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Etomidate

Pronunciation

Pronunciation

(e TOM i date)

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous:

Amidate: 2 mg/mL (10 mL, 20 mL) [contains propylene glycol]

Generic: 2 mg/mL (10 mL, 20 mL)

Solution, Intravenous [preservative free]:

Generic: 2 mg/mL (10 mL, 20 mL)

Brand Names: U.S.

  • Amidate

Pharmacologic Category

  • General Anesthetic

Pharmacology

Ultra-short-acting nonbarbiturate general anesthetic (benzylimidazole) used for rapid induction of anesthesia with minimal cardiovascular effects; produces EEG burst suppression at high doses.

Distribution

Vd: 2 to 4.5 L/kg

Metabolism

Hepatic and plasma esterases

Excretion

Urine ~ 75% (80% as metabolite; 2% as unchanged drug)

Onset of Action

30 to 60 seconds; Peak effect: 1 minute

Time to Peak

Serum: 7 minutes

Duration of Action

Dose dependent: 2 to 3 minutes (0.15 mg/kg dose); 3 to 5 minutes (0.3 mg/kg dose); rapid recovery is due to rapid redistribution

Half-Life Elimination

Terminal: 2.6 to 3.5 hours

Protein Binding

76%; decreased protein binding resulting in an increased percentage of “free” etomidate in patients with renal failure or hepatic cirrhosis

Special Populations: Hepatic Function Impairment

Vd and elimination half-life increase 2-fold in patients with cirrhosis compared with healthy subjects.

Special Populations: Elderly

Vd, total clearance, and plasma protein binding are decreased in elderly patients.

Use: Labeled Indications

General anesthesia: Induction of general anesthesia; as a supplement to subpotent anesthetic agents during maintenance of anesthesia for short operative procedures (eg, dilation and curettage, cervical conization).

Off Label Uses

Cushing syndrome

Based on the Endocrine Society’s Clinical Practice Guidelines for Treatment of Cushing’s Syndrome, etomidate, given for severe hypercortisolism in critically ill patients with Cushing syndrome, is an effective and recommended agent in patients who are not immediate surgical candidates and cannot take oral medications.

Procedural sedation

In a randomized, nonblinded, prospective trial, etomidate, although it appeared equally safe for procedural sedation in the emergency department, had lower procedural success compared to propofol in adults undergoing procedural sedation. Notably, etomidate induced myoclonus in 20% of patients compared to 1.8% of patients receiving propofol [Miner 2007]. A retrospective study for procedural sedation found that the use of etomidate was effective in 93% of subjects in the emergency department (ED) with few adverse events although many adverse events (eg, myoclonus) may not be well documented in the ED [Vinson 2002]. Additional trials may be necessary to further define the role of etomidate in procedural sedation.

Based on the American College of Emergency Physicians (ACEP) clinical policy for procedural sedation and analgesia in the ED, etomidate may be safely administered to adults for procedural sedation and analgesia in the ED. Etomidate may also be safely administered to children (lower recommendation) for procedural sedation and analgesia in the ED.

Additional Off-Label Uses

Sedation for diagnosis of seizure foci

Contraindications

Hypersensitivity to etomidate or any component of the formulation

Dosing: Adult

General anesthesia: IV: Initial: 0.3 mg/kg (range: 0.2 to 0.6 mg/kg) over 30 to 60 seconds for induction of anesthesia.

Supplementation to subpotent anesthetic agents: IV: Administer smaller increments during short operative procedures to supplement subpotent anesthetic agents, such as nitrous oxide; individualize dosage (usually smaller than the original induction dose).

Cushing syndrome (off-label use): IV: Initial: 0.04 to 0.05 mg/kg/hour (usually equates to ~2.5 to 3 mg/hour). Titrate to serum cortisol of 18 to 29 mcg/dL (500 to 800 nmol/L) in a physiologically stressed patient or 5.5 to 11 mcg/dL (150 to 300 nmol/L) in a non-physiologically stressed patient. For complete blockade, titrate infusion rate to achieve a cortisol level <5.5 mcg/dL (<150 nmol/L). Hydrocortisone IV is required if complete blockade desired rather than partial blockade (‘block and replace’) (Preda 2012). Note: Studies have not reported sedation at these etomidate doses; however, patients should be managed in an intensive care unit with sedation scoring every 2 hours initially for the first 24 hours, then every 12 hours. Cortisol levels should be measured every 4 to 6 hours (ES [Nieman 2015]; Preda 2012).

Procedural sedation (off-label use): IV: Initial: 0.1 to 0.2 mg/kg, followed by 0.05 mg/kg every 3 to 5 minutes as needed (Bahn, 2005; Miner, 2007; Vinson, 2002)

Dosing: Geriatric

Refer to adult dosing; reduced doses may be required.

