Annals of Emergency Medicine
Volume 56, Issue 2 , Pages 105-113.e5 , August 2010

The Effect of a Bolus Dose of Etomidate on Cortisol Levels, Mortality, and Health Services Utilization: A Systematic Review

  • Corinne M. Hohl, MD, FRCP(C), MHSc

      Affiliations

    • Department of Emergency Medicine, University of British Columbia, Vancouver, British Columbia, Canada
    • Department of Emergency Medicine, Vancouver General Hospital, Vancouver, British Columbia, Canada
    • Center for Clinical Epidemiology and Evaluation, Vancouver Coastal Health Research Institute, Vancouver, British Columbia, Canada
    • Corresponding Author InformationAddress for correspondence: Corinne M. Hohl, MD, FRCP(C), MHSc, Department of Emergency Medicine, Vancouver General Hospital, 855 West 12th Ave, Vancouver, BC, V5Z 1M9, Canada; 604-875-4111 ext. 63467, fax 604-875-5506
  • ,
  • Carolyn H. Kelly-Smith, MD

      Affiliations

    • Emergency Medicine Residency Training Program, University of British Columbia, Vancouver, British Columbia, Canada
  • ,
  • Titus C. Yeung, MD

      Affiliations

    • Emergency Medicine Residency Training Program, University of British Columbia, Vancouver, British Columbia, Canada
  • ,
  • David D. Sweet, MD, FRCP(C)

      Affiliations

    • Department of Emergency Medicine, University of British Columbia, Vancouver, British Columbia, Canada
    • Department of Medicine, Division of Critical Care, University of British Columbia, Vancouver, British Columbia, Canada
    • Department of Emergency Medicine, Vancouver General Hospital, Vancouver, British Columbia, Canada
  • ,
  • Mary M. Doyle-Waters, MA, MLIS

      Affiliations

    • Center for Clinical Epidemiology and Evaluation, Vancouver Coastal Health Research Institute, Vancouver, British Columbia, Canada
  • ,
  • Michael Schulzer, MD, PhD

      Affiliations

    • Departments of Medicine and Statistics, University of British Columbia, Vancouver, British Columbia, Canada
    • Center for Clinical Epidemiology and Evaluation, Vancouver Coastal Health Research Institute, Vancouver, British Columbia, Canada

Received 21 October 2009 ,Revised 21 January 2010 ,Accepted 29 January 2010.

