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Background: Cognitive aids improve the technical performance of individuals and teams dealing with high-stakes crises. Hand-held electronic cognitive aids have rarely been investigated. A randomized controlled trial was conducted to investigate the effects of a smartphone application, named MAX (for Medical Assistance eXpert), on the technical and non-technical performance of anaesthesia residents dealing with simulated crises.Methods: This single-centre randomized, controlled, unblinded trial was conducted in the simulation centre at Lyon, France. Participants were anaesthesia residents with >1 yr of clinical experience. Each participant had to deal with two different simulated crises with and without the help of a digital cognitive aid. The primary outcome was technical performance, evaluated as adherence to guidelines. Two independent observers remotely assessed performance on video recordings.Results: Fifty-two residents were included between July 2015 and February 2016. Six participants were excluded for technical issues; 46 participants were confronted with a total of 92 high-fidelity simulation scenarios (46 with MAX and 46 without). Mean (sd) age was 27 (1.8) yr and clinical experience 3.2 (1.0) yr. Inter-rater agreement was 0.89 (95% confidence interval 0.85-0.92). Mean technical scores were higher when residents used MAX [82 (11.9) vs 59 (10.8)%; P<0.001].Conclusion: The use of a hand-held cognitive aid was associated with better technical performance of residents dealing with simulated crises. These findings could help digital cognitive aids to find their way into daily medical practice and improve the quality of health care when dealing with high-stakes crises.Clinical Trial Registration: NCT02678819. [ABSTRACT FROM AUTHOR]

Objectives: We investigated whether the risk of death among noncoronavirus disease 2019 critically ill patients increased when numerous coronavirus disease 2019 cases were admitted concomitantly to the same hospital units., Design: We performed a nationwide observational study based on the medical information system from all public and private hospitals in France., Setting: Information pertaining to every adult admitted to ICUs or intermediate care units from 641 hospitals between January 1, 2020, and June 30, 2020 was analyzed., Patients: A total of 454,502 patients (428,687 noncoronavirus disease 2019 and 25,815 coronavirus disease 2019 patients) were included., Interventions: For each noncoronavirus disease 2019 patient, pandemic exposure during their stay was calculated per day using the proportion of coronavirus disease 2019 patients among all patients treated in ICU., Measurements and Main Results: We computed a multivariable logistic regression model to estimate the influence of pandemic exposure (low, moderate, and high exposure) on noncoronavirus disease 2019 patient mortality during ICU stay. We adjusted on patient and hospital confounders. The risk of death among noncoronavirus disease 2019 critically ill patients increased in case of moderate (adjusted odds ratio, 1.12; 95% CI, 1.05-1.19; p < 0.001) and high pandemic exposures (1.52; 95% CI, 1.33-1.74; p < 0.001)., Conclusions: In hospital units with moderate or high levels of coronavirus disease 2019 critically ill patients, noncoronavirus disease deaths were at higher levels., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Therapeutic drug monitoring (TDM) is essential for voriconazole to ensure optimal drug exposure, mainly in critically ill patients for whom voriconazole demonstrated a large variability. The study aimed at describing factors associated with trough voriconazole concentrations in critically ill patients and evaluating the impact of voriconazole concentrations on adverse effects. A 2-year retrospective multicenter cohort study (NCT04502771) was conducted in six intensive care units. Adult patients who had at least one voriconazole TDM were included. Univariable and multivariable linear regression analyses were performed to identify predictors of voriconazole concentrations, and univariable logistic regression analysis, to study the relationship between voriconazole concentrations and adverse effects. During the 2-year study period, 70 patients were included. Optimal trough voriconazole concentrations were reported in 37 patients (52.8%), subtherapeutic in 20 (28.6%), and supratherapeutic in 13 (18.6%). Adverse effects were reported in six (8.6%) patients. SOFA score was identified as a factor associated with an increase in voriconazole concentration (p = 0.025), mainly in the group of patients who had SOFA score ≥ 10. Moreover, an increase in voriconazole concentration was shown to be a risk factor for occurrence of adverse effects (p = 0.011). In that respect, critically ill patients who received voriconazole treatment must benefit from a TDM, particularly if they have a SOFA score ≥ 10. Indeed, identifying patients who are overdosed will help to prevent voriconazole related adverse effects. This result is of utmost importance given the recognized COVID-19-associated pulmonary aspergillosis in ICU patients for whom voriconazole is among the recommended first-line treatment., Competing Interests: The authors have declared that no competing interests exist.

