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Background Chest injuries are associated with mortality among patients admitted to the intensive care unit (ICU) and require multimodal pain management strategies, including regional anesthesia (RA). We conducted a survey to determine the current practices of physicians working in ICUs regarding RA for the management of chest trauma in patients with multiple traumas. Methods An online questionnaire was sent to medical doctors (n = 1230) working in French ICUs, using the Societe Francaise d'Anesthesie Reanimation (SFAR) mailing list of its members. The questionnaire addressed 3 categories: general characteristics, practical aspects of RA, and indications and contraindications. Results Among the 333 respondents (response rate = 27%), 78% and 40% of 156 respondents declared that they would consider using thoracic epidural analgesia (TEA) and thoracic paravertebral blockade (TPB), respectively. The main benefits declared for performing RA were the ability to have effective analgesia, a more effective cough, and early rehabilitation. For 70% of the respondents, trauma patients with a theoretical indication of RA did not receive TEA or TPB for the following reasons: the ICU had no experience of RA (62%), no anesthesiologist-intensivist working in the ICU (46%), contraindications (27%), ignorance of the SFAR guidelines (19%), and no RA protocol available (13%). In this survey, 95% of the respondents thought the prognosis of trauma patients could be influenced by the use of RA. Conclusions While TEA and TPB are underused because of several limitations related to the patterns of injuries in multitrauma patients, lack of both experience and confidence in combination with the absence of available protocols appear to be the major restraining factors, even if physicians are aware that patients' outcomes could be improved by RA. These results suggest the need to strengthen initial training and provide continuing education about RA in the ICU.

Resume La survenue d’une insuffisance respiratoire aigue (IRA), notamment hypoxemique, est frequente apres une chirurgie thoraco-abdominale majeure. L’anesthesie, la douleur postoperatoire et la chirurgie ont des repercussions respiratoires : syndrome restrictif et dysfonction du diaphragme qui sont a l’origine de l’hypoxemie et du developpement d’atelectasies. L’incidence des complications respiratoires augmente en fonction de facteurs de risque lies aux patients (âge > 60 ans, classe American Society of Anesthesiologists (ASA) 2 ou plus, obesite, dependance fonctionnelle, insuffisance cardiaque congestive, bronchopneumopathie chronique obstructive). Plusieurs etudes ont montre que l’intubation et la mise sous ventilation mecanique invasive etaient associees a une surmortalite en cas de complications pulmonaires postoperatoires. La ventilation non invasive (VNI) permet de delivrer une assistance ventilatoire tout en s’affranchissant de la mise en place d’une sonde endotracheale. En postoperatoire, la VNI ameliore les echanges gazeux, diminue le travail respiratoire et les atelectasies. L’interet de son utilisation est bien etabli pour eviter la survenue de l’IRA postoperatoire (VNI prophylactique) ou pour la traiter et eviter l’intubation (VNI curative).

The plasma soluble receptor for advanced glycation end-products (sRAGE) is a marker of lung epithelial injury with prognostic value when measured at baseline in acute respiratory distress syndrome (ARDS). However, whether changes in plasma sRAGE could inform prognosis in ARDS remains unknown. In this secondary analysis of the Lung Imaging for Ventilator Setting in ARDS (LIVE) multicenter randomized controlled trial, which evaluated a personalized ventilation strategy tailored to lung morphology, plasma sRAGE was measured upon study entry (baseline) and on days one, two, three, four and six. The association between changes in plasma sRAGE over time and 90-day survival was evaluated. Higher baseline plasma sRAGE (HR per-one log increment, 1.53, 95% CI, 1.16–2.03, p = 0.003) and an increase in sRAGE over time (HR for each one-log increment in plasma sRAGE per time unit, 1.01, 95% CI, 1.01–1.02, p &lt, 10−3) were both associated with increased 90-day mortality. Each 100-unit increase in the plasma sRAGE level per unit of time increased the risk of death at day 90 by 1% in joint modeling. Plasma sRAGE increased over time when a strategy of maximal alveolar recruitment was applied in patients with focal ARDS. Current findings suggest that the rate of change in plasma sRAGE over time is associated with 90-day survival and could be helpful as a surrogate outcome in ARDS.

