Outcomes After Endovascular Therapy With Procedural Sedation vs General Anesthesia in Patients With Acute Ischemic Stroke: The AMETIS Randomized Clinical Trial.

Importance: General anesthesia and procedural sedation are common practice for mechanical thrombectomy in acute ischemic stroke. However, risks and benefits of each strategy are unclear. Objective: To determine whether general anesthesia or procedural sedation for anterior circulation large-vessel occlusion acute ischemic stroke thrombectomy are associated with a difference in periprocedural complications and 3-month functional outcome. Design, Setting, and Participants: This open-label, blinded end point randomized clinical trial was conducted between August 2017 and February 2020, with final follow-up in May 2020, at 10 centers in France. Adults with occlusion of the intracranial internal carotid artery and/or the proximal middle cerebral artery treated with thrombectomy were enrolled. Interventions: Patients were assigned to receive general anesthesia with tracheal intubation (n = 135) or procedural sedation (n = 138). Main Outcomes and Measures: The prespecified primary composite outcome was functional independence (a score of 0 to 2 on the modified Rankin Scale, which ranges from 0 [no neurologic disability] to 6 [death]) at 90 days and absence of major periprocedural complications (procedure-related serious adverse events, pneumonia, myocardial infarction, cardiogenic acute pulmonary edema, or malignant stroke) at 7 days. Results: Among 273 patients evaluable for the primary outcome in the modified intention-to-treat population, 142 (52.0%) were women, and the mean (SD) age was 71.6 (13.8) years. The primary outcome occurred in 38 of 135 patients (28.2%) assigned to general anesthesia and in 50 of 138 patients (36.2%) assigned to procedural sedation (absolute difference, 8.1 percentage points; 95% CI, -2.3 to 19.1; P = .15). At 90 days, the rate of patients achieving functional independence was 33.3% (45 of 135) with general anesthesia and 39.1% (54 of 138) with procedural sedation (relative risk, 1.18; 95% CI, 0.86-1.61; P = .32). The rate of patients without major periprocedural complications at 7 days was 65.9% (89 of 135) with general anesthesia and 67.4% (93 of 138) with procedural sedation (relative risk, 1.02; 95% CI, 0.86-1.21; P = .80). Conclusions and Relevance: In patients treated with mechanical thrombectomy for anterior circulation acute ischemic stroke, general anesthesia and procedural sedation were associated with similar rates of functional independence and major periprocedural complications. Trial Registration: ClinicalTrials.gov Identifier: NCT03229148.

Is there a benefit for anesthesiologists of adding difficult airway scenarios for learning fiberoptic intubation skills using virtual reality training? A randomized controlled study.

Fiberoptic intubation for a difficult airway requires significant experience. Traditionally only normal airways were available for high fidelity bronchoscopy simulators. It is not clear if training on difficult airways offers an advantage over training on normal airways. This study investigates the added value of difficult airway scenarios during virtual reality fiberoptic intubation training. A prospective multicentric randomized study was conducted 2019 to 2020, among 86 inexperienced anesthesia residents, fellows and staff. Two groups were compared: Group N (control, n = 43) first trained on a normal airway and Group D (n = 43) first trained on a normal, followed by three difficult airways. All were then tested by comparing their ORSIM® scores on 5 scenarios (1 normal and 4 difficult airways). The final evaluation ORSIM® score for the normal airway testing scenario was significantly higher for group N than group D: median score 76% (IQR 56.5-90) versus 58% (IQR 51.5-69, p = 0.0039), but there was no difference in ORSIM® scores for the difficult intubation testing scenarios. A single exposure to each of 3 different difficult airway scenarios did not lead to better fiberoptic intubation skills on previously unseen difficult airways, when compared to multiple exposures to a normal airway scenario. This finding may be due to the learning curve of approximately 5-10 exposures to a specific airway scenario required to reach proficiency.

Use of volatile anesthetics for sedation in the ICU during the COVID-19 pandemic: A national survey in France (VOL'ICU 2 study).

