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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.

Volatile anaesthetic agents, especially sevoflurane, could be an alternative for sedating ICU patients. In the operating theatre, volatile anaesthetic agents are monitored using minimal alveolar concentration (MAC). In ICU, MAC may be used to assess sedation level and may replace clinical scale especially when they are unusable. Therefore, we sought to investigate the minimal sevoflurane end-tidal concentration to achieved deep sedation in critical ill patients: MAC-deep sedation (MAC-DS).In a prospective interventional study, we included patients with a Richmond Assessment Sedation Score (RASS) of 0 without any sedation. We stepwise increased sevoflurane concentration level before assessing for deep sedation (RASS≤-3). MAC-DS was defined as the minimal sevoflurane MAC fraction or sevoflurane expiratory fraction (FeSevo) to get 90% and 95% of patients in deep sedation (MAC-DS 90 and MAC-DS 95, respectively).Between June and November 2014, 30 patients were included (median age=60 years [interquartile range: 47-69]). Increasing sevoflurane MAC was correlated with a decrease in RASS values (r=-0.83, P0.001). MAC-DS 90 and MAC-DS 95 were achieved at 0.42 MAC (CI 95 [0.38-0.46]) and 0.46 MAC (CI 95 [0.42-0.51]), respectively. FeSevo to achieve MAC-DS 90 and MAC-DS 95 was 0.72 (CI 95 [0.65-0.79]) and 0.80 (CI 95 [0.72-0.89]), respectively.In this physiological study involving 30 ICU patients, MAC-DS, end-tidal sevoflurane concentration to get 95% of patients in deep sedation determined over more than 500 observations, is achieved at 0.8% of expired fraction of sevoflurane or at 0.5 age-adjusted MAC.

IntroductionDifficult airway management during tracheal intubation can lead to severe hypoxic sequelae. Routine intubation practice is to use a strict supine position, whereas a 25° head-up or reverse Trendelenburg position increases efficacy of preoxygenation, seems more comfortable for the anaesthetist and may also provide better intubation conditions in direct laryngoscopy. The 25° head-up position could be used for the whole population rather than only for obese patients, but there is no prospective randomised controlled trial with a robust design and large number of patients comparing strict supine against 25° intubation in operating room. The objective of the InSize25 study is to test the effect of these two patient positions on intubation conditions during laryngoscopy in scheduled surgery on non-obese patients.Methods and analysisInSize25 is an investigator-initiated, multicentre, open-label, two-arm, randomised controlled trial. The InSize25 study will randomise 1000 adult patients scheduled for surgery under general anaesthesia requiring intubation with neuromuscular-blocking drugs, candidates for direct laryngoscopy. The primary outcome variable is the view obtained during the first laryngoscopy without any external manipulation assessed using percentage of glottic opening. Important secondary outcomes are: Cormack-Lehane classification, number of attempts at laryngoscopy and at tracheal intubation, use of ancillary equipment (eg, bougies, alternative laryngoscope blades, videolaryngoscope) and manoeuvres (eg, laryngeal manipulation), comfort score for the anaesthetist, episodes of postinduction hypotension or desaturation and mechanical complications of intubation.Ethics and disseminationThe trial received appropriate approval from the ‘CPP Sud-Est II’ ethical review board. Informed consent is required. If the 25° head-up position proves superior for tracheal intubation without more complications, it may become the routine-standard intubation position rather than only for use with obese patients. The final results will be published in a peer-reviewed journal.Trial registration numberClinicaltrials.gov identifier (NCT03339141).

