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Rationale: Airway occlusion pressure at 100 ms (P0.1) reflects central respiratory drive. Objectives: We aimed to assess factors associated with P0.1 and whether an abnormally low or high P0.1 value is associated with higher mortality and longer duration of mechanical ventilation (MV). Methods: We performed a secondary analysis of a prospective cohort study conducted in 10 ICUs in France to evaluate dyspnea in communicative MV patients. In patients intubated for more than 24 hours, P0.1 was measured with dyspnea as soon as patients could communicate and the next day. Measurements and Main Results: Among 260 patients assessed after a median time of ventilation of 4 days, P0.1 was 1.9 (1-3.5) cm H 2 O at enrollment, 24% had P0.1 values >3.5 cm H 2 O, 37% had P0.1 values between 1.5 and 3.5 cm H 2 O, and 39% had P0.1 values <1.5 cm H 2 O. In multivariable linear regression, independent factors associated with P0.1 were the presence of dyspnea ( P  = 0.037), respiratory rate ( P  < 0.001), and Pa O 2 ( P  = 0.008). Ninety-day mortality was 33% in patients with P0.1 > 3.5 cm H 2 O versus 19% in those with P0.1 between 1.5 and 3.5 cm H 2 O and 17% in those with P0.1 < 1.5 cm H 2 O ( P  = 0.046). After adjustment for the main risk factors, P0.1 was associated with 90-day mortality (hazard ratio per 1 cm H 2 O, 1.19 [95% confidence interval, 1.04-1.37]; P  = 0.011). P0.1 was also independently associated with a longer duration of MV (hazard ratio per 1 cm H 2 O, 1.10 [95% confidence interval, 1.02-1.19]; P  = 0.016). Conclusions: In patients receiving invasive MV, abnormally high P0.1 values may suggest dyspnea and are associated with higher mortality and prolonged duration of MV.

Context: The changes in host membrane phospholipids are crucial in airway infection pathogenesis. Phospholipase A2 hydrolyzes host cell membranes, producing lyso-phospholipids and free fatty acids, including arachidonic acid (AA), which contributes significantly to lung inflammation., Aim: Follow these changes and their evolution from day 1, day 3 to day 7 in airway aspirates of 89 patients with COVID-19-associated acute respiratory distress syndrome and examine whether they correlate with the severity of the disease. The patients were recruited in three French intensive care units. The analysis was conducted from admission to the intensive care unit until the end of the first week of mechanical ventilation., Results: In the airway aspirates, we found significant increases in the levels of host cell phospholipids, including phosphatidyl-serine and phosphatidyl-ethanolamine, and their corresponding lyso-phospholipids. This was accompanied by increased levels of AA and its inflammatory metabolite prostaglandin E2 (PGE2). Additionally, enhanced levels of ceramides, sphingomyelin, and free cholesterol were observed in these aspirates. These lipids are known to be involved in cell death and/or apoptosis, whereas free cholesterol plays a role in virus entry and replication in host cells. However, there were no significant changes in the levels of dipalmitoyl-phosphatidylcholine, the major surfactant phospholipid. A correlation analysis revealed an association between mortality risk and levels of AA and PGE2, as well as host cell phospholipids., Conclusion: Our findings indicate a correlation between heightened cellular phospholipid modifications and variations in AA and PGE2 with the severity of the disease in patients. Nevertheless, there is no indication of surfactant alteration in the initial phases of the illness., Competing Interests: Declaration of competing interest There is no conflict of interest., (Copyright © 2024 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)

The impact of chronic liver disease on outcomes in patients with COVID-19 is uncertain. Hence, we aimed to explore this association. We explored the outcomes of all adult inpatients with COVID-19 in France, in 2020. We computed adjusted odds ratios to measure the associations between chronic liver disease, alcohol use disorders, mechanical ventilation and day-30 in-hospital mortality. The sample comprised 259,110 patients (median [IQR] age 70 (54–83) years; 52% men), including 15,476 (6.0%) and 10,006 (3.9%) patients with chronic liver disease and alcohol use disorders, respectively. Death occurred in 38,203 (15%) patients, including 7,475 (28%) after mechanical ventilation, and 2,941 (19%) with chronic liver disease. The adjusted odds ratios for mechanical ventilation and day-30 mortality were 1.54 (95% CI 1.44–1.64, p < 0.001) and 1.79 (1.71–1.87, p < 0.001) for chronic liver disease; 0.55 (0.47–0.64, p < 0.001) and 0.54 (0.48–0.61, p < 0.001) for mild liver disease; 0.64 (0.53–0.76; p < 0.001) and 0.71 (0.63–0.80, p < 0.001) for compensated cirrhosis; 0.65 (0.52–0.81, p < 0.001) and 2.21 (1.94–2.51, p < 0.001) for decompensated cirrhosis; 0.34 (0.24–0.50; p < 0.001) and 1.38 (1.17–1.62, p < 0.001) for primary liver cancer; and 0.82 (0.76–0.89; p < 0.001) and 1.11 (1.05–1.17; p < 0.001) for alcohol use disorders. Chronic viral hepatitis; non-viral, non-alcoholic chronic hepatitis; organ, including liver, transplantation, and acquired immunodeficiency syndrome were not associated with COVID-19-related death. Chronic liver disease increased the risk of COVID-19-related death in France in 2020. Therapeutic effort limitation may have contributed to COVID-19-related death in French residents with a liver-related complication or an alcohol use disorder. We studied the outcomes, including mechanical ventilation and day-30 mortality, of all adults with COVID-19 who were discharged from acute and post-acute care in France in 2020 (N = 259,110). Patients with mild liver disease; compensated cirrhosis; organ, including liver, transplantation; or acquired immunodepression syndrome were not at increased risk of COVID-19-related mortality. Patients with alcohol use disorders, decompensated cirrhosis, or primary liver cancer were at increased risk of COVID-19-related mortality but were less likely to receive mechanical ventilation. Our results suggest that therapeutic effort limitation may have contributed to the excess mortality in French residents with a liver-related complication or an alcohol use disorder. [Display omitted] • We assessed the association between chronic liver disease and clinical outcomes of in-patients with COVID-19. • Chronic liver disease increased the risk of COVID-19-related death. • Therapeutic effort limitations may have contributed to death of patients with decompensated cirrhosis, primary liver cancer, or with an alcohol use disorder. [ABSTRACT FROM AUTHOR]

Purpose: Some patients presenting with acute respiratory failure and meeting the Berlin criteria for acute respiratory distress syndrome (ARDS) lack exposure to common risk factors (CRF). These so-called ARDS mimickers often lack histological diffuse alveolar damage. We aimed to describe such ARDS mimickers lacking CRF (ARDS CRF-) in comparison with others (ARDS CRF+).Methods: Retrospective study including all patients receiving invasive mechanical ventilation for ARDS admitted to the intensive care units (ICUs) of two tertiary care centers from January 2003 to December 2012.Results: The prevalence of ARDS CRF- was 7.5 % (95 % CI [5.5-9.5]; n = 50/665). On the basis of medical history, bronchoalveolar lavage fluid cytology, and chest CT scan patterns, four etiological categories were identified: immune (n = 18; 36 %), drug-induced (n = 13; 26 %), malignant (n = 7; 14 %), and idiopathic (n = 12; 24 %). Although the ARDS CRF- patients had a lower logistic organ dysfunction score (4 [3-8] vs. 10 [6-13]; p < 0.0001) and less often shock upon ICU admission (44 vs. 80 %; p < 0.0001) than their counterparts, their overall ICU mortality rate was very high (66 % [46-74]), and the absence of CRF remained associated with ICU mortality by multivariable logistic regression analysis (adjusted OR = 2.06; 95 % CI [1.02-4.18]; p = 0.044). Among ARDS CRF- patients, the presence of potentially reversible lung lesions with corticosteroids (aOR = 0.14; 95 % CI [0.03-0.62]) was associated with ICU survival.Conclusions: The absence of CRF among patients with ARDS is common and associated with a higher risk of mortality. For such atypical ARDS, a complete diagnostic workup, including bronchoalveolar lavage fluid cytology and chest CT scan patterns, should be performed to identify those patients who might benefit from specific therapies, including corticosteroids. [ABSTRACT FROM AUTHOR]

