Search

Over the recent period, the use of induced hypothermia has gained an increasing interest for critically ill patients, in particular in brain-injured patients. The term "targeted temperature management" (TTM) has now emerged as the most appropriate when referring to interventions used to reach and maintain a specific level temperature for each individual. TTM may be used to prevent fever, to maintain normothermia, or to lower core temperature. This treatment is widely used in intensive care units, mostly as a primary neuroprotective method. Indications are, however, associated with variable levels of evidence based on inhomogeneous or even contradictory literature. Our aim was to conduct a systematic analysis of the published data in order to provide guidelines. We present herein recommendations for the use of TTM in adult and paediatric critically ill patients developed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method. These guidelines were conducted by a group of experts from the French Intensive Care Society (Société de Réanimation de Langue Française [SRLF]) and the French Society of Anesthesia and Intensive Care Medicine (Société Francaise d'Anesthésie Réanimation [SFAR]) with the participation of the French Emergency Medicine Association (Société Française de Médecine d'Urgence [SFMU]), the French Group for Pediatric Intensive Care and Emergencies (Groupe Francophone de Réanimation et Urgences Pédiatriques [GFRUP]), the French National Association of Neuro-Anesthesiology and Critical Care (Association Nationale de Neuro-Anesthésie Réanimation Française [ANARLF]), and the French Neurovascular Society (Société Française Neurovasculaire [SFNV]). Fifteen experts and two coordinators agreed to consider questions concerning TTM and its practical implementation in five clinical situations: cardiac arrest, traumatic brain injury, stroke, other brain injuries, and shock. This resulted in 30 recommendations: 3 recommendations were strong (Grade 1), 13 were weak (Grade 2), and 14 were experts' opinions. After two rounds of rating and various amendments, a strong agreement from voting participants was obtained for all 30 (100%) recommendations, which are exposed in the present article.

Background: Ventilator-associated pneumonia (VAP) is a care-related event that could be promoted by immune suppression caused by critical diseases, malignancies and cancer treatments. Low dose of hydrocortisone was proposed for modulation of immune response in the critically ill population., Methods: In this monocentric observational study, all cancer patients mechanically ventilated for more than 48 h were included. Effect of low-dose hydrocortisone administered during the first 48 h of mechanical ventilation was evaluated applying inverse probability weighting analysis after propensity score assessment. VAP impact on 1-year mortality, ICU length of stay and mechanical ventilation duration was secondarily determined., Results: Within this cohort, 190 cancer patients were followed. VAP was confirmed in 22.1% of cases in the early hydrocortisone group and confirmed in 42.6% of cases in the no or late hydrocortisone group. Early hydrocortisone exhibited a protective effect on the risk of VAP (OR 0.23; 95% CI 0.12-0.44; P < 0.0001). VAP was associated with 1-year mortality (HR 1.60; 95% CI 1.10-2.34; P = 0.017) and increased ICU length of stay (mean extra length of stay: 4.2 days; 95% CI 0.6-7.8)., Conclusions: Immune modulation with low-dose hydrocortisone administered in the first days of mechanical ventilation could protect from VAP occurrence in cancer patients.

Pseudomonas aeruginosa (PA) expresses the type III secretion system (T3SS) and effector exoenzymes that interfere with intracellular pathways. Natural killer (NK) cells play a key role in antibacterial immunity and their activation is highly dependent on IL-12 produced by myeloid cells. We studied PA and NK cell interactions and the role of IL-12 using human peripheral blood mononuclear cells, sorted human NK cells, and a human NK cell line (NK92). We used a wild-type (WT) strain of PA (PAO1) or isogenic PA-deleted strains to delineate the role of T3SS and exoenzymes. Our hypotheses were tested in vivo in a PA-pneumonia mouse model. Human NK cells or NK92 cell line produced low levels of IFN-γ in response to PA without IL-12 stimulation, whereas PA significantly increased IFN-γ after IL-12 priming. The modulation of IFN-γ production by PA required bacteria-to-cell contact. Among T3SS effectors, exoenzyme T (ExoT) upregulates IFN-γ production and control ERK activation. In vivo , ExoT also increases IFN-γ levels and the percentage of IFN-γ + NK cells in lungs during PA pneumonia, confirming in vitro data. In conclusion, our results suggest that T3SS could modulate the production of IFN-γ by NK cells after PA infection through ERK activation.

Introduction: Traumatic brain injury (TBI) is a major cause of death and severe prolonged disability. Intracranial hypertension (ICH) is a critical risk factor of bad outcomes after TBI. Continuous infusion of hyperosmolar therapy has been proposed for the prevention and the treatment of ICH. Whether an early administration of continuous hyperosmolar therapy improves long-term outcomes of patients with TBI is uncertain. The aim of the COBI study (number clinicaltrial.gov 03143751, pre-results stage) is to assess the efficiency and the safety of continuous hyperosmolar therapy in patients with TBI., Methods and Analysis: The COBI (COntinuous hyperosmolar therapy in traumatic Brain-Injured patients) trial is a multicentre, randomised, controlled, open-label, two-arms study with blinded adjudication of primary outcome. Three hundred and seventy patients hospitalised in intensive care unit with a TBI (Glasgow Coma Scale ≤12 and abnormal brain CT scan) are randomised in the first 24 hours following trauma to standard care or continuous hyperosmolar therapy (20% NaCl) plus standard care. Continuous hyperosmolar therapy is maintained for at least 48 hours in the treatment group and continued for as long as is necessary to prevent ICH. The primary outcome is the score on the Extended Glasgow Outcome Scale at 6 months. The treatment effect is estimated with ordinal logistic regression adjusted for prespecified prognostic factors and expressed as a common OR., Ethics and Dissemination: The COBI trial protocol has been approved by the ethics committee of Paris Ile de France VIII and will be carried out according to the principles of the Declaration of Helsinki and the Good Clinical Practice guidelines. The results of this study will be disseminated through presentation at scientific conferences and publication in peer-reviewed journals. The COBI trial is the first randomised controlled trial powered to investigate whether continuous hyperosmolar therapy in patients with TBI improve long-term recovery., Trial Registration Number: Trial registration number is NCT03143751., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Pseudomonas aeruginosa is a major threat for immune-compromised patients. Bacterial pneumonia can induce uncontrolled and massive neutrophil recruitment ultimately leading to acute respiratory distress syndrome and epithelium damage. Interleukin-22 plays a central role in the protection of the epithelium. In this study, we aimed to evaluate the role of interleukin-22 and its soluble receptor IL-22BP in an acute Pseudomonas aeruginosa pneumonia model in mice. In this model, we noted a transient increase of IL-22 during Pseudomonas aeruginosa challenge. Using an antibody-based approach, we demonstrated that IL-22 neutralisation led to increased susceptibility to infection and to lung damage correlated with an increase in neutrophil accumulation in the lungs. On the contrary, rIL-22 administration or IL-22BP neutralisation led to a decrease in mouse susceptibility and lung damage associated with a decrease in neutrophil accumulation. This study demonstrated that the IL-22/IL-22BP system plays a major role during Pseudomonas aeruginosa pneumonia by moderating neutrophil accumulation in the lungs that ultimately leads to epithelium protection.

