Top

Published in:

01-10-2012 | Original

Etomidate increases susceptibility to pneumonia in trauma patients

Published in: Intensive Care Medicine | Issue 10/2012

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 (R ² = 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.

Available only for authorised users

Forman SA (2011) Clinical and molecular pharmacology of etomidate. Anesthesiology 114:695–707PubMedCrossRef

Reynolds SF, Heffner J (2005) Airway management of the critically ill patient: rapid-sequence intubation. Chest 127:1397–1412PubMedCrossRef

Annane D (2005) ICU physicians should abandon the use of etomidate! Intensive Care Med 31:325–326PubMedCrossRef

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 34:714–719PubMedCrossRef

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 31:388–392PubMedCrossRef

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 35:1012–1018PubMedCrossRef

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 374:293–300PubMedCrossRef

Albert SG, Ariyan S, Rather A (2011) The effect of etomidate on adrenal function in critical illness: a systematic review. Intensive Care Med 37:901–910PubMedCrossRef

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 35:1868–1876PubMedCrossRef

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 40:29–35PubMedCrossRef

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 129:433–440PubMed

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 97:807–813PubMedCrossRef

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 33:2737–2743PubMedCrossRef

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 33:2358–2366PubMedCrossRef

15.

Burchard K (2001) A review of the adrenal cortex and severe inflammation: quest of the “eucorticoid” state. J Trauma 51:800–814PubMedCrossRef

16.

Offner PJ, Moore EE, Ciesla D (2002) The adrenal response after severe trauma. Am J Surg 184:649–653PubMedCrossRef

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 305:1201–1209PubMedCrossRef

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 65:573–579PubMedCrossRef

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 171:388–416CrossRef

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 22:32–37PubMedCrossRef

21.

Marik PE (2009) Critical illness-related corticosteroid insufficiency. Chest 135:181–193PubMedCrossRef

22.

Bornstein SR (2009) Predisposing factors for adrenal insufficiency. N Engl J Med 360:2328–2339PubMedCrossRef

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 12:321–338PubMedCrossRef

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 174:1319–1326PubMedCrossRef

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 36:1937–1949PubMedCrossRef

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 58:64–68PubMedCrossRef

27.

Moore FA, Sauaia A, Moore EE, Haenel JB, Burch JM, Lezotte DC (1996) Postinjury multiple organ failure: a bimodal phenomenon. J Trauma 40:501–510PubMedCrossRef

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 89:1218–1227PubMedCrossRef

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 53:245–250PubMedCrossRef

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 36:1845–1851PubMedCrossRef

31.

Beisel WR, Rapoport MI (1969) Inter-relations between adrenocortical functions and infectious illness. N Engl J Med 280:596–604PubMedCrossRef

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 34:344–349PubMedCrossRef

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 29:1456–1463PubMedCrossRef

34.

Webster JI, Tonelli L, Sternberg EM (2002) Neuroendocrine regulation of immunity. Annu Rev Immunol 20:125–163PubMedCrossRef

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 91:4255–4264PubMed

36.

Rhen T, Cidlowski JA (2005) Antiinflammatory action of glucocorticoids—new mechanisms for old drugs. N Engl J Med 353:1711–1723PubMedCrossRef

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 116:3389–3397PubMedCrossRef

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 167:512–520PubMedCrossRef

39.

Huang C-J (2006) Association between adrenal insufficiency and ventilator weaning. Am J Respir Crit Care Med 173:276–280PubMedCrossRef

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 171:242–248PubMedCrossRef

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 38:831–837PubMedCrossRef

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:R161PubMedCrossRef

43.

Annane D, Bellissant E, Cavaillon J-M (2005) Septic shock. Lancet 365:63–78PubMedCrossRef

Title: Etomidate increases susceptibility to pneumonia in trauma patients
Publication date: 01-10-2012
Published in: Intensive Care Medicine / Issue 10/2012
Print ISSN: 0342-4642
Electronic ISSN: 1432-1238
DOI: https://doi.org/10.1007/s00134-012-2619-8

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Etomidate increases susceptibility to pneumonia in trauma patients

Abstract

Purpose

Methods

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 10/2012

Comment on O’Brien et al.: prevalence and outcome of cirrhosis patients admitted to UK intensive care: a comparison against dialysis-dependent chronic renal failure patients

Surrogate decision makers’ attitudes towards research decision making for critically ill patients

Adverse cardiac events during catecholamine therapy: a role for hydrocortisone?

ICU admission characteristics and mortality rates among elderly and very elderly patients

The effects of three specific conditions related to critical care on adrenal function in children

Avoiding invasive mechanical ventilation by extracorporeal carbon dioxide removal in patients failing noninvasive ventilation