Etomidate


Article Author:
Lesley Williams


Article Editor:
Brian Fitzgerald


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Updated:
3/23/2019 12:16:12 AM

Indications

Etomidate is an ultrashort-acting, non-barbiturate hypnotic intravenous anesthetic agent.[1] Etomidate does not have any analgesic properties. It is administered only by intravenous route. Etomidate has a very favorable hemodynamic profile on induction, with a minimal amount of blood pressure depression making it an ideal choice for shock trauma, hypovolemic patients, or patients with significant cardiovascular disease.[2] Etomidate has been approved for use during induction of general anesthesia and rapid sequence intubation.[3] Etomidate is also indicated for sedation, during maintenance of anesthesia, and for short operative procedures such as a reduction of dislocated joints, tracheal intubation, cardioversion,[4] dilation and curettage, or cervical conization.[5][6] Etomidate is used to increase the seizure duration potential and has shown to be superior to propofol and thiopental.[7] Etomidate has been used off-label for Inhibition of steroidogenesis in patients with Cushing syndrome.

Mechanism of Action

Etomidate contains a carboxylated imidazole ring-containing anesthetic compound (R-1-ethyl-1-[a-methylbenzyl] imidazole-5-carboxylate) and is structurally unrelated to other anesthetic agents. The imidazole ring provides water solubility in acidic solutions and lipid solubility at physiological pH. Therefore, etomidate is dissolved in propylene glycol, which often causes pain on injection but can be reduced by a prior intravenous injection of lidocaine.

Etomidate has a chiral carbon atom and exists in the form of 2 enantiomers. Only the R (+) isomer is hypnotically active. The S (-) enantiomer has a 20-fold lower hypnotic effect.[2] Etomidate interacts with gamma-Aminobutyric acid type A (GABA) receptors by binding directly to specific sites and increasing the affinity of the inhibitory neurotransmitter GABA (positive modulation of GABA-mediated activity).[5] GABA is the principal inhibitory neurotransmitter within the central nervous system (CNS) and works with the adrenergic neurotransmitter system to counterbalance the action of excitatory neurotransmitters. Etomidate may have disinhibitory effects on the parts of the nervous system that control extrapyramidal motor activity. This disinhibition offers a potential explanation for the 30% to 60% incidence of myoclonus during induction with etomidate.

Administration

Etomidate is an agent for IV anesthesia induction, and it offers several advantages[5]:

  •  Simple dose regimen
  •  Fast onset of action
  •  Short duration of effect
  •  Rapid metabolism
  •  Low risk of histamine release
  •  Hemodynamic stability on bolus injection 

The dose for induction of anesthesia in adult and pediatric patients above the age of 10 years varies between 0.2 and 0.6 mg/kg of body weight. Use is not recommended in patients below 10 years old because there is insufficient data to support dosage recommendations for induction of anesthesia. Geriatric patients may require reduced doses of etomidate due to the natural progression of declining renal function. Clinical studies suggest that etomidate may induce cardiac depression in elderly patients with hypertension. A common induction dose of etomidate at 0.2 to 0.3 mg/kg, injected over 30 to 60 seconds, produces a rapid onset of anesthesia, usually in less than one minute. The use of narcotics and other neuroactive drugs utilized during anesthesia may decrease the required Etomidate dosage. The duration of action is directly correlated to the dose with each 0.1 mg/kg providing about 100 seconds of unconsciousness.

Recovery depends on redistribution to inactive tissue sites. Metabolism is primarily hepatic by ester hydrolysis to inactive metabolites, which are 78% excreted in urine and 22% in bile. Less than 3% of an administered dose of etomidate is excreted unchanged in the urine. Like most intravenous anesthetics, etomidate is highly protein bound (77%). Thus, in low albumin states, it can achieve a higher concentration in the brain since it will be less bound to albumin and more free-drug would be available in the brain. Because of its minimal effects on hemodynamics and short context-sensitive half-time, larger doses and repeated boluses can safely be administered.

Adverse Effects

Transient inhibition of adrenal steroid synthesis is considered the most significant adverse effect of etomidate. A single bolus dose causes a dose-dependent inhibition of 11beta-hydroxylase lasting 6 to 12 hours. This enzyme is responsible for converting 11-deoxycortisol to cortisol, which results in adrenocortical suppression. This poses at least a theoretical risk of impairing a patient’s ability to produce an adequate stress response. 80% of patients were found to have etomidate-induced adrenal inhibition at 12 hours, and most patients’ suppression had resolved by 48 hours.[8] Etomidate is no longer administered by continuous infusion because of the risks of sustained suppression of endogenous cortisol and aldosterone production.

