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Low-tidal-volume ventilation with positive end-expiratory pressure is the standard of care in acute respiratory distress syndrome. In this trial, the use of protective ventilation during surgery, as compared with nonprotective ventilation, reduced postoperative complications. Worldwide, more than 230 million patients undergoing major surgery each year require general anesthesia and mechanical ventilation. 1 Postoperative pulmonary complications adversely affect clinical outcomes and health care utilization, 2 so prevention of these complications has become a measure of the quality of hospital care. 3 Previous, large cohort studies have shown that 20 to 30% of patients undergoing surgery with general anesthesia are at intermediate to high risk for postoperative pulmonary complications. 4 , 5 Mechanical ventilation with the use of high tidal volumes (10 to 15 ml per kilogram of predicted body weight) has traditionally been recommended to prevent hypoxemia and atelectasis in . . .

Abstract Rationale Sevoflurane improves gas exchange, and reduces alveolar edema and inflammation in preclinical studies of lung injury, but its therapeutic effects have never been investigated in acute respiratory distress syndrome (ARDS). Objectives To assess whether sevoflurane would improve gas exchange and inflammation in ARDS. Methods We did a parallel, open-label single-center randomized controlled trial at three intensive care units from a French university hospital between April 2014 and February 2016. Adult patients were randomized within 24 hours of moderate-to-severe ARDS onset to receive either intravenous midazolam or inhaled sevoflurane for 48 hours. The primary outcome was the PaO2/FiO2 ratio on Day 2. Secondary endpoints included alveolar and plasma levels of cytokines and soluble form of the receptor for advanced glycation end-products, and safety. Investigators who did the analyses were masked to group allocation. Analysis was by intention to treat. Measurements and Main Results Twenty-five patients were assigned to the sevoflurane group and 25 to the midazolam group. On Day 2, PaO2/FiO2 ratio was higher in the sevoflurane group than in the midazolam group (mean ± SD, 205 ± 56 vs. 166 ± 59, respectively; P = 0.04). There was a significant reduction over time in cytokines and soluble form of the receptor for advanced glycation end-products levels in the sevoflurane group, compared with the midazolam group, and no serious adverse event was observed with sevoflurane. Conclusions In patients with ARDS, use of inhaled sevoflurane improved oxygenation and decreased levels of a marker of epithelial injury and of some inflammatory markers, compared with midazolam. Clinical trial registered with www.clinicaltrials.gov (NCT 02166853).

Early mortality in acute myeloid leukemia (AML) remains a clinical challenge, yet robust, simple predictors are lacking. This study evaluates the prognostic value of the Endothelial Activation and Stress Index (EASIX), calculated using LDH, creatinine, and platelets, for predicting early fatal complications in newly diagnosed (ND) AML. We conducted a retrospective single-center cohort study of 158 adult patients with ND AML treated with intensive induction chemotherapy. The EASIX score was calculated at diagnosis (day 1). The co-primary endpoints were ICU admission and death from any cause within 3 months. The median log2-EASIX was 2.10. Hish-risk patients (upper quartile, threshold 3.53) had significantly higher 3-month mortality (32.5% vs. 5.1%, p < 0.001) and ICU admission rates (50% vs. 19.6%, p < 0.001). In multivariate analysis, high EASIX was an independent predictor of 3-month mortality (OR 6.60; 95% CI 1.93–22.50) and ICU admission (OR 4.05, 95% CI 1.63–10.05). The EASIX score is a simple tool that predicts early adverse outcomes in ND AML.

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. 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. 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. 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.

Background Ventilator-free days (VFDs) are a composite endpoint increasingly used as the primary outcome in critical care trials. However, because of the skewed distribution and competitive risk between components, sample size estimation remains challenging. This systematic review was conducted to systematically assess whether the sample size was congruent, as calculated to evaluate VFDs in trials, with VFDs’ distribution and the impact of alternative methods on sample size estimation. Methods A systematic literature search was conducted within the PubMed and Embase databases for randomized clinical trials in adults with VFDs as the primary outcome until December 2021. We focused on peer-reviewed journals with 2021 impact factors greater than five. After reviewing definitions of VFDs, we extracted the sample size and methods used for its estimation. The data were collected by two independent investigators and recorded in a standardized, pilot-tested forms tool. Sample sizes were calculated using alternative statistical approaches, and risks of bias were assessed with the Cochrane risk-of-bias tool. Results Of the 26 clinical trials included, 19 (73%) raised “some concerns” when assessing risks of bias. Twenty-four (92%) trials were two-arm superiority trials, and 23 (89%) were conducted at multiple sites. Almost all the trials (96%) were unable to consider the unique distribution of VFDs and death as a competitive risk. Moreover, significant heterogeneity was found in the definitions of VFDs, especially regarding varying start time and type of respiratory support. Methods for sample size estimation were also heterogeneous, and simple models, such as the Mann–Whitney–Wilcoxon rank-sum test, were used in 14 (54%) trials. Finally, the sample sizes calculated varied by a factor of 1.6 to 17.4. Conclusions A standardized definition and methodology for VFDs, including the use of a core outcome set, seems to be required. Indeed, this could facilitate the interpretation of findings in clinical trials, as well as their construction, especially the sample size estimation which is a trade-off between cost, ethics, and statistical power. Systematic review registration PROSPERO ID: CRD42021282304. Registered 15 December 2021 ( https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021282304 ).