BACKGROUND: The COVID-19 pandemic has increased the number of patients in ICUs leading to a worldwide shortage of the intravenous sedative agents obligating physicians to find alternatives including inhaled sedation. Inhaled sedation in French ICU has been previously explored in 2019 (VOL'ICU study). This survey was designed to explore the use of inhaled sedation two years after our first survey and to evaluate how the COVID-19 pandemic has impacted the use of inhaled sedation. METHODS: We designed a national survey, contacting medical directors of French ICUs between June and October 2021. Over a 50-item questionnaire, the survey covered the characteristics of the ICU, data on inhaled sedation, and practical aspects of inhaled ICU sedation for both COVID-19 and non-COVID-19 patients. Answers were compared with the previous survey, VOL'ICU. RESULTS: Among the 405 ICUs contacted, 25% of the questionnaires were recorded. Most ICU directors (87%) knew about the use of inhaled ICU sedation and 63% of them have an inhaled sedation's device in their unit. The COVID-19 pandemic increased the use of inhaled sedation in French ICUs. The main reasons said by the respondent were "need for additional sedative" (62%), "shortage of intravenous sedatives" (38%) and "involved in a clinical trial" (30%). The main reasons for not using inhaled ICU sedation were "device not available" (76%), "lack of familiarity" (60%) and "no training for the teams" (58%). More than 70% of respondents were overall satisfied with the use of inhaled sedation. Almost 80% of respondents stated that inhaled sedation was a seducing alternative to intravenous sedation for management of COVID-19 patients. CONCLUSION: The use of inhaled sedation in ICU has increased fastly in the last 2 years, and is frequently associated with a good satisfaction among the users. Even if the COVID-19 pandemic could have impacted the widespread use of inhaled sedation, it represents an alternative to intravenous sedation for more and more physicians.

Impact of Macintosh blade size on endotracheal intubation success in intensive care units: a retrospective multicenter observational MacSize-ICU study.

PURPOSE: To investigate the impact of Macintosh blade size used during direct laryngoscopy (DL) on first-attempt intubation success of orotracheal intubation in French intensive care units (ICUs). We hypothesized that success rate would be higher with Macintosh blade size No3 than with No4. METHODS: Multicenter retrospective observational study based on data from prospective trials conducted in 48 French ICUs of university, and general and private hospitals. After each intubation using Macintosh DL, patients' and operators' characteristics, Macintosh blade size, results of first DL and alternative techniques used, as well as the need of a second operator were collected. Complications rates associated with intubation were investigated. Primary outcome was success rate of first DL using Macintosh blade. RESULTS: A total of 2139 intubations were collected, 629 with a Macintosh blade No3 and 1510 with a No4. Incidence of first-pass intubation after first DL was significantly higher with Macintosh blade No3 (79.5 vs 73.3%, p = 0.0025), despite equivalent Cormack-Lehane scores (p = 0.48). Complications rates were equivalent between groups. Multivariate analysis concluded to a significant impact of Macintosh blade size on first DL success in favor of blade No3 (OR 1.44 [95% CI 1.14-1.84]; p = 0.0025) without any significant center effect on the primary outcome (p = 0.18). Propensity scores and adjustment analyses concluded to equivalent results. CONCLUSION: In the present study, Macintosh blade No3 was associated with improved first-passed DL in French ICUs. However, study design requires the conduct of a nationwide prospective multicenter randomized trial in different settings to confirm these results.

Design and Rationale of the Sevoflurane for Sedation in Acute Respiratory Distress Syndrome (SESAR) Randomized Controlled Trial.

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.

Effect of GOAL-Directed ANalgesia using ANI (Analgesia/Nociception Index) during general anesthesia on immediate postoperative pain and intraoperative hemodynamics in adult patients (GOALDAN study): a study protocol for randomized, controlled, multicenter trial.

BACKGROUND: Severe postoperative pain remains a major problem that is seen in 20 to 40% of patients. The Analgesia/Nociception Index (ANI) is a 0-100 index reflecting the relative parasympathetic activity allowing for intraoperative analgesia monitoring. We have previously shown that an ANI value < 50 immediately before extubation may predict the occurrence of immediate postoperative pain with good performance. We hypothesized that GOAL-Directed ANalgesia may provide reduced immediate postoperative pain and optimized intraoperative remifentanil administration (GOLDAN study). METHODS: The GOALDAN study is an international, multicenter, simple-blind, parallel, prospective, randomized, controlled, two-armed trial. Patients are randomly assigned in a 1:1 ratio in the control group or in the experimental group. Patients will be randomly allocated to either the intervention group (ANI) or the control group (standard care only). In the ANI group, the administration of remifentanil will be goal-directed targeting a 50-80 ANI range, with a prophylactic injection of morphine immediately after extubation if the case of ANI < 50. Our primary objective was to determine whether the prophylactic administration of morphine at the end of the procedure in patients at risk of immediate postoperative pain (ANI < 50 immediately before extubation) could reduce the incidence of the latter by 50% in the post-anesthetic care unit. Our secondary objective was to determine whether the intraoperative use of goal-directed analgesia with an ANI target of 50 to 80 could improve intraoperative hemodynamics and postoperative outcome. DISCUSSION: Because of the paucity of well-conducted trials, the authors believe that a randomized-controlled trial will improve the evidence for using analgesia monitoring during general anesthesia and strengthen current recommendations for intraoperative analgesia management. TRIAL REGISTRATION: ClinicalTrials.gov NCT03618082. Registered on 7 August 2018.