Background Current intensive care unit (ICU) sedation guidelines recommend strategies using non-benzodiazepine sedatives. This survey was undertaken to explore inhaled ICU sedation practice in France. Methods In this national survey, medical directors of French adult ICUs were contacted by phone or email between July and August 2019. ICU medical directors were questioned about the characteristics of their department, their knowledge on inhaled sedation, and practical aspects of inhaled sedation use in their department. Results Among the 374 ICUs contacted, 187 provided responses (50%). Most ICU directors (73%) knew about the use of inhaled ICU sedation and 21% used inhaled sedation in their unit, mostly with the Anaesthetic Conserving Device (AnaConDa, Sedana Medical). Most respondents had used volatile agents for sedation for Conclusion This survey highlights the widespread knowledge about inhaled ICU sedation in France but shows its limited use to date. Differences in education and knowledge, as well as the recent and relatively scarce literature on the use of volatile agents in the ICU, might explain the diverse practices that were observed. The low rate of mild adverse effects, as perceived by respondents, and the users’ satisfaction, are promising for this potentially important tool for ICU sedation.

International audience; Acute respiratory distress syndrome (ARDS) is a common cause of hypoxemic respiratory failure and death in critically ill patients, and there is an urgent need to find effective therapies. Preclinical studies have shown that inhaled halogenated agents may have beneficial effects in animal models of ARDS. The development of new devices to administer halogenated agents using modern intensive care unit (ICU) ventilators has significantly simplified the dispensing of halogenated agents to ICU patients. Because previous experimental and clinical research suggested potential benefits of halogenated volatiles, such as sevoflurane or isoflurane, for lung alveolar epithelial injury and inflammation, two pathophysiologic landmarks of diffuse alveolar damage during ARDS, we designed an animal model to understand the mechanisms of the effects of halogenated agents on lung injury and repair. After general anesthesia, tracheal intubation, and the initiation of mechanical ventilation, ARDS was induced in piglets via the intratracheal instillation of hydrochloric acid. Then, the piglets were sedated with inhaled sevoflurane or isoflurane using an ICU-type device, and the animals were ventilated with lung-protective mechanical ventilation during a 4 h period. During the study period, blood and alveolar samples were collected to evaluate arterial oxygenation, the permeability of the alveolar-capillary membrane, alveolar fluid clearance, and lung inflammation. Mechanical ventilation parameters were also collected throughout the experiment. Although this model induced a marked decrease in arterial oxygenation with altered alveolar-capillary permeability, it is reproducible and is characterized by a rapid onset, good stability over time, and no fatal complications. We have developed a piglet model of acid aspiration that reproduces most of the physiological, biological, and pathological features of clinical ARDS, and it will be helpful to further our understanding of the potential lung-protective effects of halogenated agents delivered through devices used for inhaled ICU sedation.

Background Subphenotypes were recently reported within clinical acute respiratory distress syndrome (ARDS), with distinct outcomes and therapeutic responses. Experimental models have long been used to mimic features of ARDS pathophysiology, but the presence of distinct subphenotypes among preclinical ARDS remains unknown. This review will investigate whether: 1) subphenotypes can be identified among preclinical ARDS models; 2) such subphenotypes can identify some responsive traits. Methods We will include comparative preclinical (in vivo and ex vivo) ARDS studies published between 2009 and 2019 in which pre-specified therapies were assessed (interleukin (IL)-10, IL-2, stem cells, beta-agonists, corticosteroids, fibroblast growth factors, modulators of the receptor for advanced glycation end-products pathway, anticoagulants, and halogenated agents) and outcomes compared to a control condition. The primary outcome will be a composite of the four key features of preclinical ARDS as per the American Thoracic Society consensus conference (histologic evidence of lung injury, altered alveolar-capillary barrier, lung inflammatory response, and physiological dysfunction). Secondary outcomes will include the single components of the primary composite outcome, net alveolar fluid clearance, and death. MEDLINE, Embase, and Cochrane databases will be searched electronically and data from eligible studies will be extracted, pooled, and analyzed using random-effects models. Individual study reporting will be assessed according to the Animal Research: Reporting of In Vivo Experiments guidelines. Meta-regressions will be performed to identify subphenotypes prior to comparing outcomes across subphenotypes and treatment effects. Discussion This study will inform on the presence and underlying pathophysiological features of subphenotypes among preclinical models of ARDS and should help to determine whether sufficient evidence exists to perform preclinical trials of subphenotype-targeted therapies, prior to potential clinical translation. Systematic review registration PROSPERO (ID: CRD42019157236).

