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Etomidate

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
Brands: Amidate

Introduction

Sedative and hypnotic agent.1 2

Uses for Etomidate

Induction Anesthesia

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 its minimal hemodynamic effects and decreased respiratory depressant effects relative to other IV anesthetics (barbiturates, propofol).1 2

Carefully weigh the potential benefits of the drug’s hemodynamic effects against the possible risks of very frequent transient skeletal muscle movements associated with etomidate therapy.1 2

Maintenance Anesthesia

Maintenance anesthesia to supplement subpotent anesthetic agents (e.g., nitrous oxide and oxygen) during short-term surgical procedures (e.g., dilatation and curettage, cervical conization).1 2

Etomidate Dosage and Administration

General

Premedication

  • Premedication generally includes benzodiazepines (to relieve anxiety, induce light anesthesia, and produce anterograde amnesia), barbiturates (to relieve anxiety and provide sedation), and/or opiate agonists (to relieve pain), and sometimes anticholinergic agents (e.g., atropine, scopolamine) to suppress vagal reflexes and inhibit secretions.1 2 9 10

Administration

IV Administration

Administer undiluted by direct IV injection.1 2

Do not administer by prolonged IV infusion.1 2 (See Decreased Plasma Cortisol Concentrations under Cautions.)

Should be administered only by individuals experienced in the administration of general anesthetics and in the management of possible complications associated with these agents.1 2

Limited data indicate that inadvertent intra-arterial administration of etomidate injections 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

Use the larger 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 Anesthesia
IV

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

Maintenance Anesthesia
IV

Use smaller increments than those used for induction.1 2

Adults

Induction Anesthesia
IV

0.3 mg/kg (0.2–0.6 mg/kg).1 2 9

Maintenance Anesthesia
IV

Use smaller increments than those used for induction.1 2

Special Populations

Geriatric Patients

Geriatric patients may require lower dosages than younger patients because of pharmacokinetic differences.2

Cautions for Etomidate

Contraindications

  • Known hypersensitivity to etomidate.1 2

Warnings/Precautions

Warnings

Decreased Plasma Cortisol Concentrations

Decreased plasma concentrations of cortisol (which usually persist for 6–8 hours and are unresponsive to stimulation by corticotropin [ACTH]) may occur with 0.3-mg/kg induction doses.1 2 3 4 5 6

Because of the danger of prolonged suppression of endogenous cortisol and aldosterone secretion from the adrenal cortex, the manufacturers and some clinicians recommend that etomidate not be administered as a continuous IV infusion.1 2 6

Although decreased plasma concentrations of cortisol have not been associated with changes in vital signs or increased mortality rate, concern exists in patients undergoing severe stress;1 2 consider administration of exogenous corticosteroids in such patients.1 2

General Precautions

Musculoskeletal Effects

Transient skeletal muscle movements occur frequently (32%; range 23–63%).1 2

Most are mild to moderate in severity, although disturbing movements occur occasionally.1 2

Disturbing movements have been classified as myoclonic (74%), tonic (10%), ocular (9%), and averting movements (7%).1 2

Movements may be bilateral (of arms, legs, shoulders, neck, chest wall, trunk, and/or all extremities, with one or more muscle groups predominating), with EEG suggesting that they are manifestations of cortical disinhibition in the absence of evidence of seizure activity.1 2 Alternatively, muscle movements may be unilateral, or predominate on one side, or a mixture of bilateral and unilateral types.1 2

Administration of 0.1 mg of IV fentanyl immediately before induction may minimize incidence of skeletal muscle movements. 1 2 10

Labor and Delivery

Since safety of the drug during labor and delivery has not been fully elucidated, use is not recommended during labor and delivery, including cesarean section.1 2

Specific Populations

Pregnancy

Category C.1 2

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.)

Lactation

Not known whether IV etomidate is distributed into milk.1 2 Use with caution.1 2

Pediatric Use

Safety and efficacy of etomidate for induction anesthesia or maintenance anesthesia (to supplement subpotent anesthetic agents during surgical procedures) in children <10 years of age have not been established.1 2 10

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, especially 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.)

