Log in | Register

The effect of etomidate on adrenal function in critical illness: a systematic review

Stewart G. Albert| Srividya Ariyan| Ayesha Rather
Original
Volume 37, Issue 6 / June , 2011

Pages 901 - 910

Abstract

Purpose

Although etomidate is a preferred anesthetic agent for rapid sequence intubation (RSI) in critical illness, as an inhibitor of cortisol synthesis (11β-hydroxylase), it may be associated with adrenal dysfunction. The objectives are to review the effects of etomidate versus comparator anesthetics in critical illness for: primary outcome of mortality and secondary outcome of adrenal insufficiency (AI).

Methods

Studies were extracted using MEDLINE and SCOPUS, regardless of language, between 1983 and 2010 using the keywords etomidate, intensive care units (ICU), critical illness, intensive care, glucocorticoids, and adrenal insufficiency. Studies of single dose etomidate versus comparator anesthetics with outcomes of adrenal function and/or mortality were included. All reviewers performed electronic data searches. One reviewer extracted data, which were checked by the other reviewers. Authors of trials were contacted for supplemental data. Primary outcome was 28-day mortality. AI was defined per article.

Results

Two hundred sixty-three articles were screened, and 21 articles (19 independent data sets) were evaluated. Meta-analysis comparing etomidate versus non-etomidate anesthesia demonstrated an increased risk ratio (RR) for AI of 1.64 (range 1.52–1.77; 14 studies, 2,854 patients, P < 0.0001, I2 = 88%) and an increased RR for mortality of 1.19 (1.10–1.30; 14 studies, 3,516 patients, P < 0.0001, I2 = 64%). Significance of re-analysis for mortality within the subset of sepsis was maintained [RR 1.22 (1.11–1.35), 7 studies, n = 1,767, I2 = 74%, P < 0.0001], but not for trials without sepsis [RR = 1.15 (0.97–1.35), 7 studies, n = 1,749, I2 = 53%, P = 0.10].

Conclusions

There is an increased rate of AI and mortality in critically ill patients who received etomidate.

