Brand name: Amidate
Drug class: General Anesthetics, Miscellaneous
VA class: CN203
Chemical name: 1-(1-Phenylethyl)-1H-imidazole-5-carboxylic acid ethyl ester
Molecular formula: C₁₄H₁₆N₂O₂
CAS number: 33125-97-2

Medically reviewed by Drugs.com on Oct 11, 2023. Written by ASHP.

Introduction

Sedative and hypnotic agent used for general anesthesia.^{1 2 3 4 5 756 765}

Uses for Etomidate

Induction of Anesthesia

Used for induction of general anesthesia.^{1 2 3 4 5} Induction results in dose-related hypnotic effects (progressing from light sleep to unconsciousness).^{1 2 3 4 5 6 9}

Particularly useful in patients with compromised cardiopulmonary function because of minimal hemodynamic effects and decreased respiratory depressant effects relative to other IV anesthetics (e.g., barbiturates, propofol).^a

Carefully weigh potential benefits of the drug’s hemodynamic effects against possible risk of myoclonus.^{1 2 774} (See Common Adverse Effects under Cautions.)

Maintenance of Anesthesia

May be used during maintenance of anesthesia to supplement subpotent anesthetic agents (e.g., nitrous oxide and oxygen) during short surgical procedures (e.g., dilatation and curettage, cervical conization).^{1 2} Use for longer procedures not recommended due to risk of prolonged adrenal suppression.^{1 2} (See Adrenal Suppression under Cautions.)

Rapid Sequence Intubation

Commonly used for rapid sequence intubation because of rapid onset of action and favorable hemodynamic profile.^{12 754 755 761 765 767 768 772 773} However, risk of adrenal suppression may limit use in critically ill patients (particularly those with sepsis).^{12 766 767 769 774}

Procedural Sedation

Has been used for procedural sedation^{† [off-label]}.^{756 757 758 759 760 763 821 822 823} Because of its short duration of action, the drug is best suited for short procedures.^{756 759}

Time to onset of sedation and recovery with etomidate are comparable to those achieved with propofol, but considerably shorter than with midazolam.^{758 760 761 762 763 822} However, etomidate is associated with increased risk of myoclonus and pain at the injection site compared with other sedative agents.^{758 760 761 821} Although respiratory depression or apnea reported in some patients, incidence is generally the same or less than with other sedative agents.^{756 760 761 763 765}

Etomidate Dosage and Administration

General

Administration Precautions

Administer only by individuals experienced in the use and management of possible complications of general anesthetic agents.^{1 2 764 770 771 823}

Premedication

• May administer premedications such as benzodiazepines (to relieve anxiety and produce anterograde amnesia) and opiate agonists (to relieve pain) as appropriate.^{1 2 9 10}

Administration

Administer by IV injection.¹

May be administered by intraosseous (IO) injection^{† [off-label]} in the setting of pediatric rapid sequence intubation.¹³

Has been administered by continuous IV infusion^{† [off-label]}; however, this method of delivery is not recommended because of risk of adrenal toxicity.^{1 2 6 765} (See Adrenal Suppression under Cautions.)

Limited data indicate that inadvertent intra-arterial administration of etomidate injection does not appear to be associated with tissue necrosis distant from the injection site; however, intra-arterial use of the drug is not recommended.^{1 2 9}

IV Administration

Administer undiluted by direct IV injection.^{1 2 10}

Administer into larger, more proximal, veins of the forearm, rather than the smaller, distal hand or wrist veins to minimize pain at injection site.^{1 2}

To prevent needlestick injuries, do not recap, bend, or break needles by hand.^{1 2}

Rate of Administration

For induction of anesthesia, administer by rapid (over 30–60 seconds) IV injection in children >10 years of age and adults.^{1 2}

Dosage

Because individual response is variable, adjust dosage according to individual requirements and response, age, physical and clinical status, underlying pathologic conditions (e.g., shock, intestinal obstruction, malnutrition, anemia, burns, advanced malignancy, ulcerative colitis, uremia, alcoholism), and the type and amount of premedication or concomitant medication(s).^{1 2 9} Titrate dosage according to clinical effect.⁹

Pediatric Patients

Induction of Anesthesia

IV

Children >10 years of age: 0.3 mg/kg (0.2–0.6 mg/kg).^{1 2 9}

Maintenance of Anesthesia

IV

Use smaller increments than those used for induction.^{1 2}

Rapid Sequence Intubation

IV or IO† [off-label]

Manufacturers state inadequate data to make dosage recommendations for pediatric patients <10 years of age.^{1 2} In published reports, average dose of 0.3 mg/kg has been used in pediatric patients as young as 18 days of age.^{772 773}

