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Le baclofène, initialement utilisé comme traitement antispastique, est depuis plusieurs années prescrit chez les patients alcoolodépendants pour favoriser le sevrage alcoolique. La France présente la spécificité d’avoir autorisé la mise sur le marché du baclofène dans cette indication depuis 2018. Les patients alcoolodépendants présentent un risque accru de tentative de suicide, notamment par intoxication volontaire. L’incidence des intoxications volontaires au baclofène s’est majoré sur la dernière décennie. Comparativement aux autres intoxications, celle-ci présente un recours fréquent à la ventilation mécanique (50% des cas) et une léthalité significative (plus de 2% des cas). Le toxidrome de l’intoxication aiguë au baclofène se résume principalement à une dépression du système nerveux central, pouvant aller de la sédation jusqu’au coma, et nécessitant une surveillance continue pour des doses suspectées ingérées supérieures à 200 mg. Le dosage plasmatique du baclofène permet de confirmer le diagnostic et de suivre l’évolution de l’élimination de la molécule. La principale voie d’élimination est rénale, motivant une surveillance accrue de la fonction rénale dans ce contexte. L’épuration extrarénale pourra se discuter dans les intoxications les plus sévères associées à une insuffisance rénale aiguë. Le reste de la prise en charge reste symptomatique, sans antidote existant. Le syndrome de sevrage au baclofène se rencontre lors d’un arrêt brutal du traitement, et peut être composé des symptômes suivants : spasticité, hyperthermie, agitation, rhabdomyolyse. Il peut compliquer l’hospitalisation de patients traités au long cours admis pour une intoxication aiguë. Son traitement nécessite une réintroduction précautionneuse du baclofène.

Case Presentation A 78-year-old woman was admitted to the ED with a 10-day history of diarrhea and recent onset of dry cough, fever, and asthenia. She had a medical history of obesity (BMI 32) and arterial hypertension treated with irbesartan. In the context of a large-scale lockdown in France during the COVID-19 pandemic, she only had physical contact with her husband, who did not report any symptoms. She required mechanical ventilation because of severe hypoxemia within 1 hour after admission to the ED.

Aims We aimed at assessing the effectiveness of renal replacement therapy in patients severely self-poisoned with baclofen and with normal kidney function. Methods A population pharmacokinetic model was built using analytical data extracted from 26 baclofen poisoning cases reported to a French Poison Centre: 8 patients underwent renal replacement therapy (RRT), 18 did not. In the RRT group, 2 patients suffered from kidney failure. Mechanical ventilation was required for 20 patients with normal kidney function; 15 were not treated by RRT and 5 were. Pharmacokinetic profiles of baclofen were measured in 28 patients and further modelled by a non-parametric approach (PMetrics®). The total data set was divided into a building data set (26 patients, 57 observations) and a validation set (2 external patients, 6 observations). Then, the estimated elimination half-life of baclofen and the duration of intubation were compared in patients with or without RRT using Wilcoxon–Mann–Whitney test. Results A model using three parameters plus a lag time and bioavailability was necessary to determine the pharmacokinetics of baclofen. Estimated elimination half-life in the ‘RRT’ group and the ‘no RRT’ group were respectively 3.1 [2.2−4.8] h (n = 6 patients) and 3.4 [1.4−5.5] h (n = 19 patients, p = 0.53). The median duration of intubation was not significantly different between groups (72 [48−72] h and 72 [24−96] h, respectively; p = 0.38). Conclusion Renal replacement therapy did not appear to significantly increase baclofen clearance in patients without kidney failure.

Purpose To describe acute respiratory distress syndrome (ARDS) severity, ventilation management, and the outcomes of ICU patients with laboratory-confirmed COVID-19 and to determine risk factors of 90-day mortality post-ICU admission. Methods COVID-ICU is a multi-center, prospective cohort study conducted in 138 hospitals in France, Belgium, and Switzerland. Demographic, clinical, respiratory support, adjunctive interventions, ICU length-of-stay, and survival data were collected. Results From February 25 to May 4, 2020, 4643 patients (median [IQR] age 63 [54–71] years and SAPS II 37 [28–50]) were admitted in ICU, with day-90 post-ICU admission status available for 4244. On ICU admission, standard oxygen therapy, high-flow oxygen, and non-invasive ventilation were applied to 29%, 19%, and 6% patients, respectively. 2635 (63%) patients were intubated during the first 24 h whereas overall 3376 (80%) received invasive mechanical ventilation (MV) at one point during their ICU stay. Median (IQR) positive end-expiratory and plateau pressures were 12 (10–14) cmH2O, and 24 (21–27) cmH2O, respectively. The mechanical power transmitted by the MV to the lung was 26.5 (18.6–34.9) J/min. Paralyzing agents and prone position were applied to 88% and 70% of patients intubated at Day-1, respectively. Pulmonary embolism and ventilator-associated pneumonia were diagnosed in 207 (9%) and 1209 (58%) of these patients. On day 90, 1298/4244 (31%) patients had died. Among patients who received invasive or non-invasive ventilation on the day of ICU admission, day-90 mortality increased with the severity of ARDS at ICU admission (30%, 34%, and 50% for mild, moderate, and severe ARDS, respectively) and decreased from 42 to 25% over the study period. Early independent predictors of 90-day mortality were older age, immunosuppression, severe obesity, diabetes, higher renal and cardiovascular SOFA score components, lower PaO2/FiO2 ratio and a shorter time between first symptoms and ICU admission. Conclusion Among more than 4000 critically ill patients with COVID-19 admitted to our ICUs, 90-day mortality was 31% and decreased from 42 to 25% over the study period. Mortality was higher in older, diabetic, obese and severe ARDS patients. Electronic supplementary material The online version of this article (10.1007/s00134-020-06294-x) contains supplementary material, which is available to authorized users.

Background Since the 2000s, opioid-free anesthesia (OFA) protocols have been spreading worldwide in anesthesia daily practice. These protocols avoid using opioid drugs during anesthesia to prevent short- and long-term opioid side effects while ensuring adequate analgesic control and optimizing postoperative recovery. Proofs of the effect of OFA protocol on optimizing postoperative recovery are still scarce. The study aims to compare the effects of an OFA protocol versus standard anesthesia protocol on the early quality of postoperative recovery (QoR) from major surgeries. Methods The SOFA trial is a prospective, randomized, parallel, single-blind, monocentric study. Patients (n = 140) scheduled for major plastic, visceral, urologic, gynecologic, or ear, nose, and throat (ENT) surgeries will be allocated to one of the two groups. The study group (OFA group) will receive a combination of clonidine, magnesium sulfate, ketamine, and lidocaine. The control group will receive a standard anesthesia protocol based on opioid use. Both groups will receive others standard practices for general anesthesia and perioperative care. The primary outcome measure is the QoR-15 value assessed at 24 h after surgery. Postoperative data such as pain intensity, the incidence of postoperative complication, and opioid consumption will be recorded. We will also collect adverse events that may be related to the anesthetic protocol. Three months after surgery, the incidence of chronic pain and the quality of life will be evaluated by phone interview. Discussion This will be the first study powered to evaluate the effect of OFA versus a standard anesthesia protocol using opioids on global postoperative recovery after a wide range of major surgeries. The SOFA trial will also provide findings concerning the OFA impact on chronic pain incidence and long-term patient quality of life. Trial registration ClinicalTrials.gov NCT04797312. Registered on 15 March 2021

When anesthesia checklists and preparations are performed urgently, omissions may occur and be deleterious to the patient. The aim of this study was to evaluate in simulation the interest of a cognitive aid to effectively prepare an anesthetic room for an emergency. In a prospective single-center simulation-based study, 32 anesthesia residents had to prepare an anesthetic room in an emergency scenario, without cognitive aid in the first phase. Three months later (phase 2), they were randomly assigned to receive a cognitive aid (aid group) or no additional aid (control) and were involved in the same scenario. The primary outcome was the validation rate of each essential item in the first 5 min in phase 2. Eight items were significantly more frequently completed in the first 5 min in the aid group in phase 2 (vs. phase 1), compared with two only in the control group. However, there were no significant differences in the overall number of completed items between the two groups, as both groups completed significantly more items in phase 2, either in the first 5 min (19 (14–23) vs. 13 (9–15) in phase 1 for all residents, p < 0.001) or without time limit. Preparation times were reduced in phase 2 in both groups. In conclusion, the use of a cognitive aid allowed anesthesia residents to complete some safety items of a simulated urgent anesthesia preparation more frequently. In addition, despite daily clinical experience, a single simulation session improved anesthesia preparation and reduced the preparation time with or without cognitive aid.

International audience; Background: Ventilator-associated pneumonia (VAP) is the most frequent health care-associated infection in severely ill patients, and aspiration of contaminated oropharyngeal content around the cuff of the tracheal tube is the main route of contamination.Research question: Is continuous regulation of tracheal cuff pressure using a pneumatic device superior to manual assessment three times daily using a portable manometer (routine care) in preventing VAP in patients with severe trauma?Study design and methods: In this open-label, randomized controlled superiority trial conducted in 13 French ICUs, adults (age ≥ 18 years) with severe trauma (Injury Severity Score > 15) and requiring invasive mechanical ventilation for ≥ 48 h were enrolled. Patients were randomly assigned (1:1) via a secure Web-based random number generator in permuted blocks of variable sizes to one of two groups according to the method of tracheal cuff pressure control. The primary outcome was the proportion of patients developing VAP within 28 days following the tracheal intubation, as determined by two assessors masked to group assignment, in the modified intention-to-treat population. This study is closed to new participants.Results: A total of 434 patients were recruited between July 31, 2015, and February 15, 2018, of whom 216 were assigned to the intervention group and 218 to the control group. Seventy-three patients (33.8%) developed at least one episode of VAP within 28 days following the tracheal intubation in the intervention group compared with 64 patients (29.4%) in the control group (adjusted subdistribution hazard ratio, 0.96; 95% CI, 0.76-1.20; P = .71). No serious adverse events related to the use of the pneumatic device were noted.Interpretation: Continuous regulation of cuff pressure of the tracheal tube using a pneumatic device was not superior to routine care in preventing VAP in patients with severe trauma.Clinical trial registration: ClinicalTrials.gov; No.: NCT02534974; URL: www.clinicaltrials.gov.

We aim to assess physicians’ level of resilience and define factors that improve or decrease the resilience level during the COVID-19 pandemic. Physicians from hospitals located in areas with different COVID-19 caseload levels, were invited to participate in a national e-survey between April and May 2020. Study participants were mainly emergency physicians, and anaesthesiologists, infectious disease consultants, and intensive care. The survey assessed participant’s characteristics, factors potentially associated with resilience, and resilience using the Connor-Davidson Resilience Scale (RISC-25), with higher scores indicative of greater resilience. Factors associated with the resilience score were assessed using a multivariable linear regression. Of 451 responding physicians involved in the care of COVID-19 patients, 442 were included (98%). Age was 36.1 ± 10.3 years and 51.8% were male; 63% worked in the emergency department (n = 282), 10.4% in anesthesiology (n = 46), 9.9% in infectious disease department (n = 44), 4.8% in intensive care unit (n = 21) or other specialties (n = 49). The median RISC-25 score was at 69 (IQR 62–75). Factors associated with higher RISC scores were anesthesia as a specialty, parenthood, no previous history of anxiety or depression and nor increased anxiety. To conclude, this study is the first to characterize levels of resilience among physicians involved in COVID-19 unit. Our data points to certain protective characteristics and some detrimental factors, such as anxiety or depression, that could be amenable to remediating or preventing strategies to promote resilience and support caregivers in a pandemic.

Aims Baclofen has gained interest in treating alcohol use disorder patients. These patients are at risk of voluntary drug intoxications. Understanding the context of baclofen's widespread use for alcohol use disorder, a recent evaluation of the epidemiology, morbidity and mortality of baclofen self-poisoning episodes is necessary. Methods All baclofen self-poisoning reported to the Western France Poison Control Centre between January 2008 and December 2015 were included for analysis in this retrospective study. Baclofen poisoning cases were compared to the 31,859 non-baclofen voluntary poisoning cases declared over the same period. Results Number of baclofen poisoning grew from 8 cases in 2008 to 91 cases in 2015, attributable to patients purposely treated for alcohol use disorder. Overall, 190 cases were considered: 111 patients (59%) had Glasgow coma score (GCS) ≤12 at hospital admission and 77 had GCS > 12 (41%). Eighty patients required mechanical ventilation (42.6%). Neurological severity (GCS ≤ 12) was associated with seizures (n = 24, 22% vs. n = 2, 3%, P < 0.001). Two patients were deceased at first medical evaluation and three died in the hospital (mortality rate 2.6%). Non-baclofen cases had lower rate of endotracheal intubation (n = 1833, 6%, P < 0.001) and mortality rate (n = 299, 0.1%, P = 0.02). Conclusions Baclofen self-poisoning cases has risen in recent years due to baclofen intake for alcohol use disorder therapies. The risk-benefit ratio may be evaluated before baclofen is safely prescribed.

Reintubation after weaning from mechanical ventilation is relatively common and is associated with poor outcomes. Different methods to decrease the reintubation rate post extubation, including noninvasive ventilation, and more recently high-flow oxygen (HFO) therapy, have been proposed. In this study, we aimed to assess the safety of introducing HFO in the post-extubation care of intensive care unit (ICU) patients. We conducted a single-center cohort study of extubated adult patients hospitalized in a surgical ICU and previously mechanically ventilated for > 1 day. Our study consisted of two phases: Phase 1 (before the introduction of HFO from April 2015 to April 2016) and Phase P2 (after the introduction of HFO from April 2017 to April 2018). The primary endpoint was the reintubation rate within 48 hours of extubation. In total, 290 patients (median age 65 years [50–74]; 190 men [65.5%]) were included in the analysis (181 and 109 in Phases 1 and 2, respectively). The results of the post-extubation use of noninvasive methods (noninvasive ventilation and/or HFO) were not significantly different between the two phases (41 [22.7%] versus 29 [26.6%] patients; p = 0.480), however these methods were implemented earlier in Phase 2 (0 versus 4 hours; p = 0.009) and HFO was used significantly more often than noninvasive ventilation (24 [22.0%] versus 25 [13.8%] patients; p = 0.039). The need for reintubation within 48 hours post extubation was significantly lower in Phase 2 (4 [3.7%] versus 20 [11.0%] patients; p = 0.028) but was not significantly different at 7 days post extubation (10 [9.2%] versus 30 [16.6%] patients; p = 0.082). The earlier implementation of noninvasive methods and the increased use of HFO beginning in Phase 2 were safe and effective based on the reintubation rates within the first 48 hours post extubation and after 7 days.

International audience

International audience; In this paper, we present work conducted in order to explain the results of a commercial software used for real-time decision support for the flow management of a combined and sanitary wastewater system. This tool is deployed in many major cities and is used on a daily basis. We apply decision trees to build rules for classifying and interpreting the solutions of the optimization model. Our main goal is to build a classifier that would help a user to understand why a proposed solution is good and why other solutions are worse. We demonstrate the feasibility of the approach to our industrial application by generating a large dataset of feasible solutions and classifying them as satisfactory or not based on whether the objective function is a certain percentage higher than the optimal objective. We evaluate the performance of the learned classifier on unseen examples. Our results show that our approach is very promising according to reactions from analysts and potential users.