Importance: The role of herpes simplex virus (HSV) reactivation on morbidity and mortality in patients in the intensive care unit requiring mechanical ventilation remains unknown., Objective: To determine whether preemptive treatment with intravenous acyclovir reduces the duration of mechanical ventilation in patients with HSV oropharyngeal reactivation., Design, Setting, and Participants: A double-blind, placebo-controlled randomized clinical trial was conducted in 16 intensive care units in France. Participants included 239 adults (age, >18 years) who received mechanical ventilation for at least 96 hours and continued to receive mechanical ventilation for 48 hours or more, with HSV oropharyngeal reactivation. Patients were enrolled between February 2, 2014, and February 22, 2018., Interventions: Participants were randomized to receive intravenous acyclovir, 5 mg/kg, 3 times daily for 14 days or a matching placebo., Main Outcomes and Measures: The primary end point was ventilator-free days from randomization to day 60. Prespecified secondary outcomes included mortality at 60 days. Main analyses were conducted on an intention-to-treat basis., Results: Of 239 patients enrolled and randomized, 1 patient withdrew consent, leaving 238 patients, with 119 patients in both the acyclovir and placebo (control) groups (median [IQR] age, 61 [50-70] years; 76 [32%] women) available for primary outcome measurement. On day 60, the median (IQR) numbers of ventilator-free days were 35 (0-53) for acyclovir recipients and 36 (0-50]) for controls (P = .17 for between-group comparison). Among secondary outcomes, 26 patients (22%) and 39 patients (33%) had died at day 60 (risk difference, 0.11, 95% CI, -0.004 to 0.22, P = .06). The adverse event frequency was similar for both groups (28% in the acyclovir group and 23% in the placebo group, P = .40), particularly acute renal failure post randomization affecting 3 acyclovir recipients (3%) and 2 controls (2%). Four patients (3%) in the acyclovir group vs none in the placebo group stopped the study drug for treatment-related adverse events., Conclusions and Relevance: In patients receiving mechanical ventilation for 96 hours or more with HSV reactivation in the throat, use of acyclovir, 5 mg/kg, 3 times daily for 14 days, did not increase the number of ventilator-free days at day 60, compared with placebo. These findings do not appear to support routine preemptive use of acyclovir in this setting., Trial Registration: ClinicalTrials.gov identifier: NCT02152358.

Lidocaine has been shown to be clinically beneficial during bariatric surgery. However, information about lidocaine serum concentrations in this setting is scarce. This prospective clinical trial included 42 obese patients undergoing laparoscopic bariatric surgery. They received lidocaine based on adjusted body weight. Administration began with a 1.5 mg·kg bolus of intravenous lidocaine followed by a continuous infusion of 2 mg·kg·hour. After skin closure, administration was decreased to 1 mg·kg·hour until discharge from the recovery room. No serum concentrations of lidocaine were outside the usual accepted range (1.5-5 µg·mL).

Background: Obesity-hypoventilation syndrome (OHS) is defined as the combination of obesity (body mass index ≥ 30 kg/m 2 ) and daytime arterial hypercapnia (P aCO 2 > 45 mm Hg) in the absence of other causes of hypoventilation, and can lead to acute hypercapnic respiratory failure in the ICU. Our objective was to describe the ventilatory management and outcomes of subjects with OHS who were admitted to the ICU for acute hypercapnic respiratory failure., Methods: We retrospectively built a cohort of subjects with OHS who were admitted for acute hypercapnic respiratory failure in 4 ICUs of the university teaching hospital in Lyon, France, between 2013 and 2017. The main end point was the rate of success of noninvasive ventilation (NIV). Secondary end points were survival from OHS diagnosis to the last follow-up and risk factors for ICU admission and long-term survival., Results: One hundred fifteen subjects with OHS were included. Thirty-seven subjects (32.1%) were admitted to the ICU for acute hypercapnic respiratory failure. Congestive heart failure was the leading cause of acute hypercapnic respiratory failure (54%). At ICU admission, pH before NIV use was median (range) 7.26 (7.22-7.31) and P aCO 2 was 70 (61-76) mm Hg. NIV was used as first-line ventilatory support in 36 subjects (97.2%) and was successful in 33 subjects (91.7%). ICU mortality was low (2.7%). The subjects admitted to the ICU were significantly older and had a lower FEV 1 and vital capacity at the time of an OHS diagnosis. The difference in the restricted mean survival time was 663 d in favor of subjects not admitted to the ICU. Multivariate analysis showed that lower vital capacity at an OHS diagnosis was significantly associated with a higher risk of ICU admission. No factor was independently associated with long-term overall mortality in multivariate analysis., Conclusions: Acute hypercapnic respiratory failure in subjects with OHS was generally responsive to NIV and was frequently associated with congestive heart failure., Competing Interests: The authors have disclosed no conflicts of interest., (Copyright © 2019 by Daedalus Enterprises.)

