Usage
- Etomidate is primarily used for the induction of general anesthesia for short procedures. It is particularly useful for patients with compromised cardiovascular function due to its minimal hemodynamic effects. Off-label uses include procedural sedation and, in intensive care, the suppression of steroidogenesis in severe Cushing’s syndrome.
- Pharmacological classification: Hypnotic, general anesthetic, short-acting sedative-hypnotic.
- Mechanism of Action: Etomidate enhances the inhibitory effects of gamma-aminobutyric acid (GABA) by binding to GABAA receptors in the central nervous system. This leads to increased chloride ion influx, hyperpolarization of neurons, and suppression of the reticular activating system, resulting in hypnosis and anesthesia.
Alternate Names
- Etomidate is the generic name.
- Brand names: Amidate, Hypnomidate, Etomidat-Lipuro.
How It Works
- Pharmacodynamics: Etomidate depresses the reticular activating system, resulting in hypnosis and loss of consciousness. It has minimal cardiovascular and respiratory depressant effects compared to other anesthetic agents. It also reduces cerebral metabolic rate, cerebral blood flow, and intracranial pressure. Etomidate inhibits 11β-hydroxylase, suppressing adrenal cortisol synthesis.
- Pharmacokinetics:
- Absorption: Rapid onset of action (30-60 seconds) after intravenous administration.
- Metabolism: Rapidly metabolized in the liver by ester hydrolysis and hepatic conjugation.
- Elimination: Primarily eliminated via renal excretion of metabolites, with a small amount excreted unchanged in urine. Elimination half-life is approximately 4-5 hours for the unchanged drug and 2-4 minutes for initial hypnotic effects due to redistribution from the plasma to other tissues.
- Mode of Action: Etomidate acts as a GABAA receptor agonist, enhancing the receptor’s affinity for GABA and increasing chloride ion conductance. This hyperpolarizes neurons, leading to decreased neuronal excitability and the hypnotic effect.
- Elimination Pathways: Primarily hepatic metabolism followed by renal excretion of metabolites. A small fraction is excreted unchanged in the urine.
Dosage
Standard Dosage
Adults:
- Induction of general anesthesia: 0.2-0.6 mg/kg IV over 30-60 seconds; usual dose is 0.3 mg/kg IV.
- Procedural sedation: 0.1-0.3 mg/kg IV bolus, repeated as needed; Max single dose: 20 mg. Lower doses (0.15mg/kg) may be considered for obtunded patients.
Children:
- Children > 10 years old: 0.2-0.3 mg/kg IV. Dosages over 0.3 mg/kg have been observed in practice.
- Children < 10 years old: Use is not recommended due to insufficient data. However, 0.2-0.3 mg/kg IV has been used in clinical practice, especially in emergency situations. Pediatric safety considerations: Close monitoring of respiratory and cardiovascular function.
Special Cases:
- Elderly Patients: Reduced doses due to age-related decline in renal and hepatic function; initiate with 0.15-0.2 mg/kg and titrate to effect. Closely monitor cardiovascular function.
- Patients with Renal Impairment: No specific dosage adjustments; however, monitor renal function and consider reduced doses due to increased risk of toxicity.
- Patients with Hepatic Dysfunction: No specific dosage adjustments; however, monitor liver function tests and consider reduced doses.
- Patients with Comorbid Conditions: Use with caution in patients with sepsis, hypovolemia, adrenal insufficiency, or those requiring vasopressor support. Adjust dosage accordingly and monitor closely.
Clinical Use Cases
- Intubation: 0.3 mg/kg IV for rapid sequence intubation. Lower doses (0.15 mg/kg IV) may be used for unstable patients.
- Surgical Procedures: 0.2-0.6 mg/kg IV for induction. Smaller supplemental doses may be used during short procedures.
- Mechanical Ventilation: Not routinely recommended for prolonged sedation due to adrenal suppression; however, infusions of 0.04-0.1 mg/kg/hour have been used in the ICU with careful monitoring and hydrocortisone supplementation if needed.
- Intensive Care Unit (ICU) Use: For suppression of steroidogenesis in Cushing’s syndrome: 0.04-0.1 mg/kg/hour continuous IV infusion. Very low starting doses (0.02 mg/kg/h) have been utilized outside the ICU, with titration to achieve target cortisol levels.
- Emergency Situations: 0.3 mg/kg IV bolus for rapid sequence intubation in unstable patients.
Dosage Adjustments
- Adjust dosage based on patient’s response, age, physical status, and co-existing medical conditions.
- Consider reduced doses for elderly, patients with renal or hepatic impairment, and those with cardiovascular instability.
