Etomidate

Last updated
Etomidate
Etomidate.svg
(R)-etomidate
Clinical data
Trade names Amidate, Hypnomidate, Tomvi
AHFS/Drugs.com Monograph
License data
Routes of
administration 		Intravenous
ATC code
Legal status
Legal status
Pharmacokinetic data
Protein binding 76%
Metabolism Ester hydrolysis in plasma and liver
Elimination half-life 75 minutes
Excretion Urine (85%) and Bile duct (15%)
Identifiers
  • Ethyl 3-[(1R)-1-phenylethyl]imidazole-5-carboxylate
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.046.700 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C14H16N2O2
Molar mass 244.294 g·mol−1
3D model (JSmol)
Melting point 67 °C (153 °F)
Boiling point 392 °C (738 °F)
  • O=C(OCC)c1cncn1C(c2ccccc2)C
  • InChI=1S/C14H16N2O2/c1-3-18-14(17)13-9-15-10-16(13)11(2)12-7-5-4-6-8-12/h4-11H,3H2,1-2H3 Yes check.svgY
  • Key:NPUKDXXFDDZOKR-UHFFFAOYSA-N Yes check.svgY
   (verify)

Etomidate [3] (USAN, INN, BAN; marketed as Amidate) is a short-acting intravenous anaesthetic agent used for the induction of general anaesthesia and sedation [4] for short procedures such as reduction of dislocated joints, tracheal intubation, cardioversion and electroconvulsive therapy. It was developed at Janssen Pharmaceutica in 1964 and was introduced as an intravenous agent in 1972 in Europe and in 1983 in the United States. [5]

Contents

The most common side effects include venous pain on injection and skeletal muscle movements. [6]

Medical uses

Sedation and anesthesia

In emergency settings, etomidate can be used as a sedative hypnotic agent. It is used for conscious sedation [7] [8] and as a part of a rapid sequence induction to induce anaesthesia. [9] [10] It is used as an anaesthetic agent since it has a rapid onset of action and a safe cardiovascular risk profile, and therefore is less likely to cause a significant drop in blood pressure than other induction agents. [11] [12] In addition, etomidate is often used because of its easy dosing profile, limited suppression of ventilation, lack of histamine liberation and protection from myocardial and cerebral ischemia. [10] Thus, etomidate is a good induction agent for people who are hemodynamically unstable. [9] Etomidate also has interesting characteristics for people with traumatic brain injury because it is one of the only anesthetic agents able to decrease intracranial pressure and maintain a normal arterial pressure. [5] [13] [14] [15] [16]

In those with sepsis, one dose of the medication does not appear to affect the risk of death. [17]

Speech and memory test

Another use for etomidate is to determine speech lateralization in people prior to performing lobectomies to remove epileptogenic centres in the brain. This is called the etomidate speech and memory test, or eSAM, and is used at the Montreal Neurological Institute. [18] [19] However, only retrospective cohort studies support the use and safety of etomidate for this test. [20]

Steroidogenesis inhibitor

In addition to its action and use as an anesthetic, etomidate has also been found to directly inhibit the enzymatic biosynthesis of steroid hormones, including corticosteroids in the adrenal gland. [21] [22] As the only adrenal steroidogenesis inhibitor available for intravenous or parenteral administration, it is useful in situations in which rapid control of hypercortisolism is necessary or in which oral administration is unfeasible. [21] [22] [23]

Use in executions

The U.S. state of Florida used the drug in a death penalty procedure when Mark James Asay, 53, was executed on August 24, 2017. He became the first person in the U.S. to be executed with etomidate as one of the drugs. Etomidate replaces midazolam as the sedative. Drug companies have made it harder to buy midazolam for executions. The etomidate was followed by rocuronium bromide, a paralytic, and finally, potassium acetate in place of the commonly used potassium chloride injection to stop the heart. Potassium acetate was first used for this purpose inadvertently in a 2015 execution in Oklahoma. [24]