In this research agenda on the acute and critical care management of trauma patients, we concentrate on the major factors leading to death, namely haemorrhage and traumatic brain injury (TBI). In haemostasis biology, the results of randomised controlled trials have led to the therapeutic focus moving away from the augmentation of coagulation factors (such as recombinant factor VIIa) and towards fibrinogen supplementation and administration of antifibrinolytics such as tranexamic acid. Novel diagnostic techniques need to be evaluated to determine whether an individualised precision approach is superior to current empirical practice. The timing and efficacy of platelet transfusions remain in question, while new blood products need to be developed and evaluated, including whole blood variants, lyophilised products and novel red cell storage modalities. The current cornerstones of TBI management are intracranial pressure control, maintenance of cerebral perfusion pressure and avoidance of secondary insults (such as hypotension, hypoxaemia, hyperglycaemia and pyrexia). Therapeutic hypothermia and decompressive craniectomy are controversial therapies. Further research into these strategies should focus on identifying which subgroups of patients may benefit from these interventions. Prediction of the long-term outcome early after TBI remains challenging. Early magnetic resonance imaging has recently been evaluated for predicting the long-term outcome in mild and severe TBI. Novel biomarkers may also help in outcome prediction and may predict chronic neurological symptoms. For trauma in general, rehabilitation is complex and multidimensional, and the optimal timing for commencement of rehabilitation needs investigation. We propose priority areas for clinical trials in the next 10 years.

Introduction: Severe trauma represents the leading cause of mortality worldwide. While 80% of deaths occur within the first 24 hours after trauma, 20% occur later and are mainly due to healthcare-associated infections, including ventilator-associated pneumonia (VAP). Preventing underinflation of the tracheal cuff is recommended to reduce microaspiration, which plays a major role in the pathogenesis of VAP. Automatic devices facilitate the regulation of tracheal cuff pressure, and their implementation has the potential to reduce VAP. The objective of this work is to determine whether continuous regulation of tracheal cuff pressure using a pneumatic device reduces the incidence of VAP compared with intermittent control in severe trauma patients., Methods and Analysis: This multicentre randomised controlled and open-label trial will include patients suffering from severe trauma who are admitted within the first 24 hours, who require invasive mechanical ventilation to longer than 48 hours. Their tracheal cuff pressure will be monitored either once every 8 hours (control group) or continuously using a pneumatic device (intervention group). The primary end point is the proportion of patients that develop VAP in the intensive care unit (ICU) at day 28. The secondary end points include the proportion of patients that develop VAP in the ICU, early (≤7 days) or late (>7 days) VAP, time until the first VAP diagnosis, the number of ventilator-free days and antibiotic-free days, the length of stay in the ICU, the proportion of patients with ventilator-associated events and that die during their ICU stay., Ethics and Dissemination: This protocol has been approved by the ethics committee of Poitiers University Hospital, and will be carried out according to the principles of the Declaration of Helsinki and the Good Clinical Practice guidelines. The results of this study will be disseminated through presentation at scientific conferences and publication in peer-reviewed journals., Trial Registration: Clinical Trials NCT02534974., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Patients with brain injury are at high risk of extubation failure., Methods: We conducted a prospective observational cohort study in four intensive care units of three university hospitals. The aim of the study was to create a score that could predict extubation success in patients with brain injury., Results: A total of 437 consecutive patients with brain injury were included, and 338 patients (77.3%) displayed successful extubation. In the multivariate analysis, four features were associated with success the day of extubation: age less than 40 yr, visual pursuit, swallowing attempts, and a Glasgow coma score greater than 10. In the score, each item counted as one. A score of 3 or greater was associated with 90% extubation success. The area under the receiver-operator curve was 0.75 (95% CI, 0.69 to 0.81). After internal validation by bootstrap, the area under the receiver-operator curve was 0.73 (95% CI, 0.68 to 0.79). Extubation success was significantly associated with shorter duration of mechanical ventilation (11 [95% CI, 5 to 17 days] vs. 22 days [95% CI, 13 to 29 days]; P < 0.0001), shorter intensive care unit length of stay (15 [95% CI, 9 to 23 days] vs. 27 days [95% CI, 21 to 36 days]; P < 0.0001), and lower in-intensive care unit mortality (4 [1.2%] vs. 11 [11.1%]; P < 0.0001)., Conclusions: Our score exploring both airway functions and neurologic status may increase the probability of successful extubation in patients with severe brain injury.

Lung infections cause prolonged immune alterations and elevated susceptibility to secondary pneumonia. We found that, after resolution of primary viral or bacterial pneumonia, dendritic cells (DC), and macrophages exhibited poor antigen-presentation capacity and secretion of immunogenic cytokines. Development of these "paralyzed" DCs and macrophages depended on the immunosuppressive microenvironment established upon resolution of primary infection, which involved regulatory T (Treg) cells and the cytokine TGF-β. Paralyzed DCs secreted TGF-β and induced local Treg cell accumulation. They also expressed lower amounts of IRF4, a transcription factor associated with increased antigen-presentation capacity, and higher amounts of Blimp1, a transcription factor associated with tolerogenic functions, than DCs present during primary infection. Blimp1 expression in DC of humans suffering sepsis or trauma correlated with severity and complicated outcomes. Our findings describe mechanisms underlying sepsis- and trauma-induced immunosuppression, reveal prognostic markers of susceptibility to secondary infections and identify potential targets for therapeutic intervention., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: We assessed outcomes in brain-injured patients after implementation of a multi-faceted approach to reduce respiratory complications in intensive care units., Methods: Prospective nationwide before-after trial. Consecutive adults with acute brain injury requiring mechanical ventilation for ≥24 h in 20 French intensive care units (ICUs) were included. The management of invasive ventilation in brain-injured patients admitted between 1 July 2013 and 31 October 2013 (4 months) was monitored and analysed. After the baseline period (1 November 2013-31 December 2013), ventilator settings and decision to extubate were selected as targets to hasten weaning from invasive ventilation. During the intervention period, low tidal volume (≤7 ml/kg), moderate positive end-expiratory pressure (PEEP, 6-8 cm H 2 O) and an early extubation protocol were recommended. The primary endpoint was the number of days free of invasive ventilation at day 90. Comparisons were performed between the two periods and between the compliant and non-compliant groups., Results: A total of 744 patients from 20 ICUs were included (391 pre-intervention; 353 intervention). No difference in the number of invasive ventilation-free days at day 90 was observed between the two periods [71 (0-80) vs. 67 (0-80) days; P = 0.746]. Compliance with the complete set of recommendations increased from 8 (2%) to 52 (15%) patients after the intervention (P < 0.001). At day 90, the number of invasive ventilation-free days was higher in the 60 (8%) patients whose care complied with recommendations than in the 684 (92%) patients whose care deviated from recommendations [77 (66-82) and 71 (0-80) days, respectively; P = 0.03]. The mortality rate was 10% in the compliant group and 26% in the non-compliant group (P = 0.023). Both multivariate analysis [hazard ratio (HR) 1.78, 95% confidence interval (95% CI) 1.41-2.26; P < 0.001] and propensity score-adjusted analysis (HR 2.25, 95% CI 1.56-3.26, P < 0.001) revealed that compliance was an independent factor associated with the reduction in the duration of mechanical ventilation., Conclusions: Adherence to recommendations for low tidal volume, moderate PEEP and early extubation seemed to increase the number of ventilator-free days in brain-injured patients, but inconsistent adoption limited their impact. Trail registration number: NCT01885507.