Dosing: Pediatric

General anesthesia: IV: Children >10 years and Adolescents: Initial: 0.3 mg/kg (range: 0.2 to 0.6 mg/kg) over 30 to 60 seconds for induction of anesthesia.

Dosing: Renal Impairment

There are no dosage adjustments provided in the manufacturer's labeling; use with caution, risk of toxicity is greater in patients with renal impairment.

Dosing: Hepatic Impairment

There are no dosage adjustments provided in the manufacturer's labeling.

Administration

Administer IV push over 30 to 60 seconds. Solution is highly irritating; avoid administration into small vessels; in some cases, preadministration of lidocaine may be considered.

Storage

Store at 20°C to 25°C (68°F to 77°F).

Drug Interactions

There are no known significant interactions.

Adverse Reactions

>10%:

Central nervous system: Myoclonus (33%)

Endocrine & metabolic: Adrenal suppression

Gastrointestinal: Nausea, vomiting (on emergence from anesthesia)

Local: Pain at injection site (30% to 80%)

Neuromuscular & skeletal: Musculoskeletal disease (transient skeletal movements)

Ophthalmic: Nystagmus

1% to 10%: Gastrointestinal: Hiccups

<1% (Limited to important or life-threatening): Apnea, bradycardia, cardiac arrhythmia, decreased cortisol (decreased cortisol synthesis), hypertension, hyperventilation, hypotension, hypoventilation, laryngospasm, muscle spasm (masseter; Bozeman 2002), tachycardia

Warnings/Precautions

Concerns related to adverse effects:

• Adrenal steroid production: Etomidate inhibits 11-B-hydroxylase, an enzyme important in adrenal steroid production. A single induction dose blocks the normal stress-induced increase in adrenal cortisol production for 6 to 8 hours, up to 24 hours in elderly and debilitated patients. Continuous infusion of etomidate for sedation in the ICU may increase mortality because patients may not be able to respond to stress. Administration by continuous infusion is not recommended by the manufacturer. No increase in mortality has been identified with a single dose for induction of anesthesia (McPhee 2013).

Disease-related concerns:

• Heart failure: In a scientific statement from the American Heart Association, etomidate has been determined to be an agent that may exacerbate underlying myocardial dysfunction (magnitude: moderate) (AHA [Page 2016]).

• Renal impairment: Risk of toxicity is greater in patients with renal impairment; use with caution and monitor renal function.

Special populations:

• Elderly: May induce cardiac depression in elderly patients, especially those with hypertension; may require lower doses.

• Pediatric neurotoxicity: In pediatric and neonatal patients <3 years and patients in third trimester of pregnancy (ie, times of rapid brain growth and synaptogenesis), the repeated or lengthy exposure to sedatives or anesthetics during surgery/procedures may have detrimental effects on child or fetal brain development and may contribute to various cognitive and behavioral problems. Epidemiological studies in humans have reported various cognitive and behavioral problems, including neurodevelopmental delay (and related diagnoses), learning disabilities, and ADHD. Human clinical data suggest that single, relatively short exposures are not likely to have similar negative effects. No specific anesthetic/sedative has been found to be safer. For elective procedures, risks versus benefits should be evaluated and discussed with parents/caregivers/patients; critical surgeries should not be delayed (FDA 2016).

Other warnings/precautions:

• Appropriate use: When considering use, weigh etomidate hemodynamic properties against the high frequency of transient skeletal muscle movements.

• Experienced personnel: According to the manufacturer, etomidate should only be administered by experienced personnel trained in the administration of general anesthetics and in the management of complications encountered during the conduct of general anesthesia. Consult local regulations and individual institutional policies and procedures.

Monitoring Parameters

Cardiac monitoring; blood pressure; renal function (in renal impairment)

Pregnancy Considerations

Adverse events have been observed in animal reproduction studies. Based on animal data, repeated or prolonged use of general anesthetic and sedation medications that block N-methyl-D- aspartate receptors and/or potentiate GABA activity may affect brain development. Human fetuses may be most vulnerable during the third trimester. Until additional information is available, the benefits and risks of maternal treatment with etomidate during pregnancy should be evaluated, especially for procedures lasting more than 3 hours. The ACOG recommends that pregnant women should not be denied medically indicated surgery or procedures, regardless of trimester. If the procedure is elective, it should be delayed until after delivery (ACOG 2011).

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience fatigue, nausea, vomiting, or twitching. Have patient report immediately to prescriber severe dizziness, passing out, vision changes, difficulty breathing, slow breathing, shallow breathing, tachycardia, bradycardia, abnormal heartbeat, involuntary eye movements, muscle rigidity, abnormal movements, severe headache, or injection site irritation (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

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