References 

  1. Walls RM, Murphy MF, Luten RC. Manual of Emergency Airway Management. 2nd ed.. Philadelphia, PA: Lippincott Williams & Wilkins; 2004;
  2. Bergen JM, Smith DC. A review of etomidate for rapid sequence intubation in the emergency department. J Emerg Med. 1997;15:221–230
  3. Jackson WL. Should we use etomidate as an induction agent for endotracheal intubation in patients with septic shock? (a critical appraisal). Chest. 2005;127:1031–1038
  4. Jacoby J, Heller M, Nicholas J, et al. Etomidate versus midazolam for out-of-hospital intubation: a prospective, randomized trial. Ann Emerg Med. 2006;47:525–530
  5. Jellish WS, Riche H, Salord F, et al. Etomidate and thiopental-based anesthetic induction: comparisons between different titrated levels of electrophysiologic cortical depression and response to laryngoscopy. J Clin Anesth. 1997;9:36–41
  6. Mulier JP, Wouters PF, Van Aken H, et al. Cardiodynamic effects of propofol in comparison with thiopental: assessment with a transesophageal echocardiographic approach. Anesth Analg. 1991;72:28–35
  7. Oglesby AJ. Should etomidate be the induction agent of choice for rapid sequence intubation in the emergency department?. Emerg Med J. 2004;21:655–659
  8. Ostwald P, Doenicke AW. Etomidate revisited. Curr Opin Anaesthesiol. 1998;11:391–398
  9. Plewa M, King R, Johnson D, et al. Etomidate use during emergency intubation of trauma patients. Am J Emerg Med. 1997;15:98–100
  10. Annane D. Etomidate and intensive care physicians. Intensive Care Med. 2005;31:1454
  11. Annane D. ICU physicians should abandon the use of etomidate!. Intensive Care Med. 2005;31:325–326
  12. Annane D, Sebille V, Bellissant E. Corticosteroids for patients with septic shock. JAMA. 2003;289:43–44
  13. Sacchetti A. Etomidate as an induction agent for endotracheal intubation in patients with sepsis. Ann Emerg Med. 2009;53:406
  14. Sacchetti A. Etomidate: not worth the risk in septic patients. Ann Emerg Med. 2009;52:15–16
  15. Walls RM, Murphy MF. Continue to use etomidate for intubation of patients with septic shock. Ann Emerg Med. 2008;52:13–14
  16. Walls RM, Murphy MF. Etomidate as an induction agent for endotracheal intubation in patients with sepsis. Ann Emerg Med. 2009;53:406
  17. Manoach S. Corticosteroids for septic shock. N Engl J Med. 2008;358:2070
  18. Lipiner-Friedman D, Sprung CL, Laterre PF, et al. Adrenal function in sepsis: the retrospective CORTICUS cohort study. Crit Care Med. 2007;35:1012–1018
  19. Kamp R, Kress JP. Etomidate, sepsis, and adrenal function: not as bad as we thought?. Crit Care. 2007;11:145–146
  20. Annane D, Sébille V, Charpentier C, et al. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA. 2002;288:862–871
  21. Sprung C, Annane D, Keh D, et al. Hydrocortisone therapy for patients with septic shock. N Engl J Med. 2008;358:111–124
  22. Ledingham I, Finlay W, Watt I, et al. Etomidate and adrenocortical function. Lancet. 1883;321:1434
  23. Ledingham I, Watt I. Influence of sedation on mortality in critically ill multiple trauma patients. Lancet. 1983;321:1270
  24. Fellows IW, Bastow MD, Byrne AJ, et al. Adrenocortical suppression in multiply injured patients: a complication of etomidate treatment. Br Med J. 1983;287:1835–1837
  25. Fry DE, Griffiths H. The inhibition by etomidate of the 11 beta-hydroxylation of cortisol. Clin Endocrinol. 1984;20:625–629
  26. Watt I, Ledingham I. Mortality amongst multiple trauma patients admitted to an intensive therapy unit. Anaesthesia. 1984;39:973–981
  27. Allolio B, Dörr H, Stuttmann R, et al. Effect of a single bolus of etomidate upon eight major corticosteroid hormones and plasma ACTH. Clin Endocrinol. 1985;22:281–286
  28. Allolio B, Stuttmann R, Leonhard U, et al. Adrenocortical suppression by a single induction dose of etomidate. Klin Wochenschr. 1984;62:1014–1017
  29. Allolio B, Stuttmann R, Winkelmann W, et al. Effects of etomidate on adrenocortical function. Acta Endocrinol. 1984;105:115
  30. Börner U, Gips H, Boldt J, et al. Effect of an introductory dose of etomidate, methohexital and midazolam on adrenal cortex function before and after ACTH-stimulation. Dtsch Med Wochenschr. 1985;110:750–752
  31. De Coster R, Helmers JHJH, Noorduin H. Effect of etomidate on cortisol biosynthesis: site of action after induction of anaesthesia. Acta Endocrinol. 1985;110:526–531
  32. Fellows IW, Yeoman PM, Selby C, et al. The effect of anaesthetic induction with etomidate on the endocrine response to surgical trauma. Eur J Anaesthesiol. 1985;2:285–290
  33. Fragen RJ, Shanks CA, Molteni A, et al. Effects of etomidate on hormonal responses to surgical stress. Anesthesiology. 1984;61:652–656
  34. Sear JW, Edwards CRW, Atherden SM. Dual effect of etomidate on mineralocorticoid biosynthesis. Acta Anaesthesiol Belg. 1988;39:87–94
  35. Sebel PS, Verghese C, Makin HLJ. Effect on plasma cortisol concentrations of a single induction dose of etomidate or thiopentone. Lancet. 1983;2:625
  36. Wagner RL, White PF. Etomidate inhibits adrenocortical function in surgical patients. Anesthesiology. 1984;61:647–651
