Amidate

Name: Amidate

Dosing & Uses

Dosage Forms & Strengths

injectable solution

  • 2mg/mL

General Anesthesia Induction

0.3-0.6 mg/kg IVP over 30-60 sec 

Cushing Syndrome (Off-label)

Inhibition of steroidogenesis in patients with Cushing syndrome

0.2-0.6 mg/kg IV infused over 30-60 seconds for induction of anesthesia blocks normal stress-induced increase in adrenal cortisol production for 4-8 h 

ICU continuous infusion: 0.04-0.05 mg/kg/hr IV; continuous monitoring required

Dosing considerations

  • Used rarely; often toxic at doses required to reduce cortisol secretion
  • Long-term use limited by the requirement for repeated IV administration

Sedation (Off-label)

0.1 mg/kg IV bolus x1-3 doses; other dosing regimens may exist 

Dosage Forms & Strengths

injectable solution

  • 2mg/mL

General Anesthesia Induction

<10 years: Safety and efficacy not established

>10 years: Same as adults; 0.3-0.6 mg/kg IVP over 30-60 sec 

Sedation (Off-label)

0.1-0.4 mg/kg IV bolus x1; additional doses may be necessary; other dosing regimens may exist 

Clinical pharmacology

Etomidate is a hypnotic drug without analgesic activity. Intravenous injection of etomidate produces hypnosis characterized by a rapid onset of action, usually within one minute. Duration of hypnosis is dose dependent but relatively brief, usually three to five minutes when an average dose of 0.3 mg/kg is employed. Immediate recovery from anesthesia (as assessed by awakening time, time needed to follow simple commands and time to perform simple tests after anesthesia as well as they were performed before anesthesia), based upon data derived from short operative procedures where intravenous etomidate was used for both induction and maintenance of anesthesia, is about as rapid as, or slightly faster than, immediate recovery after similar use of thiopental. These same data revealed that the immediate recovery period will usually be shortened in adult patients by the intravenous administration of approximately 0.1 mg of intravenous fentanyl, one or two minutes before induction of anesthesia, probably because less etomidate is generally required under these circumstances (consult the package insert for fentanyl before using).

The most characteristic effect of intravenous etomidate on the respiratory system is a slight elevation in arterial carbon dioxide tension (PaCO2). See also ADVERSE REACTIONS.

Reduced cortisol plasma levels have been reported with induction doses of 0.3 mg/kg etomidate. These persist for approximately 6 to 8 hours and appear to be unresponsive to ACTH administration.

The intravenous administration of up to 0.6 mg/kg of etomidate to patients with severe cardiovascular disease has little or no effect on myocardial metabolism, cardiac output, peripheral circulation or pulmonary circulation. The hemodynamic effects of etomidate have in most cases been qualitatively similar to those of thiopental sodium, except that the heart rate tended to increase by a moderate amount following administration of thiopental under conditions where there was little or no change in heart rate following administration of etomidate. However, clinical data indicates that etomidate administration in geriatric patients, particularly those with hypertension, may result in decreases in heart rate, cardiac index, and mean arterial blood pressure. There are insufficient data concerning use of etomidate in patients with recent severe trauma or hypovolemia to predict cardiovascular response under such circumstances.

Clinical experience and special studies to date suggest that standard doses of intravenous etomidate ordinarily neither elevate plasma histamine nor cause signs of histamine release.

Limited clinical experiene, as well as animal studies, suggests that inadvertent intra-arterial injection of etomidate, unlike thiobarbiturates, will not usually be followed by necrosis of tissue distal to the injection site. Intra-arterial injection of etomidate is, however, not recommended.

Etomidate induction is associated with a transient 20-30% decrease in cerebral blood flow. This reduction in blood flow appears to be uniform in the absence of intracranial space occupying lesions. As with other intravenous induction agents, reduction in cerebral oxygen utilization is roughly proportional to the reduction in cerebral blood flow. In patients with and without intracranial space occupying lesions, etomidate induction is usually followed by a moderate lowering of intracranial pressure, lasting several minutes. All of these studies provided for avoidance of hypercapnia. Information concerning regional cerebral perfusion in patients with intracranial space occupying lesions is too limited to permit definitive conclusions.

Preliminary data suggests that etomidate will usually lower intraocular pressure moderately.