Background: Sepsis is the leading cause of mortality for critically ill patients worldwide. Patients develop T lymphocyte dysfunctions leading to T-cell exhaustion associated with increased risk of death. As interleukin-7 (IL-7) is currently tested in clinical trials to reverse these dysfunctions, it is important to evaluate the expression of its specific CD127 receptor on the T-cell surface of patients with septic shock. Moreover, the CD127 low PD-1 high phenotype has been proposed as a T-cell exhaustion marker in chronic viral infections but has never been evaluated in sepsis. The objective of this study was first to evaluate CD127 and CD127 low PD-1 high phenotype in septic shock in parallel with functional T-cell alterations. Second, we aimed to reproduce septic shock-induced T-cell alterations in an ex vivo model., Methods: CD127 expression was followed at the protein and mRNA levels in patients with septic shock and healthy volunteers. CD127 low PD-1 high phenotype was also evaluated in parallel with T-cell functional alterations after ex vivo activation. To reproduce T-cell alterations observed in patients, purified T cells from healthy volunteers were activated ex vivo and their phenotype and function were evaluated., Results: In patients, neither CD127 expression nor its corresponding mRNA transcript level was modified compared with normal values. However, the percentage of CD127 low PD-1 high T cells was increased while T cells also presented functional alterations. CD127 low PD-1 high T cells co-expressed HLA-DR, an activation marker, suggesting a role for T-cell activation in the development of this phenotype. Indeed, T-cell receptor (TCR) activation of normal T lymphocytes ex vivo reproduced the increase of CD127 low PD-1 high T cells and functional alterations following a second stimulation, as observed in patients. Finally, in this model, as observed in patients, IL-7 could improve T-cell proliferation., Conclusions: The proportion of CD127 low PD-1 high T cells in patients was increased compared with healthy volunteers, although no global CD127 regulation was observed. Our results suggest that TCR activation participates in the occurrence of this T-cell population and in the development of T-cell alterations in septic shock. Furthermore, we provide an ex vivo model for the investigation of the pathophysiology of sepsis-induced T-cell immunosuppression and the testing of innovative immunostimulant treatments.

Objectives: Septic shock is the primary cause of death in ICUs. A better comprehension of its pathophysiology, in particular, the immune alteration mechanisms, opened new therapeutic perspectives such as the recombinant interleukin-7. The use of biomarkers could improve the identification of eligible patients for this therapy. The soluble form of the interleukin-7 appears as a promising candidate in this regard since an association between its high plasmatic level and mortality in critically ill patients has been demonstrated. Because there are no data available on the transcriptional regulation of the interleukin-7 receptor in such patients, this study aimed to explore the expression level of different interleukin-7 receptor transcripts after septic shock and evaluate their association with mortality., Design: Retrospective discovery cohort (30 patients) and validation cohort (177 patients)., Setting: Two French ICUs (discovery study) and six French ICUs (validation study)., Patients: Adult septic shock patients., Interventions: None., Measurements and Main Results: The quantification of several interleukin-7 receptor transcripts using specific reverse transcription quantitative polymerase chain reaction designs allowed for global evaluation of interleukin-7 receptor gene expression in whole blood. In the discovery cohort, all interleukin-7 receptor transcripts studied were expressed at lower levels in septic shock patients than in healthy volunteers. Interleukin-7 receptor gene expression at day 3 after septic shock diagnosis was associated with day 28 mortality. Patients at a lower risk of death showed higher expression levels. These results were confirmed in the independent validation cohort. Interestingly, using a threshold obtained on the discovery cohort, we observed in the validation cohort a high negative predictive value for day 28 mortality for the transcript encoding the membrane form of interleukin-7 receptor (0.86; 95% CI, 0.79-0.93)., Conclusions: Interleukin-7 receptor transcripts appear as biomarkers of impaired adaptive immune response in septic shock patients and as a promising tool for patient stratification in clinical trials evaluating immunoadjuvant therapies.