Changes in Plasma Soluble Receptor for Advanced Glycation End-Products Are Associated with Survival in Patients with Acute Respiratory Distress Syndrome.

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 < 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.

Use of volatile agents for sedation in the intensive care unit: A national survey in France.

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 <5 years (63%) and in <20 patients per year (75%), with their main indications being: failure of intravenous sedation, severe asthma or bronchial obstruction, and acute respiratory distress syndrome. Sevoflurane and isoflurane were mainly used (88% and 20%, respectively). The main reasons for not using inhaled ICU sedation were: "device not available" (40%), "lack of medical interest" (37%), "lack of familiarity or knowledge about the technique" (35%) and "elevated cost" (21%). Most respondents (80%) were overall satisfied with the use of inhaled sedation. Almost 75% stated that inhaled sedation was a seducing alternative to intravenous sedation. 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.

Effects of Low Intraperitoneal Pressure on Quality of Postoperative Recovery after Laparoscopic Surgery for Genital Prolapse in Elderly Patients Aged 75 Years or Older.

STUDY OBJECTIVE: Previous clinical trials for laparoscopic surgery have included few elderly patients aged ≥75 years. We aimed to evaluate the quality of postoperative recovery after laparoscopic surgery using low intraperitoneal pressure (IPP) (6 mm Hg) and warmed, humidified carbon dioxide gas for genital prolapse in elderly patients aged ≥75 years. DESIGN: Prospective consecutive case series. SETTING: University hospital. PATIENTS: Consecutive patients (n = 30) aged ≥75 years planning to undergo laparoscopic surgery for genital prolapse by the same surgeon were recruited from October 2016 through December 2019. INTERVENTIONS: Laparoscopic promontofixation for the treatment of genital prolapse was performed using low IPP and warmed, humidified carbon dioxide gas. When a promontory could not be easily identified, laparoscopic pectopexy was alternatively performed. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the Quality of Recovery-40 (QoR-40) score at 24 hours postoperatively. The secondary outcomes were postoperative pain using a 100-mm visual analog scale and the length of hospital stay after surgery (LHSS). For the global QoR-40 score and for 4 dimensions of the QoR-40, "emotional state," "physical comfort," "psychologic support," and "pain," no differences were observed between the baseline score and the score at 24 hours. The score for the "physical independence" dimension at 24 hours was significantly lower than the baseline score (p <.001). No patient had visual analog scale pain scores >30 out of 100 at 12 hours or later. LHSS was <48 hours in 22 patients (73.3%) and <72 hours in 8 patients (26.7%). Multivariable analysis showed that the odds of an LHSS >48 hours were more than 8 times higher in patients who were discharged from the operating room in the afternoon compared with those with a morning discharge. CONCLUSION: The use of a low IPP is feasible, safe, and has clinical benefits for elderly patients aged ≥75 years who undergo laparoscopic surgery for genital prolapse.

Halogenated Agent Delivery in Porcine Model of Acute Respiratory Distress Syndrome via an Intensive Care Unit Type Device.

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.

Early Changes Over Time in the Radiographic Assessment of Lung Edema Score Are Associated With Survival in ARDS.

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.

Minimal alveolar concentration for deep sedation (MAC-DS) in intensive care unit patients sedated with sevoflurane: A physiological study.

BACKGROUND: 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). METHODS: 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). RESULTS: 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, P<0.001). 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. CONCLUSION: 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.

Effect of Hydroxyethyl Starch vs Saline for Volume Replacement Therapy on Death or Postoperative Complications Among High-Risk Patients Undergoing Major Abdominal Surgery: The FLASH Randomized Clinical Trial.