  37. Wagner RL, White PF. Etomidate versus thiopental: comparative effects on adrenocortical function. Anesthesiology. 1984;61:A353
  38. Wagner RL, White PF, Kan PB, et al. Inhibition of adrenal steroidogenesis by the anesthetic etomidate. N Engl J Med. 1984;310:1415–1421
  39. Wanscher M, Tonnesen E, Huttel M, et al. Etomidate infusion and adrenocortical function (A study in elective surgery). Acta Anaesthesiol Scand. 1985;29:483–485
  40. den Brinker M, Joosten KF, Liem O, et al. Adrenal insufficiency in meningococcal sepsis: bioavailable cortisol levels and impact of interleukin-6 levels and intubation with etomidate on adrenal function and mortality. J Clin Endocrinol Metab. 2005;90:5110–5117
  41. Cuthbertson BH, Sprung CL, Annane D, et al. The effects of etomidate on adrenal responsiveness and mortality in patients with septic shock. Intensive Care Med. 2009;35:1868–1876
  42. Malerba G, Romano-Girard F, Cravoisy A, et al. Risk factors of relative adrenocortical deficiency in intensive care patients needing mechanical ventilation. Intensive Care Med. 2005;31:388–392
  43. Sivilotti ML, Filbin MR, Murray HE, et al. Does the sedative agent facilitate emergency rapid sequence intubation?. Acad Emerg Med. 2003;10:612–620
  44. Current Controlled Trials Ltd. Current controlled trials. http://www.controlled-trials.comAccessed November 25, 2007
  45. National Health Service. The National Research Register (Update software). http://www.dh.gov.uk/en/Publicationsandstatistics/Publications/PublicationsPolicyAndGuidance/DH_4075210Accessed November 20, 2007
  46. National Institutes of Health. ClinicalTrails.gov http://clinicaltrials.govAccessed November 21, 2007
  47. Hildreth AN, Mejia VA, Maxwell RA, et al. Adrenal suppression following a single dose of etomidate for rapid sequence induction: a prospective randomized study. J Trauma. 2008;65:573–579
  48. Tekwani KL, Watts HF, Rzechula KH, et al. A prospective observational study of the effect of etomidate on septic patient mortality and length of stay. Acad Emerg Med. 2009;16:11–14
  49. Jabre P, Combes X, Lapostolle F, et al. Etomidate versus ketamine for rapid sequence intubation in acutely ill patients: a multicentre randomised controlled trial. Lancet. 2009;374:293–300
  50. Jadad A, Moore R, Carroll D, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary?. Control Clin Trials. 1996;17:1–12
  51. Stroup D, Berlin J, Morton SC, et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting (Meta-analysis of Observational Studies in Epidemiology (MOOSE) group). JAMA. 2000;283:2008–2012
  52. Follmann D, Elliott P, Suh I, et al. Variance imputation for overviews of clinical trials with continuous response. J Clin Epidemiol. 1992;45:769–773
  53. Bendel S, Ruokonen E, Polonen P, et al. Propofol causes more hypotension than etomidate in patients with severe aortic stenosis: a double-blind, randomized study comparing propofol and etomidate. Acta Anaesthesiol Scand. 2007;51:284–289
  54. Absalom A, Pledger D, Kong A. Adrenocortical function in critically ill patients 24 h after a single dose of etomidate. Anaesthesia. 1999;54:861–867
  55. Cooper SC, Lell WA. Hormonal effects of an induction dose of etomidate for patients undergoing urgent myocardial revascularization. J Cardiothorac Anesth. 1988;2:171–176
  56. Montalban C, Del Moral I, Garcia-Unzueta TM, et al. Perioperative response of leptin and the tumor necrosis factor alpha system in morbidly obese patients (Influence of cortisol inhibition by etomidate). Acta Anaesthesiol Scand. 2001;45:207–212
  57. Saranteas T, Voukena V, Zotos N, et al. Lipid kinetics in obese patients undergoing laparoscopy (The impact of cortisol inhibition by etomidate). Eur J Drug Metab Pharmacokinet. 2004;29:187–192
  58. Schenarts CL, Burton JH, Riker RR. Adrenocortical dysfunction following etomidate induction in emergency department patients. Acad Emerg Med. 2001;8:1–7
  59. Ray DC, McKeown DW. Effect of induction agent on vasopressor and steroid use, and outcome in patients with septic shock. Crit Care. 2007;11:1–8
  60. Snapinn SM. Noninferiority trials. Curr Control Trials Cardiovasc Med. 2000;1:19–21

 Funding and support: By Annals policy, all authors are required to disclose any and all commercial, financial, and other relationships in any way related to the subject of this article that might create any potential conflict of interest. The authors have stated that no such relationships exist. See the Manuscript Submission Agreement in this issue for examples of specific conflicts covered by this statement. This work was supported by a grant from the Vancouver Coastal Health Research Institute In It for Life fund. During the study period, Dr. Corinne Hohl was supported by a Mentored Clinician Scientist award from the Vancouver Coastal Health Research Institute.

 Supervising editor: Kathy J. Rinnert, MD, MPH

 Reprints not available from the authors.

 Publication date: Available online March 25, 2010.

PII: S0196-0644(10)00103-4

doi: 10.1016/j.annemergmed.2010.01.030

Annals of Emergency Medicine
Volume 56, Issue 2 , Pages 105-113.e5 , August 2010