Keywords

References

  1. Bergen JM, Smith DC (1997) A review of etomidate for rapid sequence intubation in the emergency department. J Emerg Med 15:221–230
    • View reference on PubMed
    • View reference on publisher's website
  2. Annane D (2005) ICU physicians should abandon the use of etomidate! Intensive Care Med 31:325–326
  3. Jackson WL Jr (2005) Should we use etomidate as an induction agent for endotracheal intubation in patients with septic shock: a critical appraisal. Chest 127:1031–1038
    • View reference on PubMed
    • View reference on publisher's website
  4. Ledingham IM, Watt I (1983) Influence of sedation on mortality in critically ill multiple trauma patients. [Letter] Lancet 1(8336):1270
    • View reference on PubMed
    • View reference on publisher's website
  5. De Jong FH, Mallios C, Jansen C, Scheck PA, Lamberts SW (1984) Etomidate suppresses adrenocortical function by inhibition of 11 beta-hydroxylation. J Clin Endocrinol Metab 59:1143–1147
    • View reference on PubMed
    • View reference on publisher's website
  6. Schenarts CL, Burton JH, Riker RR (2001) Adrenocortical dysfunction following etomidate induction in emergency department patients. Acad Emerg Med 8:1–7
    • View reference on PubMed
    • View reference on publisher's website
  7. Absalom A, Pledger D, Kong A (1999) Adrenocortical function in critically ill patients 24 h after a single dose of etomidate. Anaesthesia 54:861–867
    • View reference on PubMed
    • View reference on publisher's website
  8. Vinclair M, Broux C, Faure P, Brun J, Genty C, Jacquot C, Chabre O, Payen JF (2008) Duration of adrenal inhibition following a single dose of etomidate in critically ill patients. Intensive Care Med 34:714–719
  9. Bloomfield R, Noble DW (2006) Etomidate, pharmacological adrenalectomy and the critically ill: a matter of vital importance. Crit Care 10:161
    • View reference on PubMed
    • View reference on publisher's website
  10. Kamp R, Kress JP (2007) Etomidate, sepsis, and adrenal function: not as bad as we thought? Crit Care 11:145
    • View reference on PubMed
    • View reference on publisher's website
  11. Borenstein M, Hedges LV, Higgins JPT, Rothstein HR (2009) Introduction to Meta-analysis. Wiley, West Sussex
  12. Guyatt GH, Oxman AD, Vist GE, Kunz R, Falck-Ytter Y, Alonso-Coello P, Schünemann HJ, for the GRADE Working Group GRADE (2008) An emerging consensus on rating quality of evidence and strength of recommendations. BMJ 336:924–926
    • View reference on PubMed
    • View reference on publisher's website
  13. Bax L, Yu LM, Ikeda N, Tsuruta H, Moons KGM (2006) Development and validation of MIX: comprehensive free software for meta-analysis of causal research data. BMC Med Res Methodol 6:50
    • View reference on PubMed
    • View reference on publisher's website
  14. Bax L, Yu LM, Ikeda N, Tsuruta H, Moons KGM (2008) MIX: comprehensive free software for metaanalysis of causal research data, version 1.7. http://mix-for-meta-analysis.info
  15. Hildreth AN, Mejia VA, Maxwell RA, Smith PW, Dart BW, Barker DE (2008) Adrenal suppression following a single dose of etomidate for rapid sequence induction: a prospective randomized study. J Trauma Inj Infect Crit Care 65:573–579
    • View reference on publisher's website
  16. Jabre P, Combes X, Lapostolle F, for the KETASED collaborative Study Group et al (2009) Etomidate versus ketamine for rapid sequence intubation in acutely ill patients: a multicentre randomized controlled trial. Lancet 374:293–300
    • View reference on PubMed
    • View reference on publisher's website
  17. Oppert M, Schindler R, Husung C, Offermann K, Graf K-J, Boenisch O, Barckow D, Frei U, Eckardt K-U (2005) Low-dose hydrocortisone improves shock reversal and reduces cytokine levels in early hyperdynamic septic shock. Crit Care 33:2457–2464
    • View reference on publisher's website
  18. Annane D, Sebille V, Troche G, Raphael J-C, Gajdos P, Bellisant E (2000) A 3-level prognostic classification in septic shock based on cortisol levels and cortisol response to corticotropin. JAMA 283:1038–1045
    • View reference on PubMed
    • View reference on publisher's website
  19. Annane D, Sebille V, Charpentier C, Bollaert P-E, Francois B, Korach J-M, Capellier G, Cohen Y, Azoulay E, Troche G, Chaumet-Riffaut P, Bellisant E (2002) Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA 288:862–871
    • View reference on PubMed
    • View reference on publisher's website
  20. Sprung CL, Annane D, Keh D, Moreno R, Singer M, Freivogel K, Weiss YG, Benbenishty J, Kalenka A, Forst H, Laterre P-F, Reinhart K, Cuthbertson BH, Payen D, Briegel J, for the Corticus Study Group (2008) Hydrocortisone therapy for patients with septic shock. N Eng J Med 358:111–124
    • View reference on publisher's website
  21. Cuthbertson BH, Sprung CL, Annane D, Chevret S, Garfield M, Goodman S, Laterre PF, Vincent JL, Freivogel K, Reinhart K, Singer M, Payen D, Weiss YG (2009) The effects of etomidate on adrenal responsiveness and mortality in patients with septic shock. Intensive Care Med 35:1868–1876
  22. Lipiner-Friedman D, Sprung CL, Laterre PF, Weiss Y, Goodman SV, Vogeser M, Briegel J, Keh D, Singer M, Moreno R, Bellissant E, Annane D, and Corticus Study Group (2007) Adrenal function in sepsis: the retrospective Corticus cohort study. Crit Care Med 35:1012–1018