Blood samples from 32 patients with severe Traumatic brain injury (TBI) were studied and compared with 11 cardiac surgery patients, and 29 healthy controls. A dramatic decreased expression of HLA class I molecules on monocytes was associated with increased KIR+ NK cell frequency in TBI patients. Overall, the phenotype of TBI NK cells marked by KIR and CD57 expression and lower level of NKp46 and DNAM-1 reflected a differentiated state. The NK-cell response to missing self was marked by lower degranulation and lower IFN-γ production after stimulation with HLA class I deficient cell line. In contrast, the NK-cell ADCC was not altered. IL-12 was able to restore both IFN-γ production and the cytotoxicity capacities of NK cells. This study provides the first extensive description of the phenotype and functions of NK cells in TBI patients. Further evaluation of IL-12 treatment to overcome immunosuppression-induced nosocomial infections is warranted., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Cutibacterium acnes (formerly Propionibacterium acnes) is recognized as a pathogen in foreign-body infections (arthroplasty or spinal instrumentation). To date, the direct impact of C. acnes on bone cells has never been explored. The clade of 11 C. acnes clinical isolates was determined by MLST. Human osteoblasts and osteoclasts were infected by live C. acnes. The whole genome sequence of six isolates of this collection was analyzed. CC36 C. acnes strains were significantly less internalized by osteoblasts and osteoclasts than CC18 and CC28 C. acnes strains (p ≤ 0.05). The CC18 C. acnes ATCC6919 isolate could survive intracellularly for at least 96 hours. C. acnes significantly decreased the resorption ability of osteoclasts with a major impact by the CC36 strain (p ≤ 0.05). Genome analysis revealed 27 genes possibly linked to these phenotypic behaviors. We showed a direct impact of C. acnes on bone cells, providing new explanations about the development of C. acnes foreign-body infections.

Background: During ARDS, CT can reveal two distinct lung imaging patterns, focal or nonfocal, with different responses to positive end-expiratory pressure, recruitment maneuvers, and prone position. Nevertheless, their association with plasma biomarkers and their distinct functional/pathobiological mechanisms are unknown. The objective of this study was to characterize focal and nonfocal patterns of lung CT-based imaging with plasma markers of lung injury., Methods: A prospective multicenter cohort study involving 119 consecutive patients with ARDS. Plasma biomarkers (soluble form of the receptor for advanced glycation end product [sRAGE], plasminogen activator inhibitor-1, soluble intercellular adhesion molecule-1, and surfactant protein-D) were measured within 24 h of ARDS onset. Lung CT scan was performed within the first 48 h to assess lung morphology., Results: Thirty-two (27%) and 87 (73%) patients had focal and nonfocal ARDS, respectively. Plasma levels of sRAGE were significantly higher in nonfocal ARDS, compared with focal ARDS. A cut-off of 1,188 pg/mL differentiated focal from nonfocal ARDS with a sensitivity of 94% and a specificity of 84%. Nonfocal patterns were associated with higher 28- and 90-day mortality than focal patterns (31% vs 12%, P = .038 and 46% vs 21%, P = .026, respectively). Plasma levels of plasminogen activator inhibitor-1 were significantly higher in nonfocal ARDS. There was no difference in other biomarkers., Conclusions: Plasma sRAGE is associated with a nonfocal ARDS. Such novel findings may suggest a role for RAGE pathway in an underlying endotype of impaired alveolar fluid clearance and stimulate future research on the association between ARDS phenotypes and therapeutic responses., (Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Continuous and intermittent noninvasive measurements of arterial blood pressure (BP) have not been compared in the same population. In a large panel of intensive care unit patients, we assessed the agreement between CNAP™ (Continuous Noninvasive Arterial Pressure) finger cuff beat-to-beat monitoring of BP and reference intraarterial measurements. Two automated oscillometric brachial cuff devices were also tested: CNAP brachial cuff (used for CNAP finger cuff calibration) and an alternative device. The performance for detecting hypotension (intraarterial mean BP <65 mm Hg or systolic BP <90 mm Hg), response to therapy (therapy-induced increase in mean BP >10%), and hypertension (intraarterial systolic BP >140 mm Hg) was evaluated. We also assessed the between-calibration drift of CNAP finger cuff BP in specific situations: cardiovascular intervention or no intervention., Methods: With each device, 3 pairs of noninvasive and intraarterial measurements were prospectively collected and analyzed according to current guidelines, the International Organization for Standardization (ISO) standard. The trending ability and drift of the CNAP finger cuff BP were assessed over a 15-minute observation period., Results: In 182 patients, CNAP finger cuff and CNAP brachial cuff readings did not conform to ISO standard requirements (mean bias ± SD exceeding the maximum tolerated 5 ± 8 mm Hg), whereas the alternative automated brachial cuff succeeded for mean and diastolic BP. CNAP finger cuff trending ability was poor (concordance rate <70% over a 15-minute period) owing to a significant drift since calibration, especially if a cardiovascular intervention was performed (n = 75, -7.5 ± 10.2 mm Hg at the 14th minute, ie, before recalibration, versus -2.9 ± 7.9 mm Hg if no cardiovascular intervention occurred, n = 103, P = 0.0008). However, a similar and reliable performance was observed for the detection of hypotension with the CNAP finger cuff (within 4 minutes after calibration) and with the 2 automated brachial cuffs (area under the receiver operating characteristic curve ≥0.91, positive and negative likelihood ratios ≥5 and ≤0.20, respectively). The performance for the detection of response to therapy or of hypertension was slightly lower., Conclusions: In a large population of intensive care unit patients, CNAP did not fulfill the ISO criteria and exhibited a relevant between-calibration drift. However, CNAP measurements collected within 4 minutes after calibration were reliable for detecting hypotension, as were oscillometric devices, while providing beat-to-beat measurements. Interestingly, an alternative automated brachial cuff was more reliable than the native one, used for calibration. This information is important to clinicians using those devices and for further development of the CNAP technology.

Background: Alcohol is the leading psychoactive substance consumed in France, with about 15 million regular consumers. The National institute on Alcohol Abuse and Alcoholism (NIAAA) considers alcohol abuse to be more than 14 units of alcohol a week for men and 7 units for women. The specific complication of alcoholism is the alcohol withdrawal syndrome. Its incidence reaches up to 30 % and its main complications are delirium tremens, restlessness, extended hospital stay, higher morbidity, and psychiatric and cognitive impairment. Without appropriate treatment, delirium tremens can lead to death in up to 50 % of patients., Methods/design: This prospective, double-blind, randomised controlled study versus placebo will be conducted in twelve French intensive care units (ICU). Patients with an alcohol intake level higher than the NIAAA threshold, who are under mechanical ventilation, will be included. The primary objective is to determine whether baclofen is more efficient than placebo in preventing restlessness-related side effects in the ICU. Secondary outcomes include mechanical ventilation duration, length of ICU stay, and cumulative doses of sedatives and painkillers received within 28 days of ICU admission. Restlessness-related side effects in the ICU are defined as unplanned extubation, medical disposal removal (such as urinary catheter, venous or arterial line or surgical drain), falling out of bed, ICU runaway (leaving ICU without physician's approval), immobilisation device removal, self-aggression or aggression towards medical staff. Daily doses of baclofen/placebo will be guided by daily creatinine clearance assessment., Discussion: Restlessness in alcoholic patients is a life-threatening issue in ICUs. BACLOREA is a randomised study assessing the capacity of baclofen to prevent agitation in mechanically ventilated patients. Enrolment of 314 patients will begin in June 2016 and is expected to end in October 2018., Trial Registration: ClinicalTrials.gov Identifier: NCT02723383 , registered on 3 March 2016.