Importance: It is not known if use of colloid solutions containing hydroxyethyl starch (HES) to correct for intravascular deficits in high-risk surgical patients is either effective or safe. Objective: To evaluate the effect of HES 130/0.4 compared with 0.9% saline for intravascular volume expansion on mortality and postoperative complications after major abdominal surgery. Design, Setting, and Participants: Multicenter, double-blind, parallel-group, randomized clinical trial of 775 adult patients at increased risk of postoperative kidney injury undergoing major abdominal surgery at 20 university hospitals in France from February 2016 to July 2018; final follow-up was in October 2018. Interventions: Patients were randomized to receive fluid containing either 6% HES 130/0.4 diluted in 0.9% saline (n = 389) or 0.9% saline alone (n = 386) in 250-mL boluses using an individualized hemodynamic algorithm during surgery and for up to 24 hours on the first postoperative day, defined as ending at 7:59 am the following day. Main Outcomes and Measures: The primary outcome was a composite of death or major postoperative complications at 14 days after surgery. Secondary outcomes included predefined postoperative complications within 14 days after surgery, durations of intensive care unit and hospital stays, and all-cause mortality at postoperative days 28 and 90. Results: Among 826 patients enrolled (mean age, 68 [SD, 7] years; 91 women [12%]), 775 (94%) completed the trial. The primary outcome occurred in 139 of 389 patients (36%) in the HES group and 125 of 386 patients (32%) in the saline group (difference, 3.3% [95% CI, -3.3% to 10.0%]; relative risk, 1.10 [95% CI, 0.91-1.34]; P = .33). Among 12 prespecified secondary outcomes reported, 11 showed no significant difference, but a statistically significant difference was found in median volume of study fluid administered on day 1: 1250 mL (interquartile range, 750-2000 mL) in the HES group and 1500 mL (interquartile range, 750-2150 mL) in the saline group (median difference, 250 mL [95% CI, 83-417 mL]; P = .006). At 28 days after surgery, 4.1% and 2.3% of patients had died in the HES and saline groups, respectively (difference, 1.8% [95% CI, -0.7% to 4.3%]; relative risk, 1.76 [95% CI, 0.79-3.94]; P = .17). Conclusions and Relevance: Among patients at risk of postoperative kidney injury undergoing major abdominal surgery, use of HES for volume replacement therapy compared with 0.9% saline resulted in no significant difference in a composite outcome of death or major postoperative complications within 14 days after surgery. These findings do not support the use of HES for volume replacement therapy in such patients. Trial Registration: ClinicalTrials.gov Identifier: NCT02502773.

Transcultural validation of a French version of the Iowa Satisfaction with Anesthesia Scale (ISAS-F).

PURPOSE: We sought to validate a French translation of the Iowa Satisfaction with Anesthesia Scale (ISAS), a tool to assess the patient's satisfaction with monitored anesthesia care for surgery. The ISAS tool is particularly pertinent as surgery with monitored anesthesia care is increasingly used in ambulatory surgery settings. METHODS: We studied content validity, internal consistency, convergent validity (vs physician-estimated satisfaction), and test-retest reliability of the French version of the ISAS (ISAS-F) in 122 adult patients undergoing a brief outpatient invasive procedure under conscious sedation. The ISAS-F was answered twice by the patient, once in the postanesthesia care unit and once before discharge from the ambulatory care unit. RESULTS: The median [interquartile range (IQR)] time of completion at the first assessment was 2 [2-4] min. The total median [IQR] ISAS-F score was 2.3 [1.8-2.7]. Internal consistency of the ISAS-F was found to be good (Cronbach's α = 0.68). Test-retest reliability was significant, with an intra-class correlation coefficient at 0.74 (95% confidence interval [CI], 0.63 to 0.85). The ISAS-F score correlated with the physician-estimated satisfaction score, with an intra-class correlation coefficient of 0.28 (95% CI, 0.12 to 0.44; P = 0.01). DISCUSSION: This validated version of the ISAS can now be used by French-speaking researchers and physicians to assess patient satisfaction with the anesthesia technique.

RéSUMé: OBJECTIF: Nous avons voulu valider une traduction française de l'échelle de satisfaction par rapport à l'anesthésie de l'Iowa (ISAS), un outil d'évaluation de la satisfaction du patient par rapport aux soins sous surveillance anesthésique lors de chirurgies. L'outil ISAS est particulièrement pertinent étant donné que les chirurgies réalisées sous surveillance anesthésique sont de plus en plus fréquemment utilisées dans le contexte de chirurgie ambulatoire. MéTHODE: Nous avons étudié la validité de contenu, la cohérence interne, la validité convergente (vs la satisfaction estimée par le médecin) et la fiabilité de test-retest de la version française de l'ISAS (ISAS-F) auprès de 122 patients adultes subissant une courte intervention ambulatoire sous sédation légère. Les patients ont répondu deux fois au ISAS-F, soit une fois en salle de réveil et une seconde fois avant de recevoir leur congé de l'unité de soins ambulatoires. RéSULTATS: Le temps médian [écart interquartile (ÉIQ)] pour compléter le test lors de la première évaluation était de 2 [2­4] min. Le score total médian [ÉIQ] sur l'ISAS-F était de 2,3 [1,8­2,7]. La cohérence interne de l'ISAS-F était bonne (α de Cronbach = 0,68). La fiabilité de test-retest était appréciable, avec un coefficient de corrélation intraclasse de 0,74 (intervalle de confiance [IC] 95 %, 0,63 à 0,85). Le score sur l'ISAS-F était corrélé au score de satisfaction tel qu'estimé par le médecin, avec un coefficient de corrélation intraclasse de 0,28 (IC 95 %, 0,12 à 0,44; P = 0,01). DISCUSSION: Cette version validée de l'ISAS peut désormais être utilisée par les chercheurs et médecins francophones afin d'évaluer la satisfaction des patients avec la technique anesthésique employée.