Adverse effects

Etomidate suppresses corticosteroid synthesis in the adrenal cortex by reversibly inhibiting 11β-hydroxylase, an enzyme important in adrenal steroid production; it leads to primary adrenal suppression. [25] [26] Using a continuous etomidate infusion for sedation of critically ill trauma patients in intensive care units has been associated with increased mortality due to adrenal suppression. [27] Continuous intravenous administration of etomidate leads to adrenocortical dysfunction. The mortality of patients exposed to a continuous infusion of etomidate for more than 5 days increased from 25% to 44%, mainly due to infectious causes such as pneumonia. [27]

Because of etomidate-induced adrenal suppression, its use for patients with sepsis is controversial. Cortisol levels have been reported to be suppressed up to 72 hours after a single bolus of etomidate in this population at risk for adrenal insufficiency. [10] For this reason, many authors have suggested that etomidate should never be used for critically ill patients with septic shock [28] [29] [30] because it could increase mortality. [30] [31] However, other authors continue to defend etomidate's use for septic patients because of etomidate's safe hemodynamic profile and lack of clear evidence of harm. [13] [32] A study by Jabre et al. showed that a single dose of etomidate used for Rapid Sequence Induction prior to endrotracheal intubation has no effect on mortality compared to ketamine even though etomidate did cause transient adrenal suppression. [33] In addition, a recent meta-analysis done by Hohl could not conclude that etomidate increased mortality. [10] The authors of this meta-analysis concluded more studies were needed because of lack of statistical power to conclude definitively about the effect of etomidate on mortality. Thus, Hohl suggests a burden to prove etomidate is safe for use in septic patients, and more research is needed before it is used. [10] Other authors [34] [35] [36] advise giving a prophylactic dose of steroids (e.g. hydrocortisone) if etomidate is used, but only one small prospective controlled study [36] in patients undergoing colorectal surgery has verified the safety of giving stress dose corticosteroids to all patients receiving etomidate.

In a retrospective review of almost 32,000 people, etomidate, when used for the induction of anaesthesia, was associated 2.5-fold increase in the risk of dying compared with those given propofol. [37] People given etomidate also had significantly greater odds of having cardiovascular morbidity and significantly longer hospital stay. [37] Given the retrospective design of this study, it is difficult to draw any firm conclusions from the data.

In people with traumatic brain injury, etomidate use is associated with a blunting of an ACTH stimulation test. [26] The clinical impact of this effect has yet to be determined.

In addition, concurrent use of etomidate with opioids and/or benzodiazepines, is hypothesized to exacerbate etomidate-related adrenal insufficiency. [38] [39] However, only retrospective evidence of this effect exists and prospective studies are needed to measure the clinical impact of this interaction.

Etomidate is associated with a high incidence of burning on injection, postoperative nausea and vomiting, and superficial thrombophlebitis (with rates higher than propofol). [40]

Pharmacology

Side view of the EM structure of the a1b3g2 GABAA receptor. GABA and etomidate are coloured magenta. Subunits in different colours. One alpha and one beta subunit is hidden. Green chloride ions illustrated in the channel pore. 6x3v GABAA-Rezeptorstruktur.png
Side view of the EM structure of the α1β3γ2 GABAA receptor. GABA and etomidate are coloured magenta. Subunits in different colours. One alpha and one beta subunit is hidden. Green chloride ions illustrated in the channel pore.

Pharmacodynamics

(R)-Etomidate is tenfold more potent than its (S)-enantiomer. At low concentrations (R)-etomidate is a modulator at GABAA receptors [42] containing β2 and β3 [43] subunits. At higher concentrations, it can elicit currents in the absence of GABA and behaves as an allosteric agonist. Its binding site is located in the transmembrane section of this receptor between the beta and alpha subunits (β+α−). β3-containing GABAA receptors are involved in the anesthetic actions of etomidate, while the β2-containing receptors are involved in some of the sedation and other actions that can be elicited by this drug. [44]

Pharmacokinetics

At the typical dose, anesthesia is induced for the duration of about 5–10 minutes, though the half-life of drug metabolism is about 75 minutes, because etomidate is redistributed from the plasma to other tissues.