    • View reference on PubMed
    • View reference on publisher's website
  23. Mohammad Z, Afessa B, Finkielman JD (2006) The incidence of relative adrenal insufficiency in patients with septic shock after the administration of etomidate. Crit Care 10:R105
    • View reference on PubMed
    • View reference on publisher's website
  24. Kim TY, Rhee JE, Kim KS, Cha WC, Suh GJ, Jung SK (2008) Etomidate should be used carefully for emergent endotracheal intubation in patients with septic shock. J Korean Med Sci 23:988–991
    • View reference on PubMed
    • View reference on publisher's website
  25. Cotton BA, Guillamondegui OD, Fleming SB, Carpenter RO, Patel SH, Morris JA Jr, Arbogast PG (2008) Increased risk of adrenal insufficiency following etomidate exposure in critically injured patients. Arch Surg 143:62–67
    • View reference on PubMed
    • View reference on publisher's website
  26. Malerba G, Romano-Girard F, Cravoisy A, Dousset B, Nace L, Kevy B, Bollaert P-E (2005) Risk factors of relative adrenocortical deficiency in intensive care patients needing mechanical ventilation. Intensive Care Med 31:388–392
  27. Cohan P, Wang C, McArthur DL, Cook SW, Dusick JR, Armin B, Swerdloff R, Vespa P, Muizelar JP, Cryer HG, Christenson PD, Kelly DF (2005) Acute secondary adrenal insufficiency after traumatic brain injury: a prospective study. Crit Care Med 33:2358–2366
    • View reference on PubMed
    • View reference on publisher's website
  28. De Jong MFC, Beishuizen A, Spijkstra J-J, Girbes ARJ, Strack van Schijndel RJM, Twisk JWR, Groeneveld ABJ (2007) Predicting a low cortisol response to adrenocorticotrophic hormone in the critically ill: a retrospective cohort study. Crit Care 11(3):R61
    • View reference on publisher's website
  29. Riche FC, Boutron CM, Valleur P, Berton C, Laisne M-J, Launay J-M, Chappuis P, Peynet J, Vicaut E, Payen D, Cholley BP (2007) Adrenal response in patients with septic shock of abdominal origin: relationship to survival. Intensive Care Med 33:1761–1766
  30. den Brinker M, Joosten KF, Liem O, de Jong FH, Hop WCJ, Hazelzet JA, van Dijk M, Hokken-Koelega ACS (2005) Adrenal insufficiency in meninogococcal sepsis: bioavailable cortisol levels and impact of interleukin-6 level and intubation with etomidate on adrenal function and mortality. J Clin Endocrinol Metab 90:5110–5117
    • View reference on publisher's website
  31. den Brinker M, Hokken-Koelega AC, Hazelzet JA, de Jong FH, Hop WC, Joosten KF (2008) One single dose of etomidate negatively influences adrenocortical performance for at least 24 h in children with meningococcal sepsis. Intensive Care Med 34:163–168
  32. Baird CRW, Hay AW, McKeown DW, Ray DC (2009) Rapid sequence induction in the emergency department: induction dug and outcome of patients admitted to the intensive care unit. Emerg Med J 26:576–579
    • View reference on PubMed
    • View reference on publisher's website
  33. Ray DC, McKeown DW (2007) Effect of induction agent on vasopressor and steroid use, and outcome in patients with septic shock. Crit Care 11:R56
    • View reference on PubMed
    • View reference on publisher's website
  34. Tekwani KL, Watts HF, Rzechula KH, Sweis RT, Kulstad EB (2009) A prospective observational study of the effect of etomidate on septic patient mortality and length of stay. Acad Emerg Med 16:11–14
    • View reference on PubMed
    • View reference on publisher's website
  35. Marik PE, Pastores SM, Annane D, Meduri U, Sprung CL, Arlt W, Keh D, Briegel J, Beishuizen A, Dimopoulou I, Tsagarakis S, Singer M, Chrousos GP, Zaloga G, Bokhari F, Vogeser M (2008) Recommendations for the diagnosis and management of corticosteroids insufficiency in critically ill adult patients: consensus statement from an international task force by the American College of Critical Care Medicine. Crit Care Med 36:1337–1349
  36. Arafah BM (2006) Review: hypothalamic pituitary adrenal function during critical illness limitations of current assessment methods. J Clin Endocrinol Metab 91:3725–3745
    • View reference on PubMed
    • View reference on publisher's website
  37. Meduri GU, Yates CR (2004) Systemic inflammation-associated glucocorticoid resistance and outcomes of ARDS. Ann NY Acad Sci 1024:24–53
    • View reference on PubMed
    • View reference on publisher's website
  38. Annane D, Bellissant E, Bolaert P-E, Briegle J, Confalonieri M, De Gaudio R, Keh D, Kupfer Y, Oppert M, Meduri GU (2009) Corticosteroids in the treatment of severe sepsis and septic shock in adult. A systematic review. JAMA 301:2362–2375
    • View reference on PubMed
    • View reference on publisher's website
  39. Stewart PM (2008) The adrenal cortex, in Williams textbook of Endocrinology. In: Kronenberg HM, Melmed S, Polonsky KS, Larsen PR (eds) 11th ed. Saunders, Philadelphia, p 482
  40. Hohl CM, Kelly-Smith CH, Yeung TC, Sweet DD, Doyle-Waters MM, Schulzer M (2010) The effect of a bolus dose of etomidate on cortisol levels, mortality, and health services utilization: a systematic review. Ann Emerg Med 56:105–113
    • View reference on PubMed
    • View reference on publisher's website

Sign In

Connect with ICM

Top 5 Articles Editors Picks Supplement