Protein biomarker discovery has inherent challenges linked to the validation of the analytical method used or to the impact of biological matrices. Matrix influences must be mastered to guarantee the reliability of the identified biomarkers to monitor human diseases. In this study, multiplexed mass spectrometry assays in selected reaction monitoring (SRM) mode have been developed to measure 107 inflammatory putative proteins in matched serum and plasma from 36 ICU trauma patients. The assays' validation directly in clinical samples was shown to be valuable to manage intersample variability. Using the validation process developed here, assays were validated for 58 biomarkers in serum, 57 in plasma, and 55 in both matrices. Correlation analyses demonstrated that the quantitation using SRM of most of the validated biomarkers (45/55) was impacted by the biological matrix and that the matrix impact was biomarker-dependent. Among the 45 impacted biomarkers, 23 were nevertheless correlated between serum and plasma, whereas the quantitation was shown to be equivalent in both for the 10 last proteins. Matrix selection using SRM is therefore suggested to be suitable prior to clinical evaluation of biomarkers in a large cohort of patients.

Background: To assess the performance of transcranial Doppler (TCD) in predicting neurologic worsening after mild to moderate traumatic brain injury., Methods: The authors conducted a prospective observational study across 17 sites. TCD was performed upon admission in 356 patients (Glasgow Coma Score [GCS], 9 to 15) with mild lesions on cerebral computed tomography scan. Normal TCD was defined as a pulsatility index of less than 1.25 and diastolic blood flow velocity higher than 25 cm/s in the two middle cerebral arteries. The primary endpoint was secondary neurologic deterioration on day 7., Results: Twenty patients (6%) developed secondary neurologic deterioration within the first posttraumatic week. TCD thresholds had 80% sensitivity (95% CI, 56 to 94%) and 79% specificity (95% CI, 74 to 83%) to predict neurologic worsening. The negative predictive values and positive predictive values of TCD were 98% (95% CI, 96 to 100%) and 18% (95% CI, 11to 28%), respectively. In patients with minor traumatic brain injury (GCS, 14 to 15), the sensitivity and specificity of TCD were 91% (95% CI, 59 to 100%) and 80% (95% CI, 75 to 85%), respectively. The area under the receiver operating characteristic curve of a multivariate predictive model including age and GCS was significantly improved with the adjunction of TCD. Patients with abnormal TCD on admission (n = 86 patients) showed a more altered score for the disability rating scale on day 28 compared to those with normal TCD (n = 257 patients)., Conclusions: TCD measurements upon admission may provide additional information about neurologic outcome after mild to moderate traumatic brain injury. This technique could be useful for in-hospital triage in this context. (Anesthesiology 2016; 125:346-54).

Escherichia coli is one of the first causes of Gram-negative orthopedic implant infections (OII). Those infections, usually hematogenous, mostly originate from the urinary tract. We investigated the strategies developed by E. coli in this context to evade host innate immune responses, i.e. complement and polymorphonuclear neutrophils (PMN). Twenty strains from OII were compared with 20 strains from bacteremia in patients with non-infected orthopedic implant. In both groups, 6/20 (30 %) strains lysed PMNs, due to the production of the pore-forming toxin α-hemolysin (HlyA). For the others, resistance to phagocytic killing by PMN was not significantly different between both groups. In contrast, resistance to complement-mediated serum killing was significantly higher in OII strains than in the others (65 % vs 10 %; P <0.001). In E. coli, different mechanisms have been involved in complement resistance. Here, serum resistance was not linked to a group 2 capsule, or a loss of outer membrane permeability, or the recruitment of the complement inhibitor C4bp, but was significantly associated with the synthesis of long-chain LPS, regardless of the O-antigen. Thus, serum resistance could promote seeding of peri-implant tissues by helping E. coli to either persist in blood and reach the site of infection or overcome localized complement activation.

Issues regarding recommendations on empiric antimicrobial therapy for ventilator-associated pneumonia (VAP) have emerged in specific populations.To develop and validate a score to guide empiric therapy in brain-injured patients with VAP, we prospectively followed a cohort of 379 brain-injured patients in five intensive care units. The score was externally validated in an independent cohort of 252 brain-injured patients and its extrapolation was tested in 221 burn patients.The multivariate analysis for predicting resistance (incidence 16.4%) showed two independent factors: preceding antimicrobial therapy ≥48 h (p<0.001) and VAP onset ≥10 days (p<0.001); the area under the receiver operating characteristic curve (AUC) was 0.822 (95% CI 0.770-0.883) in the learning cohort and 0.805 (95% CI 0.732-0.877) in the validation cohort. The score built from the factors selected in multivariate analysis predicted resistance with a sensitivity of 83%, a specificity of 71%, a positive predictive value of 37% and a negative predictive value of 96% in the validation cohort. The AUC of the multivariate analysis was poor in burn patients (0.671, 95% CI 0.596-0.751).Limited-spectrum empirical antimicrobial therapy has low risk of failure in brain-injured patients presenting with VAP before day 10 and when prior antimicrobial therapy lasts <48 h., (Copyright ©ERS 2016.)

Background: The optimal scheme of thromboprophylaxis in bariatric surgery remains uncertain, because clinical practice is different between countries and randomized trials are lacking., Objectives: The primary objective of this randomized multicenter study was to determine the optimal regimen of enoxaparin providing an antifactor Xa peak activity between .3 and .5 IU/mL at equilibrium and to evaluate the course of procoagulant microparticles (MPs)., Setting: University hospital., Methods: A total of 164 patients scheduled for gastric bypass were allocated to 3 groups (A, B, and C) of enoxaparin treatment (4000, 6000, or 2×4000 IU, respectively). Antifactor Xa activity was measured before and 4 hours after each injection from D0 to D2. Doppler screening of the lower limbs was performed at D1, D9, and D30. Bleeding (BE) and thrombotic events (TE) were recorded during the first postoperative month. Total MPs were measured at D0, D9, and D30. MPs of leucocyte, platelet, and granulocyte origin were assessed in one third of the patients from each group. The 3 groups were compared by ANOVA., Results: A total of 135 patients were analyzed. The equilibrium of antifactor Xa peak levels was obtained 52 hours after the presurgery injection and 12.8%, 56.4%, and 27.3% of the patients reached the target in groups A, B, and C, respectively (P<.001). No TE was detected. BE occurred in 1, 2, and 6 patients in groups A, B, and C, respectively). Total MPs remained unchanged over time. While no significant variation was observed in the other groups, platelet GP1 b(+)-MPs increased (P = .01) at D9 in group C, suggesting an incomplete control of anticoagulation leading to cell activation and procoagulant MP release that was confirmed by the higher MP levels measured at D30 (P = .04). CD66(+)-MPs were also highly elevated at J9 and D30 in group C indicating a granulocyte contribution., Conclusions: This study shows that a single dose of enoxaparin 6000 IU/d allowed most of the patients to reach the target range of antifactor Xa activity without increasing the bleeding risk, with the most likely efficient reduction of procoagulant MPs. (Surg Obes Relat Dis 2015;0:000-000.) © 2015 American Society for Metabolic and Bariatric Surgery. All rights reserved., (Copyright © 2016 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Purpose: Stress cardiomyopathy is a common life-threatening complication after aneurysmal subarachnoid hemorrhage (SAH). We hypothesized that left ventricular (LV) longitudinal strain alterations assessed with speckle tracking could identify early systolic function impairment., Methods: This was an observational single-center prospective pilot controlled study conducted in a neuro-intensive care unit. Forty-six patients with severe SAH with a World Federation of Neurological Surgeons grade (WFNS) ≥ III were included. Transthoracic echocardiography (TTE) was performed on day 1, day 3, and day 7 after the patient's admission. A cardiologist blinded to the patient's management analyzed the LV global longitudinal strain (GLS). The control group comprised normal subjects matched according to gender and age., Results: On day 1 median (25th-75th percentile) GLS was clearly impaired in SAH patients compared to controls [-16.7 (-18.7/-13.7) % versus -20 (-22/-19) %, p < 0.0001], whereas LVEF was preserved [65 (59-70) %]. GLS was severely impaired in patients with a WFNS score of V versus III-IV [-15.6 (-16.9/-12.3) % versus -17.8 (-20.6/-15.8) %, p = 0.008]. Seventeen (37 %) patients had a severe GLS alteration (>- 16 %). In these patients, GLS improved from day 1 [-12.4 (-14.8/-10.9) %] to last evaluation [-16.2 (-19/-14.6) %, p = 0.0007] in agreement with the natural evolution of stress cardiomyopathy., Conclusions: On the basis of LV GLS assessment, we demonstrated for the first time that myocardial alteration compatible with a stress cardiomyopathy is detectable in up to 37 % of patients with severe SAH while LVEF is preserved. GLS could be used for sensitive detection of stress cardiomyopathy. This is critical because cardiac impairment remains a major cause of morbidity and mortality after SAH.