Context A recent trial showed that placing patients with acute lung injury in the prone position did not increase survival; however, whether those results hold true for patients with hypoxemic acute respiratory failure (ARF) is unclear. Objective To determine whether prone positioning improves mortality in ARF patients. Design, Setting, and Patients Prospective, unblinded, multicenter controlled trial of 791 ARF patients in 21 general intensive care units in France using concealed randomization conducted from December 14, 1998, through December 31, 2002. To be included, patients had to be at least 18 years, hemodynamically stable, receiving mechanical ventilation, and intubated and had to have a partial pressure of arterial oxygen (PaO2) to fraction of inspired oxygen (FIO2) ratio of 300 or less and no contraindications to lying prone. Interventions Patients were randomly assigned to prone position placement (n = 413), applied as early as possible for at least 8 hours per day on standard beds, or to supine position placement (n = 378). Main Outcome Measures The primary end point was 28-day mortality; secondary end points were 90-day mortality, duration of mechanical ventilation, incidence of ventilator-associated pneumonia (VAP), and oxygenation. Results The 2 groups were comparable at randomization. The 28-day mortality rate was 32.4% for the prone group and 31.5% for the supine group (relative risk [RR], 0.97; 95% confidence interval [CI], 0.79-1.19; P = .77). Ninety-day mortality for the prone group was 43.3% vs 42.2% for the supine group (RR, 0.98; 95% CI, 0.84-1.13; P = .74). The mean (SD) duration of mechanical ventilation was 13.7 (7.8) days for the prone group vs 14.1 (8.6) days for the supine group (P = .93) and the VAP incidence was 1.66 vs 2.14 episodes per 100-patients days of intubation, respectively (P = .045). The PaO2/FIO2 ratio was significantl... [ABSTRACT FROM AUTHOR]

Importance: The optimal approach to the use of venoarterial extracorporeal membrane oxygenation (ECMO) during cardiogenic shock is uncertain., Objective: To determine whether early use of moderate hypothermia (33-34 °C) compared with strict normothermia (36-37 °C) improves mortality in patients with cardiogenic shock receiving venoarterial ECMO., Design, Setting, and Participants: Randomized clinical trial of patients (who were eligible if they had been endotracheally intubated and were receiving venoarterial ECMO for cardiogenic shock for <6 hours) conducted in the intensive care units at 20 French cardiac shock care centers between October 2016 and July 2019. Of 786 eligible patients, 374 were randomized. Final follow-up occurred in November 2019., Interventions: Early moderate hypothermia (33-34 °C; n = 168) for 24 hours or strict normothermia (36-37 °C; n = 166)., Main Outcomes and Measures: The primary outcome was mortality at 30 days. There were 31 secondary outcomes including mortality at days 7, 60, and 180; a composite outcome of death, heart transplant, escalation to left ventricular assist device implantation, or stroke at days 30, 60, and 180; and days without requiring a ventilator or kidney replacement therapy at days 30, 60, and 180. Adverse events included rates of severe bleeding, sepsis, and number of units of packed red blood cells transfused during venoarterial ECMO., Results: Among the 374 patients who were randomized, 334 completed the trial (mean age, 58 [SD, 12] years; 24% women) and were included in the primary analysis. At 30 days, 71 patients (42%) in the moderate hypothermia group had died vs 84 patients (51%) in the normothermia group (adjusted odds ratio, 0.71 [95% CI, 0.45 to 1.13], P = .15; risk difference, -8.3% [95% CI, -16.3% to -0.3%]). For the composite outcome of death, heart transplant, escalation to left ventricular assist device implantation, or stroke at day 30, the adjusted odds ratio was 0.61 (95% CI, 0.39 to 0.96; P = .03) for the moderate hypothermia group compared with the normothermia group and the risk difference was -11.5% (95% CI, -23.2% to 0.2%). Of the 31 secondary outcomes, 30 were inconclusive. The incidence of moderate or severe bleeding was 41% in the moderate hypothermia group vs 42% in the normothermia group. The incidence of infections was 52% in both groups. The incidence of bacteremia was 20% in the moderate hypothermia group vs 30% in the normothermia group., Conclusions and Relevance: In this randomized clinical trial involving patients with refractory cardiogenic shock treated with venoarterial ECMO, early application of moderate hypothermia for 24 hours did not significantly increase survival compared with normothermia. However, because the 95% CI was wide and included a potentially important effect size, these findings should be considered inconclusive., Trial Registration: ClinicalTrials.gov Identifier: NCT02754193.

Background: Staphylococcus aureus remains a common cause of ventilator-associated pneumonia, with little change in incidence over the past 15 years. We aimed to evaluate the efficacy of suvratoxumab, a monoclonal antibody targeting the α toxin, in reducing the incidence of S aureus pneumonia in patients in the intensive care unit (ICU) who are on mechanical ventilation., Methods: We did a multicentre, randomised, double-blind, placebo-controlled, parallel-group, phase 2 pilot trial at 31 hospitals in Belgium, the Czech Republic, France, Germany, Greece, Hungary, Portugal, Spain, and Switzerland. Eligible patients were in the ICU, aged ≥18 years, were intubated and on mechanical ventilation, were positive for S aureus colonisation of the lower respiratory tract, as assessed by quantitative PCR (qPCR) analysis of endotracheal aspirate, and had not been diagnosed with new-onset pneumonia. Patients were excluded if they had confirmed or suspected acute ongoing staphylococcal disease; had received antibiotics for S aureus infection for more than 48 h within 72 h of randomisation; had a Clinical Pulmonary Infection Score of 6 or higher; had an acute physiology and chronic health evaluation II score of 25 or higher with a Glasgow coma scale (GCS) score of more than 5, or an acute physiology and chronic health evaluation II score of at least 30 with a GCS score of 5 or less; had a Sequential Organ Failure Assessment score of 9 or higher; or had active pulmonary disease that would impair the ability to diagnose pneumonia. Colonised patients were randomly assigned (1:1:1), by use of an interactive voice or web response system, to receive either a single intravenous infusion of suvratoxumab 2000 mg, suvratoxumab 5000 mg, or placebo. Randomisation was done in blocks of size four, stratified by country and by whether patients had received systemic antibiotics for S aureus infection. Patients, investigators, and study staff involved in the treatment or clinical evaluation of patients were masked to patient assignment. The primary efficacy endpoint was the incidence of S aureus pneumonia at 30 days, as determined by a masked independent endpoint adjudication committee, in all patients who received their assigned treatment (modified intention-to-treat [ITT] population). Primary safety endpoints were the incidence of treatment-emergent adverse events at 30 days, 90 days, and 190 days after treatment, and the incidence of treatment-emergent serious adverse events, adverse events of special interest, and new-onset chronic disease at 190 days after treatment. All primary safety endpoints were assessed in the modified ITT population. This trial is registered with ClinicalTrials.gov (NCT02296320) and the EudraCT database (2014-001097-34)., Findings: Between Oct 10, 2014, and April 1, 2018, 767 patients were screened, of whom 213 patients with confirmed S aureus colonisation of the lower respiratory tract were randomly assigned to the suvratoxumab 2000 mg group (n=15), the suvratoxumab 5000 mg group (n=96), or the placebo group (n=102). Two patients in the placebo group did not receive treatment after randomisation because their clinical conditions changed and they no longer met the eligibility criteria for dosing. As adjudicated by the data monitoring committee at an interim analysis, the suvratoxumab 2000 mg group was discontinued on the basis of predefined pharmacokinetic criteria. At 30 days after treatment, 17 (18%) of 96 patients in the suvratoxumab 5000 mg group and 26 (26%) of 100 patients in the placebo group had developed S aureus pneumonia (relative risk reduction 31·9% [90% CI -7·5 to 56·8], p=0·17). The incidence of treatment-emergent adverse events at 30 days were similar between the suvratoxumab 5000 mg group (87 [91%]) and the placebo group (90 [90%]). The incidence of treatment-emergent serious adverse events at 30 days were also similar between the suvratoxumab 5000 mg group (36 [38%]) and the placebo group (32 [32%]). No significant difference in the incidence of treatment-emergent adverse events between the two groups at 90 days (89 [93%] in the suvratoxumab 5000 mg group vs 92 [92%] in the placebo group) and at 190 days (93 [94%] vs 93 [93%]) was observed. 40 (40%) patients in the placebo group and 50 (52%) in the suvratoxumab 5000 mg group had a serious adverse event at 190 days. In the suvratoxumab 5000 mg group, one (1%) patient reported at least one treatment-emergent serious adverse event related to treatment, two (2%) patients reported an adverse event of special interest, and two (2%) reported a new-onset chronic disease., Interpretation: In patients in the ICU receiving mechanical ventilation with qPCR-confirmed S aureus colonisation of the lower respiratory tract, the incidence of S aureus pneumonia at 30 days was not significantly lower following treatment with 5000 mg suvratoxumab than with placebo. Despite these negative results, monoclonal antibodies still represent one promising therapeutic option to reduce antibiotic consumption that require further exploration and studies., Funding: AstraZeneca, with support from the Innovative Medicines Initiative Joint Undertaking., Competing Interests: Declaration of interests BF reports personal fees from AM-Pharma, Aridis, Ashai-Kasai, Biomérieux, Enlivex, Ferring, Inotrem, Polyphor, and Transgene, outside the submitted work. JC reports personal fees from Combacte Magnet during the conduct of the study; personal fees from Bayer, Inotrem, Shionogi, and TiGenix (Takeda) outside the submitted work; and grants from Medimmune (AstraZeneca) outside the submitted work. PE reports personal fees from the COMBACTE-MAGNET Consortium during the conduct of the study. P-FD reports personal fees from the Associations pour la Promotion de la Réanimation Médicale, University Hospital, Tours, France during the conduct of the study. MJB reports grants from Jansen Vaccines, Merck, and Sanofi outside the submitted work; consultancy fees from Jansen Vaccines outside the submitted work; and Data and Safety Monitoring Board fees from Merck (all paid to the University Medical Center Utrecht) outside the submitted work. HSJ, OA, KS, PR, AR, VP, MTE, FD, YW, SC, and TBe report being employees of AstraZeneca. HSJ, OA, KS, PR, AR, VP, MTE, FD, YW, and SC report holding stock in AstraZeneca. HSJ, OA, KS, PR, AR, VP, MTE, FD, YW, SC report holding stock options in AstraZeneca. OA was an employee of AstraZeneca during the conduct of the study, and is now an employee of and holds stock options in Viela Bio. All other authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Introduction: An amphibious assault ship was deployed on 22 March in Corsica to carry out medical evacuation of 12 critical patients infected with COVID-19. The ship has on-board hospital capacity and is the first time that an amphibious assault ship is engaged in this particular condition. The aim is to evaluate the feasibility and safety of prolonged medical evacuation of critical patients with COVID-19., Methods: We included 12 patients with confirmed COVID-19 infection: six ventilated patients with acute respiratory distress syndrome and six non-ventilated patients with hypoxaemia. Transfer on an amphibious assault ship lasted 20 hours. We collected patients' medical records: age, comorbidities, COVID-19 history and diagnosis, ventilation supply and ventilator settings, and blood gas results. We calculated oxygen consumption (OC)., Results: All patients had a medical history. The median delay from onset of symptoms to hospitalisation was 8 (7-10) days. The median Sequential Organ Failure Assessment score on admission was 3 (2-5). There was no significant increase in oxygen during ship transport and no major respiratory complication. There was no significant increase in arterial oxygen pressure to fractional inspired oxygen ratio among ventilated patients during ship transport. Among ventilated patients, the median calculated OC was 255 L (222-281) by hours and 5270 L (4908-5616) during all ship transport. Among non-ventilated patients, the median calculated OC was 120 L (120-480) by hours and 2400 L (2400-9600) during all ship transport., Conclusion: The present work contributes to assessing the feasibility and safety condition of critical COVID-19 evacuation on an amphibious assault ship during an extended transport. The ship needs to prepare a plan and a specialised intensive team and conduct patient screening for prolonged interhospital transfers., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: During the COVID-19 pandemic, as the number of available Intensive Care beds in France did not meet the needs, it appeared necessary to transfer a large number of patients from the most affected areas to the less ones. Mass transportation resources were deemed necessary. To achieve that goal, the concept of a Collective Critical Care Ambulance (CCCA) was proposed in the form of a long-distance bus re-designed and equipped to accommodate up to six intensive care patients and allow Advanced Life Support (ALS) techniques to be performed while en route., Methods: The expected benefit of the CCCA, when compared to ALS ambulances accommodating a single patient, was to reduce the resources requirements, in particular by a lower personnel headcount for several patients being transferred to the same destination. A foreseen prospect, comparing to other collective transportation vectors such as airplanes, was the door-to-door capability, minimalizing patients' handovers for safety concerns and time efficiency. With the project of a short-distance transfer of several Intensive Care Unit (ICU) patients together, the opportunity came to test the CCCA under real-life conditions and evaluate safely its technical feasibility and impact in time and resources saving, before it could be proposed for longer distances., Results: Four COVID-19 patients were transported over 37 km. All patients were intubated and under controlled ventilation. One of them was under Norepinephrine support. Mean loading time was 1 min 39 s. Transportation time was 29 min. At destination, the mean unloading time was 1 min 15 s. No serious adverse effect, in particular regarding hemodynamic instability or ventilation disorder, has been observed. No harmful incident has occurred., Conclusions: It was a very instructive test. Collective medical evacuation by bus for critically ill patients under controlled ventilation is suitable and easy to implement. Design, ALS equipment, power autonomy, safety and resources saving, open the way for carrying up to 6 ICU-patients over a long distance. The CCCA could bring a real added-value in an epidemic context and could also be helpful in many other events generating multiple victims such as an armed conflict, a terrorist attack or a natural disaster.