Metabolism

Etomidate is highly protein-bound in blood plasma and is metabolised by hepatic and plasma esterases to inactive products. It exhibits a biexponential decline.[ citation needed ]

Formulation

Etomidate is usually presented as a clear colourless solution for injection containing 2 mg/mL of etomidate in an aqueous solution of 35% propylene glycol, although a lipid emulsion preparation (of equivalent strength) has also been introduced. Etomidate was originally formulated as a racemic mixture, [45] but the R form is substantially more active than its enantiomer. [46] It was later reformulated as a single-enantiomer drug, becoming the first general anesthetic in that class to be used clinically. [47]

Related Research Articles

<span class="mw-page-title-main">Ketamine</span> Dissociative anesthetic and anti-depressant

Ketamine is a dissociative anesthetic used medically for induction and maintenance of anesthesia. It is also used as a treatment for depression and pain management. It is a novel compound that was derived from phencyclidine in 1962 in pursuit of a safer anesthetic with fewer hallucinogenic effects.

<span class="mw-page-title-main">Shock (circulatory)</span> Medical condition of insufficient blood flow

Shock is the state of insufficient blood flow to the tissues of the body as a result of problems with the circulatory system. Initial symptoms of shock may include weakness, fast heart rate, fast breathing, sweating, anxiety, and increased thirst. This may be followed by confusion, unconsciousness, or cardiac arrest, as complications worsen.

<span class="mw-page-title-main">Sepsis</span> Life-threatening organ dysfunction triggered by infection

Sepsis is a potentially life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs.

<span class="mw-page-title-main">General anaesthesia</span> Medically induced loss of consciousness

General anaesthesia (UK) or general anesthesia (US) is a method of medically inducing loss of consciousness that renders a patient unarousable even with painful stimuli. This effect is achieved by administering either intravenous or inhalational general anaesthetic medications, which often act in combination with an analgesic and neuromuscular blocking agent. Spontaneous ventilation is often inadequate during the procedure and intervention is often necessary to protect the airway. General anaesthesia is generally performed in an operating theater to allow surgical procedures that would otherwise be intolerably painful for a patient, or in an intensive care unit or emergency department to facilitate endotracheal intubation and mechanical ventilation in critically ill patients. Depending on the procedure, general anaesthesia may be optional or required. Regardless of whether a patient may prefer to be unconscious or not, certain pain stimuli could result in involuntary responses from the patient that may make an operation extremely difficult. Thus, for many procedures, general anaesthesia is required from a practical perspective.

<span class="mw-page-title-main">Propofol</span> Intravenous medication used in anesthesia

Propofol is the active component of an intravenous anesthetic formulation used for induction and maintenance of general anesthesia. It is chemically termed 2,6-diisopropylphenol. The formulation was approved under the brand name Diprivan. Numerous generic versions have since been released. Intravenous administration is used to induce unconsciousness after which anesthesia may be maintained using a combination of medications. It is manufactured as part of a sterile injectable emulsion formulation using soybean oil and lecithin, giving it a white milky coloration.

<span class="mw-page-title-main">Anesthetic</span> Drug that causes anesthesia

An anesthetic or anaesthetic is a drug used to induce anesthesia ⁠— ⁠in other words, to result in a temporary loss of sensation or awareness. They may be divided into two broad classes: general anesthetics, which result in a reversible loss of consciousness, and local anesthetics, which cause a reversible loss of sensation for a limited region of the body without necessarily affecting consciousness.