Objectives: The objective of the study was to estimate the length of stay of patients with hospital-acquired infections hospitalized in ICUs using a multistate model., Design: Active prospective surveillance of hospital-acquired infection from January 1, 1995, to December 31, 2012., Setting: Twelve ICUs at the University of Lyon hospital (France)., Patients: Adult patients age greater than or equal to 18 years old and hospitalized greater than or equal to 2 days were included in the surveillance. All hospital-acquired infections (pneumonia, bacteremia, and urinary tract infection) occurring during ICU stay were collected., Interventions: None., Measurements and Main Results: The competitive risks of in-hospital death, transfer, or discharge were considered in estimating the change in length of stay due to infection(s), using a multistate model, time of infection onset. Thirty-three thousand four-hundred forty-nine patients were involved, with an overall hospital-acquired infection attack rate of 15.5% (n = 5,176). Mean length of stay was 27.4 (± 18.3) days in patients with hospital-acquired infection and 7.3 (± 7.6) days in patients without hospital-acquired infection. A multistate model-estimated mean found an increase in length of stay by 5.0 days (95% CI, 4.6-5.4 d). The extra length of stay increased with the number of infected site and was higher for patients discharged alive from ICU. No increased length of stay was found for patients presenting late-onset hospital-acquired infection, more than the 25th day after admission., Conclusions: An increase length of stay of 5 days attributable to hospital-acquired infection in the ICU was estimated using a multistate model in a prospective surveillance study in France. The dose-response relationship between the number of hospitalacquired infection and length of stay and the impact of early-stage hospital-acquired infection may strengthen attention for clinicians to focus interventions on early preventions of hospital-acquired infection in ICU.

Objective: Since the implementation of two French laws in 2002 and 2005 and the implementation of guidelines about End-of-Life (EoL) decisions, few studies concerning EoL practices in French intensive care units (ICUs) have been reported. This study was aimed at assessing compliance with recommendations and current legislation concerning EoL decisions., Method: Prospective observational study based on 1-day audit conducted from January to May 2009 in 66 southern French ICUs., Results: Six hundred and twenty-five patients were included (median age: 63 [52-76] years, median SAPS II: 46 [34-58]). The written designation of a surrogate decision-maker was reported for 87 (15%) patients. Advance directives were completed for only 4% of patients. The EoL decision-making process consisted in a multidisciplinary approach for 99 (47%) patients and was recorded in the medical chart for 63 (64%) cases. Families were informed about medical decisions in 58% of cases. This proportion was higher (87%) if a decision to forego life-sustaining therapy was made. EoL decisions consisted of withholding treatments for 72 (94%) patients and withdrawal of treatments for 5 (6%) patients. In the multivariate stepwise logistic regression, four variables were independently associated with a decision to forego life support: preexisting dependence on others (P<0.0001), advance directives (P=0.01), age (P=0.008) and the SAPS 2 score (P=0.009)., Conclusion: The major finding of the present study is the existence of a gap between the widely approved EoL recommendations made by scientific societies and the daily practice of southern French ICUs. Even if EoL decisions are mostly shared with relatives, their written documentation in medical charts remains insufficient. Concerning EoL practices, the withdrawal of treatment remains an uncommon decision., (Copyright © 2015 Société française d’anesthésie et de réanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved.)