Background: In ICU patients with normal serum creatinine (SCr), a state of increased renal drug excretion has been described (creatinine clearance ≥130 ml/min/1.73 m(2)), and named augmented renal clearance (ARC). In ICU patients, the accuracy of GFR estimates is insufficient. However, in clinical practice, the physician has not at one's disposal patient measured creatinine clearance (CrCl) when prescribing. The primary objective of this study was to assess the accuracy of 4 formulas to estimate GFR (Cockcroft-Gault (CG), Robert, sMDRD, and CKD-EPI formulas) with other covariates to detect ARC in ICU patients., Methods: We enroled 360 consecutive ICU patients with normal SCr in this prospective observational study conducted in a primary teaching hospital. Comparisons between CrCl values and 4 estimated GFR (eGFR) formulas were estimated., Results: In these 360 patients, ARC was observed in 33 % of patients most of them trauma. Individual predictive values of equations were poor and the phenomenon increased in ARC subgroup. CG and CKD-EPI were more accurate to detect an ARC. Multivariable analysis showed that the best-fitting model included 3 factors independently correlated to ARC: trauma patients, cut-off values of age ≤58 years, and CKD-EPI more than 108 ml/min/1.73 m(2)., Conclusions: In ICU patients with normal SCr, eGFR formulas are imprecise in assessing CrCl. If measured CrCl must be ideally used to detect modifications of the renal function, in clinical practice, age, reason for admission, and CKD-EPI could be used as screening tool to identify ARC.

Background: Brain injuries (BI) induce a state of systemic immunosuppression, leading to a high risk of pneumonia. In this pilot study, we investigated the status of B cell compartment in BI patients., Methods: A prospective observational study was performed in 2 intensive care units in a university hospital. Blood samples were collected in 14 patients at day 1 and day 7 after acute BI. The phenotype and the ability of B cells to secrete IL-10 were compared to 11 healthy volunteers (HV)., Results: Among the circulating lymphocytes, the frequency of B cells was significantly higher in BI patients compared to HV (p<0.001). B cells from BI patients displayed an activated profil on day 7 after BI, reflected by a significantly higher proportion of CD27(+) memory (p=0.01) and CD27(+) IgD(-) switched memory B cells (p=0.02), as well as a significantly higher blood level of IgA (p=0.001) and IgM (p<0.001) as compared to day 1. The frequency of IL-10 secreting B cells (IL-10(+) B cells) on day 1 and day 7 was significantly lower in BI patients compared to HV (p<0.05). Interestingly, we observed that all BI patients with high frequency of IL-10(+) B cells on day 1 displayed an episode of pneumonia, and had a longer duration of mechanical ventilation and ICU stay compared to BI patients with low proportion of IL-10(+) B cells., Conclusion: This study provides an extensive description of the phenotype and function of B cells in BI patients. Our results suggest that IL-10(+) B cells could play a major role in immunosuppression after BI., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Escherichia coli is one of the first causes of Gram-negative orthopedic implant infections (OII), but little is known about the pathogenicity of this species in such infections that are increasing due to the ageing of the population. We report how this pathogen interacts with human osteoblastic MG-63 cells in vitro, by comparing 20 OII E. coli strains to two Staphylococcus aureus and two Pseudomonas aeruginosa strains. LDH release assay revealed that 6/20 (30%) OII E. coli induced MG-63 cell lysis whereas none of the four control strains was cytotoxic after 4 h of coculture. This high cytotoxicity was associated with hemolytic properties and linked to hlyA gene expression. We further showed by gentamicin protection assay and confocal microscopy that the non-cytotoxic E. coli were not able to invade MG-63 cells unlike S. aureus strains (internalization rate <0.01% for the non-cytotoxic E. coli versus 8.88 ± 2.31% and 4.60 ± 0.42% for both S. aureus). The non-cytotoxic E. coli also demonstrated low adherence rates (<7%), the most adherent E. coli eliciting higher IL-6 and TNF-α mRNA expression in the osteoblastic cells. Either highly cytotoxic or slightly invasive OII E. coli do not show the same infection strategies as S. aureus towards osteoblasts., (© FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: Cerebral non-invasive monitoring of oxygen saturation by near-infrared spectroscopy (rSO2) during paediatric cardiac surgery is supposed to decrease the risk of neurological complications. Since haemoglobin level is one of the factors changing rSO2, we aimed to explore if rSO2 monitoring influences intra-operative RBC (red blood cell) transfusion threshold and volumes, as well as the duration of ICU stay., Methods: The design was a retrospective analysis involving 91 children less than 2 years of age (including 16 neonates) with a congenital heart disease requiring surgical treatment with or without cardiopulmonary bypass from January 2006 to August 2009. Systematic rSO2 monitoring was introduced after September 2007 (n=56). The independent factors associated with the intra-operative transfusion threshold haemoglobin (Hb) level>9.5g/dL, total volume of intra-operative RBC transfusion<30mL/kg and ICU stay<6 days were identified by multivariate analysis logistic regression. Data were expressed as medians (25-75%)., Results: Cardiac malformations and demographic characteristics were similar in both periods. Two independent factors, weight and rSO2 monitoring, were identified as independent factors associated with the three end-points. The transfusion threshold, total transfusion volume and ICU stay with and without rSO2 were 9.8 (8.9 to 10.3) versus 8.7 (8.2 to 9.6) g/dL (P<0.0001), 20 (14-49) versus 36 (22.5-51.5) mL/kg (P=0.0165) and 5 (3-8) versus 7 (5-10.7) days (P=0.0084), respectively., Conclusion: rSO2 monitoring changed our transfusion strategy with an earlier transfusion but a reduced total RBC volume and decreased the length of ICU stay., (Copyright © 2015 Société française d’anesthésie et de réanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved.)