Introduction The purpose of this study was to evaluate the clinical relevance of high values of central venous-to-arterial carbon dioxide difference (PCO 2 gap) in high-risk surgical patients admitted to a postoperative ICU. We hypothesized that PCO 2 gap could serve as a useful tool to identify patients still requiring hemodynamic optimization at ICU admission. Methods One hundred and fifteen patients were included in this prospective single-center observational study during a 1-year period. High-risk surgical inclusion criteria were adapted from Schoemaker and colleagues. Demographic and biological data, PCO 2 gap, central venous oxygen saturation, lactate level and postoperative complications were recorded for all patients at ICU admission, and 6 hours and 12 hours after admission. Results A total of 78 (68%) patients developed postoperative complications, of whom 54 (47%) developed organ failure. From admission to 12 hours after admission, there was a significant difference in mean PCO 2 gap (8.7 ± 2.8 mmHg versus 5.1 ± 2.6 mmHg; P  = 0.001) and median lactate values (1.54 (1.1-3.2) mmol/l versus 1.06 (0.8-1.8) mmol/l; P  = 0.003) between patients who developed postoperative complications and those who did not. These differences were maximal at admission to the ICU. At ICU admission, the area under the receiver operating characteristic curve for occurrence of postoperative complications was 0.86 for the PCO 2 gap compared to Sequential Organ Failure Assessment score (0.82), Simplified Acute Physiology Score II score (0.67), and lactate level (0.67). The threshold value for PCO 2 gap was 5.8 mmHg. Multivariate analysis showed that only a high PCO 2 gap and a high Sequential Organ Failure Assessment score were independently associated with the occurrence of postoperative complications. A high PCO 2 gap (≥6 mmHg) was associated with more organ failure, an increase in duration of mechanical ventilation and length of hospital stay. Conclusion A high PCO 2 gap at admission in the postoperative ICU was significantly associated with increased postoperative complications in high-risk surgical patients. If the increase in PCO 2 gap is secondary to tissue hypoperfusion then the PCO 2 gap might be a useful tool complementary to central venous oxygen saturation as a therapeutic target.

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. 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. 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. 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.

PurposeTo 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.MethodsMulticenter 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.ResultsA 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.ConclusionIn 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.

Background Findings from preclinical studies and one pilot clinical trial suggest potential benefits of epidural analgesia in acute pancreatitis. We aimed to assess the efficacy of thoracic epidural analgesia, in addition to usual care, in improving clinical outcomes of intensive care unit patients with acute pancreatitis. Methods A multicenter, open-label, randomized, controlled trial including adult patients with a clinical diagnosis of acute pancreatitis upon admission to the intensive care unit. Participants were randomly assigned (1:1) to a strategy combining thoracic epidural analgesia and usual care (intervention group) or a strategy of usual care alone (control group). The primary outcome was the number of ventilator-free days from randomization until day 30. Results Between June 2014 and January 2019, 148 patients were enrolled, and 135 patients were included in the intention-to-treat analysis, with 65 patients randomly assigned to the intervention group and 70 to the control group. The number of ventilator-free days did not differ significantly between the intervention and control groups (median [interquartile range], 30 days [15–30] and 30 days [18–30], respectively; median absolute difference of − 0.0 days, 95% CI − 3.3 to 3.3; p  = 0.59). Epidural analgesia was significantly associated with longer duration of invasive ventilation (median [interquartile range], 14 days [5–28] versus 6 days [2–13], p  = 0.02). Conclusions In a population of intensive care unit adults with acute pancreatitis and low requirement for intubation, this first multicenter randomized trial did not show the hypothesized benefit of epidural analgesia in addition to usual care. Safety of epidural analgesia in this setting requires further investigation. Trial registration : ClinicalTrials.gov registration number NCT02126332 , April 30, 2014.

Proteinuria results from kidney damage and can be a predictor of illness severity and mortality in the intensive care unit (ICU). However, the optimal timing of proteinuria measurements and the reference values remain undetermined. Our objective was to identify the patterns of proteinuria change associated with mortality in ICU patients with sepsis or shock. This monocentric retrospective cohort study performed from April 2010 to April 2018 involved all ICU patients with sepsis or shock and at least two measurements of proteinuria from a 24h-urine collection during the first 10 days of ICU stay, the first of which was made within 48h after ICU admission. We identified proteinuria trajectories by a semi-parametric mixture model and analysed the association between the trajectories and the mortality at day 28 by Cox proportional-hazards model. A total of 3,344 measurements of proteinuria from 659 patients were analysed. Four proteinuria trajectories were identified. Trajectories 1, 2, 3 and 4 comprised 127, 421, 60 and 51 patients, and were characterized by a first proteinuria of 1.14 [0.66-1.55], 0.52 [0.26-0.91], 2.92 [2.38-3.84] and 2.58 [1.75-3.32] g/24h (p2g/24h). Only, the proteinuria of trajectory 4 increased within 3 days following the first measurement and was associated with increased mortality at day 28 (hazard ratio: 2.36 95%CI [1.07-5.19], p = 0.03), regardless of acute renal failure. The factors associated with trajectory 4 were cancer (relative risk: 8.91 95%CI [2.09-38.02], p = 0.003) and use of inotropic drugs (relative risk: 0.17 95%CI [0.04-0.69], p = 0.01). This exploratory study of ICU patients with sepsis or shock identified four proteinuria trajectories with distinct patterns of proteinuria change over time and mortality rates. These results provide novel insights into renal pathophysiology and may be helpful to investigate subphenotypes of kidney injury among ICU patients in future studies.