Introduction: Coronavirus disease 2019 or COVID-19 is a new infectious disease responsible for potentially severe respiratory impairment associated with initial immunosuppression. Similarly to influenza, several authors have described a higher risk of fungal infection after COVID-19, in particular for invasive pulmonary aspergillosis. The main objective here is to define the prevalence of invasive pulmonary aspergillosis (IPA) in a cohort of COVID-19 patients with moderate to severe acute respiratory disease syndrome (ARDS)., Material and Methods: We conducted a large monocentric retrospective study investigating all the ventilated COVID-19 patients with ARDS hospitalized at Valenciennes' general hospital, France, between March 15, 2020 and April 30, 2020. In the center a systematic IPA screening strategy was carried out for all ARDS patients, with weekly tests of serum galactomannan and beta-D-glucan. Bronchoalveolar lavage with culture and chest CT scan were performed when the serum assays were positives., Results: A total of 54 patients were studied. Their median age was 65 years, and 37 of the patients (71%) were male. Two patients had chronic immunosuppression and among all the patients, only 2 non-immunocompromised presented a putative IPA during their stay., Conclusion: The prevalence of IPA in this cohort of COVID-19 patients (3.7%) is not higher than what is described in the other ARDS populations in the literature. These results are however different from the previous publications on COVID-19 patients and must therefore be confirmed by larger and multicentric studies., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Objective: To evaluate the association of early continuous infusions of opioids and/or midazolam with survival and sensorimotor outcomes at age 2 years in very premature infants who were ventilated., Study Design: This national observational study included premature infants born before 32 weeks of gestation intubated within 1 hour after birth and still intubated at 24 hours from the French EPIPAGE 2 cohort. Infants only treated with bolus were excluded. Treated infants received continuous opioid and/or midazolam infusion started before 7 days of life and before the first extubation. Naive infants did not receive these treatments before the first extubation, or received them after the first week of life, or never received them. This study compared treated (n = 450) vs naive (n = 472) infants by using inverse probability of treatment weighting after multiple imputation in chained equations. The primary outcomes were survival and survival without moderate or severe neuromotor or sensory impairment at age 2 years., Results: Survival at age 2 years was significantly higher in the treated group (92.5% vs 87.9%, risk difference, 4.7%; 95% CI, 0.3-9.1; P = .037), but treated and naive infants did not significantly differ for survival without moderate or severe neuromotor or sensory impairment (86.6% vs 81.3%; risk difference, 5.3%; 95% CI -0.3 to 11.0; P = .063). These results were confirmed by sensitivity analyses using 5 alternative models., Conclusions: Continuous opioid and/or midazolam infusions in very premature infants during initial mechanical ventilation that continued past 24 hours of life were associated with improved survival without any difference in moderate or severe sensorimotor impairments at age 2 years., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Patients affected with aneurysmal subarachnoid hemorrhage (aSAH) often require intensive care, and then present distinctive outcome from less severe patients. We aimed to specify their long-term outcome and to identify factors associated with poor outcome., Methods: We conducted a retrospective study in a French university hospital intensive care unit. Patients with aSAH requiring mechanical ventilation hospitalized between 2010 and 2015 were included. At least one year after initial bleeding, survival and degree of disability were assessed using the modified Rankin Scale (mRS) via telephone interviews. A multivariable logistic regression analysis was performed to determine independent factors associated with poor outcome defined as mRS≥3., Results: Two-hundred thirty-six patients were included. Among them, 7 were lost to follow-up, and 229 were analyzed: 73 patients (32%) had a good outcome (mRS<3), and 156 (68%) had a poor outcome (mRS≥3). The estimated 1-year survival rate was 63%. One-hundred sixty-three patients patients (71%) suffered from early brain injuries (EBI), 33 (14%) from rebleeding, 80 (35%) from vasospasm and 63 (27%) from delayed cerebral ischemia (DCI). Multivariable logistic regression identified independent factors associated with poor outcome including delay between aSAH diagnosis and mRS assessment (OR, 0.96; 95% CI, 0.95-0.98; p<.0001), age (OR per 10 points, 1.57; 95% CI, 1.12-2.19; p = 0.008), WFNS V versus WFNS III (OR, 5.71; 95% CI 1.51-21.61; p = 0.004), subarachnoid rebleeding (OR, 6.47; 95% CI 1.16-36.06; p = 0.033), EBI (OR, 4.52; 95% CI 1.81-11.29; p = 0.001) and DCI (OR, 4.73; 95% CI, 1.66-13.49; p = 0.004)., Conclusion: Among aSAH patients requiring assisted ventilation, two-third of them survived at one year, and one-third showed good long-term outcome. As it appears as an independant factor associated with poor outcome, DCI shoud retain particular attention in future studies beyond angiographic vasospasm., Competing Interests: The authors have declared that no competing interests exist.