Background: Since arrhythmia induces irregular pulse waves, it is widely considered to cause flawed oscillometric brachial cuff measurements of blood pressure (BP). However, strong data are lacking. We assessed whether the agreement of oscillometric measurements with intra-arterial measurements is worse during arrhythmia than during regular rhythm., Methods: Among patients of three intensive care units (ICUs), a prospective comparison of three pairs of intra-arterial and oscillometric BP readings was performed among patients with arrhythmia and an arterial line already present. After each inclusion in the arrhythmia group, one patient with regular rhythm was included as a control. International Organization for Standardization (ISO) standard validation required a mean bias <5 (sd 8) mm Hg., Results: In 135 patients with arrhythmia, the agreement between oscillometric and intra-arterial measurements of systolic, diastolic and mean BP was similar to that observed in 136 patients with regular rhythm: for mean BP, similar mean bias [-0.1 (sd 5.2) and 1.9 (sd 5.9) mm Hg]. In both groups, the ISO standard was satisfied for mean and diastolic BP, but not for systolic BP (sd >10 mm Hg) in our ICU population. The ability of oscillometry to detect hypotension (systolic BP <90 mm Hg or mean BP <65 mm Hg), response to therapy (>10% increase in mean BP after cardiovascular intervention) and hypertension (systolic BP >140 mm Hg) was good and similar during arrhythmia and regular rhythm (respective areas under the receiver operating characteristic curves ranging from 0.89 to 0.96, arrhythmia vs regular rhythm between-group comparisons all associated with P>0.3)., Conclusions: Contrary to widespread belief, arrhythmia did not cause flawed automated brachial cuff measurements., (© The Author 2015. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Purpose: Intubation of hypoxemic patients is associated with life-threatening adverse events. High-flow therapy by nasal cannula (HFNC) for preoxygenation before intubation has never been assessed by randomized study. Our objective was to evaluate the efficiency of HFNC for preoxygenation, compared to high fraction-inspired oxygen facial mask (HFFM)., Methods: Multicenter, randomized, open-labelled, controlled PREOXYFLOW trial (NCT 01747109) in six French intensive care units. Acute hypoxemic adults requiring intubation were randomly allocated to HFNC or HFFM. Patients were eligible if PaO2/FiO2 ratio was below 300 mmHg, respiratory rate at least 30/min and if they required FiO2 50% or more to obtain at least 90% oxygen saturation. HFNC was maintained throughout the procedure, whereas HFFM was removed at the end of general anaesthesia induction. Primary outcome was the lowest saturation throughout intubation procedure. Secondary outcomes included adverse events related to intubation, duration of mechanical ventilation and death., Results: A total of 124 patients were randomized. In the intent-to-treat analysis, including 119 patients (HFNC n = 62; HFFM n = 57), the median (interquartile range) lowest saturation was 91.5% (80-96) for HFNC and 89.5% (81-95) for the HFFM group (p = 0.44). There was no difference for difficult intubation (p = 0.18), intubation difficulty scale, ventilation-free days (p = 0.09), intubation-related adverse events including desaturation <80% or mortality (p = 0.46)., Conclusions: Compared to HFFM, HFNC as a preoxygenation device did not reduce the lowest level of desaturation.

Background: In the intensive care unit (ICU), the outcomes of patients with acute mesenteric ischemia (AMI) are poorly documented. This study aimed to determine the risk factors for death in ICU patients with AMI., Methods: A retrospective, observational, non-interventional, multicenter study was conducted in 43 ICUs of 38 public institutions in France. From January 2008 to December 2013, all adult patients with a diagnosis of AMI during their hospitalization in ICU were included in a database. The diagnosis was confirmed by at least one of three procedures (computed tomography scan, gastrointestinal endoscopy, or upon surgery). To determine factors associated with ICU death, we established a logistic regression model. Recursive partitioning analysis was applied to construct a decision tree regarding risk factors and their interactions most critical to determining outcomes., Results: The death rate of the 780 included patients was 58 %. Being older, having a higher sequential organ failure assessment (SOFA) severity score at diagnosis, and a plasma lactate concentration over 2.7 mmol/l at diagnosis were independent risk factors of ICU mortality. In contrast, having a prior history of peripheral vascular disease or an initial surgical treatment were independent protective factors against ICU mortality. Using age and SOFA severity score, we established an ICU mortality score at diagnosis based on the cutoffs provided by recursive partitioning analysis. Probability of survival was statistically different (p < 0.001) between patients with a score from 0 to 2 and those with a score of 3 and 4., Conclusion: Acute mesenteric ischemia in ICU patients was associated with a 58 % ICU death rate. Age and SOFA severity score at diagnosis were risk factors for mortality. Plasma lactate concentration over 2.7 mmol/l was also an independent risk factor, but values in the normal range did not exclude the diagnosis of AMI.

Objective: To evaluate whether the Script Concordance Test (SCT) can discriminate between levels of experience among anesthesiology residents and attending physicians., Study Type: Multicenter (Toulouse, Nantes, Bordeaux and Limoges), prospective, observational study., Patients and Methods: A SCT made of 60 items was used to evaluate "junior residents" (n=60), "senior residents" (n=47) and expert anesthesiologists (n=10)., Results: There were no missing data in our study. Mean scores (±SD) were 69.9 (±6.1), 73.1 (±6.5) and 82.0 (±3.5) out of a potential score of 100 for "junior residents", "senior residents" and expert anesthesiologists, respectively. Results were statistically different between the 3 groups (P=0.001) using the Kruskall-Wallis test. The Cronbach's α score was 0.63., Conclusions: The SCT is a valid and useful tool for discriminating between anesthesia providers with varying levels of experience in anesthesiology. It may be a useful tool for documenting the progression of reasoning during anesthesia residency., (Copyright © 2015 Société française d’anesthésie et de réanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved.)

Speckle-tracking analysis is a new available tool in order to assess left ventricular function in cardiology. Its novelty relies on the technological ability to track natural acoustic markers (known as speckle) within the myocardium during the cardiac cycle. This technology allows the evaluation of myocardium strain during systole and diastole. To date, global longitudinal strain (GLS) has been extensively studied in cardiology. It is now well established that GLS is more sensitive than left ventricular ejection fraction with 2D echocardiography in detecting systolic function impairment. It is also superior to left ventricular ejection fraction in the prediction of major cardio-vascular events. In the intensive care unit (ICU) setting, data are scarce. In experimental model and human studies in septic shock, speckle-tracking analysis suggests that GSL is impaired along with preserved left ventricular ejection fraction. Recent data also suggest that GLS impairment could predict in-ICU mortality in septic shock. In severe subarachnoid haemorrhage patients, speckle-tracking analysis could be more sensitive in detecting stress cardiomyopathy. However, there are many gaps to fill in the critically ill patient. For instance, the influence of mechanical ventilation on GLS is not fully elucidated, and there are, to date, too few data to exactly assess potential GLS alterations on the patient's outcome. Nonetheless, this new tool provides objective and sensitive data with acceptable intra and inter-observer variability and may be of primary interest in the evaluation of left-ventricular systolic function in the ICU.