Awareness under anesthesia, also referred to as intraoperative awareness or accidental awareness during general anesthesia (AAGA), is a rare complication of general anesthesia where patients regain varying levels of consciousness during their surgical procedures. While anesthesia awareness is possible without resulting in any long-term memory of the experience, it is also possible for victims to have awareness with explicit recall, where they can remember the events related to their surgery.

In immunology, systemic inflammatory response syndrome (SIRS) is an inflammatory state affecting the whole body. It is the body's response to an infectious or noninfectious insult. Although the definition of SIRS refers to it as an "inflammatory" response, it actually has pro- and anti-inflammatory components.

<span class="mw-page-title-main">Remifentanil</span> Synthetic opioid analgesic

Remifentanil, marketed under the brand name Ultiva is a potent, short-acting synthetic opioid analgesic drug. It is given to patients during surgery to relieve pain and as an adjunct to an anaesthetic. Remifentanil is used for sedation as well as combined with other medications for use in general anesthesia. The use of remifentanil has made possible the use of high-dose opioid and low-dose hypnotic anesthesia, due to synergism between remifentanil and various hypnotic drugs and volatile anesthetics.

An induced coma – also known as a medically induced coma (MIC), barbiturate-induced coma, or drug-induced coma – is a temporary coma brought on by a controlled dose of an anesthetic drug, often a barbiturate such as pentobarbital or thiopental. Other intravenous anesthetic drugs such as midazolam or propofol may be used.

In anaesthesia and advanced airway management, rapid sequence induction (RSI) – also referred to as rapid sequence intubation or as rapid sequence induction and intubation (RSII) or as crash induction – is a special process for endotracheal intubation that is used where the patient is at a high risk of pulmonary aspiration. It differs from other techniques for inducing general anesthesia in that several extra precautions are taken to minimize the time between giving the induction drugs and securing the tube, during which period the patient's airway is essentially unprotected.

Distributive shock is a medical condition in which abnormal distribution of blood flow in the smallest blood vessels results in inadequate supply of blood to the body's tissues and organs. It is one of four categories of shock, a condition where there is not enough oxygen-carrying blood to meet the metabolic needs of the cells which make up the body's tissues and organs. Distributive shock is different from the other three categories of shock in that it occurs even though the output of the heart is at or above a normal level. The most common cause is sepsis leading to a type of distributive shock called septic shock, a condition that can be fatal.

<span class="mw-page-title-main">SOFA score</span> Medical assessment

The sequential organ failure assessment score, previously known as the sepsis-related organ failure assessment score, is used to track a person's status during the stay in an intensive care unit (ICU) to determine the extent of a person's organ function or rate of failure. The score is based on six different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems.

<span class="mw-page-title-main">Dexmedetomidine</span> Anxiolytic, sedative, and pain medication

Dexmedetomidine, sold under the trade name Precedex among others, is a drug used in humans for sedation. Veterinarians use dexmedetomidine for similar purposes in treating cats, dogs, and horses. It is also used in humans to treat acute agitation associated with schizophrenia or bipolar I or II disorder.

Critical illness–related corticosteroid insufficiency is a form of adrenal insufficiency in critically ill patients who have blood corticosteroid levels which are inadequate for the severe stress response they experience. Combined with decreased glucocorticoid receptor sensitivity and tissue response to corticosteroids, this adrenal insufficiency constitutes a negative prognostic factor for intensive care patients.

Procedural sedation and analgesia (PSA) is a technique in which a sedating/dissociative medication is given, usually along with an analgesic medication, in order to perform non-surgical procedures on a patient. The overall goal is to induce a decreased level of consciousness while maintaining the patient's ability to breathe on their own. Airway protective reflexes are not compromised by this process and therefore endotracheal intubation is not required. PSA is commonly used in the emergency department, in addition to the operating room.