Data are lacking on the impact of ACEI/ARB exposure on unfavorable outcome in the population of patients hospitalized for COVID-19 with hypertension/cardiovascular disease, particularly in Europe. The ACE-CoV study was designed to assess this question. The study was conducted in the Covid-Clinic-Toul cohort, which contains data about all patients hospitalized at Toulouse University hospital, France with a SARS-CoV-2 infection since March, 2020. We selected the patients with a history of cardiovascular disease (heart failure or coronary disease) and/or arterial hypertension. We conducted a subgroup analysis in patients with arterial hypertension. ACEI/ARB exposures at admission were assessed. The outcome was composite: admission to intensive care unit, need of mechanical ventilation or death during the 14 days after admission to hospital. We used logistic regression models with propensity scores (PS) weighted by overlap weighting (OW) and inverse probability of treatment weighting (IPTW). Between March 2020 and April 20, 2020, the Covid-Clinic-Toul included 263 patients. Among them, 111 were included in the ACE-CoV study population. In OW-PS-adjusted analyses, the association of exposure to ACEIs or ARBs with outcome occurrence was OR: 1.56 (95% CI: 0.73-3.33). It was 0.99 (95% CI: 0.68-1.45) for ACEIs and 1.64 (95% CI: 0.77-3.50) for ARBs. Analyses with weighting by the IPTW-PS method gave similar results. Results were similar when considering the subgroup of patients with arterial hypertension. The ACE-CoV study found no association between exposure to ACEIs or ARBs and unfavorable outcome in hospitalized patients for COVID-19 with a history of cardiovascular disease/arterial hypertension., (© 2020 Société Française de Pharmacologie et de Thérapeutique.)

Background: Excess visceral fat (VF) or high body mass index (BMI) is risk factors for severe COVID-19. The receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is expressed at higher levels in the VF than in the subcutaneous fat (SCF) of obese patients., Aim: To show that visceral fat accumulation better predicts severity of COVID-19 outcome compared to either SCF amounts or BMI., Methods: We selected patients with symptomatic COVID-19 and a computed tomography (CT) scan. Severe COVID-19 was defined as requirement for mechanical ventilation or death. Fat depots were quantified on abdominal CT scan slices and the measurements were correlated with the clinical outcomes. ACE 2 mRNA levels were quantified in fat depots of a separate group of non-COVID-19 subjects using RT-qPCR., Results: Among 165 patients with a mean BMI of 26.1 ± 5.4 kg/m 2 , VF was associated with severe COVID-19 (p = 0.022) and SCF was not (p = 0.640). Subcutaneous fat was not different in patients with mild or severe COVID-19 and the SCF/VF ratio was lower in patients with severe COVID-19 (p = 0.010). The best predictive value for severe COVID-19 was found for a VF area ≥128.5 cm 2 (ROC curve), which was independently associated with COVID-19 severity (p < 0.001). In an exploratory analysis, ACE 2 mRNA positively correlated with BMI in VF but not in SCF of non-COVID-19 patients (r 2  = 0.27 vs 0.0008)., Conclusion: Severe forms of COVID-19 are associated with high visceral adiposity in European adults. On the basis of an exploratory analysis ACE 2 in the visceral fat may be a trigger for the cytokine storm, and this needs to be clarified by future studies., Competing Interests: Declaration of competing interest None for any of the authors., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Rationale: Whether severe coronavirus disease (COVID-19) is a significant risk factor for the development of invasive fungal superinfections is of great medical interest and remains, for now, an open question. Objectives: We aim to assess the occurrence of invasive fungal respiratory superinfections in patients with severe COVID-19. Methods: We conducted the study on patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related pneumonia admitted to five ICUs in France who had respiratory and serum sampling performed for specific screening of fungal complications. Measurements and Main Results: The study population included a total of 145 patients; the median age was 55 years old. Most of them were male ( n  = 104; 72%), were overweight ( n  = 99; 68%), and had hypertension ( n  = 83; 57%) and diabetes ( n  = 46; 32%). Few patients presented preexisting host risk factors for invasive fungal infection ( n  = 20; 14%). Their global severity was high; all patients were on invasive mechanical ventilation, and half ( n  = 73, 54%) were on extracorporeal membrane oxygenation support. Mycological analysis included 2,815 mycological tests (culture, galactomannan, β-glucan, and PCR) performed on 475 respiratory samples and 532 sera. A probable/putative invasive pulmonary mold infection was diagnosed in 7 (4.8%) patients and linked to high mortality. Multivariate analysis indicates a significantly higher risk for solid organ transplant recipients (odds ratio,  = 4.66; interquartile range, 1.98-7.34; P  = 0.004). False-positive fungal test and clinically irrelevant colonization, which did not require the initiation of antifungal treatment, was observed in 25 patients (17.2%). Conclusions: In patients with no underlying immunosuppression, severe SARS-CoV-2-related pneumonia seems at low risk of invasive fungal secondary infection, especially aspergillosis.

Introduction: Despite many efforts to improve mechanical ventilation strategies and the use of rescue strategies, ARDS-related mortality remains high. The primary objective of this study was to determine the incidence and 90-day mortality of ARDS patients admitted to all French ICUs following the introduction of the Berlin definition of ARDS., Patients and Methods: The data source for this nationwide cohort study was the French national hospital database (Programme de Médicalisation des Systèmes d'Information (PMSI)), which systematically collects administrative and medical information related to all patients hospitalised and hospital stays. Patient-level data were obtained from the PMSI database for all patients admitted to an ICU from the 1 st of January 2017, through the 31 st of December 2017. The inclusion criteria were as follows: ICU patients ≥ 18 years old with at least one International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10) diagnosis code of J80 (ARDS), either as a primary diagnosis or a secondary diagnosis, during their ICU stay., Results: A total of 12,846 ICU adult patients with ARDS were included. The crude incidence of ARDS was 24.6 per 100,000 person-years, varying with age from 6.7 per 100,000 person-years for those 18 through 40 years of age to 51.9 per 100,000 person-years for those 68 through 76 years of age. The in-hospital mortality rate was 51.1%. Day-90 mortality (day-1 being the ICU admission) was 51.2% and increased with age from 29.0% for patients 18 through 40 years of age to 69.3% for patients 77 years of age or older (p < 0.001). Only 53.9% of the survivors were transferred home directly after hospital discharge., Conclusions: The incidence and mortality of ARDS in adults in France are higher than that generally reported in other countries., (Copyright © 2020 Société française d'anesthésie et de réanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved.)

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) cmH 2 O, and 24 (21-27) cmH 2 O, 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 PaO 2 /FiO 2 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.

Background: Although immune modulation is a promising therapeutic avenue in coronavirus disease 2019 (COVID-19), the most relevant targets remain to be found. COVID-19 has peculiar characteristics and outcomes, suggesting a unique immunopathogenesis., Methods: Thirty-six immunocompetent non-COVID-19 and 27 COVID-19 patients with severe pneumonia were prospectively enrolled in a single center, most requiring intensive care. Clinical and biological characteristics (including T cell phenotype and function and plasma concentrations of 30 cytokines) and outcomes were compared., Results: At similar baseline respiratory severity, COVID-19 patients required mechanical ventilation for significantly longer than non-COVID-19 patients (15 [7-22] vs. 4 (0-15) days; p = 0.0049). COVID-19 patients had lower levels of most classical inflammatory cytokines (G-CSF, CCL20, IL-1β, IL-2, IL-6, IL-8, IL-15, TNF-α, TGF-β), but higher plasma concentrations of CXCL10, GM-CSF and CCL5, compared to non-COVID-19 patients. COVID-19 patients displayed similar T-cell exhaustion to non-COVID-19 patients, but with a more unbalanced inflammatory/anti-inflammatory cytokine response (IL-6/IL-10 and TNF-α/IL-10 ratios). Principal component analysis identified two main patterns, with a clear distinction between non-COVID-19 and COVID-19 patients. Multivariate regression analysis confirmed that GM-CSF, CXCL10 and IL-10 levels were independently associated with the duration of mechanical ventilation., Conclusion: We identified a unique cytokine response, with higher plasma GM-CSF and CXCL10 in COVID-19 patients that were independently associated with the longer duration of mechanical ventilation. These cytokines could represent the dysregulated immune response in severe COVID-19, as well as promising therapeutic targets. ClinicalTrials.gov: NCT03505281.