Investigator-initiated, multicentre, open-label, two-arm, randomised controlled trial comparing intubating conditions in 25° head-up position and supine: the InSize25 study protocol.

INTRODUCTION: Difficult 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 ANALYSIS: InSize25 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 DISSEMINATION: The 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 NUMBER: Clinicaltrials.gov identifier (NCT03339141).

Sedation versus general anaesthesia in endovascular therapy for anterior circulation acute ischaemic stroke: the multicentre randomised controlled AMETIS trial study protocol.

INTRODUCTION: Endovascular 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 ANALYSIS: Anesthesia 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 DISSEMINATION: The 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 NUMBER: NCT03229148.

Personalised mechanical ventilation tailored to lung morphology versus low positive end-expiratory pressure for patients with acute respiratory distress syndrome in France (the LIVE study): a multicentre, single-blind, randomised controlled trial.

BACKGROUND: 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. METHODS: 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. FINDINGS: 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 (p<0·001). 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. INTERPRETATION: 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. FUNDING: French Ministry of Health (Programme Hospitalier de Recherche Clinique InterRégional 2013).

French legal approach to clinical research.

Since 1988, France has been committed to drafting laws regulating clinical research. These laws must both reflect general legal standards relating to personal data protection and patient information and comply with EU regulations, which are supra-national norms. The 2012 legislation known as "Jardé law" came into force in 2016 and distinguishes between 3 different types of research involving human subjects: category 1:interventional research implying an intervention on the patient which is not justified by their usual treatment. Category 2: interventional research, which does not focus on medicinal products and only entails minimal risks and constraints. Category 3: non-interventional research implying one or multiple acts or proceedings devoid of listed risks. These studies require preliminary favourable opinions from the French Ethical Research Committees (CPP), who are appointed by the State, and must ensure the protection of personal data. For the other types of studies (retrospective data, practice surveys), French legislation only requires that the protection of personal data is ensured. However, it is highly recommended to submit these studies to an Institutional Review Board (IRB) in order to confirm that human subjects are not involved and to obtain an ethical opinion in the event of a scientific journal submission. These laws are constantly evolving in order to comply with the various international recommendations and European regulations, which are binding in France.

In Vitro Method to Control Concentrations of Halogenated Gases in Cultured Alveolar Epithelial Cells.

Acute respiratory distress syndrome (ARDS) is a syndrome of diffuse alveolar injury with impaired alveolar fluid clearance and severe inflammation. The use of halogenated agents, such as sevoflurane or isoflurane, for the sedation of intensive care unit (ICU) patients can improve gas exchange, reduce alveolar edema, and attenuate inflammation during ARDS. However, data on the use of inhaled agents for continuous sedation in the ICU to treat or prevent lung damage is lacking. To study the effects of halogenated agents on alveolar epithelial cells under "physiologic" conditions, we describe an easy system to culture cells at the air-liquid interface and expose them to halogenated agents to provide precise controlled "air" fractions and "medium" concentrations for these agents. We developed a sealed air-tight chamber in which plates with human alveolar epithelial immortalized cells could be exposed to a precise, controlled fraction of sevoflurane or isoflurane using a continuous gas flow provided by an anesthetic machine circuit. Cells were exposed to 4% of sevoflurane and 1% of isoflurane for 24 hours. Gas mass spectrometry was performed to determine the concentration of halogenated agents dissolved in the medium. After the first hour, the concentrations of sevoflurane and isoflurane in the medium were 251 mg/L and 25 mg/L, respectively. The curves representing the concentrations of both sevoflurane and isoflurane dissolved in the medium showed similar courses over time, with a plateau reached at one hour after exposure. This protocol was specifically designed to reach precise and controlled concentrations of sevoflurane or isoflurane in vitro to improve our understanding of mechanisms involved in epithelial lung injury during ARDS and to test novel therapies for the syndrome.