Hydrocortisone and fludrocortisone for prevention of hospital-acquired pneumonia in patients with severe traumatic brain injury (Corti-TC): a double-blind, multicentre phase 3, randomised placebo-controlled trial

Asehnoune, Karim; Séguin, Philippe; Allary, Jérémy; Feuillet, Fanny; Lasocki, Sigismond; Cook, Fabrice; Floch, H. Le; Chabanne, Russell; Geeraerts, Thomas; Roger, Claire; Perrigault, Pierre François; Hanouz, Jean‐Luc; Lukaszewicz, Anne Claire; Biais, Matthieu; Boucheix, Perrine; Dahyot‐Fizelier, Claire; Capdevila, Xavier; Mahé, Pierre; Maguet, Pascale Le; Paugam–Burtz, Catherine; Gergaud, Soizic; Plaud, Benoît; Constantin, Jean Michel; Malledant, Yannick; Flet, Laurent; Sebille, Véronique; Roquilly, Antoine

doi:10.1016/s2213-2600(14)70144-4

Cited by 107 publications

(64 citation statements)

References 32 publications

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“…The author’s hypothesis was that early hydrocortisone administration could blunt the hyper-inflammatory response associated with trauma, and prevent the subsequent associated immunosuppression. However, these results were not confirmed in a second multicenter trial published recently [48]. In combination with our current results, this raises the question of: (1) the timing of hydrocortisone administration after injury, and (2) the duration of hydrocortisone administration.…”

Section: Discussioncontrasting

confidence: 79%

Transcriptome modulation by hydrocortisone in severe burn shock: ancillary analysis of a prospective randomized trial

et al. 2017

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BackgroundDespite shortening vasopressor use in shock, hydrocortisone administration remains controversial, with potential harm to the immune system. Few studies have assessed the impact of hydrocortisone on the transcriptional response in shock, and we are lacking data on burn shock. Our objective was to assess the hydrocortisone-induced transcriptional modulation in severe burn shock, particularly modulation of the immune response.MethodsWe collected whole blood samples during a randomized controlled trial assessing the efficacy of hydrocortisone administration in burn shock. Using whole genome microarrays, we first compared burn patients (n = 32) from the placebo group to healthy volunteers to describe the transcriptional modulation induced by burn shock over the first week. Then we compared burn patients randomized for either hydrocortisone administration or placebo, to assess hydrocortisone-induced modulation.ResultsStudy groups were similar in terms of severity and major outcomes, but shock duration was significantly reduced in the hydrocortisone group. Many genes (n = 1687) were differentially expressed between burn patients and healthy volunteers, with 85% of them exhibiting a profound and persistent modulation over seven days. Interestingly, we showed that hydrocortisone enhanced the shock-associated repression of adaptive, but also innate immunity.ConclusionsWe found that the initial host response to burn shock encompasses wide and persistent modulation of gene expression, with profound modulation of pathways associated with metabolism and immunity. Importantly, hydrocortisone administration may worsen the immunosuppression associated with severe injury. These data should be taken into account in the risk ratio of hydrocortisone administration in patients with inflammatory shock.Trial registrationClinicalTrials.gov, NCT00149123. Registered on 6 September 2005.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-017-1743-9) contains supplementary material, which is available to authorized users.

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Section: Discussioncontrasting

confidence: 79%

Transcriptome modulation by hydrocortisone in severe burn shock: ancillary analysis of a prospective randomized trial

et al. 2017

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“…Corticosteroid therapy did not increase the risk of gastroduodenal bleeding (n = 12 trials; RR = 1.22, 95% CI 0.90-1.65) or superinfection (n = 7 trials; RR = 0.93, 95% CI 0.80-1.08). Two trials examined the effects of hydrocortisone [65] and hydrocortisone plus fludrocortisone [66] specifically in trauma-associated CIRCI, as defined by a change in baseline cortisol at 60 min of <9 µg/dl after cosyntropin (250 µg) administration. In the first trial (n = 113 multiple trauma patients with CIRCI), hydrocortisone therapy prevented the development of hospitalacquired pneumonia by day 28 [hazard ratio (HR) 0.47, 95% CI 0.25-0.86] and increased by 6 days (95% CI 2-11) the number of mechanical ventilation-free days.…”

Section: Rationalementioning

confidence: 99%

Guidelines for the diagnosis and management of critical illness-related corticosteroid insufficiency (CIRCI) in critically ill patients (Part I): Society of Critical Care Medicine (SCCM) and European Society of Intensive Care Medicine (ESICM) 2017

et al. 2017

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“…Other prophylactic measures have not proven effective. Corticosteroid administration was not effective in preventing nosocomial pneumonia in TBI patients, although the overall incidence of pneumonia in this study was lower than expected [32]. The effectiveness of beta-blockers [33, 34], or statins [35, 36], in preventing pneumonia in stroke patients is controversial and must be tested in future trials.…”

Section: Discussionmentioning

confidence: 63%

Systemic antibiotics for preventing ventilator-associated pneumonia in comatose patients: a systematic review and meta-analysis

Righy

Brasil

Vallès

et al. 2017

Ann. Intensive Care

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BackgroundEarly-onset ventilator-associated pneumonia (EO-VAP) is the leading cause of morbidity and mortality in comatose patients. However, VAP prevention bundles focus mainly on late-onset VAP and may be less effective in preventing EO-VAP in comatose patients. Systemic antibiotic administration at the time of intubation may have a role in preventing EO-VAP. Therefore, we evaluated the effectiveness of systemic antibiotic administration in VAP prevention in comatose patients through a systematic review and meta-analysis. MethodsWe searched for studies published through December 2015 that evaluated systemic antibiotic prophylaxis in comatose patients. Two authors independently selected and evaluated full-length reports of randomized clinical trials or prospective cohorts in patients aged >16 years that evaluated the impact of systemic antibiotics at the time of intubation on EO-VAP compared to placebo or no prophylaxis. The outcome variables were the incidence of EO-VAP, the duration of mechanical ventilation, ICU length of stay, and ICU mortality. ResultsWe identified 10,988 citations, yielding 26 articles for further analysis; three studies with 267 patients were finally analyzed. Most patients (n = 135) were comatose due to head trauma. Systemic antibiotic administration was associated with decreased incidence of EO-VAP (RR 0.32; 95% CI 0.19–0.54) and shorter ICU LOS (standardized mean difference −0.32; 95% CI −0.56 to −0.08), but had no effect on mortality (RR 1.03; 95% CI 0.7–1.53) or duration of mechanical ventilation (standardized mean difference −0.16; 95% CI −0.41 to 0.08). ConclusionsAntibiotic prophylaxis in comatose patients reduced the incidence of EO-VAP and decreased the ICU stay slightly. Future trials are needed to confirm these results.

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Hydrocortisone and fludrocortisone for prevention of hospital-acquired pneumonia in patients with severe traumatic brain injury (Corti-TC): a double-blind, multicentre phase 3, randomised placebo-controlled trial

Cited by 107 publications

References 32 publications

Transcriptome modulation by hydrocortisone in severe burn shock: ancillary analysis of a prospective randomized trial

Transcriptome modulation by hydrocortisone in severe burn shock: ancillary analysis of a prospective randomized trial

Guidelines for the diagnosis and management of critical illness-related corticosteroid insufficiency (CIRCI) in critically ill patients (Part I): Society of Critical Care Medicine (SCCM) and European Society of Intensive Care Medicine (ESICM) 2017

Systemic antibiotics for preventing ventilator-associated pneumonia in comatose patients: a systematic review and meta-analysis

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