Background: Community-acquired bacterial pneumonia (CABP) can lead to sepsis and is associated with high mortality rates in patients presenting with shock and/or respiratory failure and who require mechanical ventilation and admission to intensive care units, thus reflecting the limited effectiveness of current therapy. Preclinical studies support the efficacy of expanded allogeneic adipose-derived mesenchymal stem cells (eASCs) in the treatment of sepsis. In this study, we aim to test the safety, tolerability and efficacy of eASCs as adjunctive therapy in patients with severe CABP (sCABP)., Methods: In addition to standard of care according to local guidelines, we will administer eASCs (Cx611) or placebo intravenously as adjunctive therapy to patients with sCABP. Enrolment is planned for approximately 180 patients who will be randomised to treatment groups in a 1:1 ratio according to a pre-defined randomization list. An equal number of patients is planned for allocation to each group. Cx611 will be administered on Day 1 and on Day 3 at a dose of 160 million cells (2 million cells / mL, total volume 80 mL) through a 20-30 min (240 mL/hr) intravenous (IV) central line infusion after dilution with Ringer Lactate solution. Placebo (Ringer Lactate) will also be administered through a 20-30 min (240 mL/hr) IV central line infusion at the same quantity (total volume of 80 mL) and following the same schedule as the active treatment. The study was initiated in January 2017 and approved by competent authorities and ethics committees in Belgium, Spain, Lithuania, Italy, Norway and France; monitoring will be performed at regular intervals. Funding is from the European Union's Horizon 2020 Research and Innovation Program., Discussion: SEPCELL is the first trial to assess the effects of eASCs in sCABP. The data generated will advance understanding of the mode of action of Cx611 and will provide evidence on the safety, tolerability and efficacy of Cx611 in patients with sCABP. These data will be critical for the design of future confirmatory clinical investigations and will assist in defining endpoints, key biomarkers of interest and sample size determination., Trial Registration: NCT03158727 , retrospectively registered on 9 May 2017.

Introduction: In intensive care unit (ICU), the decision of extubation is a critical time because mortality is particularly high in case of reintubation. To reduce that risk, guidelines recommend to systematically perform a spontaneous breathing trial (SBT) before extubation in order to mimic the postextubation physiological conditions. SBT is usually performed with a T-piece disconnecting the patient from the ventilator or with low levels of pressure-support ventilation (PSV). However, work of breathing is lower during PSV than during T-piece. Consequently, while PSV trial may hasten extubation, it may also increase the risk of reintubation. We hypothesise that, compared with T-piece, SBT performed using PSV may hasten extubation without increasing the risk of reintubation., Methods and Analysis: This study is an investigator-initiated, multicentre randomised controlled trial comparing T-piece vs PSV for SBTs in patients at high risk of reintubation in ICUs. Nine hundred patients will be randomised with a 1:1 ratio in two groups according to the type of SBT. The primary outcome is the number of ventilator-free days at day 28, defined as the number of days alive and without invasive mechanical ventilation between the initial SBT (day 1) and day 28. Secondary outcomes include the number of days between the initial SBT and the first extubation attempt, weaning difficulty, the number of patients extubated after the initial SBT and not reintubated within the following 72 hours, the number of patients extubated within the 7 days following the initial SBT, the number of patients reintubated within the 7 days following extubation, in-ICU length of stay and mortality in ICU, at day 28 and at day 90., Ethics and Dissemination: The study has been approved by the central ethics committee 'Ile de France V' (2019-A02151-56) and patients will be included after informed consent. The results will be submitted for publication in peer-reviewed journals., Trial Registration Number: NCT04227639., Competing Interests: Competing interests: AWT reports financial support (payment for lectures and travel expenses coverage to attend scientific meetings) by Fisher & Paykel, Covidien, Maquet—Getinge, GE Healthcare. J-PF reports consulting fees from Fisher & Paykel and SOS oxygène., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The life expectancy of individuals with Duchenne muscular dystrophy has improved considerably with the use of mechanical ventilation to manage respiratory insufficiency. The choice between continuous noninvasive ventilation (NIV) and invasive ventilation is guided both by local logistical considerations and by clinical considerations, but the choice depends largely on patient preference. It is important to know the effects of ventilatory dependence and the method used (ie, continuous NIV or invasive ventilation) on subjects' quality of life., Methods: This was a cross-sectional prospective survey of 192 subjects with Duchenne muscular dystrophy using mechanical ventilation in France. Subjects were grouped and compared according to dependence on mechanical ventilation and the ventilation methods used., Results: Regardless of the mechanical ventilation method, subjects with gastrostomy tubes reported more frequent emergency consultations for digestive problems (22.5% vs 4.6%, P = .001). Subjects with invasive ventilation reported more insomnia than those with continuous NIV (23.8% vs 8.5%, P = .04). The latter reported more ineffective cough than the invasive ventilation group (72.3% vs 49.2%, P = .02). Overall, the subjects in our sample were satisfied with their medical care, regardless of dependence level or ventilation type. More specifically, 86.1% of subjects with intermittent NIV and 83.6% of ventilator-dependent subjects were satisfied., Conclusions: Continuous and invasive mechanical ventilation did not affect the perception of quality of life for our subjects with Duchenne muscular dystrophy, apart from more insomnia, which can be explained by the fact that they required frequent repositioning in bed. Different pressure-relief mattresses should be tested and compared to prevent the development of pressure ulcers, which may improve the sleep patterns of these patients., Competing Interests: This work was supported in part by AFM Téléthon. The authors have no disclosed no conflicts of interest., (Copyright © 2020 by Daedalus Enterprises.)

Background: Data on SARS-CoV-2 load in lower respiratory tract (LRT) are scarce. Our objectives were to describe the viral shedding and the viral load in LRT and to determine their association with mortality in critically ill COVID-19 patients., Methods: We conducted a binational study merging prospectively collected data from two COVID-19 reference centers in France and Switzerland. First, we described the viral shedding duration (i.e., time to negativity) in LRT samples. Second, we analyzed viral load in LRT samples. Third, we assessed the association between viral presence in LRT and mortality using mixed-effect logistic models for clustered data adjusting for the time between symptoms' onset and date of sampling., Results: From March to May 2020, 267 LRT samples were performed in 90 patients from both centers. The median time to negativity was 29 (IQR 23; 34) days. Prolonged viral shedding was not associated with age, gender, cardiac comorbidities, diabetes, immunosuppression, corticosteroids use, or antiviral therapy. The LRT viral load tended to be higher in non-survivors. This difference was statistically significant after adjusting for the time interval between onset of symptoms and date of sampling (OR 3.78, 95% CI 1.13-12.64, p = 0.03)., Conclusions: The viral shedding in LRT lasted almost 30 days in median in critically ill patients, and the viral load in the LRT was associated with the 6-week mortality.

Introduction: No therapy has proven to be effective yet to reduce mortality and/or invasive mechanical ventilation (IMV) requirement in COVID-19. Tocilizumab (TCZ) in patients with severe COVID-19 could be an effective treatment., Methods: We conducted a retrospective case-control study in the Nord Franche-Comté Hospital, France. We compared the outcome of patients treated with TCZ and patients without TCZ considering a combined primary endpoint: mortality and/or IMV requirement., Results: Thirty patients were treated with TCZ and 176 patients were treated without TCZ. TCZ was used in patients in critical condition (oxygen therapy flow at TCZ onset was 10.5 L/min and 14/30 patients had ≥ 50% lung involvement on CT scan) as a rescue treatment (8/30 patients who died were not admitted in USC in regard to their comorbidities). However, mortality and/or IMV requirement were lower in patients with TCZ than in patients without TCZ (27% vs 52%, p = 0.009)., Conclusion: Despite the small sample size in the TCZ group, this result suggests that TCZ reduces mortality and/or IMV requirement in patients with severe SARS-CoV-2 pneumonia. This notion needs to be confirmed and spread in the medical community., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Management of critically ill patients requiring mechanical ventilation in austere environments or during disaster response is a logistic challenge. Availability of oxygen cylinders for mechanically ventilated patient may be difficult in such a context. A solution to ventilate patients requiring high fraction of inspired oxygen (FiO2) is to use a ventilator able to be supplied by a low-pressure oxygen source connected with two oxygen concentrators (OCs). We tested the Elisée 350 (ResMedBella Vista, Australia) ventilator paired with two Newlife Intensity 10 (Airsep, Ball Ground, Georgia) OCs and evaluated the delivered FiO2 across a range of minute volumes and combinations of ventilator settings., Methods: The ventilators were attached to a test lung, OC flow was adjusted with a Certifier FA ventilator test systems from 2 to 10 L/min and injected into the oxygen inlet port of the Elisée 350. The FiO2 was measured by the analyzer integrated in the ventilator, controlled by the ventilator test system. Several combinations of ventilator settings were evaluated to determine the factors affecting the delivered FiO2., Results: The Elisée 350 ventilator is a turbine ventilator able to deliver high FiO2 when functioning with two OCs. However, modifications of the ventilator settings such as an increase in minute ventilation affect delivered FiO2 even if oxygen flow is constant on the OC., Conclusion: The ability of two OCs to deliver high FiO2 when used with a turbine ventilator makes this method of oxygen delivery a viable alternative to cylinders to ventilate patients requiring an FiO2 of ≥80% in austere place or during disaster response., Level of Evidence: Feasibility study on test bench, level V.