IntroductionEndovascular thrombectomy is the standard of care for anterior circulation acute ischaemic stroke (AIS) secondary to emergent large vessel occlusion in patients who qualify. General anaesthesia (GA) or conscious sedation (CS) is usually required to ensure patient comfort and avoid agitation and movement during thrombectomy. However, the question of whether the use of GA or CS might influence functional outcome remains debated. Indeed, conflicting results exist between observational studies with better outcomes associated with CS and small monocentric randomised controlled trials favouring GA. Therefore, we aim to evaluate the effect of CS versus GA on functional outcome and periprocedural complications in endovascular mechanical thrombectomy for anterior circulation AIS.Methods and analysisAnesthesia Management in Endovascular Therapy for Ischemic Stroke (AMETIS) trial is an investigator initiated, multicentre, prospective, randomised controlled, two-arm trial. AMETIS trial will randomise 270 patients with anterior circulation AIS in a 1:1 ratio, stratified by centre, National Institutes of Health Stroke Scale (≤15 or >15) and association of intravenous thrombolysis or not to receive either CS or GA. The primary outcome is a composite of functional independence at 3 months and absence of perioperative complication occurring by day 7 after endovascular therapy for anterior circulation AIS. Functional independence is defined as a modified Rankin Scale score of 0–2 by day 90. Perioperative complications are defined as intervention-associated arterial perforation or dissection, pneumonia or myocardial infarction or cardiogenic acute pulmonary oedema or malignant stroke evolution occurring by day 7.Ethics and disseminationThe AMETIS trial was approved by an independent ethics committee. Study began in august 2017. Results will be published in an international peer-reviewed medical journal.Trial registration numberNCT03229148.

The effect of personalised mechanical ventilation on clinical outcomes in patients with acute respiratory distress syndrome (ARDS) remains uncertain and needs to be evaluated. We aimed to test whether a mechanical ventilation strategy that was personalised to individual patients' lung morphology would improve the survival of patients with ARDS when compared with standard of care.We designed a multicentre, single-blind, stratified, parallel-group, randomised controlled trial enrolling patients with moderate-to-severe ARDS in 20 university or non-university intensive care units in France. Patients older than 18 years with early ARDS for less than 12 h were randomly assigned (1:1) to either the control group or the personalised group using a minimisation algorithm and stratified according to the study site, lung morphology, and duration of mechanical ventilation. Only the patients were masked to allocation. In the control group, patients received a tidal volume of 6 mL/kg per predicted bodyweight and positive end-expiratory pressure (PEEP) was selected according to a low PEEP and fraction of inspired oxygen table, and early prone position was encouraged. In the personalised group, the treatment approach was based on lung morphology; patients with focal ARDS received a tidal volume of 8 mL/kg, low PEEP, and prone position. Patients with non-focal ARDS received a tidal volume of 6 mL/kg, along with recruitment manoeuvres and high PEEP. The primary outcome was 90-day mortality as established by intention-to-treat analysis. This study is registered online with ClinicalTrials.gov, NCT02149589.From June 12, 2014, to Feb 2, 2017, 420 patients were randomly assigned to treatment. 11 patients were excluded in the personalised group and nine patients were excluded in the control group; 196 patients in the personalised group and 204 in the control group were included in the analysis. In a multivariate analysis, there was no difference in 90-day mortality between the group treated with personalised ventilation and the control group in the intention-to-treat analysis (hazard ratio [HR] 1·01; 95% CI 0·61-1·66; p=0·98). However, misclassification of patients as having focal or non-focal ARDS by the investigators was observed in 85 (21%) of 400 patients. We found a significant interaction between misclassification and randomised group allocation with respect to the primary outcome (p0·001). In the subgroup analysis, the 90-day mortality of the misclassified patients was higher in the personalised group (26 [65%] of 40 patients) than in the control group (18 [32%] of 57 patients; HR 2·8; 95% CI 1·5-5·1; p=0·012.Personalisation of mechanical ventilation did not decrease mortality in patients with ARDS, possibly because of the misclassification of 21% of patients. A ventilator strategy misaligned with lung morphology substantially increases mortality. Whether improvement in ARDS phenotyping can decrease mortality should be assessed in a future clinical trial.French Ministry of Health (Programme Hospitalier de Recherche Clinique InterRégional 2013).

International audience; BackgroundSevoflurane has anti-inflammatory proprieties and short lasting effects making it of interest for procedural sedation in critically ill patients. We evaluated the pharmacokinetics of sevoflurane and metabolites in severely ill burn patients and controls. The secondary objective was to assess potential kidney injury.MethodsProspective interventional study in a burn and a surgical intensive care unit; 24 mechanically ventilated critically ill patients (12 burns, 12 controls) were included. The sevoflurane was administered with an expired fraction target of 2% during short-term procedural sedation. Plasma concentrations of sevoflurane, hexafluoroisopropanolol (HFIP) and free fluoride ions were recorded at different times. Kinetic Pro (Wgroupe, France) was used for pharmacokinetic analysis. Kidney injury was assessed with neutrophil gelatinase-associated lipocalin (NGAL).ResultsThe mean total burn surface area was 36 ± 11%. The average plasma concentration of sevoflurane was 70.4 ± 37.5 mg·L−1 in burns and 57.2 ± 28.1 mg·L−1 in controls at the end of the procedure (P = 0.58). The volume of distribution was higher (46.8 ± 7.2 vs 22.2 ± 2.50 L, P < 0.001), and the drug half-life longer in burns (1.19 ± 0.28 h vs 0.65 ± 0.04 h, P < 0.0001). Free metabolite HFIP was higher in burns. Plasma fluoride was not different between burns and controls. NGAL did not rise after procedures.ConclusionWe observed an increased volume of distribution, slower elimination rate, and altered metabolism of sevoflurane in burn patients compared to controls. Repeated use for procedural sedation in burn patients needs further evaluation. No renal toxicity was detected.

Laparoscopic surgery technology continues to advance. However, much less attention has been focused on how alteration of the laparoscopic surgical environment might improve clinical outcomes. We conducted a randomized, 2 × 2 factorial trial to evaluate whether low intraperitoneal pressure (IPP) (8 mmHg) and/or warmed, humidified CO2 (WH) gas are better for minimizing the adverse impact of a CO2 pneumoperitoneum on the peritoneal environment during laparoscopic surgery and for improving clinical outcomes compared to the standard IPP (12 mmHg) and/or cool and dry CO2 (CD) gas. Herein we show that low IPP and WH gas may decrease inflammation in the laparoscopic surgical environment, resulting in better clinical outcomes. Low IPP and/or WH gas significantly lowered expression of inflammation-related genes in peritoneal tissues compared to the standard IPP and/or CD gas. The odds ratios of a visual analogue scale (VAS) pain score >30 in the ward was 0.18 (95% CI: 0.06, 0.52) at 12 hours and 0.06 (95% CI: 0.01, 0.26) at 24 hours in the low IPP group versus the standard IPP group, and 0.16 (95% CI: 0.05, 0.49) at 0 hours and 0.29 (95% CI: 0.10, 0.79) at 12 hours in the WH gas group versus the CD gas group.

Different acute respiratory distress syndrome (ARDS) phenotypes may explain controversial results in clinical trials. Lung-morphology is one of the ARDS-phenotypes and physiological studies suggest different responses in terms of positive-end-expiratory-pressure (PEEP) and recruitment-manoeuvres (RM) according to loss of aeration. To evaluate whether tailored ventilator regimens may impact ARDS outcomes, our group has designed a randomised-clinical-trial of ventilator settings according to lung morphology in moderate-to-severe ARDS (LIVE study). Method Patients will be enrolled within the first 12 hours of ARDS onset. In both groups, volume-controlled ventilation with low tidal-volumes (Vt) will be used to target a plateau pressure ≤ 30 cmH 2 O. In the control group, the PEEP level and inspired fraction of oxygen (FiO 2 ) will be set using the ARDSNet table; a Vt of 6 mL/kg of predicted body weight (PBW) will be set and prone position (PP) will be applied. In the intervention arm, the ventilator will be set according to lung morphology (focal/non-focal) that will be assessed according to CT-scan ± chest x-ray + lung echography. For focal ARDS patients, a Vt of 8 mL/kg PBW will be used along with low PEEP and PP. For non-focal ARDS patients, a Vt of 6 mL/kg PBW will be used with RM and PEEP to reach a plateau pressure ≤ 30 cmH 2 O. The primary outcome is all-cause 90-day mortality and the secondary outcomes are: in-hospital mortality, mortality at day 28, 60, 180 and 365; ventilator-free days at day 30, quality of life at one year; ventilator-associated pneumonia rate; barotrauma; ICU and hospital length of stay. This RCT is registered on Clinicaltrials.gov under identifier NCT02149589 .

The rationale for the use of recruitment maneuvers (RMs) in acute respiratory distress syndrome (ARDS) is to promote alveolar recruitment, leading to an increased end-expiratory lung volume and thus decreased ventilator-induced lung injury (VILI). RMs consists of a transient increase in transpulmonary pressure that can re-open previously collapsed alveoli. RMs represents a physiological response to lung aggression in different conditions by re-opening the collapsed part of the lung and decreasing lung oedema. This process can be accomplished through a variety of methods. The RM that has probably been used most commonly is sustained inflation, but recruitment can be achieved by a prolonged sigh, leading to a lesser increase in transpulmonary pressure for a longer period of time. This extended sigh seems to be more efficient, with less haemodynamic compromise. Knowledge of physiological determinants is crucial to selecting good levels of pressure and time required to perform an efficient and well-tolerated RM. Identifying ARDS patients who may benefit from RMs is a major issue, depending essentially on the amount of recruitable lung involved. In any case, however, RMs should be done at the early phase of ARDS.

The creation of a pneumoperitoneum for laparoscopic surgery is performed by the insufflation of carbon dioxide (CO2). The insufflated CO2 is generally at room temperature (20–25 °C) and dry (0–5 % relative humidity). However, these physical characteristics could lead to alterations of the peritoneal cavity, leading to operative and postoperative complications. Warming and humidifying the insufflated gas has been proposed to reduce the iatrogenic effects of laparoscopic surgery, such as pain, hypothermia and peritoneal alterations. Two medical devices are currently available for laparoscopic surgery with warm and humidified CO2. Clinical studies were identified by searching PubMed with keywords relating to humidified and warmed CO2 for laparoscopic procedures. Analysis of the literature focused on postoperative pain, analgesic consumption, duration of hospital stay and convalescence, surgical techniques and hypothermia. Bibliographic analyses reported 114 publications from 1977 to 2015, with only 17 publications of clinical interest. The main disciplines focused on were gynaecological and digestive surgery ). Analysis of the studies selected reported only a small beneficial effect of warmed and humidified laparoscopy compared to standard laparoscopy on immediate postoperative pain and per procedure hypothermia. No difference was observed for later postoperative shoulder pain, morphine equivalent daily doses, postoperative body core temperature, recovery room and hospital length of stay, lens fogging and procedure duration. Only few beneficial effects on immediate postoperative pain and core temperature have been identified in this meta-analysis. Although more studies are probably needed to close the debate on the real impact of warmed and humidified CO2 for laparoscopic procedures.

Background The acute respiratory distress syndrome (ARDS) is a heterogeneous syndrome that encompasses multiple phenotypes, e.g. with regards to lung morphology as assessed by computed tomography (CT). Focal or non-focal lung morphology may influence the response to positive end-expiratory pressure (PEEP), recruitment manoeuvres and prone position. Lung morphology has been hypothesized to be associated with alveolar fluid clearance (AFC), thus explaining various responses to such therapeutic interventions; however, this hypothesis has not been specifically studied in humans. Methods We measured net AFC rates in 30 patients with ARDS as a secondary data analysis of a prospective single-centre study. Net AFC rates were compared between patients with focal ARDS and those with non-focal ARDS, as assessed by lung CT-scans. Results Net AFC rates were significantly lower in patients with non-focal ARDS (n = 23; median [interquartile range], 1.5 [0–5.5] %/h) as compared to those with focal ARDS (n = 7; 10.3 [4.5–15] %/h) (P = 0.01). The area under the receiver-operating characteristic curve when net AFC rates were used to differentiate the presence from absence of non-focal ARDS was 0.93 (95% confidence interval, 0.81–1). Tidal volumes and PEEP levels differed between focal and non-focal ARDS patients, but there was no difference in arterial oxygenation or in alveolar-capillary permeability. Conclusions Non-focal lung morphology may be characterized by a functional endotype consistent with marked AFC impairment. Despite study limitations and the need for validating studies in larger cohorts, such novel findings may reinforce our understanding of the association between ARDS phenotypes and therapeutic responses.

International audience; Rationale: Postextubation distress after a successful spontaneous breathing trial (SBT) is associated with increased morbidity and mortality. Lung ultrasound determination of changes in lung aeration predicts weaning failure. It remains unknown whether this derecruitment is related to alveolar epithelial dysfunction or not. Objective: To verify whether lung alveolar type I epithelial cell injury marker sRAGE (soluble form of the receptor for advanced glycation end-products) is predictive of postextubation distress and weaning failure or not, and to verify whether plasma sRAGE levels can be related to lung derecruitment during the process of weaning from mechanical ventilation or not. Interventions, Measurements: 88 patients from 2 intensive care units were included in this observational prospective study. Plasma sRAGE levels were measured in duplicate by ELISA before, at the end of a 60-minute SBT, and 4 hours after extubation. To quantify lung aeration, a lung ultrasound score was calculated. Main Results: 34% of extubated patients experienced postextubation distress. Patients with or without postextubation distress had comparable sRAGE levels before SBT, after SBT, and 4 hours after extubation. In patients with postextubation distress, sRAGE levels were not predictive of the need for mechanical ventilation. sRAGE levels were not associated with lung aeration as assessed by echography. Patients who succeeded SBT (86%) and those who failed (14%) had no differences in sRAGE levels, before (median 1111 vs 1021 pg/mL, p = 0,87) and at the end of SBT (1165 vs 1038 pg/mL, p = 0.74). Conclusions: Plasma levels of sRAGE do not predict postextubation distress or SBT failure/success in patients weaning from mechanical ventilation. Lung aeration loss during a successful weaning trial predicts postextubation distress, but may not be evaluable by plasma levels of sRAGE, a marker of alveolar type I epithelial cell injury. Trial Registration: ClinicalTrials.gov NCT01098773 Citation: Jabaudon M, Perbet S, Pereira B, Soummer A, Roszyk L, et al. (2013) Plasma Levels of sRAGE, Loss of Aeration and Weaning Failure in ICU Patients: A Prospective Observational Multicenter Study. PLoS ONE 8(5): e64083.

International audience; Introduction: Central venous oxygen saturation (ScvO 2) is a useful therapeutic target in septic shock and high-risk surgery. We tested the hypothesis that central venous-to-arterial carbon dioxide difference (P(cv-a)CO 2), a global index of tissue perfusion, could be used as a complementary tool to ScvO 2 for goal-directed fluid therapy (GDT) to identify persistent low flow after optimization of preload has been achieved by fluid loading during high-risk surgery. Methods: This is a secondary analysis of results obtained in a study involving 70 adult patients (ASA I to III), undergoing major abdominal surgery, and treated with an individualized goal-directed fluid replacement therapy. All patients were managed to maintain a respiratory variation in peak aortic flow velocity below 13%. Cardiac index (CI), oxygen delivery index (DO 2 i), ScvO 2 , P(cv-a)CO 2 and postoperative complications were recorded blindly for all patients. Results: A total of 34% of patients developed postoperative complications. At baseline, there was no difference in demographic or haemodynamic variables between patients who developed complications and those who did not. In patients with complications, during surgery, both mean ScvO 2 (78 ± 4 versus 81 ± 4%, P = 0.017) and minimal ScvO 2 (minScvO 2) (67 ± 6 versus 72 ± 6%, P = 0.0017) were lower than in patients without complications, despite perfusion of similar volumes of fluids and comparable CI and DO 2 i values. The optimal ScvO 2 cutoff value was 70.6% and minScvO 2 < 70% was independently associated with the development of postoperative complications (OR = 4.2 (95% CI: 1.1 to 14.4), P = 0.025). P(cv-a)CO 2 was larger in patients with complications (7.8 ± 2 versus 5.6 ± 2 mmHg, P < 10-6). In patients with complications and ScvO 2 ≥71%, P(cv-a)CO 2 was also significantly larger (7.7 ± 2 versus 5.5 ± 2 mmHg, P < 10-6) than in patients without complications. The area under the receiver operating characteristic (ROC) curve was 0.785 (95% CI: 0.74 to 0.83) for discrimination of patients with ScvO 2 ≥71% who did and did not develop complications, with 5 mmHg as the most predictive threshold value.

Introduction: Tracheal intubation and anaesthesia promotes lung collapse and hypoxemia. In acute lung injury patients, recruitment maneuvers (RMs) increase lung volume and oxygenation, and decrease atelectasis. The aim of this study was to evaluate the efficacy and safety of RMs performed immediately after intubation. Methods: This randomized controlled study was conducted in two 16-bed medical-surgical intensive care units within the same university hospital. Consecutive patients requiring intubation for acute hypoxemic respiratory failure were included. Patients were randomized to undergo a RM immediately (within 2 minutes) after intubation, consisting of a continuous positive airway pressure (CPAP) of 40 cmH 2 O over 30 seconds (RM group), or not (control group). Blood gases were sampled and blood samples taken for culture before, within 2 minutes, 5 minutes, and 30 minutes after intubation. Haemodynamic and respiratory parameters were continuously recorded throughout the study. Positive end expiratory pressure (PEEP) was set at 5 cmH2O throughout. Results: The control (n = 20) and RM (n = 20) groups were similar in terms of age, disease severity, diagnosis at time of admission, and PaO 2 obtained under 10-15 L/min oxygen flow immediately before (81 ± 15 vs 83 ± 35 mmHg, P = 0.9), and within 2 minutes after, intubation under 100% FiO2 (81 ± 15 vs 83 ± 35 mmHg, P = 0.9). Five minutes after intubation, PaO 2 obtained under 100% FiO 2 was significantly higher in the RM group compared with the control group (93 ± 36 vs 236 ± 117 mmHg, P = 0.008). The difference remained significant at 30 minutes with 110 ± 39 and 180 ± 79 mmHg, respectively, for the control and RM groups. No significant difference in haemodynamic conditions was observed between groups at any time. Following tracheal intubation, 15 patients had positive blood cultures, showing microorganisms shared with tracheal aspirates, with no significant difference in the incidence of culture positivity between groups. Conclusions: Recruitment maneuver following intubation in hypoxemic patients improved short-term oxygenation, and was not associated with increased adverse effects. Trial registration: NCT01014299

Background Pulmonary function is impaired during pneumoperitoneum mainly as a result of atelectasis formation. We studied the effects of 10 cm H2O of positive end-expiratory pressure (PEEP) and PEEP followed by a recruitment maneuver (PEEP+RM) on end-expiratory lung volume (EELV), oxygenation and respiratory mechanics in patients undergoing laparoscopic surgery. Methods Sixty consecutive adult patients (30 obese, 30 healthy weight) in reverse Trendelenburg position were prospectively studied. EELV, static elastance of the respiratory system, dead space, and gas exchange were measured before and after pneumoperitoneum insufflation with zero end-expiratory pressure, with PEEP alone, and with PEEP+RM. Results are presented as mean ± SD. Results Pneumoperitoneum reduced EELV (healthy weight, 1195 ± 405 vs. 1724 ± 774 ml; obese, 751 ± 258 vs. 886 ± 284 ml) and worsened static elastance and dead space in both groups (in all P < 0.01 vs. zero-end expiratory pressure before pneumoperitoneum) whereas oxygenation was unaffected. PEEP increased EELV (healthy weight, 570 ml, P < 0.01; obese, 364 ml, P < 0.01) with no effect on oxygenation. Compared with PEEP alone, EELV and static elastance were further improved after RM in both groups (P < 0.05), as was oxygenation (P < 0.01). In all patients, RM-induced change in EELV was 16% (P = 0.04). These improvements were maintained 30 min after RM. RM-induced changes in EELV correlated with change in oxygenation (r = 0.42, P < 0.01). Conclusion RM combined with 10 cm H2O of PEEP improved EELV, respiratory mechanics, and oxygenation during pneumoperitoneum whereas PEEP alone did not.

Background Lemierre's syndrome presents a classic clinical picture, the pathophysiology of which remains obscure. Attempts have been made to trace genetic predispositions that modify the host detection of pathogen or the resultant systemic reaction. Case presentation A 17-year old female, with no previous medical history, was admitted to the intensive care unit for septic shock, acute respiratory distress syndrome and Lemierre's syndrome. Her DNA was assayed for single nucleotide polymorphisms previously incriminated in the detection of the pathogen, the inflammatory response and the coagulation cascade. We observed functional variations in her Toll like 5 receptor (TLR 5) gene and two coagulation variations (Tissue Factor (TF) 603 and Plasminogen-Activator-Inhibitor-1 (PAI-1) 4G-4G homozygosity) associated with thrombotic events. Conclusion The innate immune response and the prothrombogenic mutations could explain, at least in part, the symptoms of Lemierre's syndrome. Genomic study of several patients with Lemierre's syndrome may reveal its pathophysiology.

Background Central venous catheters play an important role in patient care. Real-time ultrasound-guided subclavian central venous (SCV) cannulation may reduce the incidence of complications and the time between skin penetration and the aspiration of venous blood into the syringe. Ultrasonic diagnosis of catheter misplacement and pneumothorax related to central venous catheterization is rapid and accurate. It is unclear, however, whether ultrasound real-time guidance and examination can reduce procedure times and complication rates when compared with landmark guidance and radiographic examination for SCV catheterization. Methods/Design The Subclavian Central Venous Catheters Guidance and Examination by UltraSound (SUBGEUS) study is an investigator-initiated single center, randomized, controlled two-arm trial. Three hundred patients undergoing SCV catheter placement will be randomized to ultrasound real-time guidance and examination or landmark guidance and radiographic examination. The primary outcome is the time between the beginning of the procedure and control of the catheter. Secondary outcomes include the times required for the six components of the total procedure, the occurrence of complications (pneumothorax, hemothorax, or misplacement), failure of the technique and occurrence of central venous catheter infections. Discussion The SUBGEUS trial is the first randomized controlled study to investigate whether ultrasound real-time guidance and examination for SCV catheter placement reduces all procedure times and the rate of complications. Trial registration ClinicalTrials.gov Identifier: NCT01888094

Introduction Adequate volume expansion (VE) in patients with evidence of hypoperfusion should be aimed not only at achieving an increase in stroke volume (SV) and cardiac index (CI) but also at improved tissue perfusion and oxygenation. Our aim in this study was to assess the dynamic changes in muscle tissue oxygen saturation (StO2) during hypovolaemia and in response to VE. Methods We conducted a prospective study of 42 fluid challenges in patients undergoing major abdominal surgery with evidence of hypovolaemia, defined as pulse pressure variation (PPV) >13% and SV variation (SVV) >12%. CI, SV, SVV (FloTrac/Vigileo) and PPV were measured before and after VE. Fluid responsiveness was defined as an increase of SV >15% after a 500-mL colloid infusion over 15 minutes. In all patients, the muscle StO2 and its changes during a standardised vascular occlusion test were analysed using a near-infrared spectroscopy device after anaesthesia induction (which defined the baseline state) and before and after each VE. Results No patients were preload-responsive after anaesthesia induction. Twenty-nine of forty-two fluid challenges (69%) were positive for VE, with a statistically significant (P < 0.001) difference in SV changes between positive and negative responses to VE. There was a statistically significant difference in PPV and SVV values before VE in the positive and negative fluid responses [PPV: 16% (15% to 18%) vs. 14% (13% to 15%), P = 0.001; and SVV: 14% (13% to 16%) vs. 16% (15% to 16%), P = 0.03 or positive and negative fluid responses, respectively]. Data are presented as medians and 25th and 75th percentiles Before VE there was no significant difference in StO2 values relative to baseline [86% (78% to 88%) vs. 84% (77% to 91%), P = 0.83], without a significant difference (P = 0.36) between positive and negative fluid challenges. Hypovolaemia was associated with a significant reduction (P = 0.004) in StO2 recovery slope, with a significant difference (P = 0.02) between positive and negative fluid challenges. The VE-induced increase in the StO2 recovery slope was 62 ± 49% (P < 0.001) for positive fluid challenges and 26 ± 34% (P = 0.04) for negative fluid challenges. Conclusions Hypovolaemia significantly affects the muscle StO2 recovery slope. Restoring effective intravascular volume with fluid loading significantly improves the StO2 recovery slope, despite apparently ineffective changes in systemic haemodynamics.

