Etomidate (etomidate)

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.

There is no enhanced messaging for this drug.

There are no contraindication interactions for this drug.

Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

Agents That May Cause Respiratory Depression/Sodium Oxybate

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Oxybate by itself may be associated with severe somnolence or respiratory depression. Concurrent use with other CNS depressants may further increase the risk for respiratory depression or loss of consciousness.(1-3)

CLINICAL EFFECTS: Concurrent use of sodium oxybate and sedative hypnotics or alcohol may further increase the risk for profound sedation, respiratory depression, coma, and/or death.(1,2) Fatalities have been reported.(3)

PREDISPOSING FACTORS: Based upon FDA evaluation of deaths in patients taking sodium oxybate, risk factors may include: use of multiple drugs which depress the CNS, more rapid than recommended oxybate dose titration, exceeding the maximum recommended oxybate dose, and prescribing for unapproved uses such as fibromyalgia, insomnia or migraine. Note that in oxybate clinical trials for narcolepsy 78% - 85% of patients were also receiving concomitant CNS stimulants.(1-3)

PATIENT MANAGEMENT: Avoid use of concomitant opioids, benzodiazepines, sedating antidepressants, sedating antipsychotics, general anesthetics, or muscle relaxants, particularly when predisposing risk factors are present. If combination use is required, dose reduction or discontinuation of one or more CNS depressants should be considered. If short term use of an opioid or general anesthetic is required, consider interruption of sodium oxybate treatment.(1,2) Respiratory depression can occur at any time during opioid therapy, especially during therapy initiation and following dosage increases. The risk of opioid-related overdose or overdose-related death is increased with higher opioid doses, and this risk persists over the course of therapy. Consider these risks when using concurrently with other agents that may cause CNS depression.(4) Discuss opioid reversal agents (e.g., naloxone, nalmefene) with all patients when prescribing or renewing an opioid analgesic or medicine to treat opioid use disorder (OUD). Consider prescribing an opioid reversal agent (e.g., naloxone, nalmefene) to patients prescribed medicines to treat OUD or opioid analgesics who are at increased risk of opioid overdose (such as those taking CNS depressants) and when a patient has household members/close contacts at risk for accidental overdose. Discuss the options for obtaining an opioid reversal agent (e.g., prescription, over-the-counter, or as part of a community-based program).(5)

DISCUSSION: The FDA evaluated sodium oxybate postmarket fatal adverse event reports from the FDA Adverse Event Reporting System(AERS)and from the manufacturer. Although report documentation was not always optimal or complete, useful information was obtained. Factors which may have contributed to fatal outcome: concomitant use of one or more drugs which depress the CNS, more rapid than recommended oxybate dose titration, exceeding the maximum recommended oxybate dose, and prescribing for unapproved uses such as fibromyalgia, insomnia or migraine. Many deaths occurred in patients with serious psychiatric disorders such as depression and substance abuse. Other concomitant diseases may have also contributed to respiratory and CNS depressant effects of oxybate.(3)

Moderate Interaction: Assess the risk to the patient and take action as needed.

Anesthesia Agents/Glp-1 Receptor Agonists

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: GLP-1 receptor agonists can cause delayed gastric emptying.(1,2)

CLINICAL EFFECTS: Gastric contents may remain in the stomach after preoperative fasting, which could increase the risk of regurgitation and aspiration.(1,2)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The American Society of Anesthesiologists (ASA) recommends the following for patients receiving elective procedures: - For patients on daily dosing, consider holding GLP-1 agonists on the day of the procedure. For patients on weekly dosing, consider holding GLP-1 agonists a week prior to the procedure. - Consult an endocrinologist for patients taking GLP-1 agonists for diabetes management if the GLP-1 agonist is held longer than the dosing schedule to avoid hyperglycemia. - For patients requiring urgent or emergent procedures, proceed and treat the patient as 'full stomach.'(3)

DISCUSSION: In one case report, a 31-year-old patient taking semaglutide followed preoperative fasting guidelines but food residue was discovered upon endoscopy, leading to cancellation of the surgical procedure.(4) In a case report, a semaglutide-treated patient experienced regurgitation upon induction of general anesthesia despite a 20 hour preoperative fasting period. The patient received semaglutide two days before the scheduled procedure.(5) A case report of a 42-year-old patient after fasting for 18 hours showed substantial gastric content upon endoscopy. The patient experienced intraoperative pulmonary aspiration of gastric contents which were suctioned from the trachea and bronchi using bronchoscopy.(6)

Known hypersensitivity to etomidate.

There are no contraindication contraindications for this drug.

• Adrenocortical insufficiency
• Hypotension

There are no moderate contraindications for this drug.

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.

More Frequent

• Nausea
• Vomiting

Rare or Very Rare

• Bradycardia
• Bradypnea
• Hypertension
• Hyperventilation
• Hypotension
• Hypoventilation
• Laryngismus
• Tachycardia
• Tachypnea

More Frequent

• Injection site sequelae
• Involuntary muscle movement

Rare or Very Rare

• Hiccups
• Snoring

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.)