Background The Radiographic Assessment of Lung Edema (RALE) score is associated with the severity of ARDS, and treatments targeted at reducing pulmonary edema such as conservative fluid management cause a reduction in RALE score over time. Research Question Are early changes in RALE score over time associated with survival in patients with ARDS? Study Design and Methods Data from patients enrolled in three centers in the Lung Imaging for Ventilation sEtting in ARDS (LIVE) trial with available chest radiographs at baseline (day 0) and days 2 or 3 were used. The RALE was scored by two independent reviewers. The primary end point was death by day 90, considering RALE score both at baseline and as a time-varying covariate in a marginal Cox survival model. Results RALE was scored from 135, 64, and 88 radiographs on days 0, 2, and 3, respectively. Both baseline RALE (hazard ratio [HR] for each one-point increment, 1.04; 95% CI, 1.01-1.08; P = .006) and the change in RALE over time (HR for each one-point decrease per unit of time, 0.99; 95% CI, 0.99-0.99; P = .03) were associated with death by day 90, even after adjustment for age, sex, BMI, Simplified Acute Physiology Score II, vasopressor use, and total volume of fluids received since study entry. Interpretation The change in RALE during the first days after ARDS onset is independently associated with survival and may be useful as a surrogate end point in future clinical trials of new therapeutics in ARDS.

International audience; Re-epithelialization of the alveolar surface is a key process of lung alveolar epithelial barrier repair after acute lung injury. The receptor for advanced glycation end-products (RAGE) pathway plays key roles in lung homeostasis, and its involvement in wound repair has been already reported in human bronchial epithelial cells. However, its effects on lung alveolar epithelial repair after injury remain unknown. We investigated whether RAGE stimulation with its ligands high-mobility group box 1 protein (HMGB1) or advanced glycation end-products (AGEs), alone or associated with RAGE inhibition using RAGE antagonist peptide, affects in vitro wound healing in human alveolar epithelial A549 cells. We further asked whether these effects could be associated with changes in cell proliferation and migration. We found that treatment of A549 cells with HMGB1 or AGEs promotes RAGE-dependent wound healing after a scratch assay. In addition, both RAGE ligands increased cell proliferation in a RAGE-dependent manner. Treatment with HMGB1 increased migration of alveolar epithelial cells at 12 h, independently of RAGE, whereas AGEs stimulated migration as measured 48 h after injury in a RAGE-dependent manner. Taken together, these results suggest that RAGE pathway is involved in lung alveolar epithelial wound repair, possibly through enhanced cell migration and proliferation.

Preclinical studies have shown that volatile anesthetics may have beneficial effects on injured lungs, and pilot clinical data support improved arterial oxygenation, attenuated inflammation, and decreased lung epithelial injury in patients with acute respiratory distress syndrome (ARDS) receiving inhaled sevoflurane compared to intravenous midazolam. Whether sevoflurane is effective in improving clinical outcomes among patients with ARDS is unknown, and the benefits and risks of inhaled sedation in ARDS require further evaluation. Here, we describe the SESAR (Sevoflurane for Sedation in ARDS) trial designed to address this question. SESAR is a two-arm, investigator-initiated, multicenter, prospective, randomized, stratified, parallel-group clinical trial with blinded outcome assessment designed to test the efficacy of sedation with sevoflurane compared to intravenous propofol in patients with moderate to severe ARDS. The primary outcome is the number of days alive and off the ventilator at 28 days, considering death as a competing event, and the key secondary outcome is 90 day survival. The planned enrollment is 700 adult participants at 37 French academic and non-academic centers. Safety and long-term outcomes will be evaluated, and biomarker measurements will help better understand mechanisms of action. The trial is funded by the French Ministry of Health, the European Society of Anaesthesiology, and Sedana Medical.

BackgroundThe receptor for advanced glycation end products (RAGE) modulates the pathogenesis of acute respiratory distress syndrome (ARDS). RAGE inhibition was recently associated with attenuated lung injury and restored alveolar fluid clearance (AFC) in a mouse model of ARDS. However, clinical translation will first require assessment of this strategy in larger animals.MethodsForty-eight anaesthetised Landrace piglets were randomised into a control group and three treatment groups. Animals allocated to treatment groups underwent orotracheal instillation of hydrochloric acid i) alone; ii) in combination with intravenous administration of a RAGE antagonist peptide (RAP), a S100P-derived peptide that prevents activation of RAGE by its ligands, or iii) in combination with intravenous administration of recombinant soluble (s)RAGE that acted as a decoy receptor. The primary outcome measure was net AFC at 4 h. Arterial oxygenation was assessed hourly for 4 h and alveolar-capillary permeability, alveolar inflammation, lung histology and lung mRNA expression of the epithelial sodium channel (α1-ENaC), α1-Na,K-ATPase and aquaporin (AQP)-5 were assessed at 4 h.FindingsTreatment with either RAP or sRAGE improved net AFC rates (median [interquartile range], 21.2 [18.8–21.7] and 19.5 [17.1–21.5] %/h, respectively, versus 12.6 [3.2–18.8] %/h in injured, untreated controls), improved oxygenation and decreased alveolar inflammation and histological evidence of tissue injury after acid-induced ARDS. RAGE inhibition also restored lung mRNA expression of α1-Na,K-ATPase and AQP-5.InterpretationRAGE inhibition restored AFC and attenuated lung injury in a piglet model of acid-induced ARDS.FundingAuvergne Regional Council, Agence Nationale de la Recherche, Direction Générale de l’Offre de Soins.Research in ContextEvidence before this studyThe acute respiratory distress syndrome (ARDS), a clinical syndrome of diffuse pulmonary oedema and inflammation, currently lacks effective therapies and is associated with high mortality and morbidity. The degrees of lung epithelial injury and of alveolar fluid clearance (AFC) impairment, as evaluated by plasma levels of soluble receptor for glycation end-products (RAGE), are major prognostic factors in ARDS and potential therapeutic targets for ongoing research. For example, targeting RAGE with recombinant sRAGE or an anti-RAGE monoclonal antibody has proven beneficial in a translational mouse model of acid-induced ARDS.Added value of this studyIn a piglet model of acid-induced ARDS, treatment with RAGE antagonist peptide or recombinant sRAGE restored AFC and attenuated the features of lung injury, thereby confirming, in the closest evolutionary model species to humans, previous evidence from rodent models that modulation of RAGE may be a therapeutic option for ARDS. Although this is an important step towards future clinical translation, future studies should assess the best methods to modulate RAGE and further confirm the safety of manipulating this pathway in patients with ARDS.

International audience; Acute respiratory distress syndrome (ARDS) is heterogeneous by definition and patient response varies depending on underlying biology and their severity of illness. Although ARDS subtypes have been identified with different prognoses in past studies, the concept of phenotypes or endotypes does not extend to the clinical definition of ARDS. This has possibly hampered the development of therapeutic interventions that target select biological mechanisms of ARDS. Recently, a major advance may have been achieved as it may now be possible to identify ARDS subtypes that may confer different responses to therapy. The aim of personalised medicine is to identify, select, and test therapies that are most likely to be associated with a favourable outcome in a specific patient. Several promising approaches to ARDS subtypes capable of predicting therapeutic response, and not just prognosis, are highlighted in this perspective paper. An overview is also provided of current and future directions regarding the provision of personalised ARDS medicine. The importance of delivering the right care, at the right time, to the right patient, is emphasised.

