Etomidate is an ultrashort acting nonbarbiturate hypnotic drug that also blocks the adrenal enzyme, 11-Beta hydroxylase. It is used as an anesthetic for short procedures such as joint dislocation and endotracheal intubation.

Etomidate Uses:

• General anesthesia:

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

• Off Label Use of Etomidate in Adults:

  • Procedural sedation
  • Cushing syndrome

Etomidate Dose in Adults

Etomidate Dose in General anesthesia:

• IV: Initial: For the induction of anaesthesia, use 0.3 mg/kg (range: 0.2 to 0.6 mg/kg) over 30 to 60 seconds.

Etomidate Dose as Supplementation to sub potent anesthetic agents:

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

Etomidate Dose in the treatment of Cushing syndrome (off-label):

• IV: Initial: 0.04 to 0.05 mg/kg/hour (usually equates to ~2.5 to 3 mg per hour).
• Titrate to serum cortisol concentrations of 18 to 29 mcg/dL (500 to 800 nmol/L) in patients who are physiologically stressed or 5.5 to 11 mcg/dL (150 to 300 nmol/L) in patients who are not.
• Adjust the infusion rate until the cortisol level is less than 5.5 mcg/dL (150 nmol/L) for full blockage.
• Hydrocortisone IV is required if complete blockade desired rather than partial blockade (‘block and replace’).

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.

Etomidate Dose in the Procedural sedation (off-label):

• IV: Initial: 0.1 to 0.2 mg/kg, then 0.05 mg/kg as required every 3 to 5 minutes.

Etomidate Dose in Children

Etomidate Dose in the Anesthesia for induction:

• Infants: Very limited data available:

  • IV: 0.2 to 0.3 mg/kg/dose given as a single dose; dosage determined by two pharmacokinetic investigations and a prospective observational experiment.

• Children less than 10 years:

  • IV: 0.2 to 0.3 mg/kg administered once.

• Children of 10 years and more than 10 years and Adolescents:

  • Usual dose: IV: 0.3 mg/kg/dose given once
  • range: 0.2 to 0.6 mg/kg/dose

Etomidate Dose in the Procedural sedation:

• Infants 6 months and more than 6 months, Children, and Adolescents:

  • IV: Usual initial dose: 0.2 mg/kg/dose prior to procedure (reported range: 0.1 to 0.4 mg/kg/dose);
  • repeat doses may be required depending on patient response and duration of the procedure;
  • repeat doses vary in the literature and range from 0.1 to 0.2 mg/kg/dose;
  • reported total dose ranged from 0.3 to 0.6 mg/kg/procedure;
  • dosing based on several prospective and retrospective studies primarily in the ED setting; procedures included orthopedic reductions and sedation for CT scans.
  • Note:
    • Etomidate does not have analgesic properties;
    • additional therapy (eg, fentanyl) may be required for painful procedures.

Etomidate Dose in the Rapid sequence intubation (RSI): 

• Infants, Children, and Adolescents:

  • IV, Intraosseous: 0.2 to 0.4 mg/kg/dose as a single dose;
  • maximum dose: 20 mg per dose.
  • Note: Not recommended for patients in septic shock due to an association between transient adrenocortical suppression and increased mortality rate.

Etomidate Pregnancy Risk Category: C

• The placenta is crossed by Etomidate
• Human fetuses could be at their most vulnerable during the third-trimester.
• Animal studies suggest that repeated or protracted use of sedatives and general anaesthetics that block N-methyl D-aspartate receptors or enhance GABA activities may have an impact on brain development.
• It is important to evaluate the risks and benefits of maternal treatment with etomidate in pregnancy, particularly for prolonged procedures that last more than three hours.
• It has been reported that etomidate can be used to induce anesthesia before cesarean delivery.
• Other agents might be used more often.
• The second trimester is not the time for routine surgery.
• Whether they are in the third trimester or not, ACOG advises against denying medically necessary surgeries or procedures to pregnant women.
• If it is elective, the procedure should be postponed until after delivery.

Use of etomidate during breastfeeding

• The breast milk contains etomidate.
• Etomidate was used as an induction agent for 40 women who had to have cesarean deliveries. It was found in the colostrum both 30 minutes after maternal injection and 2 hours later.
• After the maternal dose, etomidate was absent from breast milk four hours later.
• Although caution is recommended when giving etomidate as a medication to breastfeeding women, it is acceptable.
• The Academy of Breast Feeding Medicine suggests that elective surgery be delayed until the child is more mature and established in breastfeeding.
• If the child is fully-term and healthy, breastfeeding can be resumed. Milk may also be given once the mother is awake after a period of recovery.
• When possible, it is best to express milk before any surgery.
• Milk may be saved for later use by children at lower risk.

Dose in Kidney Disease:

No dosage changes are mentioned in the manufacturer's labelling; use it with caution as the risk of toxicity is higher in individuals with renal impairment.

Dose in Liver disease:

The manufacturer's labelling does not provide any dosage modifications.

Common Side Effects of Etomidate:

• Central nervous system:

  • Myoclonus

• Endocrine & metabolic:

  • Adrenal suppression

• Gastrointestinal:

  • Nausea
  • Vomiting (on emergence from anesthesia)

• Local:

  • Pain at injection site

• Neuromuscular & skeletal:

  • Musculoskeletal disease (transient skeletal movements)

• Ophthalmic:

  • Nystagmus

Less Common Side Effects of Etomidate:

• Gastrointestinal:

  • Hiccups

Contraindications to Etomidate:

• Hypersensitivity to etomidate and any component of the formulation

Warnings and precautions

• Production of adrenal steroid:

  • Patients may be less able to cope with stress if they are given etomidate in continuous infusions in the ICU.
  • Manufacturers do not recommend continuous infusion.
  • A single dose of induction of anesthesia has not been shown to cause any increase in mortality.
  • Etomidate inhibits 11B-hydroxylase, which is an important enzyme in adrenal steroid production.
  • One induction dose can block the normal stress-induced rise in adrenal cortisol for 6-8 hours or up to 24 hours for elderly and disabled patients.

• Heart Failure:

  • According to the American Heart Association's scientific statement, etomidate may be an agent that can exacerbate myocardial dysfunction.

• Renal impairment

  • Patients with impaired renal function are at greater risk of toxic effects.
  • Take care and keep track of your renal function.

Etomidate: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitoring parameters:

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

How to administer Etomidate?

IV:

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

Mechanism of action of Etomidate:

The ultra-short acting nonbarbiturate general sedative (benzylimidazole), is used to induce anesthesia quickly with minimal cardiovascular side effects. It causes EEG burst suppression high in the High doses.

The onset of action:

• 30 to 60 seconds

Peak effect:

• 1 minute

Duration:

• 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.

Protein binding:

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

Metabolism:

• Hepatic and plasma esterases

Half-life elimination:

• Terminal: 2.6 to 3.5 hours

Time to peak,

• serum: 7 minutes

Excretion:

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

International Brand Names of Etomidate:

• Etomidat-Lipuro
• Etomidato-Lipuro
• Hypnomidate
• Amidate
• Endata
• Etomid

Etomidate Brand Names in Pakistan: