Dynamic assessment of prealbumin for nutrition support effectiveness in critically ill patients.

BACKGROUND & AIMS: Serum prealbumin is considered to be a sensitive predictor of clinical outcomes and a quality marker for nutrition support. However, its susceptibility to inflammation restricts its usage in critically ill patients according to current guidelines. We assessed the performance of the initial value of prealbumin and dynamic changes for predicting the ICU mortality and the effectiveness of nutrition support in critically ill patients. METHODS: This monocentric study included patients admitted to the ICU between 2009 and 2016, having at least one initial prealbumin value available. Prospectively recorded data were extracted from the electronic ICU charts. We used both univariable and multivariable logistic regressions to estimate the performance of prealbumin for the prediction of ICU mortality. Additionally, the association between prealbumin dynamic changes and nutrition support was assessed via a multivariable linear mixed-effects model and multivariable linear regression. Performing subgroup analysis assisted in identifying patients for whom prealbumin dynamic assessment holds specific relevance. RESULTS: We included 3136 patients with a total of 4942 prealbumin levels available. Both prealbumin measured at ICU admission (adjusted odds-ratio (aOR) 0.04, confidence interval (CI) 95% 0.01-0.23) and its change over the first week (aOR 0.02, CI 95 0.00-0.19) were negatively associated with ICU mortality. Throughout the entire ICU stay, prealbumin dynamic changes were associated with both cumulative energy (estimate: 33.2, standard error (SE) 0.001, p < 0.01) and protein intakes (1.39, SE 0.001, p < 0.01). During the first week of stay, prealbumin change was independently associated with mean energy (6.03e-04, SE 2.32e-04, p < 0.01) and protein intakes (1.97e-02, SE 5.91e-03, p < 0.01). Notably, the association between prealbumin and energy intake was strongest among older or malnourished patients, those suffering from increased inflammation and those with high disease severity. Finally, prealbumin changes were associated with a positive mean nitrogen balance at day 7 only in patients with SOFA <4 (p = 0.047). CONCLUSION: Prealbumin measured at ICU admission and its change during the first-week serve as an accurate predictor of ICU mortality. Prealbumin dynamic assessment may be a reliable tool to estimate the effectiveness of nutrition support in the ICU, especially among high-risk patients.

Safety and Efficacy of Mini-invasive left atrial appendage closure : a propensity score analysis.

BACKGROUND: Left atrial appendage closure (LAAC) for stroke prevention is validated in patients with non-valvular atrial fibrillation (NVAF) contraindicated to oral anticoagulation. General anesthesia (GA) is often used for procedural guidance by trans-oesophageal echocardiography (TEE); however, its use may be challenging in some patients. The aim of the study was to evaluate the safety and the mid-term efficacy of a mini-invasive LAAC strategy using micro-TEE under procedural sedation. METHODS: Comparison by propensity score of two cohorts of consecutive patients who underwent LAAC: standard TEE-guided LAAC (3D-TEE under GA) and, mini-invasive LAAC strategy (micro-TEE under procedural sedation). The primary endpoint was a composite of embolic or bleeding events, significant per-procedural complication, and cardiovascular deaths within 3 months after LAAC. RESULTS: In total, 432 patients were included (78.7±8 years old, 32.4% of women, CHA2DS2VASC score:4.9±1.1); 127 patients underwent mini-invasive LAAC strategy and were compared to 305 patients standard TEE-guided LAAC. The mini-invasive strategy was acheived in 122/127 (96.1%) planned patients. The primary endpoint occurred in 11.2% of patients from the mini-invasive LAAC strategy group and in 10.3% of patients from the standard TEE group (absolute difference = 0.9%[-6.4; 4.5], hazard-ratio=1.11[0.56; 2.19], p=0.76). Procedural times, fluoroscopy duration and hospital stays were shorter in the mini-invasive LAAC strategy group (p<0.001). CONCLUSIONS: The mini-invasive LAAC strategy is safe and effective compared to the standard TEE-guided LAAC strategy. A mini-invasive LAAC strategy may also be an important tool to help physicians to treat more patients as LAAC indications evolve in the future.

Cost awareness among intensivists in their daily clinical practice: a prospective multicentre study.

BACKGROUND: Better cost-awareness is a prerogative in achieving the best benefit/risk/cost ratio in the care. We aimed to assess the cost-awareness of intensivists in their daily clinical practice and to identify factors associated with accurate estimate of cost (50-150% of the real cost). METHODS: We performed a prospective observational study in seven French ICUs. We compared the estimate of intensivists of the daily costs of caring with the real costs on a given day. The estimates covered five categories (drugs, laboratory tests, imaging modalities, medical devices, and waste) whose sum represented the overall cost. RESULTS: Of the 234 estimates made by 65 intensivists, 70 (29.9%) were accurate. The median overall cost estimate (€330 [170; 620]) was significantly higher than the real cost (€178 [124; 239], p < 0.001). This overestimation was found in four categories, in particular for waste (€40 [15; 100] vs. €1.1 [0.6; 2.3], p < 0.001). Only the laboratory tests were underestimated (€65 [30; 120] vs. €106 [79; 138], p < 0.001). Being aware of the financial impact of prescriptions was factor associated with accurate estimate (OR: 5.05, 95%CI:1.47-17.4, p = 0.01). However, feeling able to accurately perform estimation was factor negatively associated with accurate estimate (OR: 0.11, 95%CI: 0.02-0.71, p = 0.02). CONCLUSION: French intensivists have a poor awareness of costs in their daily clinical practice. Raising awareness of the financial impact of prescriptions, and of the cost of laboratory tests and waste are the main areas for improvement that could help achieve the objective of the best care at the best cost.

Prevalence of FGF23 elevation in patients with hypophosphatemia.

BACKGROUND AND AIMS: To investigate the contribution of FGF23 in explaining the cases of hypophosphatemia observed in clinical practice, we aimed to determine for the first time the prevalence of FGF23 elevation in patients with hypophosphatemia and to describe the different mechanisms of FGF23-related hypophosphatemic disorders. MATERIALS AND METHODS: We performed a prospective, observational, multicenter, cohort study of 260 patients with hypophosphatemia. Blood measurements (PTH, 1,25-dihydroxyvitamin D, bone alkaline phosphatase, 25-hydroxyvitamin D, and FGF23) were performed on a Liaison XL® (DiaSorin) analyzer. RESULTS: Primary elevation of FGF23 (>95.4 pg/mL) was reported in 10.4% (95CI: 7.0-14.7) of patients (n = 27) with hypophosphatemia, suggesting that at least 1 in 10 cases of hypophosphatemia was erroneously attributed to an etiology other than FGF23 elevation. Patients with elevated blood FGF23 were grouped according to the etiology of the FGF23 elevation. Thus, 10 patients had a renal pathology, chronic kidney disease or post-renal transplantation condition. The remaining patients (n = 17) had the following etiologies: malignancies (n = 9), benign pancreatic tumor (n = 1), post-cardiac surgery (n = 4), cirrhosis (n = 2), and chronic obstructive pulmonary disease (n = 1). CONCLUSION: In order to improve patient management, it seems essential to better integrate plasma FGF23 measurement into the routine evaluation of hypophosphatemia.

Intraoperative blood pressure: could less be more?

Retrospective observational studies have reported a significant association between intraoperative hypotension and postoperative morbidity. However, association does not imply causation, and whether preventing intraoperative hypotension can improve patient outcome remains to be demonstrated. In this issue of the British Journal of Anaesthesia, D'Amico and colleagues meta-analysed 10 prospective randomised trials comparing low (≤60 mm Hg) and higher mean arterial pressure targets during anaesthesia and surgery. They did not observe an increase in postoperative morbidity and mortality in the low target group. In contrast, they reported a statistically significant (but not clinically relevant) reduction in postoperative cardiac arrhythmia and hospital length of stay when targeting mean arterial pressure ≤60 mm Hg. These findings suggest that during most surgical cases, intraoperative hypotension is a marker of the severity, frailty, or both rather than a mediator of postoperative complications.

Sample size estimation in clinical trials using ventilator-free days as the primary outcome: a systematic review.

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 ).

Pulse contour techniques for perioperative hemodynamic monitoring: A nationwide carbon footprint and cost estimation.

BACKGROUND: The question of environmentally sustainable perioperative medicine represents a new challenge in an era of cost constraints and climate crisis. The French Society of Anaesthesia and Intensive Care (SFAR) recommends stroke volume optimization in high-risk surgical patients. Pulse contour techniques have become increasingly popular for stroke volume monitoring during surgery. Some require the use of specific disposable pressure transducers (DPTs), whereas others can be used with standard DPTs. OBJECTIVE: Quantify and compare the carbon footprint and cost of pulse contour techniques using specific and standard DPTs on a yearly basis and at a national level. METHODS: We estimated the number of high-risk surgical patients monitored every year in France with a pulse contour technique, and the plastic waste, carbon footprint and cost associated with the use of specific and standard DPTs. MAIN FINDINGS: When compared to pulse contour techniques working with a standard DPT, techniques requiring a specific DPT are responsible for an increase in carbon dioxide emission estimated at 65-83 tons/yr and for additional hospital cost estimated at €67 million/yr. If, as recommended by the SFAR, all high-risk surgical patients were monitored, the difference would reach 179-227 tons/yr for the environmental impact and €187 million/yr for the economic impact. CONCLUSION: From an environmental and economic standpoint, pulse contour techniques working with standard DPTs should be recommended for the perioperative hemodynamic monitoring of high-risk surgical patients.

Thoracic epidural analgesia in intensive care unit patients with acute pancreatitis: the EPIPAN multicenter randomized controlled trial.

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.

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.

Predicting intraoperative hypotension: from hope to hype and back to reality.

The analysis of arterial pressure waveforms with machine learning algorithms has been proposed to predict intraoperative hypotension. The ability to forecast arterial hypotension 5-15 min ahead of the fall in blood pressure allows clinicians to be pro-active instead of reactive, and could potentially decrease postoperative morbidity. However, the predictive value of machine learning algorithms has been overestimated due to selection bias in several clinical studies, and they might not be superior to mere observation of arterial pressure. Continuous blood pressure monitoring enables immediate detection of hypotension, and giving fluid, vasopressors or inotropes to patients who are not yet (and might never become) hypotensive based on an algorithm is questionable. Finally, recent prospective interventional studies suggest that reducing intraoperative hypotension does not improve postoperative outcomes.

Ionized Magnesium: Interpretation and Interest in Atrial Fibrillation.

BACKGROUND: Magnesium (Mg) is often used to manage de novo atrial fibrillation (AF) in the emergency department (ED) and intensive care unit (ICU). Point of care measurement of ionized magnesium (iMg) allows a rapid identification of patients with impaired magnesium status, however, unlike ionized calcium, the interpretation of iMg is not entirely understood. Thus, we evaluated iMg reference values, correlation between iMg and plasmatic magnesium (pMg), and the impact of pH and albumin variations on iMg levels. Secondary objectives were to assess the incidence of hypomagnesemia in de novo AF. METHODS: A total of 236 emergency department and intensive care unit patients with de novo AF, and 198 control patients were included. Reference values were determined in the control population. Correlation and concordance between iMg and pMg were studied using calcium (ionized and plasmatic) as a control in the whole study population. The impact of albumin and pH was assessed in the discordant iMg and pMg values. Lastly, we assessed the incidence of ionized hypomagnesemia (hypoMg) among de novo AF. RESULTS: The reference range values established in our study for iMg were: 0.48-0.65 mmol/L (the manufacturers were: 0.45-0.60 mmol/L). A strong correlation was observed between pMg and iMg (r = 0.85), but, unlike for calcium values, there was no significant impact of pH and albumin in iMg/pMg interpretation. The incidence of hypoMg among de novo AF patients was 8.5% (12.7% using our ranges). When using our ranges, we found a significant link (p = 0.01) between hyopMg and hypokalemia. CONCLUSION: We highlight the need for more accurate reference range values of iMg. Furthermore, our results suggest that blood Mg content is not identical to that of calcium. The incidence of ionized hypomagnesemia among de novo AF patients in our study is 8.5%.

Effect of non-invasive ventilation after extubation in critically ill patients with obesity in France: a multicentre, unblinded, pragmatic randomised clinical trial.

BACKGROUND: Non-invasive ventilation (NIV) and oxygen therapy (high-flow nasal oxygen [HFNO] or standard oxygen) following extubation have never been compared in critically ill patients with obesity. We aimed to compare NIV (alternating with HFNO or standard oxygen) and oxygen therapy (HFNO or standard oxygen) following extubation of critically ill patients with obesity. METHODS: In this multicentre, parallel group, pragmatic randomised controlled trial, conducted in 39 intensive care units in France, critically ill patients with obesity undergoing extubation were randomly assigned (1:1) to either the NIV group or the oxygen therapy group. Two randomisations were performed: first, randomisation to either NIV or oxygen therapy, and second, randomisation to either HFNO or standard oxygen (also 1:1), which was nested within the first randomisation. Blinding of the randomisation was not possible, but the statistician was masked to group assignment. The primary outcome was treatment failure within 3 days after extubation, a composite of reintubation for mechanical ventilation, switch to the other study treatment, or premature discontinuation of study treatment. The primary outcome was analysed by intention to treat. Effect of medical and surgical status was assessed. The reintubation within 3 days was analysed by intention to treat and after a post-hoc crossover analysis. This study is registered with ClinicalTrials.gov, number NCT04014920. FINDINGS: From Oct 2, 2019, to July 17, 2021, of the 1650 screened patients, 981 were enrolled. Treatment failure occurred in 66 (13·5%) of 490 patients in the NIV group and in 130 (26·5%) of 491 patients in the oxygen-therapy group (relative risk 0·43; 95% CI 0·31-0·60, p<0·0001). Medical or surgical status did not modify the effect of NIV group on the treatment-failure rate. Reintubation within 3 days after extubation was similar in the non-invasive ventilation group and in the oxygen therapy group in the intention-to-treat analysis (48 (10%) of 490 patients and 59 (12%) of 491 patients, p=0·26) and lower in the NIV group than in the oxygen-therapy group in the post-hoc cross-over (51 (9%) of 560 patients and 56 (13%) of 421 patients, p=0·037) analysis. No severe adverse events were reported. INTERPRETATION: Among critically ill adults with obesity undergoing extubation, the use of NIV was effective to reduce treatment-failure within 3 days. Our results are relevant to clinical practice, supporting the use of NIV after extubation of critically ill patients with obesity. However, most of the difference in the primary outcome was due to patients in the oxygen therapy group switching to NIV, and more evidence is needed to conclude that an NIV strategy leads to improved patient-centred outcomes. FUNDING: French Ministry of Health.

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.

Effect of oral antimicrobial prophylaxis on surgical site infection after elective colorectal surgery: multicentre, randomised, double blind, placebo controlled trial.

OBJECTIVE: To investigate whether oral antimicrobial prophylaxis as an adjunct to intravenous antibiotic prophylaxis reduces surgical site infections after elective colorectal surgery. DESIGN: Multicentre, randomised, double blind, placebo controlled trial. SETTING: 11 university and non-university hospitals in France between 25 May 2016 and 8 August 2019. PARTICIPANTS: 926 adults scheduled for elective colorectal surgery. INTERVENTION: Patients were randomised to receive either a single 1 g dose of ornidazole (n=463) or placebo (n=463) orally 12 hours before surgery, in addition to intravenous antimicrobial prophylaxis before surgical incision. MAIN OUTCOME MEASURES: The primary outcome was the proportion of patients with surgical site infection within 30 days after surgery. Secondary outcomes included individual types of surgical site infections and major postoperative complications (Clavien-Dindo classification grade 3 or higher) within 30 days after surgery. RESULTS: Of the 960 patients who were enrolled, 926 (96%) were included in the analysis. The mean age of participants was 63 years and 554 (60%) were men. Surgical site infection within 30 days after surgery occurred in 60 of 463 patients (13%) in the oral prophylaxis group and 100 of 463 (22%) in the placebo group (absolute difference -8.6%, 95% confidence interval -13.5% to -3.8%; relative risk 0.60, 95% confidence interval 0.45 to 0.80). The proportion of patients with deep infections was 4.8% in the oral prophylaxis group and 8.0% in the placebo group (absolute difference -3.2%, 95% confidence interval -6.4% to -0.1%). The proportion of patients with organ space infections was 5.0% in the oral prophylaxis group and 8.4% in the placebo group (absolute difference -3.4%, -6.7% to -0.2%). Major postoperative complications occurred in 9.1% patients in the oral prophylaxis group and 13.6% in the placebo group (absolute difference -4.5%, -8.6% to -0.5%). CONCLUSION: Among adults undergoing elective colorectal surgery, the addition of a single 1 g dose of ornidazole compared with placebo before surgery significantly reduced surgical site infections. TRIAL REGISTRATION: ClinicalTrials.gov NCT02618720.

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.

Association between proteinuria trajectories and outcomes in critically ill patients with sepsis or shock.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 (p<0.001) and a mortality of 24.4%, 38%, 20% and 43% (p = 0.002), respectively. Trajectories 3 and 4 had a high first proteinuria (>2g/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). CONCLUSION: 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.

One-year patient outcomes based on lung morphology in acute respiratory distress syndrome: secondary analysis of LIVE trial.

BACKGROUND: Acute respiratory distress syndrome (ARDS) has different phenotypes and distinct short-term outcomes. Patients with non-focal ARDS have a higher short-term mortality than focal ones. The aim of this study was to assess the impact of the morphological phenotypes of ARDS on long-term outcomes. METHODS: This was a secondary analysis of the LIVE study, a prospective, randomised control trial, assessing the usefulness of a personalised ventilator setting according to lung morphology in moderate-to-severe ARDS. ARDS was classified as focal (consolidations only in the infero-posterior part of the lungs) or non-focal. Outcomes were assessed using mortality and functional scores for quality of life at the 1-year follow-up. RESULTS: A total of 124 focal ARDS and 236 non-focal ARDS cases were included. The 1-year mortality was higher for non-focal ARDS than for focal ARDS (37% vs. 24%, p = 0.012). Non-focal ARDS (hazard ratio, 3.44; 95% confidence interval, 1.80-6.59; p < 0.001), age, McCabe score, haematological cancers, SAPS II, and renal replacement therapy were independently associated with 1-year mortality. This difference was driven by mortality during the first 90 days (28 vs. 16%, p = 0.010) but not between 90 days and 1 year (7 vs. 6%, p = 0.591), at which point only the McCabe score was independently associated with mortality. Morphological phenotypes had no impact on patient-reported outcomes. CONCLUSION: Lung morphologies reflect the acute phase of ARDS and its short-term impact but not long-term outcomes, which seem only influenced by comorbidities. TRIAL REGISTRATION: NCT02149589; May 29, 2014.

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.

Intraoperative protective mechanical ventilation in patients requiring emergency abdominal surgery: the multicentre prospective randomised IMPROVE-2 study protocol.

IntroductionEmergency abdominal surgery is associated with a high risk of postoperative complications. One of the most serious is postoperative respiratory failure (PRF), with reported rates up to 20%-30% and attributable 30-day mortality that can exceed 20%.Lung-protective ventilation, especially the use of low tidal volume, may help reducing the risk of lung injury. The role of positive end-expiratory pressure (PEEP) and recruitment manoeuvre (RM) remains however debated. We aim to evaluate whether a strategy aimed at increasing alveolar recruitment by using higher PEEP levels and RM could be more effective at reducing PRF and mortality after emergency abdominal surgery than a strategy aimed at minimising alveolar distension by using lower PEEP levels without RM. METHODS AND ANALYSIS: The IMPROVE-2 study is a multicentre randomised, parallel-group clinical trial of 680 patients requiring emergency abdominal surgery under general anaesthesia. Patients will be randomly allocated in a 1:1 ratio to receive either low PEEP levels (≤5 cm H2O) without RM or high PEEP levels individually adjusted according to driving pressure in addition to RM, stratified by centre and according to the presence of shock and hypoxaemia at randomisation. The primary endpoint is a composite of PRF and all-cause mortality by day 30 or hospital discharge. Data will be analysed on the intention-to-treat principle and a per-protocol basis. ETHICS AND DISSEMINATION: IMPROVE-2 trial has been approved by an independent ethics committee for all study centres. Participant recruitment began in February 2021. Results will be submitted for publication in international peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03987789.