The most common adverse reaction associated with the use of etomidate is transient intravenous pain on injection. Pain appears to be less frequent when larger, more proximal arm veins are used or when IV lidocaine is given before an etomidate bolus. Transient skeletal muscle movements or myoclonus were observed in about 32% of the patients. Electroencephalographic studies have failed to expose seizure activity and suggest that these muscle movements are a demonstration of disinhibition of cortical activity. Severe, disturbing movements was decreased when 0.1 mg of fentanyl was given immediately before induction. According to several studies, pretreatment with midazolam, dexmedetomidine, narcotics, propofol, dezocine, or ketamine all reduce the incidence and severity of myoclonus after a bolus dose of etomidate.[9][10][11][12][13][14]

Postoperative nausea and vomiting with etomidate are comparable to the general frequency of PONV. The incidence of PONV was higher when etomidate was used for both induction and maintenance of anesthesia in short procedures such as dilation and curettage, or when analgesia was insufficient.[15]

Contraindications

Etomidate is contraindicated in any patient with a known hypersensitivity reaction.

Etomidate is a commonly used sedative during rapid sequence intubation (RSI). Septic patients have an increased risk of developing adrenal suppression, which has been associated with increased mortality in some studies.[16] Since etomidate affects cortisol production, its use in septic patients is controversial.[17][18] However, data are still lacking to prove that etomidate should be avoided in this patient population.

Etomidate is known to be excreted by the kidney. Therefore, the risk of toxic reactions to this drug may be higher in patients with impaired renal function. Because elderly patients have a natural progression of decreased renal function, care should be taken in dose selection, and it may be beneficial to monitor renal function.

Caution should be used when administering etomidate to patients with hepatic disease since the liver primarily metabolizes it. These patients may need lower doses and may be at increased risk for adverse effects.

Monitoring

The ASA recommends standard monitoring including oxygenation, circulation, ventilation, and temperature for all anesthetics. Trained anesthesia personnel must be continually present during all anesthetic cases requiring general anesthesia, monitored anesthesia care, or regional anesthesia.

Cardiovascular Effects

Etomidate has minimal effects on the cardiovascular system and is the major reason for choosing this drug as an induction agent. It causes a mild reduction in peripheral vascular resistance which is responsible for a decline in arterial blood pressure. Myocardial contractility and cardiac output are usually unchanged. Etomidate does not release histamine. However, etomidate by itself, even in large doses, produces relatively light anesthesia for laryngoscopy, and marked increases in heart rate and blood pressure may be recorded when Etomidate is solely used for induction.

Respiratory Effects

Ventilation is not significantly affected. Induction doses do not result in apnea unless opioids have also been administered. The most distinctive effect of on the respiratory system is a slight rise in arterial carbon dioxide tension (PaCO2).

Central Nervous System Effects

Etomidate decreases cerebral metabolic rate, cerebral blood flow, and intracranial pressure. Because of minimal cardiovascular effects, cerebral perfusion pressure is well maintained. Etomidate increases the amplitude of somatosensory evoked potentials making it use beneficial for ECT. Postoperative nausea and vomiting is more common with Etomidate than with propofol or barbiturate induction but appears to have the same frequency as general anesthesia. Etomidate lacks analgesic properties.

Toxicity

Pediatric Neurotoxicity

Published animal studies demonstrate that the use of anesthetic agents during the period of rapid brain growth or synaptogenesis increase neuronal apoptosis in the developing brain and result in long-term cognitive deficits when used for more than 3 hours. These changes may correlate with exposure to the drug in the third trimester of gestation through the first several months of life but may extend to about 3 years of age.

Although uncommon, overdosage may occur from rapid or repeated injections. A decrease in blood pressure may follow rapid injection. No adverse cardiovascular or respiratory effects due to etomidate overdose have been reported.

Enhancing Healthcare Team Outcomes

Since etomidate is intended for the induction of general anesthesia, any practitioner who administers etomidate must be trained in the administration of general anesthesia and the management of complications encountered. Emergency equipment must be readily available and in good working order.

The decision to use etomidate as an induction agent is ultimately up to the provider based on the physiologic state of their patient. Large, prospective controlled trials are still needed to determine the final role of etomidate, especially in critically ill patients. In the specific case of increasing the seizure duration potential, etomidate has been shown (Level III) to be superior to propofol and thiopental.[7]


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Etomidate - Questions

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A 65-year-old undergoing hip replacement experiences seizure-like activity after induction. Which drug is most likely the cause?