Some clinicians recommend a dose of 0.3 mg/kg by IV or IO^{† [off-label]} injection for pediatric rapid sequence intubation.¹³

Procedural Sedation†

IV

Doses are usually less than those used for induction of anesthesia; in clinical studies, initial etomidate dose of 0.1–0.2 mg/kg usually administered, followed by additional doses of 0.05–0.1 mg/kg as needed (average total dose of up to 0.26 mg/kg per procedure).^{756 758 759 760 761 762 763}

Some studies have found that a dose of 0.2 mg/kg was most effective initial dose for short pediatric procedures in the emergency department.⁷⁵⁶

Adults

Induction of Anesthesia

IV

0.3 mg/kg (0.2–0.6 mg/kg).^{1 2 9}

Maintenance of Anesthesia

IV

Use smaller increments than those used for induction.^{1 2}

Rapid Sequence Intubation

IV

Usual dose of 0.3 mg/kg.^{12 754 755 768}

Procedural Sedation†

IV

Doses are usually less than those used for induction of anesthesia; in clinical studies, initial etomidate dose of 0.1–0.2 mg/kg usually administered, followed by additional doses of 0.05–0.1 mg/kg as needed (average total dose of up to 0.26 mg/kg per procedure).^{756 758 759 760 761 762 763}

Special Populations

Geriatric Patients

Geriatric patients may require lower dosages than younger patients because of pharmacokinetic differences (e.g., reduced protein binding and reduced clearance).^{2 765}

Cautions for Etomidate

Contraindications

• Known hypersensitivity to etomidate.^{1 2}

Warnings/Precautions

Administration Precautions

To minimize risk of adverse effects, follow recommendations for administration and monitoring of etomidate therapy.¹ (See Dosage and Administration.)

Adrenal Suppression

Causes adrenal suppression by inhibiting 11-β-hydroxylase activity, the enzyme responsible for production of cortisol and aldosterone.^{1 766 768}

Decreased plasma concentrations of cortisol (which usually persist for 6–8 hours and are unresponsive to stimulation by corticotropin [ACTH]) reported following IV administration of a single 0.3-mg/kg induction dose.^{1 2 3 4 5 6 768}

Because of risk of prolonged adrenal suppression, do not administer as a continuous IV infusion.^{1 2 6}

Although it is well established that etomidate causes adrenal suppression, there is controversy regarding the clinical importance.^{12 766 767 768} While evidence from one study showed increased mortality in critically ill patients (e.g., sepsis patients), other studies have not found such an association.^{766 767 768 769 774}

Specific Populations

Pregnancy

No adequate and well controlled studies in pregnant women; reduced pup survival and maternal toxicity observed in animal reproduction studies.¹

Based on animal data, repeated or prolonged use of general anesthetics and sedation drugs, including etomidate, during the third trimester of pregnancy may result in adverse neurodevelopmental effects in the fetus.^{750 753} (See Pediatric Use under Cautions and also see Advice to Patients.)

Insufficient data to support use during labor and delivery; not recommended for obstetric use (e.g., cesarean section).^{1 2}

Lactation

Not known whether etomidate is distributed into milk.^{1 2} Use with caution.^{1 2}

Pediatric Use

Manufacturers state safety and efficacy not established in children <10 years of age.^{1 2 10} However, the drug has been used for rapid sequence intubation in pediatric patients as young as 18 days of age.^{772 773} Also has been used in children of all ages for procedural sedation^† in the emergency department.^{756 757 758 759 762}

Repeated or prolonged use of general anesthetics and sedation drugs, including etomidate, in children <3 years of age or during the third trimester of pregnancy may adversely affect neurodevelopment.^{750 753} In animals, use for >3 hours of anesthetic and sedation drugs that block N-methyl-d-aspartic acid (NMDA) receptors and/or potentiate GABA activity leads to widespread neuronal apoptosis in the brain and long-term deficits in cognition and behavior;^{750 751 752 753} clinical relevance to humans is unknown.⁷⁵⁰

Some evidence suggests similar deficits may occur in children following repeated or prolonged exposure to anesthesia early in life.^{750 752} Some evidence also indicates that a single, relatively brief exposure to general anesthesia in generally healthy children is unlikely to cause clinically detectable deficits in global cognitive function or serious behavioral disorders.^{750 751 752} Most studies to date have substantial limitations; further research needed to fully characterize effects, particularly for prolonged or repeated exposures and in more vulnerable populations (e.g., less healthy children).⁷⁵⁰

Consider benefits and potential risks when determining the timing of elective procedures requiring anesthesia.⁷⁵⁰ FDA states that medically necessary procedures should not be delayed or avoided.^{750 753} (See Advice to Patients.)