Background: Critically ill patients with systemic rheumatic disease (SRD) have benefited from better provision of rheumatic and critical care in recent years. Recent comprehensive data regarding in-hospital mortality rates and, most importantly, long-term outcomes are scarce., Research Question: The aim of this study was to assess short and long-term outcome of patients with SRD who were admitted to the ICU., Study Design and Methods: All records of patients with SRD who were admitted to ICU between 2006 and 2016 were reviewed. In-hospital and one-year mortality rates were assessed, and predictive factors of death were identified., Results: A total of 525 patients with SRD were included. Causes of admission were most frequently shock (40.8%) and acute respiratory failure (31.8%). Main diagnoses were infection (39%) and SRD flare-up (35%). In-hospital and one-year mortality rates were 30.5% and 37.7%, respectively. Predictive factors that were associated with in-hospital and one-year mortalities were, respectively, age, prior corticosteroid therapy, simplified acute physiology score II ≥50, need for invasive mechanical ventilation, or need for renal replacement therapy. Knaus scale C or D and prior conventional disease modifying antirheumatic drug therapy was associated independently with death one-year after ICU admission., Interpretation: Critically ill patients with SRD had a fair outcome after an ICU stay. Increased age, prior corticosteroid therapy, and severity of critical illness were associated significantly with short- and long-term mortality rates. The one-year mortality rate was also associated with prior health status and conventional disease modifying antirheumatic drug therapy., (Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Objectives: The main objective was to demonstrate the feasibility of percutaneous tracheostomy performed under difficult conditions by military ENT physicians during their deployment in the military intensive care field hospital of the French Military Medical Service in Mulhouse to confront the exceptional COVID-19 pandemic. The secondary objective was to assess reliability and safety for patient and caregivers, with a risk of iatrogenic viral contamination., Material and Methods: A single-center retrospective study was conducted between March 25 and April 25, 2020, in 47 COVID-19 patients requiring prolonged mechanical ventilation. The inclusion criterion was having undergone percutaneous tracheostomy., Results: Eighteen consecutively included patients had successfully undergone percutaneous tracheostomy despite unfavorable anatomical conditions (short neck: 83.3%, overweight or obese: 88.9%). Median time to completion was 11 days after intubation, with an average duration of 7minutes. The procedure was technically compliant in 83.3% of cases, and considered easy (on self-assessment) in 72.2%, with 2 minor per-procedural complications. No crossover to surgery was required. There was only 1 major post-procedural complication (late hemorrhage)., Conclusion: This study showed the feasibility of percutaneous tracheostomy by an ENT physician under COVID-19 biohazard conditions. The technique was fast, easy and safe and met safety requirements for patient and staff., (Copyright © 2020. Published by Elsevier Masson SAS.)

Introduction: Protective ventilation is now a standard of care in adults. However, management of ventilation is heterogeneous in children and little is known regarding the mechanical ventilation parameters actually used during pediatric anesthesia., Aim: The aim of the study was to assess current ventilatory practices during pediatric anesthesia in France and to compare them with pediatric experts' statements, with a specific focus on tidal volume., Patients and Methods: We conducted a prospective multicenter observational study, regarding the ventilatory management and the mechanical ventilation parameters, over two days (21 and 22 June 2017) in 29 pediatric centers in France. All children undergoing general anesthesia during these 2 days were eligible; those who required extracorporeal circulation or one-lung ventilation were excluded., Results: A total of 701 children were included; median [IQR] age was 60 [24-120] months. Among the patients in whom controlled ventilation was used, 254/515 (49.3%) had an expired tidal volume >8 mL/kg and 44 children (8.8%) an expired tidal volume ≥10 mL/kg. Lower weight and use of a supraglottic airway device were significantly associated with provision of a tidal volume ≥10 mL/kg (odds ratio 0.94, 95% confidence interval [0.92; 0.97], P < .001 and 2.28 [1.20; 4.31], P = .012, respectively). The positive end-expiratory pressure was set at a median [IQR] of 4 [3-5] cmH 2 O; it was <3 cmH 2 O in 15.7% of children and not used in 56/499 (9.3%). Among intubated children, 57 (18.3%) received a tidal volume < 10 mL/kg with a positive end-expiratory pressure ≥3 cmH 2 O in association with recruitment maneuvers., Conclusions: Ventilatory practices in children were heterogenous, and a large proportion of children were not ventilated as it is currently recommended by some experts., (© 2020 John Wiley & Sons Ltd.)

Background: Respiratory ICUs (RICUs) have recently been implemented in France to fill the gap between ICUs and respiratory wards for patients who will require prolonged mechanical ventilation (PMV). The aim of this study was to describe the outcomes of subjects with tracheostomy who were undergoing PMV before and after implementing a RICU in our hospital., Methods: Two cohorts were studied and followed up for 1 year. Cohort 1 included 66 subjects from December 2010 to December 2012, before implementing the RICU. Cohort 2 included 103 consecutive subjects included in the RICU from January 2016 to June 2017., Results: In cohort 2, lung and airway diseases were the main causes of chronic respiratory failure in 91.3% of the subjects versus 47.0% of the subjects in cohort 1 ( P < .001). During the follow-up, 34.8% and 24.3% of the subjects in cohorts 1 and 2, respectively, were readmitted at least once ( P = .14), which corresponded to 109 and 137 stays for cohorts 1 and 2. The median (95% CI) length of stay was 42 (37-50) d in the pre-RICU period versus 29 (26-33) d in the RICU period ( P < .001). A complete or partial weaning was achieved in 30.3% of stays in the pre-RICU period versus 69.3% of stays in the RICU period ( P < .001). The in-hospital mortality rate was 14.7% and 7.3% in the pre-RICU and RICU periods, respectively ( P = .10). The 1-year survival did not differ between cohorts: 60.6% versus 53.9% in cohorts 1 versus 2; P = .42)., Conclusions: Implementing a RICU improved the outcomes of the subjects with tracheostomy who were undergoing PMV by reducing the length of stay and increasing complete or partial weaning. However, the 1-year survival remained unchanged., Competing Interests: Dr Herer has no conflicts to disclose., (Copyright © 2020 by Daedalus Enterprises.)

Background: Care pathways and long-term outcomes of acute stroke patients requiring mechanical ventilation have not been thoroughly studied., Methods and Results: Stroke Prognosis in Intensive Care (SPICE) is a prospective multicenter cohort study which will be conducted in 34 intensive care units (ICUs) in the Paris, France area. Patients will be eligible if they meet all of the following inclusion criteria: (1) age of 18 years or older; (2) acute stroke (i.e., ischemic stroke, intracranial hemorrhage, or subarachnoid hemorrhage) diagnosed on neuroimaging; (3) ICU admission within 7 days before or after stroke onset; and (4) need for mechanical ventilation for a duration of at least 24 h. Patients will be excluded if they meet any of the following: (1) stroke of traumatic origin; (2) refusal to participate; and (3) privation of liberty by administrative or judicial decision. The primary endpoint is poor functional outcome at 1 year, defined by a score of 4 to 6 on the modified Rankin scale (mRS), indicating severe disability or death. Main secondary endpoints will include decisions to withhold or withdraw care, mRS scores at 3 and 6 months, and health-related quality of life at 1 year., Conclusions: The SPICE multicenter study will investigate 1-year outcomes, ethical issues, as well as care pathways of acute stroke patients requiring invasive ventilation in the ICU. Gathered data will delineate human resources and facilities needs for adequate management. The identification of prognostic factors at the acute phase will help to identify patients who may benefit from prolonged intensive care and rehabilitation., Trial Registration: NCT03335995.

