Etomidate (etomidate)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Etomidate is a sedative and hypnotic agent used for general anesthesia.
Etomidate, a carboxylated imidazole, is a sedative and hypnotic agent used for general anesthesia. The drug is structurally unrelated to other currently available IV anesthetics.
Following IV injection, etomidate has a rapid onset of action and will produce loss of consciousness within 1 arm-brain circulation time (i.e., usually within about 60 seconds). Etomidate produces its anesthetic activity by enhancing the activity of gamma-aminobutyric acid (GABA), the principal inhibitory neurotransmitter in the CNS, through modulation and direct activation of the GABAA receptor complex.
Etomidate is capable of producing all levels of CNS depression--from light sleep to deep coma--depending on the dosage; however, the drug has no analgesic activity. The degree of depression and duration of action depend on dosage, rate and route of administration, and pharmacokinetics of the drug. Substantial changes on the EEG appear to occur following induction doses of etomidate.
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. Etomidate may decrease cerebral blood flow and intracranial pressure, while cerebral perfusion pressure is increased or maintained during induction of anesthesia.
Etomidate causes minimal hemodynamic changes and is associated with a decreased incidence and severity of cardiovascular effects compared with other IV anesthetic agents. Minor increases in cardiac index and slight decreases in heart rate, systemic vascular resistance, and arterial blood pressure have been reported with use of etomidate. In addition, equivalent induction doses of etomidate cause less respiratory depression than propofol or barbiturates.
Increases in carbon dioxide tension (PCO2) have been reported with administration of etomidate.
Some data suggest that etomidate usually reduces intraocular pressure (IOP).
The pharmacokinetic profile of etomidate is characterized by a rapid distribution from blood into CNS, rapid clearance from the brain, and substantial tissue uptake. Following the usual induction dose (0.3 mg/kg) of etomidate, duration of hypnosis is short (about 3-10 minutes) and dose dependent. The elimination half-life of etomidate is about 1.25-5 hours.
The drug is rapidly metabolized in the liver, principally by hydrolysis, to form etomidate carboxylic acid, which appears to be pharmacologically inactive. About 75% of an administered dose is excreted in urine within 24 hours, mainly (about 80%) as the carboxylic acid metabolite, while 13 and 10% of a dose are excreted in feces and bile, respectively.
Generic name: etomidate
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Etomidate
Indications
The following indications are listed for Etomidate:
- Administration Of General Anesthesia
- General Anesthesia Adjunct
Also known as: Adjunct General Anesthesia.
Dosing
Dosage of etomidate should be adjusted 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). In addition, dosage of the drug should be titrated to clinical effect.
Etomidate is administered by IV injection over 30-60 seconds. The drug should be injected undiluted by direct IV injection. Some clinicians state that etomidate may be administered by intraosseous (IO) injection+ in the setting of pediatric rapid sequence intubation. Although the drug has been administered as a continuous IV infusion+, this method of delivery is currently not recommended because of the risk of adrenal toxicity. (See Adrenal Suppression under Cautions: Warnings/Precautions.)
Etomidate injection should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. The injection should not be administered unless the solution is clear and the container is undamaged; unused portions should be discarded.
Limited data from clinical and animal studies 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. Pain at the injection site, which occurs frequently and usually is mild to moderate in severity (although occasionally may be severe), can be minimized if the larger, more proximal veins of the forearm, rather than the smaller, distal hand or wrist veins are used. To prevent needlestick injuries, needles should not be recapped, bent, or broken by hand.
Etomidate injection is compatible with commonly used premedicants administered prior to induction of anesthesia.
No dosing information is available for this tab.
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Drug interactions
There is no enhanced messaging for this drug.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
Known hypersensitivity to etomidate.
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
The most frequent adverse effects associated with IV use of etomidate are transient venous pain at the injection site and transient skeletal muscle movements (i.e., myoclonus), which occur in about 20% (range: 1-42%) and 32% (range: 23-63%) of patients, respectively. Although generally mild to moderate in severity, such adverse effects can occasionally be severe.
Most (74%) cases of transient skeletal muscle movements have been classified as myoclonic, but tonic movements (10%), ocular movements (9%), and averting movements (7%) also have been noted. Such movements are usually bilateral (of the arms, legs, shoulders, neck, chest wall, trunk, and/or all 4 extremities, with one or more muscle groups predominating), with an electroencephalogram (EEG) suggesting that they are manifestations of cortical disinhibition in the absence of evidence of seizure activity. Alternatively, muscle movements may be unilateral or predominate on one side (e.g., predominance of movement of the arm in which the IV was started), or a mixture of bilateral and unilateral types may occur. The incidence of skeletal muscle movements, particularly those considered disturbing, has been minimized with IV administration of fentanyl immediately before induction of anesthesia with etomidate.