Etomidate is rapidly metabolized in the liver. Minimal hypnotic plasma levels of unchanged drug are equal to or higher than 0.23 μg/mL; they decrease rapidly up to 30 minutes following injection and thereafter more slowly with a half-life value of about 75 minutes. Approximately 75% of the administered dose is excreted in the urine during the first day after injection. The chief metabolite is R-(+)-1-(1- phenylethyl)-1H-imidazole-5-carboxylic acid, resulting from hydrolysis of etomidate, and accounts for about 80% of the urinary excretion. Limited pharmacokinetic data in patients with cirrhosis and esophageal varices suggest that the volume of distribution and elimination half-life of etomidate are approximately double that seen in healthy subjects.

(Reference: H. Van Beem, et. al., Anaesthesia 38 (Supp 38:61-62, July 1983).

In clinical studies, elderly patients demonstrated decreased initial distribution volumes and total clearance of etomidate. Protein binding of etomidate to serum albumin was also significantly decreased in these individuals.

Reduced plasma cortisol and aldosterone levels have been reported following induction doses of etomidate. These results persist for approximately 6-8 hours and appear to be unresponsive to ACTH stimulation. This probably represents blockage of 11 beta-hydroxylation within the adrenal cortex.

(References: 1. R.J. Fragen, et. al., Anesthesiology 61:652-656, 1984. 2. R.L. Wagner & P.F. White, Anesthesiology 61:647-651, 1984. 3. F.H. DeJong, et. al., Clin. Endocrinology and Metabolism 59:(6):1143-1147, 1984, and three additional drafts of Metabolic Studies, all submitted to NDA 18-228 on April 1, 1985).

Amidate Drug Class

Amidate is part of the drug class:

  • Other general anesthetics

Cautions for Amidate

Contraindications

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

  • 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

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

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

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 depressionfrom light sleep to deep comadepending 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

What are some things I need to know or do while I take Amidate?

  • Tell all of your health care providers that you take Amidate. This includes your doctors, nurses, pharmacists, and dentists.
  • Avoid driving and doing other tasks or actions that call for you to be alert until the effects of this medicine wear off and you feel fully awake.
  • Talk with your doctor before you drink alcohol or use other drugs and natural products that slow your actions.
  • If you are 65 or older, use Amidate with care. You could have more side effects.
  • Studies in young animals and children have shown that frequent or long-term use of anesthesia drugs or drugs used for sleep in children younger than 3 years of age may lead to long-term brain problems. This may also happen in unborn babies if the mother uses this medicine during the third trimester of pregnancy. Talk with the doctor.
  • Use with care in children. Talk with the doctor.
  • Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using Amidate while you are pregnant.
  • Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

How is this medicine (Amidate) best taken?

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

  • It is given as a shot into a vein.

What do I do if I miss a dose?

  • This medicine is given on an as needed basis.

Contraindications

Etomidate is contraindicated in patients who have shown hypersensitivity to it.

Etomidate Levels and Effects while Breastfeeding

Summary of Use during Lactation

Amounts of etomidate in milk are very small and decrease rapidly. Existing data indicate that no waiting period is required before resuming breastfeeding after etomidate anesthesia. Breastfeeding can be resumed as soon as the mother has recovered sufficiently from general anesthesia to nurse. When a combination of anesthetic agents is used for a procedure, follow the recommendations for the most problematic medication used during the procedure.

Drug Levels

Maternal Levels. Twenty women undergoing cesarean section received 0.3 mg/kg of etomidate intravenously for induction of anesthesia. Average colostrum levels were 79.3 mcg/L (range 0 to 420 mcg/L) at 30 minutes and 16.2 mcg/L (range 0 to 60 mcg/L) at 2 hours after the dose. Etomidate was not detected in any colostrum samples 4 hours after the dose.[1]

Infant Levels. Relevant published information was not found as of the revision date.

Effects in Breastfed Infants

Relevant published information was not found as of the revision date.

Effects on Lactation and Breastmilk

Relevant published information was not found as of the revision date.

Alternate Drugs to Consider

Methohexital, Propofol, Thiopental

References

1. Esener Z, Sarihasan B, Guven H et al. Thiopentone and etomidate concentrations in maternal and umbilical plasma, and in colostrum. Br J Anaesth. 1992;69:586-8. PMID: 1467101

Administrative Information

LactMed Record Number

427

Last Revision Date

20150310

Disclaimer

Information presented in this database is not meant as a substitute for professional judgment. You should consult your healthcare provider for breastfeeding advice related to your particular situation. The U.S. government does not warrant or assume any liability or responsibility for the accuracy or completeness of the information on this Site.

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