Objectives: To update the French guidelines on the management of trauma patients with spinal cord injury or suspected spinal cord injury., Design: A consensus committee of 27 experts was formed. A formal conflict-of-interest (COI) policy was developed at the outset of the process and enforced throughout. The entire guidelines process was conducted independently of any industrial funding (i.e. pharmaceutical, medical devices). The authors were advised to follow the rules of the Grading of Recommendations Assessment, Development and Evaluation (GRADE®) system to guide assessment of quality of evidence. The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasised., Methods: The committee studied twelve questions: (1) What are the indications and arrangements for spinal immobilisation? (2) What are the arrangements for pre-hospital orotracheal intubation? (3) What are the objectives of haemodynamic resuscitation during the lesion assessment, and during the first few days in hospital? (4) What is the best way to manage these patients to improve their long-term prognosis? (5) What is the place of corticosteroid therapy in the initial phase? (6) What are the indications for magnetic resonance imaging in the lesion assessment phase? (7) What is the optimal time for surgical management? (8) What are the best arrangements for orotracheal intubation in the hospital environment? (9) What are the specific conditions for weaning these patients from mechanical ventilation for? (10) What are the procedures for analgesic treatment of these patients? (11) What are the specific arrangements for installing and mobilising these patients? (12) What is the place of early intermittent bladder sampling in these patients? Each question was formulated in a PICO (Patients, Intervention, Comparison, Outcome) format and the evidence profiles were produced. The literature review and recommendations were made according to the GRADE® Methodology., Results: The experts' work synthesis and the application of the GRADE method resulted in 19 recommendations. Among the recommendations formalised, 2 have a high level of evidence (GRADE 1+/-) and 12 have a low level of evidence (GRADE 2+/-). For 5 recommendations, the GRADE method could not be applied, resulting in expert advice. After two rounds of scoring and one amendment, strong agreement was reached on all the recommendations., Conclusions: There was significant agreement among experts on strong recommendations to improve practices for the management of patients with spinal cord injury., (Copyright © 2020 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Background: Central venous catheters (CVCs) provide a great comfort for hospitalized children. However, CVCs increase the risk of severe infection. As there are few data regarding pediatric epidemiology of catheter-related infections (CRIs), the main objective of this study was to measure the incidence rate of CRIs in our pediatric university hospital. We also sought to characterize the CRIs and to identify risk factors., Materials and Methods: We conducted an epidemiological prospective monocentric study including all CVCs, except Port-a-Caths and arterial catheters, inserted in children from birth to 18 years of age between April 2015 and March 2016 in the pediatric University Hospital of Nantes. Our main focus was the incidence rate of CRIs, defined according to French guidelines, while distinguishing between bloodstream infections (CRBIs) and non-bloodstream infections (CRIWBs). The incidence rate was also described for each pediatric ward. We analyzed the association between infection and potential risk factors using univariate and multivariate analysis by Cox regression., Results: We included 793 CVCs with 60 CRBIs and four CRIWBs. The incidence rate was 4.6/1000 catheter-days, with the highest incidence rate occurring in the neonatal intensive care unit (13.7/1000 catheter-days). Coagulase-negative staphylococci were responsible for 77.5% of the CRIs. Factors independently associated with a higher risk of infection in neonates were invasive ventilation and low gestational age., Conclusions: The incidence of CRIs in children hospitalized in our institution appears to be higher than the typical rate of CRIs reported in the literature. This was particularly true for neonates. These results should lead us to reinforce preventive measures and antibiotic stewardship but they also raise the difficulty of diagnosing with certainty CRIs in neonates., (Copyright © 2019 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.)

Objectives: To provide an update to the 1999 French guidelines on "Muscle relaxants and reversal in anaesthesia", a consensus committee of sixteen experts was convened. A formal policy of declaration and monitoring of conflicts of interest (COI) was developed at the outset of the process and enforced throughout. The entire guidelines process was conducted independently of any industrial funding (i.e. pharmaceutical, medical devices). The authors were required to follow the rules of the Grading of Recommendations, Assessment, Development and Evaluation (GRADE®) system to assess the quality of the evidence on which the recommendations were based. The potential drawbacks of making strong recommendations based on low-quality evidence were stressed. Few of the recommendations remained ungraded., Methods: The panel focused on eight questions: (1) In the absence of difficult mask ventilation criteria, is it necessary to check the possibility of ventilation via a facemask before muscle relaxant injection? Is it necessary to use muscle relaxants to facilitate facemask ventilation? (2) Is the use of muscle relaxants necessary to facilitate tracheal intubation? (3) Is the use of muscle relaxants necessary to facilitate the insertion of a supraglottic device and management of related complications? (4) Is it necessary to monitor neuromuscular blockade for airway management? (5) Is the use of muscle relaxants necessary to facilitate interventional procedures, and if so, which procedures? (6) Is intraoperative monitoring of neuromuscular blockade necessary? (7) What are the strategies for preventing and treating residual neuromuscular blockade? (8) What are the indications and precautions for use of both muscle relaxants and reversal agents in special populations (e.g. electroconvulsive therapy, obese patients, children, neuromuscular diseases, renal/hepatic failure, elderly patients)? All questions were formulated using the Population, Intervention, Comparison and Outcome (PICO) model for clinical questions and evidence profiles were generated. The results of the literature analysis and the recommendations were then assessed using the GRADE® system., Results: The summaries prepared by the SFAR Guideline panel resulted in thirty-one recommendations on muscle relaxants and reversal agents in anaesthesia. Of these recommendations, eleven have a high level of evidence (GRADE 1±) while twenty have a low level of evidence (GRADE 2±). No recommendations could be provided using the GRADE® system for five of the questions, and for two of these questions expert opinions were given. After two rounds of discussion and an amendment, a strong agreement was reached for all the recommendations., Conclusion: Substantial agreement exists among experts regarding many strong recommendations for the improvement of practice concerning the use of muscle relaxants and reversal agents during anaesthesia. In particular, the French Society of Anaesthesia and Intensive Care (SFAR) recommends the use of a device to monitor neuromuscular blockade throughout anaesthesia., (Copyright © 2020 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Objective: To determine the prevalence and risk markers of anemia at PICU discharge., Design: Bicenter retrospective cohort study., Setting: Two multidisciplinary French PICUs., Patients: All children admitted during a 5-year period, staying in the PICU for at least 2 days, and for whom a hemoglobin was available at PICU discharge., Interventions: None., Measurements and Main Results: Patient, admission, and PICU stay characteristics were retrospectively collected in the electronic medical records of each participating PICU. Anemia was defined according to the World Health Organization criteria. Among the 3,170 patients included for analysis, 1,868 (58.9%) were anemic at discharge from PICU. The proportion of anemic children differed between age categories, whereas the median hemoglobin level did not exhibit significant variations according to age. After multivariate adjustment, anemia at PICU admission was the strongest predictor of anemia at PICU discharge, and the strength of this association varied according to age (interaction). Children anemic at PICU admission had a reduced risk of anemia at PICU discharge if transfused with RBCs during the PICU stay, if less than 6 months old, or if creatinine level at PICU admission was low. Children not anemic at PICU admission had an increased risk of anemia at PICU discharge if they were thrombocytopenic at PICU admission, if they had higher C-reactive protein levels, and if they received plasma transfusion, inotropic/vasopressor support, or mechanical ventilation during the PICU stay., Conclusions: Anemia is frequent after pediatric critical illness. Anemia status at PICU admission defines different subgroups of critically ill children with specific prevalence and risk markers of anemia at PICU discharge. Further studies are required to confirm our results, to better define anemia during pediatric critical illness, and to highlight the causes of post-PICU stay anemia, its course, and its association with post-PICU outcomes.

Spinal muscular atrophy with respiratory distress type 1 (SMARD1) is a rare autosomal recessive neuromuscular disorder characterized by progressive motor and respiratory decline during the first year of life. Early and late-onset cases have recently been reported, although not meeting the established diagnostic criteria, these cases have been genotyped. We thus conducted a national multicenter observational retrospective study to determine the prognosis of children with SMARD1 according to their phenotype. We recorded all known French pediatric cases with mutations identified on the immunoglobulin μ-binding protein 2 gene and the presence of respiratory symptoms. Thirty centers provided 22 observations. A diaphragmatic palsy was diagnosed 1.5 months (p = 0.02) after first respiratory symptoms, and hypotonia preceded areflexia by 4 months (p = 0.02). Early onset of symptoms leading to specialist consultation before the age of 3 months was associated with a significantly worse prognosis (p < 0.01). Among the 6 patients who were still alive, all were tracheostomized. Only one case survived beyond 2 years without artificial ventilation. The remaining patients died at a median age of 7 months. Our results may help pediatricians to provide medical information to parents and improve the decision-making process of setting up life support., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Mechanical ventilation (MV) is a life-saving technology that restores or assists breathing. Like any treatment, MV has side effects. In some patients it can cause diaphragmatic atrophy, injury, and dysfunction (ventilator-induced diaphragmatic dysfunction, VIDD). Accumulating evidence suggests that VIDD makes weaning from MV difficult, which involves increased morbidity and mortality., Methods and Analysis: This paper describes the protocol of a randomized, controlled, open-label, multicenter trial that is designed to investigate the safety and effectiveness of a novel therapy, temporary transvenous diaphragm pacing (TTVDP), to improve weaning from MV in up to 88 mechanically ventilated adult patients who have failed at least two spontaneous breathing trials over at least 7 days. Patients will be randomized (1:1) to TTVDP (treatment) or standard of care (control) groups. The primary efficacy endpoint is time to successful extubation with no reintubation within 48 h. Secondary endpoints include maximal inspiratory pressure and ultrasound-measured changes in diaphragm thickness and diaphragm thickening fraction over time. In addition, observational data will be collected and analyzed, including 30-day mortality and time to discharge from the intensive care unit and from the hospital. The hypothesis to be tested postulates that more TTVDP patients than control patients will be successfully weaned from MV within the 30 days following randomization., Discussion: This study is the first large-scale clinical trial of a novel technology (TTVDP) aimed at accelerating difficult weaning from MV. The technology tested provides the first therapy directed specifically at VIDD, an important cause of delayed weaning from MV. Its results will help delineate the place of this therapeutic approach in clinical practice and help design future studies aimed at defining the indications and benefits of TTVDP., Trial Registration: ClinicalTrials.gov, NCT03096639 . Registered on 30 March 2017.

