ETOMIDATE: THE BAD 'WOW' FACTORS

• While it continues to be used infrequently in the UK it has been withdrawn in North America and Australia
• The most notable and potentially serious side effect of etomidate administration is the suppression of adrenocortical steroid synthesis.
• It suppresses adrenocortical function by inhibition of the enzymes 11-hydroxylase and 17-hydroxylase, resulting in inhibition of cortisol and aldosterone synthesis.
• After a single bolus dose of etomidate, this adrenocortical suppression lasts approximately 6 h in healthy individuals. However in the critically ill, such suppression can last for days. In other words the situation in which it has the best cardiovascular proile is the unwell patient in whom the consequences of steroid inhibition are likely to be the most detrimental.
• Etomidate is approximately 100-fold more potent a suppressor of adrenocortical function than it is a sedative-hypnotic. Consequently, an anesthetic
  
  induction dose of etomidate represents a massive overdose with respect to its ability to suppress adrenocortical function. And etomidate’s terminal elimination half-life is rather long. Thus, after just a single anesthetic induction dose of etomidate, many hours must pass before etomidate’s concentration in the blood falls below that which suppresses adrenocortical steroid synthesis.
• It is within this mechanistic context that the strategy emerged to design analogues of etomidate
• ANALOGUES:
• MOC-etomidate[ relatively low potency and very rapid metabolism (1.) required the administration of extremely large doses]
• CPMM etomidate[ it has an onset and offset of hypnotic action that are fast (1.) ]
• Carbo etomidate[ less adrenocortical inhibition (2.)]
• MOC-carboetomidate[ combines properties (1) and (2); but it's potency
  
  is very low which means that extremely large doses would need to be administered to maintain anesthesia ]
• Involuntary movements (myoclonus) are commonly observed after etomidate administration, with some studies reporting an incidence as high as 80 % in unpremedicated patients
• It has been suggested that it occurs because etomidate depresses inhibitory neural circuits in the central nervous system sooner and at lower concentrations than excitatory circuits.
• Regardless of the mechanism, myoclonus can be significantly reduced or completely prevented by administering a variety of drugs with central nervous system depressant effects including opiates, benzodiazepines, dexmedetomidine, thiopental, lidocaine, and magnesium.
• Pain at the injection site is another common side effect and its incidence is highly dependent upon the size of the vein into which it is injected and the formulation that is used.
• Lipid emulsion and cyclodextrin formulations may reduce TRP channel activation, leading to less pain on injection
• Postoperative nausea and vomiting is common with reported incidences as high as 40 %. It has been suggested that the emetogenic trigger in etomidate is the propylene glycol solvent and not the anesthetic itself.
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