Renal Impairment

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

Common Adverse Effects

Injection site pain, eye movement, skeletal muscle movements (e.g., myoclonic, averting, tonic, eye). 1 2 3 4 9

Interactions for Etomidate

Specific Drugs

Drug

Interaction

Comments

CNS depressants (e.g., anesthetics, sedatives, hypnotics, opiate agonists)

Additive pharmacologic effect1 2 10

Consider dosage reduction1 2 10

Neuromuscular blocking agents

Etomidate does not alter usual dosage requirements of neuromuscular blocking agents1 2

Etomidate Pharmacokinetics

Absorption

Onset

Following IV administration, rapid onset of action;1 2 3 4 5 6 loss of consciousness occurs usually 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 3–5 minutes).1 2 Recovery from anesthesia is at least as fast as with thiopental (no longer commercially available in the US),1 2 but slower than that associated with propofol.9

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

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

15–30°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

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Drug Compatibility
Y-Site CompatibilityHID

Compatible

Alfentanil HCl

Atracurium besylate

Atropine sulfate

Ephedrine sulfate

Fentanyl citrate

Lidocaine HCl

Lorazepam

Midazolam HCl

Mivacurium chloride

Morphine sulfate

Pancuronium bromide

Phenylephrine HCl

Succinylcholine chloride

Sufentanil citrate

Incompatible

Ascorbic acid injection

Vecuronium bromide

Actions

  • Structurally unrelated to other currently available IV anesthetics.6

  • Enhances the activity of GABA, the principal inhibitory neurotransmitter in the CNS,6 7 by interacting with the GABAA receptor complex.6 7

  • 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.1 3 9

  • 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. (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

Etomidate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection, for IV use

2 mg/mL (20 and 40 mg)*

Amidate (available as single-use ampuls, Abboject syringes, and vials)

Hospira

Etomidate Injection

AHFS DI Essentials. © Copyright 2017, Selected Revisions November 6, 2017. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

References

1. Bedford Laboratories. Etomidate injection prescribing information. Bedford, OH; 2004 Mar.

2. Abbott. Amidate (etomidate) injection prescribing information. North Chicago, IL; 1999.

3. Batjer HH. Cerebral protective effects of etomidate: experimental and clinical aspects. Cerebrovasc Brain Metab Rev. 1993; 5:17-32. [PubMed 8452760]

4. Giese JL Stanley TH. Etomidate: a new intravenous anesthetic induction agent. Pharmacotherapy. 1983; 3:251-8. [PubMed 6359080]

5. Preziosi P, Vacca M. Adrenocortical suppression and other endocrine effects of etomidate: minireview. Life Sci. 1988; 42:477- 89. [PubMed 3276997]

6. Carmichael FJ, Haas DA. General Anesthetics. In: Kalant H and Roschlau WH, eds. Principles of Medical Pharmacology. 6th edition. New York: Oxford University Press; 1998:278-92.

7. Hales TG, Olsen RW. Basic pharmacology of intravenous induction agents. In: Bowdle TA, Horita A, Kharasch ED. The pharmacologic basis of anesthesiology. New York: Churchill Livingstone; 1994:295-306.

8. Henthorn TK. Pharmacokinetics of intravenous induction agents. In: Bowdle TA, Horita A, Kharasch ED. The pharmacologic basis of anesthesiology. New York: Churchill Livingstone; 1994:307-9.

9. Fragen RJ. Clinical pharmacology and applications of intravenous anesthetic induction agents. In: Bowdle TA, Horita A, Kharasch ED. The pharmacologic basis of anesthesiology. New York: Churchill Livingstone; 1994:319-36.

10. Abbott Laboratories, North Chicago, IL: Personal communication.

750. US Food and Drug Administration. Drug safety communication: FDA review results in new warnings about using general anesthetics and sedation drugs in young children and pregnant women. Silver Spring, MD; 2016 Dec 14. From FDA website.

751. Davidson AJ, Disma N, de Graaff JC et al. Neurodevelopmental outcome at 2 years of age after general anaesthesia and awake-regional anaesthesia in infancy (GAS): an international multicentre, randomised controlled trial. Lancet. 2016; 387:239-50. [PubMed 26507180]

752. Sun LS, Li G, Miller TL et al. Association Between a Single General Anesthesia Exposure Before Age 36 Months and Neurocognitive Outcomes in Later Childhood. JAMA. 2016; 315:2312-20. [PubMed 27272582]

753. US Food and Drug Administration. Drug safety communication: FDA approves labeling changes for use of general anesthetic and sedation drugs in young children. Silver Spring, MD; 2017 Apr 27. From FDA website.

HID. Trissel LA. Handbook on injectable drugs. 14th ed. Bethesda, MD: American Society of Health-System Pharmacists; 2007:647-8.

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