single, relatively short exposures are not likely to have similar negative effects. Further studies are needed to fully characterize findings and ensure that these findings are not related to underlying conditions or the procedure itself. No specific anesthetic/sedative has been found to be safer. For elective procedures, risk vs benefits should be evaluated and discussed with parents/caregivers/patients; critical surgeries should not be delayed (FDA 2016).
Some dosage forms may contain propylene glycol; in neonates, large amounts of propylene glycol delivered orally, intravenously (eg, >3,000 mg/day), or topically have been associated with potentially fatal toxicities which can include metabolic acidosis, seizures, renal failure, and CNS depression; toxicities have also been reported in children and adults including hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Shehab 2009).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
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, 20 mL)
Yes
Solution (Amidate Intravenous)
2 mg/mL (per mL): $0.68
Solution (Etomidate Intravenous)
2 mg/mL (per mL): $0.27 - $1.18
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Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous:
Tomvi: 2 mg/mL (10 mL, 20 mL) [contains propylene glycol]
Generic: 2 mg/mL (11 mL, 20 mL)
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.
IV: Administer IV push over 30 to 60 seconds; very irritating; avoid administration into small vessels on the head or dorsum of the hand (Ref); preadministration of lidocaine may be beneficial (Ref).
General anesthesia: Induction of general anesthesia; as a supplement to subpotent anesthetic agents during maintenance of anesthesia for short operative procedures (eg, rapid sequence intubation, dilation and curettage, cervical conization).
Cushing syndrome; Procedural sedation
Etomidate may be confused with etidronate
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs which have a heightened risk of causing significant patient harm when used in error.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
MetroNIDAZOLE (Systemic): May enhance the adverse/toxic effect of Products Containing Propylene Glycol. A disulfiram-like reaction may occur. Risk X: Avoid combination
Ornidazole: May enhance the adverse/toxic effect of Products Containing Propylene Glycol. Specifically, a disulfiram-like reaction may occur. Risk X: Avoid combination
Secnidazole: Products Containing Propylene Glycol may enhance the adverse/toxic effect of Secnidazole. Risk X: Avoid combination
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).
Etomidate is present in breast milk (Esener 1992).
Following use of etomidate as an induction agent in 40 women undergoing cesarean delivery, etomidate was present in the colostrum at both 30 minutes and 2 hours after maternal injection. Etomidate was not present in breast milk 4 hours after the maternal dose (Esener 1992).
The manufacturer recommends that caution be exercised when administering etomidate to breastfeeding females; however, use is considered acceptable (Dalal 2014). The Academy of Breast Feeding Medicine recommends postponing elective surgery until milk supply and breastfeeding are established. Milk should be expressed ahead of surgery when possible. In general, when the child is healthy and full term, breastfeeding may resume, or milk may be expressed once the mother is awake and in recovery. For children who are at risk for apnea, hypotension, or hypotonia, milk may be saved for later use when the child is at lower risk (ABM [Reece-Stremtan 2017]).
Cardiac monitoring; blood pressure; renal function (in renal impairment); for treatment of Cushing syndrome, monitor serum cortisol levels every 4 to 6 hours (ES [Nieman 2015]).
Ultra-short-acting nonbarbiturate general anesthetic (benzylimidazole) used for rapid induction of anesthesia with minimal cardiovascular effects; produces EEG burst suppression at high doses. Decreases endogenous cortisol synthesis via inhibition of 11-beta-hydroxylase (Pence 2022).
Onset of action: 30 to 60 seconds
Peak effect: 1 minute
Duration: 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
Distribution: Vd: 2 to 4.5 L/kg
Protein binding: 76%; decreased protein binding resulting in an increased percentage of “free” etomidate in patients with renal failure or hepatic cirrhosis
Metabolism: Hepatic and plasma esterases
Half-life elimination: Terminal: 2.6 to 3.5 hours
Time to peak, serum: 7 minutes
Excretion: Urine ~75% (80% as metabolite; 2% as unchanged drug)
Hepatic function impairment: Vd and elimination half-life increase 2-fold in patients with cirrhosis compared with healthy subjects.
Older adult: Vd, total clearance, and plasma protein binding are decreased in elderly patients.
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