Side Effects
Common Side Effects:
- Myoclonus (involuntary muscle movements)
- Pain on injection
- Nausea and vomiting
- Hiccups
- Hypotension
- Apnea or hypoventilation
- Adrenal suppression
Rare but Serious Side Effects:
- Laryngospasm
- Allergic reactions
- Severe hypotension
- Cardiac arrhythmias
- Seizures
Long-Term Effects:
- Prolonged adrenal suppression with continuous infusions
- Potential impact on brain development in young children with prolonged or repeated exposure.
Adverse Drug Reactions (ADR):
- Anaphylaxis
- Adrenocortical suppression
- Severe cardiovascular depression
Contraindications
- Known hypersensitivity to etomidate
- Status asthmaticus
- Porphyria
Drug Interactions
- Enhanced hypnotic effect with opioids, benzodiazepines, and other sedatives.
- May potentiate the effects of neuromuscular blocking agents.
- May alter the dosage requirements of other anesthetic agents.
- Alcohol can enhance the hypnotic effect.
- Incompatibility with compound sodium lactate infusion (Hartmann’s solution), ascorbic acid and certain neuromuscular blocking agents (e.g. vecuronium).
Pregnancy and Breastfeeding
- Pregnancy Safety Category: C. Use only if the potential benefit justifies the potential risk to the fetus.
- Fetal risks: Potential for fetal adrenal suppression with prolonged maternal use.
- Breastfeeding: Etomidate is excreted in breast milk. Consider the risk-benefit ratio and potentially interrupt breastfeeding temporarily.
Drug Profile Summary
- Mechanism of Action: GABAA receptor agonist, enhancing GABAergic neurotransmission and causing CNS depression.
- Side Effects: Myoclonus, pain at injection site, nausea/vomiting, hypotension, apnea, adrenal suppression.
- Contraindications: Hypersensitivity, status asthmaticus, porphyria.
- Drug Interactions: Opioids, benzodiazepines, other sedatives, neuromuscular blocking agents.
- Pregnancy & Breastfeeding: Category C; use with caution; excreted in breast milk.
- Dosage: 0.2-0.6 mg/kg IV for induction; 0.1-0.3 mg/kg IV for sedation; dosage adjustments required for certain populations.
- Monitoring Parameters: Blood pressure, heart rate, respiratory rate, oxygen saturation, end-tidal CO2, level of consciousness, and cortisol levels (if prolonged use).
Popular Combinations
- Fentanyl and etomidate for rapid sequence intubation to provide analgesia and reduce the hemodynamic response to intubation.
- Succinylcholine and etomidate for neuromuscular blockade during intubation.
Precautions
- General Precautions: Thorough patient evaluation, including medical history, allergies, and medication list. Close monitoring of vital signs during and after administration.
- Specific Populations:
- Pregnant Women: Avoid if possible, especially in the third trimester, due to potential fetal adrenal suppression.
- Breastfeeding Mothers: May temporarily interrupt breastfeeding due to drug excretion in breast milk.
- Children & Elderly: Use age-appropriate dosing and careful monitoring.
- Lifestyle Considerations: Advise patients not to drive or operate machinery after receiving etomidate.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Etomidate?
A: The standard adult induction dose is 0.3 mg/kg IV over 30-60 seconds (range 0.2-0.6 mg/kg). For procedural sedation, the dose is 0.1-0.3 mg/kg IV. Dosage adjustments are needed for elderly patients, those with organ dysfunction, and other specific populations.
Q2: What is the primary use of Etomidate in clinical practice?
A: Induction of general anesthesia, particularly in patients with cardiovascular compromise.
Q3: Does Etomidate have analgesic properties?
A: No, etomidate is a hypnotic agent and does not provide analgesia. Often used in combination with an analgesic like fentanyl.
Q4: What are the common side effects of Etomidate?
A: Myoclonus, pain on injection, nausea/vomiting, hypotension, and apnea.
Q5: How does Etomidate affect adrenal function?
A: It inhibits 11β-hydroxylase, which can lead to transient adrenal suppression, especially with repeated doses or continuous infusions.
Q6: What are the contraindications to using Etomidate?
A: Known hypersensitivity to etomidate, status asthmaticus and porphyria.
Q7: What are the important drug interactions with Etomidate?
A: Other sedatives, opioids, and neuromuscular blocking agents can enhance its effects. Alcohol also potentiates etomidate’s hypnotic effect.
Q8: Can Etomidate be used in pregnant or breastfeeding women?
A: Etomidate is a Pregnancy Category C drug. Its use should be carefully weighed against potential risks to the fetus. It is present in breast milk, so breastfeeding may need to be temporarily interrupted if etomidate is necessary.
A: It is primarily metabolized in the liver through ester hydrolysis and hepatic conjugation and excreted by the kidneys.
Q10: What monitoring parameters are essential when administering Etomidate?
A: Cardiorespiratory monitoring, including blood pressure, heart rate, oxygen saturation, respiratory rate and end-tidal CO2. Also, monitor level of consciousness. If prolonged use, consider monitoring serum cortisol levels.
