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Etomidate increases susceptibility to pneumonia in trauma patients

Karim Asehnoune| Pierre Joachim Mahe| Philippe Seguin| Samir Jaber| Boris Jung| Christophe Guitton| Nolwen Chatel-Josse| Aurelie Subileau| Anne Charlotte Tellier| Françoise Masson| Benoit Renard| Yannick Malledant| Corinne Lejus| Christelle Volteau| Véronique Sébille| Antoine Roquilly
Original
Volume 38, Issue 10 / October , 2012

Pages 1673 - 1682

Abstract

Purpose

To investigate the impact of etomidate on the rate of hospital-acquired pneumonia (HAP) in trauma patients and the effects of hydrocortisone in etomidate-treated patients.

Methods

This was a sub-study of the HYPOLYTE multi-centre, randomized, double-blind, placebo-controlled trial of hydrocortisone in trauma patients (NCT00563303). Inclusion criterion was trauma patient with mechanical ventilation (MV) of ≥48 h. The use of etomidate was prospectively collected. Endpoints were the results of the cosyntropin test and rate of HAP on day 28 of follow-up.

Results

Of the 149 patients enrolled in the study, 95 (64 %) received etomidate within 36 h prior to inclusion. 79 (83 %) of 95 patients receiving etomidate and 34 of the 54 (63 %) not receiving etomidate had corticosteroid insufficiency (p = 0.006). The administration of etomidate did not alter basal cortisolemia (p = 0.73), but it did decrease the delta of cortisolemia at 60 min (p = 0.007). There was a correlation between time from etomidate injection to inclusion in the study and sensitivity to corticotropin (R2 = 0.19; p = 0.001). Forty-nine (51.6 %) patients with etomidate and 16 (29.6 %) patients without etomidate developed HAP by day 28 (p = 0.009). Etomidate was associated with HAP on day 28 in the multivariate analysis (hazard ratio 2.48; 95 % confidence interval 1.19–5.18; p = 0.016). Duration of MV with or without etomidate was not significantly different (p = 0.278). Among etomidate-exposed patients, 18 (40 %) treated with hydrocortisone developed HAP compared with 31 (62 %) treated with placebo (p = 0.032). Etomidate-exposed patients treated with hydrocortisone had fewer ventilator days (p < 0.001).

Conclusions

Among the patients enrolled in the study, etomidate did not alter basal cortisolemia, but it did decrease reactivity to corticotropin. We suggest that in trauma patients, etomidate is an independent risk factor for HAP and that the administration of hydrocortisone should be considered after etomidate use.