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Adrenal suppression is associated with which of the following anesthetic agents?



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Etomidate - References

References

Dumps C,Bolkenius D,Halbeck E, [Etomidate for intravenous induction of anaesthesia]. Der Anaesthesist. 2017 Dec     [PubMed]
Gooding JM,Corssen G, Etomidate: an ultrashort-acting nonbarbiturate agent for anesthesia induction. Anesthesia and analgesia. 1976 Mar-Apr     [PubMed]
Nestor NB,Burton JH, ED use of etomidate for rapid sequence induction. The American journal of emergency medicine. 2008 Oct     [PubMed]
Canessa R,Lema G,Urzúa J,Dagnino J,Concha M, Anesthesia for elective cardioversion: a comparison of four anesthetic agents. Journal of cardiothoracic and vascular anesthesia. 1991 Dec     [PubMed]
Erdoes G,Basciani RM,Eberle B, Etomidate--a review of robust evidence for its use in various clinical scenarios. Acta anaesthesiologica Scandinavica. 2014 Apr     [PubMed]
Ruth WJ,Burton JH,Bock AJ, Intravenous etomidate for procedural sedation in emergency department patients. Academic emergency medicine : official journal of the Society for Academic Emergency Medicine. 2001 Jan     [PubMed]
Liu J,Liu R,Meng C,Cai Z,Dai X,Deng C,Zhang J,Zhou H, Propofol decreases etomidate-related myoclonus in gastroscopy. Medicine. 2017 Jun     [PubMed]
Zhu Y,Yang Y,Zhou C,Bao Z, Using dezocine to prevent etomidate-induced myoclonus: a meta-analysis of randomized trials. Drug design, development and therapy. 2017     [PubMed]
Du X,Zhou C,Pan L,Li C, Effect of dexmedetomidine in preventing etomidate-induced myoclonus: a meta-analysis. Drug design, development and therapy. 2017     [PubMed]
An X,Li C,Sahebally Z,Wen X,Zhao B,Fang X, Pretreatment with Oxycodone Simultaneously Reduces Etomidate-Induced Myoclonus and Rocuronium-Induced Withdrawal Movements During Rapid-Sequence Induction. Medical science monitor : international medical journal of experimental and clinical research. 2017 Oct 19     [PubMed]
Wu GN,Xu HJ,Liu FF,Wu X,Zhou H, Low-Dose Ketamine Pretreatment Reduces the Incidence and Severity of Myoclonus Induced by Etomidate: A Randomized, Double-Blinded, Controlled Clinical Trial. Medicine. 2016 Feb     [PubMed]
Zhou C,Zhu Y,Liu Z,Ruan L, Effect of pretreatment with midazolam on etomidate-induced myoclonus: A meta-analysis. The Journal of international medical research. 2017 Apr     [PubMed]
St Pierre M,Dunkel M,Rutherford A,Hering W, Does etomidate increase postoperative nausea? A double-blind controlled comparison of etomidate in lipid emulsion with propofol for balanced anaesthesia. European journal of anaesthesiology. 2000 Oct     [PubMed]
Sunshine JE,Deem S,Weiss NS,Yanez ND,Daniel S,Keech K,Brown M,Treggiari MM, Etomidate, adrenal function, and mortality in critically ill patients. Respiratory care. 2013 Apr     [PubMed]
Freund Y,Jabre P,Mourad J,Lapostolle F,Reuter PG,Woimant M,Javaud N,Adnet F, Relative adrenal insufficiency in critically ill patient after rapid sequence intubation: KETASED ancillary study. Journal of critical care. 2014 Jun     [PubMed]
McPhee LC,Badawi O,Fraser GL,Lerwick PA,Riker RR,Zuckerman IH,Franey C,Seder DB, Single-dose etomidate is not associated with increased mortality in ICU patients with sepsis: analysis of a large electronic ICU database. Critical care medicine. 2013 Mar     [PubMed]
Singh PM,Arora S,Borle A,Varma P,Trikha A,Goudra BG, Evaluation of Etomidate for Seizure Duration in Electroconvulsive Therapy: A Systematic Review and Meta-analysis. The journal of ECT. 2015 Dec     [PubMed]
Payen JF,Dupuis C,Trouve-Buisson T,Vinclair M,Broux C,Bouzat P,Genty C,Monneret D,Faure P,Chabre O,Bosson JL, Corticosteroid after etomidate in critically ill patients: a randomized controlled trial. Critical care medicine. 2012 Jan     [PubMed]

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