<span class="mw-page-title-main">Propofol infusion syndrome</span> Medical condition

Propofol infusion syndrome (PRIS) is a rare syndrome which affects patients undergoing long-term treatment with high doses of the anaesthetic and sedative drug propofol. It can lead to cardiac failure, rhabdomyolysis, metabolic acidosis, and kidney failure, and is often fatal. High blood potassium, high blood triglycerides, and liver enlargement, proposed to be caused by either "a direct mitochondrial respiratory chain inhibition or impaired mitochondrial fatty acid metabolism" are also key features. It is associated with high doses and long-term use of propofol. It occurs more commonly in children, and critically ill patients receiving catecholamines and glucocorticoids are at high risk. Treatment is supportive. Early recognition of the syndrome and discontinuation of the propofol infusion reduces morbidity and mortality. Metabolic acidosis is a primary feature and may be the first laboratory evidence of the syndrome.

<span class="mw-page-title-main">Coinduction (anesthetics)</span>

Coinduction in anesthesia is a pharmacological tool whereby a combination of sedative drugs may be used to greater effect than a single agent, achieving a smoother onset of general anesthesia. The use of coinduction allows lower doses of the same anesthetic agents to be used which provides enhanced safety, faster recovery, fewer side-effects, and more predictable pharmacodynamics. Coinduction is used in human medicine and veterinary medicine as standard practice to provide optimum anesthetic induction. The onset or induction phase of anesthesia is a critical period involving the loss of consciousness and reactivity in the patient, and is arguably the most dangerous period of a general anesthetic. A great variety of coinduction combinations are in use and selection is dependent on the patient's age and health, the specific situation, and the indication for anesthesia. As with all forms of anesthesia the resources available in the environment are a key factor.

Total intravenous anesthesia (TIVA) refers to the intravenous administration of anesthetic agents to induce a temporary loss of sensation or awareness. The first study of TIVA was done in 1872 using chloral hydrate, and the common anesthetic agent propofol was licensed in 1986. TIVA is currently employed in various procedures as an alternative technique of general anesthesia in order to improve post-operative recovery.

<span class="mw-page-title-main">Ciprofol</span> Intravenous medication used in general anaesthesia

Ciprofol is a novel 2,6-disubstituted phenol derivative that is used for the intravenous induction of general anesthesia. A short-acting and highly selective γ-aminobutyric acid agonist, ciprofol is 4–6 times more potent than other phenol derivatives such as propofol or fospropofol.