Keywords

References

  1. Forman SA (2011) Clinical and molecular pharmacology of etomidate. Anesthesiology 114:695–707
    • View reference on PubMed
    • View reference on publisher's website
  2. Reynolds SF, Heffner J (2005) Airway management of the critically ill patient: rapid-sequence intubation. Chest 127:1397–1412
    • View reference on PubMed
    • View reference on publisher's website
  3. Annane D (2005) ICU physicians should abandon the use of etomidate! Intensive Care Med 31:325–326
  4. Vinclair M, Broux C, Faure P, Brun J, Genty C, Jacquot C, Chabre O, Payen J-F (2007) Duration of adrenal inhibition following a single dose of etomidate in critically ill patients. Intensive Care Med 34:714–719
  5. Malerba G, Romano-Girard F, Cravoisy AL, Dousset B, Nace L, Lvy B, Bollaert P-E (2005) Risk factors of relative adrenocortical deficiency in intensive care patients needing mechanical ventilation. Intensive Care Med 31:388–392
  6. 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, 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
  7. Jabre P, Combes X, Lapostolle F, Dhaouadi M, Ricard-Hibon A, Vivien B, Bertrand L, Beltramini A, Gamand P, Albizzati S, Perdrizet D, Lebail G, Chollet-Xemard C, Maxime V, Brun-Buisson C, Lefrant JY, Bollaert PE, Megarbane B, Ricard JD, Anguel N, Vicaut E, Adnet F, KETASED Collaborative Study Group (2009) Etomidate versus ketamine for rapid sequence intubation in acutely ill patients: a multicentre randomised controlled trial. Lancet 374:293–300
    • View reference on PubMed
    • View reference on publisher's website
  8. Albert SG, Ariyan S, Rather A (2011) The effect of etomidate on adrenal function in critical illness: a systematic review. Intensive Care Med 37:901–910
  9. 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
  10. Payen JF, Dupuis C, Trouve-Buisson T, Vinclair M, Broux C, Bouzat P, Genty C, Monneret D, Faure P, Chabre O, Bosson JL (2012) Corticosteroid after etomidate in critically ill patients: a randomized controlled trial. Crit Care Med 40:29–35
    • View reference on PubMed
    • View reference on publisher's website
  11. Cook DJ, Walter SD, Cook RJ, Griffith LE, Guyatt GH, Leasa D, Jaeschke RZ, Brun-Buisson C (1998) Incidence of and risk factors for ventilator-associated pneumonia in critically ill patients. Ann Intern Med 129:433–440
    • View reference on PubMed
  12. Hoen S, Asehnoune K, Brailly-Tabard S, Mazoit J-X, Benhamou D, Moine P, Edouard AR (2002) Cortisol response to corticotropin stimulation in trauma patients: influence of hemorrhagic shock. Anesthesiology 97:807–813
    • View reference on PubMed
    • View reference on publisher's website
  13. Hoen S, Mazoit J-X, Asehnoune K, Brailly-Tabard S, Benhamou D, Moine P, Edouard AR (2005) Hydrocortisone increases the sensitivity to alpha1-adrenoceptor stimulation in humans following hemorrhagic shock. Crit Care Med 33:2737–2743
    • View reference on PubMed
    • View reference on publisher's website
  14. Cohan P, Wang C, McArthur DL, Cook SW, Dusick JR, Armin B, Swerdloff R, Vespa P, Muizelaar 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
  15. Burchard K (2001) A review of the adrenal cortex and severe inflammation: quest of the “eucorticoid” state. J Trauma 51:800–814
    • View reference on PubMed
    • View reference on publisher's website
  16. Offner PJ, Moore EE, Ciesla D (2002) The adrenal response after severe trauma. Am J Surg 184:649–653
    • View reference on PubMed
    • View reference on publisher's website
  17. Roquilly A, Mahe PJ, Seguin P, Guitton C, Floch H, Tellier AC, Merson L, Renard B, Malledant Y, Flet L, Sebille V, Volteau C, Masson D, Nguyen JM, Lejus C, Asehnoune K (2011) Hydrocortisone therapy for patients with multiple trauma: the randomized controlled HYPOLYTE study. JAMA 305:1201–1209
    • View reference on PubMed
    • View reference on publisher's website
  18. 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 65:573–579
    • View reference on PubMed
    • View reference on publisher's website
  19. American Thoracic Society, Infectious Diseases Society of America (2005) Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med 171:388–416
    • View reference on publisher's website
  20. Lepelletier D, Roquilly A, Demeure dit latte D, Mahe PJ, Loutrel O, Champin P, Corvec S, Naux E, Naux E, Pinaud M, Lejus C, Asehnoune K (2010) Retrospective analysis of the risk factors and pathogens associated with early-onset ventilator-associated pneumonia in surgical-ICU head-trauma patients. J Neurosurg Anesthesiol 22:32–37
    • View reference on PubMed
    • View reference on publisher's website
  21. Marik PE (2009) Critical illness-related corticosteroid insufficiency. Chest 135:181–193
    • View reference on PubMed
    • View reference on publisher's website
  22. Bornstein SR (2009) Predisposing factors for adrenal insufficiency. N Engl J Med 360:2328–2339
    • View reference on PubMed
    • View reference on publisher's website
  23. Meduri GU, Muthiah MP, Carratu P, Eltorky M, Chrousos GP (2005) Nuclear factor-kappaB- and glucocorticoid receptor alpha-mediated mechanisms in the regulation of systemic and pulmonary inflammation during sepsis and acute respiratory distress syndrome. Evidence for inflammation-induced target tissue resistance to glucocorticoids. NeuroImmunoModulation 12:321–338
    • View reference on PubMed
    • View reference on publisher's website