International audience

Levels of the soluble form of the receptor for advanced glycation end-products (sRAGE) are elevated during acute respiratory distress syndrome (ARDS) and correlate with severity and prognosis. Alveolar fluid clearance (AFC) is necessary for the resolution of lung edema but is impaired in most patients with ARDS. No reliable marker of this process has been investigated to date.To verify whether sRAGE could predict AFC during ARDS.Anesthetized CD-1 mice underwent orotracheal instillation of hydrochloric acid. At specified time points, lung injury was assessed by analysis of blood gases, alveolar permeability, lung histology, AFC, and plasma/bronchoalveolar fluid measurements of proinflammatory cytokines and sRAGE. Plasma sRAGE and AFC rates were also prospectively assessed in 30 patients with ARDS.The rate of AFC was inversely correlated with sRAGE levels in the plasma and the bronchoalveolar fluid of acid-injured mice (Spearman's ρ = -0.73 and -0.69, respectively; P 10(-3)), and plasma sRAGE correlated with AFC in patients with ARDS (Spearman's ρ = -0.59; P 10(-3)). Similarly, sRAGE levels were significantly associated with lung injury severity, and decreased over time in mice, whereas AFC was restored and lung injury resolved.Our results indicate that sRAGE levels could be a reliable predictor of impaired AFC during ARDS, and should stimulate further studies on the pathophysiologic implications of RAGE axis in the mechanisms leading to edema resolution. Clinical trial registered with www.clinicaltrials.gov (NCT 00811629).

Introduction Le recepteur des produits de glycation avancee (RAGE) exprime a la surface des pneumocytes de type 1 joue un role dans la pathogenie du syndrome de detresse respiratoire aigue (SDRA). sRAGE est sa forme soluble et est un marqueur de la severite de l’atteinte pulmonaire. L’administration intraperitoneale d’une forme recombinante de sRAGE ameliore les lesions alveolaires dans un modele murin de SDRA. L’administration d’anticorps anti-RAGE ameliore la survie dans un modele murin de sepsis. Toutefois, la multiplicite des modeles experimentaux n’a permis a ce jour d’evaluer ni les effets biologiques ni l’efficacite de la modulation de RAGE au cours d’une agression alveolaire directe. Materiel et methodes La lesion alveolaire est evaluee chez des souris anesthesiees ayant subi une instillation d’acide chlorhydrique (HCl) ou non (SHAM) (n = 6–8 par groupe et par temps). L’atteinte pulmonaire est evaluee le jour de l’instillation (j0) puis a j1, j2 et j4, apres une periode de ventilation mecanique standardisee, sur des caracteristiques majeures du SDRA : l’hypoxemie, la reponse inflammatoire alveolaire et l’alteration de la permeabilite alveolocapillaire. Les effets d’une inhibition de l’activation de RAGE sont evalues sur ces criteres apres administration d’une forme recombinante de sRAGE ou d’un anticorps monoclonal anti-RAGE. Resultats L’instillation d’HCl s’accompagne d’un index de permeabilite alveolaire significativement plus eleve a j1 (20,2 [4,8–32,8] %) et j2 (10,4 [5,4–14,1] %) que dans le groupe SHAM (1,3 [0,4–1,9] %) (p Fig. 1 ). Discussion Une strategie d’inhibition de RAGE, par anticorps monoclonal anti-RAGE ou sRAGE recombinant, s’accompagne dans notre modele murin translationnel de lesion epitheliale directe d’une amelioration de l’oxygenation arterielle associee a une diminution de l’inflammation et de la permeabilite alveolaires. Les modalites therapeutiques d’une inhibition de RAGE, ainsi que la capacite de translation clinique de ces resultats preliminaires, restent toutefois a preciser.