Background: In the intensive care unit (ICU), the outcomes of patients with acute mesenteric ischemia (AMI) are poorly documented. This study aimed to determine the risk factors for death in ICU patients with AMI., Methods: A retrospective, observational, non-interventional, multicenter study was conducted in 43 ICUs of 38 public institutions in France. From January 2008 to December 2013, all adult patients with a diagnosis of AMI during their hospitalization in ICU were included in a database. The diagnosis was confirmed by at least one of three procedures (computed tomography scan, gastrointestinal endoscopy, or upon surgery). To determine factors associated with ICU death, we established a logistic regression model. Recursive partitioning analysis was applied to construct a decision tree regarding risk factors and their interactions most critical to determining outcomes., Results: The death rate of the 780 included patients was 58 %. Being older, having a higher sequential organ failure assessment (SOFA) severity score at diagnosis, and a plasma lactate concentration over 2.7 mmol/l at diagnosis were independent risk factors of ICU mortality. In contrast, having a prior history of peripheral vascular disease or an initial surgical treatment were independent protective factors against ICU mortality. Using age and SOFA severity score, we established an ICU mortality score at diagnosis based on the cutoffs provided by recursive partitioning analysis. Probability of survival was statistically different (p < 0.001) between patients with a score from 0 to 2 and those with a score of 3 and 4., Conclusion: Acute mesenteric ischemia in ICU patients was associated with a 58 % ICU death rate. Age and SOFA severity score at diagnosis were risk factors for mortality. Plasma lactate concentration over 2.7 mmol/l was also an independent risk factor, but values in the normal range did not exclude the diagnosis of AMI.

Objective: To analyze the factors influencing the choice of the specialty "anesthesiology and intensive care" by medical students at the end of the second cycle of the French medical curriculum. This study had three aims: to measure the attraction of students for this specialty, to assess the perception of this specialty at this stage of the medical studies, and to study the influence of the teaching of "anesthesiology and intensive care" during this second cycle on student perceptions of the specialty., Study Design: Descriptive study., Material and Methods: We conducted an anonymous survey among 407 medical students who were at the end of their sixth year of their medical studies, and who were enrolled in one of the four schools of medicine in Lyon, France, for the university year 2007-2008., Results: Three hundred and twenty-eight surveys were analyzed. The specialty "anesthesiology and intensive care" was ranked third overall in terms of preferred specialties. Intensive care was rated the most attractive component, and respondents in particular noted its multisystem perspective and perceived utility. Anesthesiology was in general seen as highly technical and potentially lucrative, but holding increased medicolegal risk. The hospital training courses were highly rated by the students, who believed these to be the best way to learn about this specialty. However, respondents indicated that not enough hospital training courses were available, and only training courses in the intensive care units and the prehospital care department led the students towards this specialty. Accordingly, the nature and practice of anesthesiology were less well-known by students., Conclusion: Numerous medical students want to become intensivists. Anesthesiology is less well-known at this stage of the medical studies. The teaching of the "anesthesiology and intensive care" specialty needs to be optimized., (Copyright 2010 Elsevier Masson SAS. All rights reserved.)

Coupled plasma filtration adsorption (CPFA) is a new technology proposed for septic shock, removing both pro- and anti-inflammatory mediators. We report the first use of CPFA in France. The patient was 80-years-old and was admitted to the intensive care unit because of septic shock from urinary source. Besides conventional septic shock treatment, four successive CPFA sessions were daily performed and lasted from 6 to 11 hours. At the end of the sessions, a noteworthy hemodynamic and inflammatory improvement was observed. This case confirms the feasibility and the relative simplicity of CPFA. It also illustrates the recent and few scientific data of the medical literature concerning this technology.

Purpose: In France, legislation mandates that the clinical diagnosis of brain death be confirmed by one paraclinical test before organ donation is allowed. That test may be either the electroencephalogram (EEG) or cerebral angiography. We report a case in which the clinical diagnosis of brain death was first confirmed by two EEGs performed according to the French guidelines, but ruled out by cerebral angiography. Considering that the EEG is no longer recommended to establish the diagnosis of brain death, we discuss the relevance of maintaining the EEG for brain death diagnosis in France., Clinical Findings: A 58 yr-old man was admitted to the intensive care unit because of coma secondary to a massive subarachnoid hemorrhage with herniation below the falx shown by computed tomography. Clinical criteria of brain death were rapidly present. Two EEGs first confirmed the diagnosis but a four-vessel cerebral angiography was finally performed because the patient moved spontaneously. This cerebral angiography showed flow in the right internal carotid artery. A computed tomography performed the next day definitely confirmed the absence of brain death and organ donation did not occur., Conclusions: This case demonstrates the limitations of the EEG for this indication and suggests that angiography should be preferred. French legislation is probably maladjusted and would benefit by incorporating guidelines of other countries like Canada. International harmonization of criteria for brain death diagnosis would also be welcome.