A cluster of three cases of food-borne botulism due to Clostridium baratii type F occurred in France in August 2015. All cases required respiratory assistance. Consumption of a Bolognese sauce at the same restaurant was the likely source of contamination. Clostridium baratii was isolated both from stool specimens from the three patients and ground meat used to prepare the sauce. This is the second episode reported in France caused by this rare pathogen.

Introduction: Critically ill patients with acute respiratory, neurological or cardiovascular failure requiring invasive mechanical ventilation are at high risk of difficult intubation and have organ dysfunctions associated with complications of intubation and anaesthesia such as hypotension and hypoxaemia. The complication rate increases with the number of intubation attempts. Videolaryngoscopy improves elective endotracheal intubation. McGRATH MAC is the lightest videolaryngoscope and the most similar to the Macintosh laryngoscope. The primary goal of this trial was to determine whether videolaryngoscopy increased the frequency of successful first-pass intubation in critically ill patients, compared to direct view Macintosh laryngoscopy., Methods and Analysis: MACMAN is a multicentre, open-label, randomised controlled superiority trial. Consecutive patients requiring intubation are randomly allocated to either the McGRATH MAC videolaryngoscope or the Macintosh laryngoscope, with stratification by centre and operator experience. The expected frequency of successful first-pass intubation is 65% in the Macintosh group and 80% in the videolaryngoscope group. With α set at 5%, to achieve 90% power for detecting this difference, 185 patients are needed in each group (370 in all). The primary outcome is the proportion of patients with successful first-pass orotracheal intubation, compared between the two groups using a generalised mixed model to take the stratification factors into account., Ethics and Dissemination: The study project has been approved by the appropriate ethics committee (CPP Ouest 2, # 2014-A00674-43). Informed consent is not required, as both laryngoscopy methods are considered standard care in France; information is provided before study inclusion. If videolaryngoscopy proves superior to Macintosh laryngoscopy, its use will become standard practice, thereby decreasing first-pass intubation failure rates and, potentially, the frequency of intubation-related complications. Thus, patient safety should benefit. Further studies would be warranted to determine whether videolaryngoscopy is also beneficial in the emergency room and for prehospital emergency care., Trial Registration Number: NCT02413723; Pre-results., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Objective: The objective of the study was to evaluate the intra- and interobserver agreement among obstetric experts in court regarding the retrospective review of abnormal fetal heart rate tracings and obstetrical management of patients with abnormal fetal heart rate during labor., Study Design: A total of 22 French obstetric experts in court reviewed 30 cases of term deliveries of singleton pregnancies diagnosed with at least 1 hour of abnormal fetal heart rate, including 10 cases with adverse neonatal outcome. The experts reviewed all cases twice within a 3-month interval, with the first review being blinded to neonatal outcome. For each case reviewed, the experts were provided with the obstetric data and copies of the complete fetal heart rate recording and the partogram. The experts were asked to classify the abnormal fetal heart rate tracing and to express whether they agreed with the obstetrical management performed. When they disagreed, the experts were asked whether they concluded that an error had been made and whether they considered the obstetrical management as the cause of cerebral palsy in children if any., Results: Compared with blinded review, the experts were significantly more likely to agree with the obstetric management performed (P < .001) and with the mode of delivery (P < .001) when informed about the neonatal outcome and were less likely to conclude that an error had been made (P < .001) or to establish a link with potential cerebral palsy (P = .003). The experts' intraobserver agreement for the review of abnormal fetal heart rate tracing and obstetrical management were both mediocre (kappa = 0.46-0.51 and kappa = 0.48-0.53, respectively). The interobserver agreement for the review of abnormal fetal heart rate tracing was low and was not improved by knowledge of the neonatal outcome (kappa = 0.11-0.18). The interobserver agreement for the interpretation of obstetrical management was also low (kappa = 0.08-0.19) but appeared to be improved by knowledge of the neonatal outcome (kappa = 0.15-0.32)., Conclusion: The intra- and interobserver agreement among obstetric experts in court for the review of abnormal fetal heart rate tracing and the appropriateness of obstetrical care is poor, suggesting a lack of objectivity of obstetrical expertise as currently performed in court., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: The aims of the study were to assess the knowledge of intensivists and/or anaesthesiologists concerning respiratory arterial pulse pressure variation (PPV) and to define the criteria used to indicate a fluid challenge., Study Design: A prospective observational study., Patients and Methods: Intensivists and anaesthesiologists from one region of France were evaluated for their knowledge about the prerequisites (continuous arterial pressure monitoring, regular sinus rhythm, mechanical ventilation without spontaneous breathing) and confounding factors shifting the threshold value of PPV (low tidal volume, decreased pulmonary compliance, low heart rate/respiratory rate ratio, right ventricular dysfunction, and/or intra-abdominal hypertension) using clinical vignettes. Criteria used by physicians to indicate a fluid challenge were also collected., Results: One hundred and forty-five physicians were included in the study. Among them, 87 (60%) knew prerequisites but none of them had full knowledge of all confounding factors. Criteria used to perform a fluid challenge were mainly PPV and the passive leg-raising test for the residents and PPV, blood pressure, oliguria and hydric balance for the qualified physicians., Conclusions: PPV was widely employed to indicate a fluid challenge and 60% of the physicians knew the prerequisites. However, the physicians did not correctly interpret all confounding factors., (Copyright © 2015 Société française d’anesthésie et de réanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved.)

Objective: Arterial pulse pressure variation (PPV) has been used as an accurate index to predict fluid responsiveness. However, many confounding factors have been recently described. The aims of this study were to assess the conditions of applicability of PPV in intensive care units (ICU)., Study Design: A one-day French national survey., Patients and Methods: A form assessing the suitability of PPV was completed by practitioners for each critically-ill patient included on a set day., Results: Four hundred and sixty-five patients were included in 36 ICUs. A regular sinus rhythm was noted in 408 (88%) patients and the presence of an arterial line in 324 (70%) patients. One hundred and twenty-seven (27%) patients were mechanically ventilated without spontaneous breathing. Only six patients (1.3%) had no confounding factors modifying the threshold value of the PPV., Conclusion: The incidence of ICU patients in whom PPV was suitable and without confounding factors were respectively 18% and 1.3% in this one-day French national survey., (Copyright © 2015 Société française d’anesthésie et de réanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved.)

Objectives: to understand epidemiological trends in severe COPD exacerbations through analyzes of hospitalizations and deaths during three consecutive years in a French administrative region area., Methods: Medico-administrative records of hospitalizations for COPD exacerbations were sorted from 2010 to 2012 using selected International Classification of Diseases (ICD10) codes. Four groups of hospitalization for COPD severe exacerbations were elicited leading to hospitalizations (general ward without respiratory failure, general ward with acute respiratory distress, ICU without mechanical ventilation, ICU with mechanical ventilation)., Results: Data extraction identified 5007, 4986 and 5359 admissions related to 4136, 4155 and 4460 patients in 2010, 2011 and 2012, respectively. Marked seasonal variations were observed. Duration of stay (median (IQR), 7 (7) vs 9 (8) vs 10 (9) vs 14 (16) days, P < .001), death rates (3.6% vs 14.2% vs 14.4% vs 21.2%, P < .01), number of co-morbid conditions (median (IQR), 2 (2) vs 2 (2) vs 4 (5) vs 4 (4.5), P < .01), type of institution (64.9% in public institution vs 79.9% vs 87.8% vs 76.6%, P < .01) were significantly associated with the hospitalization group and more than 8% of admissions led to death (3% to 24%). Age, type of institution and past hospitalizations were independent risk factors for deaths. Readmissions were infrequent but mainly related to the worsening of the co-morbid conditions., Conclusion: COPD severe exacerbations are frequent and lead to an important numbers of deaths related to the severity of acute respiratory failure and the number of co-morbid conditions.