Background: To determine the strategies of prevention of hospital-acquired pneumonia that reduce mortality in intensive care unit (ICU)., Methods: We followed PRISMA (Preferred Reported Items for Systemic Reviews and Meta-Analyses) guidelines. We searched MEDLINE and the Cochrane Controlled Trials Register (through 10 June 2014) as well as reference lists of articles. We included all randomized controlled trials conducted in critically ill adult patients hospitalized in ICUs and evaluating digestive prophylactic methods (selective digestive decontamination [SDD], acidification of gastric content, early enteral feeding, prevention of microinhalation); circuit prophylactic methods (closed suctioning systems, early tracheotomy, aerosolized antibiotics, humidification, lung secretion drainage, silver-coated endotracheal tubes) or oropharyngeal prophylactic methods (selective oropharyngeal decontamination, patient position, sinusitis prophylaxis, subglottic secretion drainage, tracheal cuff monitoring). One reviewer extracted data that were checked by 3 others. The primary outcome was the mortality rate in the ICU., Results: We identified 157 randomized trials to pool in a meta-analysis. The primary outcome was available in 145 studies (n = 37 156). The risk ratio (RR) for death was 0.95 (95% confidence interval [CI], .92-.99; P = .02) in the intervention groups. In subgroup analysis, only SDD significantly decreased mortality compared with control (n = 10 227; RR, 0.84 [95% CI, .76-.92; P < .001]). The RR for in-ICU death was 0.78 (95% CI, .69-.89; P < .001; I(2) = 33%) in trials investigating SDD with systemic antimicrobial therapy and 1.00 (.84-1.21; P = .96; I(2) = 0%) without systemic antimicrobial therapy., Conclusions: Selective digestive decontamination with systemic antimicrobial therapy reduced mortality and should be considered in critically ill patients at high risk for death., (© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Context and Aims: Little is known about onset and duration of sciatic block after 0.5% levobupivacaine (Levo) versus 0.5% ropivacaine (Ropi) for ultrasound-guided technique. We assessed these parameters in the ultrasound-guided block, to know for the practice., Setting and Design: A comparative randomized double-blind study was conducted in the University Hospital., Materials and Methods: Were included 35 adults of ASA I-II, scheduled for foot surgery, presenting clear imaging of their sciatic nerve at mid-thigh. A volume of 20 mL of either 0.5% Levo or 0.5% Ropi were injected around the sciatic nerve at mid-thigh using ultrasound guidance (out of the plane) followed by placement of a catheter to use, if necessary, for perioperative analgesia. A femoral single shot block was systematically performed to block the saphenous nerve. The onset times until complete foot block (primary outcome) and the sensory and motor block duration (secondary outcome) were assessed using Wilcoxon test. Values were expressed as medians (1(st)-3(rd) quartile)., Results: Except for two delayed sciatic blocks in each group, the onset time otherwise was 35 min (20-60) in Ropi versus 40 min (30-60) in Levo, P = 0.5. Sensory block lasted longer in Levo, 17 h (14-27) compared with 15 h (10-17) in Ropi, P = 0.04. No significant between-group difference was found with motor block durations, 15 h (12-18) in Levo and 15 h (12-16) in Ropi, P = 0.3., Conclusion: No difference of onset times was found in ultrasound-guided sciatic block whether using Levo or Ropi. Levo induced a longer-lasting sensory block.

Tuberculosis remains a major health problem due to the emergence of drug-resistant strains of Mycobacterium tuberculosis. Some models have provided valuable information about drug resistance and efficacy; however, the translation of these results into effective human treatments has mostly proven unsuccessful. In this study, we adapted high-content screening (HCS) technology to investigate the activities of antitubercular compounds in the context of an in vitro granuloma model. We observed significant shifts in the MIC50s between the activities of the compounds under extracellular and granuloma conditions., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

Background: Nutritional support is crucial to the management of patients receiving invasive mechanical ventilation (IMV) and the most commonly prescribed treatment in intensive care units (ICUs). International guidelines consistently indicate that enteral nutrition (EN) should be preferred over parenteral nutrition (PN) whenever possible and started as early as possible. However, no adequately designed study has evaluated whether a specific nutritional modality is associated with decreased mortality. The primary goal of this trial is to assess the hypothesis that early first-line EN, as compared to early first-line PN, decreases day 28 all-cause mortality in patients receiving IMV and vasoactive drugs for shock., Methods/design: The NUTRIREA-2 study is a multicenter, open-label, parallel-group, randomized controlled trial comparing early PN versus early EN in critically ill patients requiring IMV for an expected duration of at least 48 hours, combined with vasoactive drugs, for shock. Patients will be allocated at random to first-line PN for at least 72 hours or to first-line EN. In both groups, nutritional support will be started within 24 hours after IMV initiation. Calorie targets will be 20 to 25 kcal/kg/day during the first week, then 25 to 30 kcal/kg/day thereafter. Patients receiving PN may be switched to EN after at least 72 hours in the event of shock resolution (no vasoactive drugs for 24 consecutive hours and arterial lactic acid level below 2 mmol/L). On day 7, all patients receiving PN and having no contraindications to EN will be switched to EN. In both groups, supplemental PN may be added to EN after day 7 in patients with persistent intolerance to EN and inadequate calorie intake. We plan to recruit 2,854 patients at 44 participating ICUs., Discussion: The NUTRIREA-2 study is the first large randomized controlled trial designed to assess the hypothesis that early EN improves survival compared to early PN in ICU patients. Enrollment started on 22 March 2013 and is expected to end in November 2015., Trial Registration: ClinicalTrials.gov Identifier: NCT01802099 (registered 27 February 2013).

Objectives: Stroke is a well-described postoperative complication, after carotid and cardiac surgery. On the contrary, few studies are available concerning postoperative stroke in general non-cardiac non-carotid surgery. The high morbid-mortality of stroke justifies an extended analysis of recent literature., Article Type: Systematic review., Data Sources: Firstly, Medline and Ovid databases using combination of stroke, cardiac surgery, carotid surgery, general non-cardiac non-carotid surgery as keywords; secondly, national and European epidemiologic databases; thirdly, expert and French health agency recommendations; lastly, reference book chapters., Results: In cardiac surgery, with an incidence varying from 1.2 to 10% according to procedure complexity, stroke occurs peroperatively in 50% of cases and during the first 48 postoperative hours for the others. The incidence of stroke after carotid surgery is 1 to 20% according to the technique used as well as operator skills. Postoperative stroke is a rare (0.15% as mean, extremes around 0.02 to 1%) complication in general surgery, it occurs generally after the 24-48th postoperative hours, exceptional peroperatively, and 40% of them occurring in the first postoperative week. It concerned mainly aged patient in high-risk surgeries (hip fracture, vascular surgery). Postoperative stroke was associated to an increase in perioperative mortality in comparison to non-postoperative stroke operated patients., Conclusion: Postoperative stroke is a quality marker of the surgical teams' skill and has specific onset time and induces an increase of postoperative mortality., (Copyright © 2014 Société française d’anesthésie et de réanimation (Sfar). Published by Elsevier SAS. All rights reserved.)

Objective: Trauma induces a state of immunosuppression, which is responsible for the development of nosocomial infections. Hydrocortisone reduces the rate of pneumonia in patients with trauma. Because alterations of dendritic cells and natural killer cells play a central role in trauma-induced immunosuppression, we investigated whether hydrocortisone modulates the dendritic cell/natural killer cell cross talk in the context of posttraumatic pneumonia., Design: Experimental study., Settings: Research laboratory from an university hospital., Subjects: Bagg Albino/cJ mice (weight, 20-24 g)., Interventions: First, in an a priori substudy of a multicenter, randomized, double-blind, placebo-controlled trial of hydrocortisone (200 mg/d for 7 d) in patients with severe trauma, we have measured the blood levels of five cytokines (tumor necrosis factor-α, interleukin-6, interleukin-10, interleukin-12, interleukin-17) at day 1 and day 8. In a second step, the effects of hydrocortisone on dendritic cell/natural killer cell cross talk were studied in a mouse model of posttraumatic pneumonia. Hydrocortisone (0.6 mg/mice i.p.) was administered immediately after hemorrhage. Twenty-four hours later, the mice were challenged with Staphylococcus aureus (7 × 10 colony-forming units)., Measurements and Main Results: Using sera collected during a multicenter study in patients with trauma, we found that hydrocortisone decreased the blood level of interleukin-10, a cytokine centrally involved in the regulation of dendritic cell/natural killer cell cluster. In a mouse model of trauma-hemorrhage-induced immunosuppression, splenic natural killer cells induced an interleukin-10-dependent elimination of splenic dendritic cell. Hydrocortisone treatment reduced this suppressive function of natural killer cells and increased survival of mice with posthemorrhage pneumonia. The reduction of the interleukin-10 level in natural killer cells by hydrocortisone was partially dependent on the up-regulation of glucocorticoid-induced tumor necrosis factor receptor-ligand (TNFsf18) on dendritic cell., Conclusions: These data demonstrate that trauma-induced immunosuppression is characterized by an interleukin-10-dependent elimination of dendritic cell by natural killer cells and that hydrocortisone improves outcome by limiting this immunosuppressive feedback loop.