Introduction Le recepteur des produits de glycation avancee (RAGE) est un recepteur transmembranaire exprime a la surface des pneumocytes de type I dont l’activation semble fortement impliquee dans l’atteinte pulmonaire du syndrome de detresse respiratoire aigue (SDRA) [1] , [2] . Il a ete recemment montre que RAGE participait a la resorption de l’œdeme alveolaire en modulant la clairance alveolaire liquidienne (AFC, pour alveolar fluid clearance) par l’intermediaire des canaux ENaC [3] . L’objectif de notre travail etait de determiner si une inhibition de la voie RAGE regulait l’AFC dans un modele murin de SDRA par lesion epitheliale directe. Materiel et methodes Etude experimentale animale sur 60 souris mâles C57BL/6JT reparties en 4 groupes : trois groupes subissant une instillation intratracheale d’acide chlorhydrique et un groupe temoin « SHAM ». Les groupes instilles par l’acide chlorhydrique etaient divisees en un groupe « HCl » subissant une instillation seule d’acide chlorhydrique, un groupe « mAb » recevant en plus un traitement intraveineux par anticorps monoclonal anti-RAGE et un groupe « R », recevant en plus un traitement intraperitoneal par proteine sRAGE recombinante. j0 determinait le jour de l’instillation et du traitement pour les groupes mAb et R. A des temps specifiques (j0, j1, j2, j4), les souris recevaient, sous anesthesie generale, une instillation intratracheale d’albumine bovine avant d’etre mises sous ventilation mecanique durant 30 minutes. Apres sacrifice, le liquide alveolaire et le sang etaient preleves. L’AFC etait calculee par la difference de concentrations en proteines totales dans le liquide alveolaire avant et a la fin de la periode de ventilation. Resultats L’AFC dans le groupe temoin etait de 36 % sur 30 minutes. L’AFC etait significativement alteree a j1 (8 % p = 0,0006) et a j2 (9 % p = 0,005) dans le groupe HCl. L’inhibition de RAGE etait associee a une elevation significative de l’AFC a j1 par rapport au groupe HCl, dans les groupes mAb (8 % vs 36 %, p = 0,009) et R (8 % vs 37 %, p = 0,009). Tous temps confondus, une correlation significative entre l’AFC et les concentrations plasmatiques de sRAGE etait retrouvee (coefficient de Spearman −0,62) (IC95 [−0,78 : −0,39] p Fig. 1 ). Discussion Nos resultats suggerent qu’une inhibition de la voie RAGE pourrait ameliorer la fonction de clairance alveolaire liquidienne a j1 et a j2 d’une agression alveolaire dans notre modele murin. L’AFC est correlee avec le sRAGE plasmatique, ce qui pourrait renforcer la position de sRAGE comme biomarqueur de l’agression alveolaire au cours du SDRA. Ces resultats preliminaires suggerent l’inhibition de RAGE comme une cible therapeutique potentielle au cours du SDRA. Ces resultats necessitent d’etre confirmes et soulignent l’interet de preciser les liens biologiques entre la voie RAGE et l’AFC.

Receptor for advanced glycation endproducts (RAGE) is a transmembrane receptor expressed in the lung and primarily located on alveolar type I cells. RAGE is implicated in acute respiratory distress syndrome to alveolar inflammation and, when its soluble form sRAGE is assayed in plasma or pulmonary edema fluid, as a marker of AT I cell injury. Functional activity of AT 1 cells can be assessed by the measurement of the alveolar fluid clearance (AFC) rate [1], but the relationship between sRAGE plasma levels of sRAGE and AFC rates has never been investigated. Our objectives were to report plasma levels of sRAGE in a mouse model of direct acid-induced epithelial injury, and to test their correlation with AFC rates.