Other adverse effects reported in patients receiving etomidate include hyperventilation, hypoventilation, apnea (duration: 5-90 seconds), laryngospasm, hiccups and snoring (may be associated with partial upper airway obstruction), hypertension, hypotension, arrhythmias (e.g., tachycardia, bradycardia), and postoperative nausea and vomiting.
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
No enhanced messaging available.
The manufacturers state that safety and efficacy of etomidate for induction or maintenance of anesthesia have not been established in children younger than 10 years of age. However, the drug has been used for rapid sequence intubation in pediatric patients as young as 18 days of age. Etomidate also has been used in children of all ages for procedural sedation+ in the emergency department.
FDA warns that repeated or prolonged use of general anesthetics and sedation drugs, including etomidate, in children younger than 3 years of age or during the third trimester of pregnancy may affect brain development. Animal studies in multiple species, including nonhuman primates, have demonstrated that use for longer than 3 hours of anesthetic and sedation drugs that block N-methyl-d-aspartic acid (NMDA) receptors and/or potentiate gamma-aminobutyric acid (GABA) activity leads to widespread neuronal and oligodendrocyte cell loss and alterations in synaptic morphology and neurogenesis in the brain, resulting in long-term deficits in cognition and behavior. Across animal species, vulnerability to these neurodevelopmental changes occurs during the period of rapid brain growth or synaptogenesis; this period is thought to correlate with the third trimester of pregnancy through the first year of life in humans, but may extend to approximately 3 years of age. The clinical relevance of these animal findings to humans is not known.
While some published evidence suggests that similar deficits in cognition and behavior may occur in children following repeated or prolonged exposure to anesthesia early in life, other studies have found no association between pediatric anesthesia exposure and long-term adverse neurodevelopmental outcomes. Most studies to date have had substantial limitations, and it is not clear whether the adverse neurodevelopmental outcomes observed in children were related to the drug or to other factors (e.g., surgery, underlying illness). There is some clinical evidence 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; however, further research is needed to fully characterize the effects of exposure to general anesthetics in early life, particularly for prolonged or repeated exposures and in more vulnerable populations (e.g., less healthy children). For further information, see Cautions: Pediatric Precautions, in Propofol 28:04.92.
Anesthetic and sedation drugs are an essential component of care for children and pregnant women who require surgery or other procedures that cannot be delayed; no specific general anesthetic or sedation drug has been shown to be less likely to cause neurocognitive deficits than any other such drug. Pending further accumulation of data in humans from well-designed studies, decisions regarding the timing of elective procedures requiring anesthesia should take into consideration both the benefits of the procedure and the potential risks. When procedures requiring the use of general anesthetics or sedation drugs are considered for young children or pregnant women, clinicians should discuss with the patient, parent, or caregiver the benefits, risks (including potential risk of adverse neurodevelopmental effects), and appropriate timing and duration of the procedure. FDA states that procedures that are considered medically necessary should not be delayed or avoided.
There are no adequate and well controlled studies of etomidate in pregnant women; in animal reproduction studies, reduced pup survival and maternal toxicity have been observed.
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. The clinical relevance of these animal findings to humans is not known; the potential risk of adverse neurodevelopmental effects should be considered and discussed with pregnant women undergoing procedures requiring general anesthetics and sedation drugs. (See Pediatric Use under Warnings/Precautions: Specific Populations, in Cautions.)
There are insufficient data to support the use of etomidate during labor and delivery; use is therefore not recommended in the obstetric setting, including in patients undergoing cesarean section.
It is not known whether etomidate is distributed into milk in humans. Because many drugs are distributed into human milk, caution is advised if etomidate is used in nursing women.
Clinical data indicate that etomidate may be associated with cardiac depression (decreased heart rate and cardiac index) and decreased mean arterial blood pressure in geriatric patients, especially those with hypertension. Etomidate is substantially excreted by the kidneys and the risk of severe adverse reactions to the drug may be increased in patients with impaired renal function. Because geriatric patients may have decreased renal function, it may be useful to monitor renal function, and dosage should be selected with caution in such patients. (See Dosage and Administration: Special Populations.)
ICD codes
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Last reviewed · Source: First Databank (FDB) drug data
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