References

  1. ↑ Anvisa (2023-03-31). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 2023-04-04). Archived from the original on 2023-08-03. Retrieved 2023-08-16.
  2. ↑ "Summary Basis of Decision (SBD) for Tomvi". Health Canada. 23 October 2014. Retrieved 29 May 2022.
  3. ↑ US Patent 3354173 'Imidazole carboxylates'
  4. ↑ Vinson DR, Bradbury DR (June 2002). "Etomidate for procedural sedation in emergency medicine". Annals of Emergency Medicine. 39 (6): 592–598. doi:10.1067/mem.2002.123695. PMID   12023700.
  5. 1 2 3 Bergen JM, Smith DC (1998). "A review of etomidate for rapid sequence intubation in the emergency department". The Journal of Emergency Medicine. 15 (2): 221–230. doi:10.1016/S0736-4679(96)00350-2. PMID   9144065.
  6. ↑ "Coronavirus (COVID-19) Update: December 22, 2020". U.S. Food and Drug Administration. 22 December 2020. Retrieved 23 December 2020.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  7. ↑ Di Liddo L, D'Angelo A, Nguyen B, Bailey B, Amre D, Stanciu C (October 2006). "Etomidate versus midazolam for procedural sedation in pediatric outpatients: a randomized controlled trial". Annals of Emergency Medicine. 48 (4): 433–40, 440.e1. doi:10.1016/j.annemergmed.2006.03.004. PMID   16997680.
  8. ↑ Miner JR, Danahy M, Moch A, Biros M (January 2007). "Randomized clinical trial of etomidate versus propofol for procedural sedation in the emergency department". Annals of Emergency Medicine. 49 (1): 15–22. doi:10.1016/j.annemergmed.2006.06.042. PMID   16997421.
  9. 1 2 Sivilotti ML, Filbin MR, Murray HE, Slasor P, Walls RM (June 2003). "Does the sedative agent facilitate emergency rapid sequence intubation?". Academic Emergency Medicine. 10 (6): 612–620. doi:10.1197/aemj.10.6.612. PMID   12782521.
  10. 1 2 3 4 5 Hohl CM, Kelly-Smith CH, Yeung TC, Sweet DD, Doyle-Waters MM, Schulzer M (August 2010). "The effect of a bolus dose of etomidate on cortisol levels, mortality, and health services utilization: a systematic review". Annals of Emergency Medicine. 56 (2): 105–13.e5. doi:10.1016/j.annemergmed.2010.01.030. PMID   20346542.
  11. ↑ Zed PJ, Abu-Laban RB, Harrison DW (April 2006). "Intubating conditions and hemodynamic effects of etomidate for rapid sequence intubation in the emergency department: an observational cohort study". Academic Emergency Medicine. 13 (4): 378–383. doi: 10.1111/j.1553-2712.2006.tb00313.x . PMID   16531603.
  12. ↑ Sokolove PE, Price DD, Okada P (February 2000). "The safety of etomidate for emergency rapid sequence intubation of pediatric patients". Pediatric Emergency Care. 16 (1): 18–21. doi:10.1097/00006565-200002000-00005. PMID   10698137. S2CID   24913220.
  13. 1 2 Walls RM, Murphy MF, Schneider RE, eds. (2000). Manual of emergency airway management.
  14. ↑ Marx J (2002). Rosen's emergency medicine: concepts and clinical practice.
  15. ↑ Wadbrook PS (November 2000). "Advances in airway pharmacology. Emerging trends and evolving controversy". Emergency Medicine Clinics of North America. 18 (4): 767–788. doi:10.1016/S0733-8627(05)70158-9. PMID   11130938.
  16. ↑ Yeung JK, Zed PJ (May 2002). "A review of etomidate for rapid sequence intubation in the emergency department". CJEM. 4 (3): 194–198. doi: 10.1017/S1481803500006370 . PMID   17609005.
  17. ↑ Gu WJ, Wang F, Tang L, Liu JC (February 2015). "Single-dose etomidate does not increase mortality in patients with sepsis: a systematic review and meta-analysis of randomized controlled trials and observational studies". Chest. 147 (2): 335–346. doi:10.1378/chest.14-1012. PMID   25255427.