Introduction: Prevalence of iron deficiency (ID) at intensive care (ICU) admission is around 25 to 40%. Blood losses are important during ICU stay, leading to iron losses, but prevalence of ID at ICU discharge is unknown. ID has been associated with fatigue and muscular weakness, and may thus impair post-ICU rehabilitation. This study assessed ID prevalence at ICU discharge, day 28 (D28) and six months (M6) after and its relation with fatigue., Methods: We conducted this prospective, multicenter observational study at four University hospitals ICUs. Anemic (hemoglobin (Hb) less than 13 g/dL in male and less than 12 g/dL in female) critically ill adult patients hospitalized for at least five days had an iron profile taken at discharge, D28 and M6. ID was defined as ferritin less than 100 ng/L or less than 300 ng/L together with a transferrin saturation less than 20%. Fatigue was assessed by numerical scale and the Multidimensional Fatigue Inventory-20 questionnaire at D28 and M6 and muscular weakness by a hand grip test at ICU discharge., Results: Among 107 patients (men 77%, median (IQR) age 63 (48 to 73) years) who had a complete iron profile at ICU discharge, 9 (8.4%) had ID. At ICU discharge, their hemoglobin concentration (9.5 (87.7 to 10.3) versus 10.2 (92.2 to 11.7) g/dL, P =0.09), hand grip strength (52.5 (30 to 65) versus 49.5 (15.5 to 67.7)% of normal value, P =0.61) and visual analog scale fatigue scale (57 (40 to 80) versus 60 (47.5 to 80)/100, P =0.82) were not different from non-ID patients. At D28 (n =80 patients) and M6 (n =78 patients), ID prevalence increased (to 25 and 35% respectively) while anemia prevalence decreased (from 100% to 80 and 25% respectively, P <0.0001). ID was associated with increased fatigue at D28, after adjustment for main confounding factors, including anemia (regression coefficient (95%CI), 3.19 (0.74 to 5.64), P =0.012). At M6, this association disappeared., Conclusions: The prevalence of ID increases from 8% at discharge to 35% six months after prolonged ICU stay (more than five days). ID was associated with increased fatigue, independently of anemia, at D28.

Introduction: Hyperglycemia is a marker of poor prognosis in severe brain injuries. There is currently little data regarding the effects of intensive insulin therapy (IIT) on neurological recovery., Methods: A sub-group analysis of the randomized-controlled CGAO-REA study (NCT01002482) in surgical intensive care units (ICU) of two university hospitals. Patients with severe brain injury, with an expected ICU length of stay ≥ 48 hours were included. Patients were randomized between a conventional glucose management group (blood glucose target between 5.5 and 9 mmol.L(-1)) and an IIT group (blood glucose target between 4.4 and 6 mmol.L(-1)). The primary outcome was the day-90 neurological outcome evaluated with the Glasgow outcome scale., Results: A total of 188 patients were included in this analysis. In total 98 (52%) patients were randomized in the control group and 90 (48%) in the IIT group. The mean Glasgow coma score at baseline was 7 (± 4). Patients in the IIT group received more insulin (130 (68 to 251) IU versus 74 (13 to 165) IU in the control group, P = 0.01), had a significantly lower morning blood glucose level (5.9 (5.1 to 6.7) mmol.L(-1) versus 6.5 (5.6 to 7.2) mmol.L(-1), P <0.001) in the first 5 days after ICU admission. The IIT group experienced more episodes of hypoglycemia (P < 0.0001). In the IIT group 24 (26.6%) patients had a favorable neurological outcome (good recovery or moderate disability) compared to 31 (31.6%) in the control group (P = 0.4). There were no differences in day-28 mortality. The occurrence of hypoglycemia did not influence the outcome., Conclusions: In this sub-group analysis of a large multicenter randomized trial, IIT did not appear to alter the day-90 neurological outcome or ICU morbidity in severe brain injured patients or ICU morbidity.

Background: Hospital-acquired pneumonia is common after traumatic brain injury, and might be partly a result of traumatic brain injury-induced adrenal insufficiency. We tested the efficacy of low-dose hydrocortisone with fludrocortisone for the prevention of hospital-acquired pneumonia., Methods: We did this double-blind, phase 3, placebo-controlled trial in 19 intensive care units in France. We enrolled patients aged 15-65 years in the first 24 h after severe traumatic brain injury (Glasgow coma scale score ≤8 and trauma-associated lesion on brain CT scan). Patients were randomly assigned (1:1; fixed blocks of 12, stratified by centre and mechanism, Glasgow coma scale, age, and arterial pressure [MGAP] score) to receive either hydrocortisone (200 mg per day tapered) and fludrocortisone (50 μg tablet once per day) or matching placebo for 10 days. Before receiving study drug, adrenal function was assessed with a short corticotropin test. Treatment was stopped if patients had no adrenal insufficiency. The primary outcome was the occurrence of hospital-acquired pneumonia within 28 days after randomisation. We did an intention-to-treat analysis and a modified intention-to-treat analysis including only patients with adrenal insufficiency (adjusted for etomidate use). This study is registered with ClinicalTrials.gov, number NCT01093261., Findings: From Sept 1, 2010, to Nov 29, 2012, we enrolled 336 patients (168 assigned to each group). Eight patients withdrew consent. At day 28, 74 of 165 patients (45%) in the steroid group and 87 of 163 (53%) in the placebo group had developed one or more episodes of hospital-acquired pneumonia (hazard ratio [HR] 0.75; 95% CI 0.55-1.03, p=0.07). In intention-to-treat analysis, we recorded 86 episodes of hospital-acquired pneumonia in the steroid group versus 110 in the placebo group (median 0, IQR 0-1 vs median 1, IQR 0-1 cases per patient, p=0.07). In modified intention-to-treat analyses, the HR for hospital-acquired pneumonia with steroids versus placebo was 0.80 (95% CI 0.56-1.14, p=0.22) in patients with adrenal insufficiency, and, in an exploratory preplanned analysis, 0·48 (0·23-1·01; p=0·05) in patients with normal adrenal function. We recorded no adverse events related to treatment., Interpretation: Low-dose hydrocortisone with fludrocortisone did not improve the outcome of patients with traumatic brain injury. However, the study was underpowered because the proportion of patients with hospital-acquired pneumonia in the placebo group was lower than expected. The results were close to statistical significance for efficacy, meaning that further studies are therefore needed., Funding: Société Française d'Anesthésie Réanimation., (Copyright © 2014 Elsevier Ltd. All rights reserved.)