Introduction: Data on the epidemiology and management of anorexia nervosa (AN) in the intensive care unit (ICU) are scarce. The aim of this study was to evaluate the prevalence and associated morbidity and mortality of AN in French ICUs. Methods: We randomly selected 30 ICUs throughout France. Thereafter, we retrospectively analyzed all patients with AN admitted to any of these 30 ICUs between May 2006 and May 2008. We considered demographic data, diagnosis at admission and complications occurring during the stay, focusing on refeeding syndrome and management of refeeding. Results: Eleven of the 30 ICUs participated in the retrospective study, featuring 68 patients, including 62 women. Average body mass index at the admission was 12 ± 3 kg/m2. Twenty one were mechanically ventilated, mainly for neurological reasons. The reported average calorie intake was 22.3 ± 13 kcal/kg/24 h. Major diagnoses at admission were metabolic problems, refeeding survey and voluntary drug intoxication and infection. The most common complications were metabolic, hematological, hepatic, and infectious events, of which 10% occurred during refeeding. Seven patients developed refeeding syndrome. At day one, the average calorie intake was higher for patients who developed refeeding syndrome (23.2 ± 5 Kcal/kg/j; n = 7) versus patients without refeeding syndrome (14.1 ± 3 Kcal/kg/j; n = 61) P = 0.02. Seven patients died, two from acute respiratory distress syndrome and five from multiorgan-failure associated with major hydroelectrolytic problems. Conclusions: The frequency of AN in ICU patients is very low and the crude mortality in this group is about 10%. Prevention and early-detection of refeeding syndrome is the key point.

Adequate volume expansion for hypovolemia should improve cardiac preload and stroke volume leading to improved microvascular blood flow, tissue perfusion and oxygenation. The dynamic recovery slope of tissue oxygen saturation (StO2) during a standardized vascular occlusion test (VOT) is proposed to reflect microvascular reactivity. We aimed at evaluating the dynamic StO2 variations during fluid challenge in high-risk surgical patients.

Introduction Alveolar derecruitment may occur during low tidal volume ventilation and may be prevented by recruitment maneuvers (RMs). The aim of this study was to compare two RMs in acute respiratory distress syndrome (ARDS) patients. Methods Nineteen patients with ARDS and protective ventilation were included in a randomized crossover study. Both RMs were applied in each patient, beginning with either continuous positive airway pressure (CPAP) with 40 cm H2O for 40 seconds or extended sigh (eSigh) consisting of a positive end-expiratory pressure maintained at 10 cm H2O above the lower inflection point of the pressure-volume curve for 15 minutes. Recruited volume, arterial partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2), and hemodynamic parameters were recorded before (baseline) and 5 and 60 minutes after RM. All patients had a lung computed tomography (CT) scan before study inclusion. Results Before RM, PaO2/FiO2 was 151 ± 61 mm Hg. Both RMs increased oxygenation, but the increase in PaO2/FiO2 was significantly higher with eSigh than CPAP at 5 minutes (73% ± 25% versus 44% ± 28%; P < 0.001) and 60 minutes (68% ± 23% versus 35% ± 22%; P < 0.001). Only eSigh significantly increased recruited volume at 5 and 60 minutes (21% ± 22% and 21% ± 25%; P = 0.0003 and P = 0.001, respectively). The only difference between responders and non-responders was CT lung morphology. Eleven patients were considered as recruiters with eSigh (10 with diffuse loss of aeration) and 6 with CPAP (5 with diffuse loss of aeration). During CPAP, 2 patients needed interruption of RM due to a drop in systolic arterial pressure. Conclusion Both RMs effectively increase oxygenation, but CPAP failed to increase recruited volume. When the lung is recruited with an eSigh adapted for each patient, alveolar recruitment and oxygenation are superior to those observed with CPAP.