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Etomidate's Impact on Cortisol Production and Risk of Adrenal Insufficiency

Summary:

  • Etomidate is able to decrease the production and secretion of cortisol from the adrenal gland through a direct inhibition of the enzyme, 11-beta-hydroxylase.
  • Patients experiencing sepsis or septic shock and who receive etomidate may experience some degree of adrenal insufficiency.  The clinical relevance this is still under debate.


Editor-in-Chief:
Anthony J. Busti, MD, PharmD, FNLA, FAHA
Last Reviewed: August 2015

Explanation

  • Etomidate is a well-known general anesthetic most commonly used for procedural sedation or rapid sequence intubation because of its quick onset, short duration of action, and pharmacologic profile that does not generally does not cause clinically significant hemodynamic instability.  One side effect of etomidate is its ability to inhibit or decrease the production of cortisol in the adrenal glands.  While in most patients this is of no clinical relevance, it could be more detrimental in some patients with sepsis.

    Etomidate is able to decrease the production and secretion of cortisol from the adrenal gland through a direct inhibition of the enzyme, 11-beta-hydroxylase.  This enzyme is required to convert the precursor, 11-deoxycortisol to cortisol within the zona fasciculata with the adrenal cortex layer of the adrenal gland. Fortunately, other hormones (aldosterone and testosterone) also produced within the adrenal glands can still be made.

    As stated above, patients known to have sepsis or be in septic shock are known to be at a higher risk for adrenal insufficiency. As such, some clinicians may elect to use another sedative for procedural sedation or rapid sequence intubation in patients known to have sepsis or be in septic shock.   However, the clinical relevance of this effect is still under some debate.

    References:

    1. de Jong FH, Mallios C, Jansen C et al. Etomidate suppresses adrenocortical function by inhibition of 11 beta-hydroxylation.  J Clin Endocrinol Metab 1984;59(6):1143-7.
    2. Fry DE, Griffiths H.  The inhibtion by etomidate of the 11 beta-hydroxylation of cortisol.  Clin Endocrinol  1984;20(5):625-9.
    3. Allolio B, Dorr H, Stuttmann R et al.  Effect of a single bolus of etomidate upon eight major corticosteroid hormones and plasma ACTH.  Clin Endocrinol 1985;22(3):281-6.
    4. Mohammad Z, Afessa B, Finkielman JD.  The incidence of relative adrenal insufficiency in patients with septic shock after the administration of etomidate.  Crit Care 2006;10(4):R105.
    5. Chan CM, Mitchell AL, Shorr AF.  Etomidate is associated with mortality and adrenal insufficiency in sepsis: a meta-analysis.  Crit Care Med 2012;40(11):2945-53.

MESH Terms & Keywords

  • Etomidate cortisol production, etomidate reduction in cortisol, how etomidate inhibits cortisol, etomidate mechanism on cortisol

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