  18. ↑ Jones-Gotman M, Sziklas V, Djordjevic J (August 2009). "Intracarotid amobarbital procedure and etomidate speech and memory test". The Canadian Journal of Neurological Sciences. Le Journal Canadien des Sciences Neurologiques. 36 (Suppl 2): S51–S54. PMID   19760903.
  19. ↑ Jones-Gotman M, Sziklas V, Djordjevic J, Dubeau F, Gotman J, Angle M, et al. (December 2005). "Etomidate speech and memory test (eSAM): a new drug and improved intracarotid procedure". Neurology. 65 (11): 1723–1729. doi:10.1212/01.wnl.0000187975.78433.cb. PMID   16344513. S2CID   1835535.
  20. ↑ Patel A, Wordell C, Szarlej D (March 2011). "Alternatives to sodium amobarbital in the Wada test". The Annals of Pharmacotherapy. 45 (3): 395–401. doi:10.1345/aph.1P476. PMID   21325100. S2CID   207264114.
  21. 1 2 Davies TF (2015). A Case-Based Guide to Clinical Endocrinology. Springer. pp. 11–. ISBN   978-1-4939-2059-4.
  22. 1 2 Jameson JL, De Groot LJ (2015). Endocrinology: Adult and Pediatric E-Book. Elsevier Health Sciences. pp. 250–. ISBN   978-0-323-32195-2.
  23. ↑ McGrath M, Ma C, Raines DE (February 2018). "Dimethoxy-etomidate: A Nonhypnotic Etomidate Analog that Potently Inhibits Steroidogenesis". The Journal of Pharmacology and Experimental Therapeutics. 364 (2): 229–237. doi:10.1124/jpet.117.245332. PMC   5783534 . PMID   29203576.
  24. ↑ Dearon J. "Florida executes convicted killer Mark Asay using new drug". Sun Sentinel.
  25. ↑ Wagner RL, White PF, Kan PB, Rosenthal MH, Feldman D (May 1984). "Inhibition of adrenal steroidogenesis by the anesthetic etomidate". The New England Journal of Medicine. 310 (22): 1415–1421. doi:10.1056/NEJM198405313102202. PMID   6325910.
  26. 1 2 Archambault P, Dionne CE, Lortie G, LeBlanc F, Rioux A, Larouche G (September 2012). "Adrenal inhibition following a single dose of etomidate in intubated traumatic brain injury victims". CJEM. 14 (5): 270–282. doi: 10.2310/8000.2012.110560 . PMID   22967694.
  27. 1 2 Ledingham IM, Watt I (June 1983). "Influence of sedation on mortality in critically ill multiple trauma patients". Lancet. 1 (8336): 1270. doi:10.1016/S0140-6736(83)92712-5. PMID   6134053. S2CID   305277.
  28. ↑ Morris C, McAllister C (August 2005). "Etomidate for emergency anaesthesia; mad, bad and dangerous to know?". Anaesthesia. 60 (8): 737–740. doi:10.1111/j.1365-2044.2005.04325.x. PMID   16029220. S2CID   27825801.
  29. ↑ Jackson WL (March 2005). "Should we use etomidate as an induction agent for endotracheal intubation in patients with septic shock?: a critical appraisal". Chest. 127 (3): 1031–1038. doi:10.1378/chest.127.3.1031. PMID   15764790.
  30. 1 2 Bloomfield R, Noble DW (June 2006). "Exploring the role of etomidate in septic shock and acute respiratory distress syndrome". Critical Care Medicine. 34 (6): 1858, author reply 1858-1858, author reply 1859. doi:10.1097/01.ccm.0000220048.38438.40. PMID   16715011.
  31. ↑ Cuthbertson BH, Sprung CL, Annane D, Chevret S, Garfield M, Goodman S, et al. (November 2009). "The effects of etomidate on adrenal responsiveness and mortality in patients with septic shock". Intensive Care Medicine. 35 (11): 1868–1876. doi:10.1007/s00134-009-1603-4. PMID   19652948. S2CID   24371957.
  32. ↑ Murray H, Marik PE (March 2005). "Etomidate for endotracheal intubation in sepsis: acknowledging the good while accepting the bad". Chest. 127 (3): 707–709. doi: 10.1378/chest.127.3.707 . PMID   15764747.
  33. ↑ Jabre P, Combes X, Lapostolle F, Dhaouadi M, Ricard-Hibon A, Vivien B, et al. (July 2009). "Etomidate versus ketamine for rapid sequence intubation in acutely ill patients: a multicentre randomised controlled trial". Lancet. 374 (9686): 293–300. doi:10.1016/S0140-6736(09)60949-1. PMID   19573904. S2CID   52230993.