Geriatric Use

Cardiac depression (decreased heart rate and cardiac index) and decreased mean arterial BP may occur in geriatric patients receiving etomidate, especially in those with hypertension.²

Since geriatric patients may have decreased renal function, monitor renal function and select dosage carefully.² (See Special Populations under Dosage and Administration and see Renal Impairment under Cautions.)

Hepatic Impairment

Metabolized by the liver; patients with hepatic insufficiency may be at higher risk of adverse effects (e.g., adrenal insufficiency).⁷⁷⁴

Renal Impairment

Substantially excreted by the kidneys.² Risk of severe adverse reactions may be increased in patients with impaired renal function.²

Common Adverse Effects

Injection site pain, skeletal muscle movements (e.g., myoclonic, averting, tonic, or ocular movements), postoperative nausea and vomiting. ^{1 2 3 4 9 758 760 761 821}

Myoclonus occurs frequently.^{1 2 758 760 761 821} Most episodes are mild to moderate in severity, although disturbing movements reported occasionally.^{1 2} Usually bilateral.^{1 2} Administration of IV fentanyl immediately before induction has been shown to minimize incidence of skeletal muscle movements.^{1 2 10 11}

Drug Interactions

Specific Drugs

Etomidate Pharmacokinetics

Absorption

Onset

Following IV administration, rapid onset of action;^{1 2 3 4 5 6} loss of consciousness usually occurs within 1 minute.^{1 2 4 9}

Duration

Dose dependent.^{1 2} Following IV administration of average doses (0.3 mg/kg), duration of hypnosis is short (about 3–10 minutes).^{1 2 765 768}

Plasma Concentrations

Minimal hypnotic plasma concentrations are at least 0.23 mcg/mL.^{1 2}

Distribution

Extent

Rapidly distributed from blood into CNS with substantial tissue uptake.^{3 4}

Plasma Protein Binding

Approximately 75%.⁷⁶⁵

Elimination

Metabolism

Rapidly metabolized in the liver, principally by hydrolysis, to etomidate carboxylic acid,^{1 2 3 4 8} which appears to be pharmacologically inactive.⁴

Elimination Route

Excreted in urine (75%) within 24 hours, mainly (about 80%) as the carboxylic acid metabolite;^{1 2 4} 13 and 10% of a dose are excreted in feces and bile, respectively.⁴

Half-life

About 1.25–5 hours.^{1 2 3 4 8}

Special Populations

Elimination half-life approximately doubled in patients with cirrhosis and esophageal varices.^{1 2}

Stability

Storage

Parenteral

Injection

20–25°C.^{1 2}

Do not use the injection unless the solution is clear and the container undamaged.^{1 2}

Discard unused portion.^{1 2}

Compatibility

Parenteral

Drug Compatibility

Actions

• Structurally unrelated to other currently available IV anesthetics.⁶

• Enhances activity of GABA, the principal inhibitory neurotransmitter in the CNS,^{6 7} through modulation and direct activation of the GABA_A receptor complex.^{6 7 765}

• Capable of producing all levels of CNS depression—from light sleep to deep coma—depending on the dosage.⁹

• Has no analgesic activity.^{1 2 4}

• Substantial changes on the EEG appear to occur following induction doses.^{3 4 9} The EEG changes are indicative of the various stages of anesthesia and appear to be similar to those occurring following induction of anesthesia with barbiturates.^{3 4}

• May decrease cerebral blood flow and intracranial pressure while cerebral perfusion pressure is increased or maintained during induction of anesthesia.^{1 3 9 765}

• Causes minimal hemodynamic changes⁹ and is associated with a decreased incidence and severity of cardiovascular effects compared with other IV anesthetic agents.^{3 4 5 6 10}

• Minor increases in cardiac index and slight decreases in heart rate, systemic vascular resistance, and arterial BP reported.⁹

• Equivalent induction doses of etomidate cause less respiratory depression than propofol or barbiturates.⁹

• Increases in carbon dioxide tension (PCO₂) reported.^{1 2}

• Usually reduces intraocular pressure (IOP).^{1 2}

Advice to Patients

• When procedures requiring general anesthetics or sedation drugs, including etomidate, are considered for young children or pregnant women, importance of discussing with the patient, parent, or caregiver the benefits, risks (including potential risk of adverse neurodevelopmental effects), and appropriate timing and duration of the procedure.^{750 753}

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.^{1 2}

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹

• Importance of informing patients of other important precautionary information.¹ (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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