Introduction Le recepteur des produits de glycation avancee (RAGE) est un recepteur transmembranaire exprime a la surface des pneumocytes de type I dont l’activation semble fortement impliquee dans l’atteinte pulmonaire du syndrome de detresse respiratoire aigue (SDRA) [1] . sRAGE est la forme soluble principale de RAGE, qui agit principalement comme un leurre empechant l’activation du recepteur transmembranaire, et ainsi l’initiation d’un signal inflammatoire [2] . L’evaluation fonctionnelle du pneumocyte de type I est possible par la mesure de la clairance alveolaire liquidienne [3] ( alveolar fluid clearance [AFC]). L’objectif de notre travail experimental etait de rechercher une correlation entre les variations d’AFC et les concentrations plasmatiques de sRAGE dans un modele murin de SDRA par lesion alveolaire directe. Materiel et methodes Etude experimentale animale sur 41 souris mâles CD-1, comparant un groupe « HCl » subissant une instillation orotracheale d’acide chlorhydrique et un groupe controle « Sham » de souris indemnes. Le jour de l’instillation determinait le j0. A des temps specifiques (j0, j1, j2, j4), les souris recevaient, sous anesthesie generale, une instillation intratracheale d’albumine bovine avant d’etre mises sous ventilation mecanique durant trente minutes. Apres sacrifice, le liquide alveolaire et le sang etaient preleves. L’AFC etait calculee par la difference de concentrations en proteines bovines dans le liquide alveolaire avant (H0) et a la fin de la periode de ventilation (H30). Les concentrations plasmatiques de sRAGE etaient mesurees par Elisa et ponderees sur les proteines plasmatiques totales. Resultats L’AFC initiale etait de 35% sur 30 minutes dans le groupe HCl et etait significativement alteree a j1 ( p = 0,02) pour atteindre 16 % sur 30 minutes. Ses valeurs rejoignaient ensuite celles du groupe controle avec le temps. Les concentrations plasmatiques de sRAGE etaient significativement plus elevees chez les souris agressees que chez les controles a j1 ( p = 0,03) et a j2 ( p = 0,02). Une correlation significative entre l’AFC et les concentrations plasmatiques de sRAGE plasmatique etait retrouvee (coefficient de Spearman –0.49 (IC95 % [–0,70: –0.19] p = 0,04)) ( Fig. 1 ). Discussion Nos resultats suggerent que la mesure de l’AFC dans notre modele murin est un marqueur fiable de l’evaluation fonctionnelle du pneumocyte de type 1 chez la souris. L’agression alveolaire semble etre correlee avec les variations de sRAGE plasmatique, dont nous decrivons pour la premiere fois une cinetique d’evolution en modele murin. L’elevation importante du sRAGE plasmatique a j1 pourrait etre le reflet de cette phase d’agression epitheliale maximale. Ces resultats permettent d’envisager la poursuite de travaux experimentaux sur les liens entre l’activation de la voie RAGE et les mecanismes impliques dans l’agression alveolaire aigue et sa resolution.

RATIONALE: patient position, such as prone position, can improve prognoses in acute respiratory distress syndrome. Total verticalization is now possible using dedicated beds, but the effects of the position remain unknown.OBJECTIVES: to evaluate the physiological effects of bed verticalization on ventilation and hemodynamics in cases of early acute respiratory distress syndrome, and to assess safety and feasibility.METHODS: patients were gradually verticalized, using a dedicated bed, from a 30° semiseated position (baseline) to different levels of inclination (0°, 30°, 60°, and 90°), before returning to the baseline. The duration of each level was 30 minutes, after which hemodynamic and ventilatory parameters, end-expiratory lung volume, transpulmonary pressures, and gas exchange parameters were recorded.MEASUREMENTS AND MAIN RESULTS: thirty moderate to severe acute respiratory distress syndrome patients were included; all were successfully verticalized without serious adverse event. Transpulmonary driving pressure increased slightly from baseline to the 90° position (9 [5; 11] to 10 [7; 14] cmH2O, P