  34. ↑ den Brinker M, Joosten KF, Liem O, de Jong FH, Hop WC, Hazelzet JA, et al. (September 2005). "Adrenal insufficiency in meningococcal sepsis: bioavailable cortisol levels and impact of interleukin-6 levels and intubation with etomidate on adrenal function and mortality". The Journal of Clinical Endocrinology and Metabolism. 90 (9): 5110–5117. doi: 10.1210/jc.2005-1107 . PMID   15985474.
  35. ↑ Schulz-Stübner S (November 2005). "Sedation in traumatic brain injury: avoid etomidate". Critical Care Medicine. 33 (11): 2723, author reply 2723. doi:10.1097/01.ccm.0000187093.71107.a8. PMID   16276231.
  36. 1 2 Stuttmann R, Allolio B, Becker A, Doehn M, Winkelmann W (September 1988). "[Etomidate versus etomidate and hydrocortisone for anesthesia induction in abdominal surgical interventions]". Der Anaesthesist. 37 (9): 576–582. PMID   3056084.
  37. 1 2 Komatsu R, You J, Mascha EJ, Sessler DI, Kasuya Y, Turan A (December 2013). "Anesthetic induction with etomidate, rather than propofol, is associated with increased 30-day mortality and cardiovascular morbidity after noncardiac surgery". Anesthesia and Analgesia. 117 (6): 1329–1337. doi: 10.1213/ANE.0b013e318299a516 . PMID   24257383. S2CID   23165849.
  38. ↑ Daniell H (November 2008). "Opioid and benzodiazepine contributions to etomidate-associated adrenal insufficiency". Intensive Care Medicine. 34 (11): 2117–8. doi: 10.1007/s00134-008-1264-8 . PMID   18795258. S2CID   36288054.
  39. ↑ Daniell HW (December 2008). "Opioid contribution to decreased cortisol levels in critical care patients". Archives of Surgery. 143 (12): 1147–1148. doi:10.1001/archsurg.143.12.1147. PMID   19075164.
  40. ↑ Kosarek L, et al. Increase in Venous Complications Associated With Etomidate Use During a Propofol Shortage: An Example of Clinically Important Adverse Effects Related to Drug Substitution. The Ochsner Journal. 2011;11:143-146.
  41. ↑ Kim JJ, Gharpure A, Teng J, Zhuang Y, Howard RJ, Zhu S, et al. (September 2020). "Shared structural mechanisms of general anaesthetics and benzodiazepines". Nature. 585 (7824): 303–308. doi:10.1038/s41586-020-2654-5. PMC   7486282 . PMID   32879488.
  42. ↑ Vanlersberghe C, Camu F (2008). "Etomidate and other non-barbiturates". Modern Anesthetics. Handbook of Experimental Pharmacology. Vol. 182. pp. 267–282. doi:10.1007/978-3-540-74806-9_13. ISBN   978-3-540-72813-9. PMID   18175096.
  43. ↑ Drexler B, Jurd R, Rudolph U, Antkowiak B (September 2009). "Distinct actions of etomidate and propofol at beta3-containing gamma-aminobutyric acid type A receptors". Neuropharmacology. 57 (4): 446–455. doi:10.1016/j.neuropharm.2009.06.014. PMID   19555700. S2CID   26796180.
  44. ↑ Chiara DC, Dostalova Z, Jayakar SS, Zhou X, Miller KW, Cohen JB (January 2012). "Mapping general anesthetic binding site(s) in human α1β3 γ-aminobutyric acid type A receptors with [³H]TDBzl-etomidate, a photoreactive etomidate analogue". Biochemistry. 51 (4): 836–847. doi:10.1021/bi201772m. PMC   3274767 . PMID   22243422.
  45. ↑ International Non-Proprietary Names for Pharmaceutical Preparations – Rec. I.N.N. List 6
  46. ↑ Servin FS, Sear JW (2011). "Chapter 27. Pharmacokinetics of intravenous anesthetics". In Evers AS, Maze M, Kharasch ED (eds.). Anesthetic Pharmacology: Basic Principles and Clinical Practice (2nd ed.). Cambridge University Press.
  47. ↑ Tomlin SL, Jenkins A, Lieb WR, Franks NP (March 1998). "Stereoselective effects of etomidate optical isomers on gamma-aminobutyric acid type A receptors and animals". Anesthesiology. 88 (3): 708–717. doi: 10.1097/00000542-199803000-00022 . PMID   9523815. S2CID   11665790.

Further reading

This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.