Etomidate increases susceptibility to pneumonia in trauma patients

0 S. Jaber B. Jung Intensive Care Unit, Anaesthesia and Critical Care Department, Saint Eloi University Hospital of Montpellier , Montpellier, France 1 P. Seguin Y. Malledant Intensive Care Unit, Anaesthesia and Critical Care Department, University Hospital of Rennes , Rennes, France 2 K. Asehnoune P. J. Mahe N. Chatel-Josse C. Lejus A. Roquilly Intensive Care Unit, Anaesthesia and Critical Care Department , Hotel Dieu-HME, University Hospital of Nantes , Nantes, France 3 A. Subileau multi-centre , randomized, double- Intensive Care Unit , Anaesthesia and blind, placebo-controlled trial 4 C. Guitton Medical Intensive Care Unit, University Hospital of Nantes , Nantes, France - 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 Abstract Purpose: To investigate developed HAP by day 28 the impact of etomidate on the rate of (p = 0.009). Etomidate was associhospital-acquired pneumonia (HAP) ated with HAP on day 28 in the in trauma patients and the effects of multivariate analysis (hazard ratio hydrocortisone in etomidate-treated 2.48; 95 % confidence interval patients. Methods: This was a sub- 1.195.18; p = 0.016). Duration of study of the HYPOLYTE MV with or without etomidate was not significantly different Conclusions: Among the patients should be considered after etomidate (p = 0.278). Among etomidate- enrolled in the study, etomidate did use. exposed patients, 18 (40 %) treated not alter basal cortisolemia, but it with hydrocortisone developed HAP did decrease reactivity to cortico- Keywords Etomidate compared with 31 (62 %) treated tropin. We suggest that in trauma Adrenal insufficiency with placebo (p = 0.032). Etomi- patients, etomidate is an independent Bacterial pneumonia Trauma date-exposed patients treated with risk factor for HAP and that the Hydrocortisone hydrocortisone had fewer ventilator administration of hydrocortisone days (p \ 0.001). Materials and methods Etomidate has a favourable haemodynamic profile and is frequently used as a single bolus for rapid sequence intubation [1, 2]. However, the use of etomidate remains This study is a sub-study of the HYPOLYTE trial, a controversial in critically ill patients [3]. Etomidate multi-centre, randomized, double-blind, placebo-coninhibits 11b-hydroxylase and induces transient cortico- trolled trial of hydrocortisone in severe trauma patients steroid insufficiency [4]. Authors of clinical trials have [17]. Following approval by the Institutional Review frequently reported an increased rate of adrenal insuffi- Board of Angers (France), patients in seven French ICUs ciency and an increased risk of death with etomidate use were enrolled in the HYPOLYTE trial from 15 November [5, 6]. In a study involving a general population of 2006 to 4 August 2009. Prior to enrollment, written intensive care unit (ICU) patients, etomidate did not alter informed consent was obtained from a next-of-kin. Retspecific outcomes (organ failures, duration of mechanical rospective consent, if possible, was obtained from ventilation) or mortality compared with ketamine [7]. In a patients. recently published systematic review, the authors confirmed an increased mortality rate with the use of etomidate in a sub-group of patients with sepsis [8]. Patients However, hydrocortisone treatment after etomidate use did not reduce the mortality of septic patients [9] and did All of the 149 patients randomized in the HYPOLYTE not reduce organ failures in critically ill patients [10]. trial were included in the analysis for this sub-study. In Trauma patients are highly susceptible to nosocomial the HYPOLYTE trial, the inclusion criteria were multiple infection [11], and the impact of etomidate is poorly studied trauma, age of [15 years 3 months and the expectation in this population. It has been demonstrated that up to 70 % that mechanical ventilation would be required for [48 h. of trauma patients developed a critical illness-related cor- Exclusion criteria were previous adrenal insufficiency, ticosteroid insufficiency (CIRCI) [1214] and that this previous immunosuppression (See [17] for definitions), could increase the risk of hospital-acquired pneumonia treatment with corticosteroids within the last 6 months (HAP) [15, 16]. We have recently demonstrated that low- and pregnancy. Etomidate use was not controlled for in dose hydrocortisone decreases the rate of HAP in multiple the study. trauma patients with CIRCI [17]. Etomidate may increase the rate of post-traumatic complications, but little data are available to date on this specific population of patients [18]. Hydrocortisone therapy To the best of our knowledge, the ability of hydrocortisone to overcome the effects of etomidate has not yet been For the purpose of the HYPOLYTE trial, treatment with delineated in trauma patients. hydrocortisone or placebo were started in the first 36 h For the study reported here, we used data from the following the trauma. Hydrocortisone (Upjohn Serb , HYPOLYTE trial, a prospective multi-centre study of low- Paris, France) or placebo were administered for 7 days in dose hydrocortisone treatment in intubated trauma patients patients with CIRCI (continuous intravenous infusion, [17]. We hypothesized that a single dose of etomidate 200 mg/day for 5 days, 100 mg on day 6 and 50 mg on increases the proportion of CIRCI and the rate of HAP. We day 7) and were stopped during the first 2 days that also tested the effects of the hydrocortisone treatment on the patients were CIRCI-free (after the results of the cortiproportion of HAP in patients receiving etomidate. cotropin test had been received). Overall patient characteristics, including demographics, injury severity score and abbreviated injury score, fluid Patients infusions, vasopressors, antibiotic prophylaxis, etomidate use, surgery, infections, organ failures, length of ventilatory support, ICU hospitalization and death on day 28 of follow-up were recorded. Continuous variables are expressed as the median and interquartile range (IQR) and categorical variables as per- Of the 95 patients in the etomidate group and 54 patients centage. Characteristics and outcomes of patients with in the non-etomidate group, 79 (83 %) and 34 (63 %), Etomidate effects on basal cortisolemia and results of the corticotropin test Table 1 General characteristics of the patients No etomidate (N = 54) Etomidate (N = 95) p valuea Age (years), mean (SD) 36 (17) Men, N (%) 47 (87) Medical history, N (%) Diabetes mellitus 1 (1.85) Cardiac insufficiency 1 (1.85) Obesity 6 (11) Chronic pulmonary disease 1 (1.9) Smoking 2 (3.7) Traumatic brain injury, N (%) 29 (53.7) Injury severity score, median (IQR) 26 (2235) AIS, median (IQR) Brain/neck 3 (04) Face 0 (02) Thorax 3 (23) Abdomen/perineum 2 (03) Extremities/pelvis 2 (13) Skin 0 (01) Aspiration pneumonia, N (%) 1 (1.9) Hypotension prior to inclusion, N (%) 28 (52.8) Fluid infu (...truncated)