  24. Annane D, Maxime V, Ibrahim F, Alvarez JC, Abe E, Boudou P (2006) Diagnosis of Adrenal Insufficiency in Severe Sepsis and Septic Shock. Am J Respir Crit Care Med 174:1319–1326
    • View reference on PubMed
    • View reference on publisher's website
  25. Marik PE, Pastores SM, Annane D, Meduri GU, Sprung CL, Arlt W, Keh D, Briegel J, Beishuizen A, Dimopoulou I, Tsagarakis S, Singer M, Chrousos GP, Zaloga G, Bokhari F, Vogeser M, American College of Critical Care Medicine (2008) Recommendations for the diagnosis and management of corticosteroid insufficiency in critically ill adult patients: Consensus statements from an international task force by the American College of Critical Care Medicine. Crit Care Med 36:1937–1949
    • View reference on PubMed
    • View reference on publisher's website
  26. Varga I, Rácz K, Kiss R, Fütö L, Tóth M, Sergev O, Gláz E (1993) Direct inhibitory effect of etomidate on corticosteroid secretion in human pathologic adrenocortical cells. Steroids 58:64–68
    • View reference on PubMed
    • View reference on publisher's website
  27. Moore FA, Sauaia A, Moore EE, Haenel JB, Burch JM, Lezotte DC (1996) Postinjury multiple organ failure: a bimodal phenomenon. J Trauma 40:501–510
    • View reference on PubMed
    • View reference on publisher's website
  28. Larsen B, Hoff G, Wilhelm W, Buchinger H, Wanner GA, Bauer M (1998) Effect of intravenous anesthetics on spontaneous and endotoxin-stimulated cytokine response in cultured human whole blood. Anesthesiology 89:1218–1227
    • View reference on PubMed
    • View reference on publisher's website
  29. Bochicchio GV, Napolitano LM, Joshi M, Knorr K, Tracy JK, Ilahi O, Scalea TM (2002) Persistent systemic inflammatory response syndrome is predictive of nosocomial infection in trauma. J Trauma 53:245–250
    • View reference on PubMed
    • View reference on publisher's website
  30. Kwon YS, Suh GY, Jeon K, Park SY, Lim SY, Koh W-J, Chung MP, Kim H, Kwon OJ (2010) Serum cytokines and critical illness-related corticosteroid insufficiency. Intensive Care Med 36:1845–1851
  31. Beisel WR, Rapoport MI (1969) Inter-relations between adrenocortical functions and infectious illness. N Engl J Med 280:596–604
    • View reference on PubMed
    • View reference on publisher's website
  32. Kaufmann I, Briegel J, Schliephake F, Hoelzl A, Chouker A, Hummel T, Schelling G, Thiel M (2008) Stress doses of hydrocortisone in septic shock: beneficial effects on opsonization-dependent neutrophil functions. Intensive Care Med 34:344–349
  33. Heller AR, Heller SC, Borkenstein A, Stehr SN, Koch T (2003) Modulation of host defense by hydrocortisone in stress doses during endotoxemia. Intensive Care Med 29:1456–1463
  34. Webster JI, Tonelli L, Sternberg EM (2002) Neuroendocrine regulation of immunity. Annu Rev Immunol 20:125–163
    • View reference on PubMed
    • View reference on publisher's website
  35. Visser J, van Boxel-Dezaire A, Methorst D, Brunt T, De Kloet ER, Nagelkerken L (1998) Differential regulation of interleukin-10 (IL-10) and IL-12 by glucocorticoids in vitro. Blood 91:4255–4264
    • View reference on PubMed
  36. Rhen T, Cidlowski JA (2005) Antiinflammatory action of glucocorticoids—new mechanisms for old drugs. N Engl J Med 353:1711–1723
    • View reference on PubMed
    • View reference on publisher's website
  37. Lepelletier Y, Zollinger R, Ghirelli C, Raynaud F, Hadj-Slimane R, Cappuccio A, Hermine O, Liu Y-J, Soumelis V (2010) Toll-like receptor control of glucocorticoid-induced apoptosis in human plasmacytoid predendritic cells (pDCs). Blood 116:3389–3397
    • View reference on PubMed
    • View reference on publisher's website
  38. Keh D, Boehnke T, Weber-Cartens S, Schulz C, Ahlers O, Bercker S, Volk H-D, Doecke W-D, Falke KJ, Gerlach H (2003) Immunologic and hemodynamic effects of “low-dose” hydrocortisone in septic shock: a double-blind, randomized, placebo-controlled, crossover study. Am J Respir Crit Care Med 167:512–520
    • View reference on PubMed
    • View reference on publisher's website
  39. Huang C-J (2006) Association between adrenal insufficiency and ventilator weaning. Am J Respir Crit Care Med 173:276–280
    • View reference on PubMed
    • View reference on publisher's website
  40. Confalonieri M, Urbino R, Potena A, Piattella M, Parigi P, Puccio G, Della Porta R, Giorgio C, Blasi F, Umberger R, Meduri GU (2005) Hydrocortisone infusion for severe community-acquired pneumonia: a preliminary randomized study. Am J Respir Crit Care Med 171:242–248
    • View reference on PubMed
    • View reference on publisher's website
  41. Sartorius D, Le Manach Y, David JS, Rancurel E, Smail N, Thicoïpé M, Wiel E, Ricard-Hibon A, Berthier F, Gueugniaud PY, Riou B (2010) Mechanism, glasgow coma scale, age, and arterial pressure (MGAP): a new simple prehospital triage score to predict mortality in trauma patients. Crit Care Med 38:831–837
    • View reference on PubMed
    • View reference on publisher's website
  42. Minne L, Abu-Hanna A, de Jonge E (2008) Evaluation of SOFA-based models for predicting mortality in the ICU: a systematic review. Crit Care 12:R161
    • View reference on PubMed
    • View reference on publisher's website
  43. Annane D, Bellissant E, Cavaillon J-M (2005) Septic shock. Lancet 365:63–78
    • View reference on PubMed
    • View reference on publisher's website

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