High-level burnout in physicians and nurses working in adult ICUs: a systematic review and meta-analysis.

PURPOSE: The prevalence of burnout in intensive care unit (ICU) professionals is difficult to establish due to the variety of survey instruments used, the heterogeneity of the targeted population, the design of the studies, and the differences among countries regarding ICU organization. METHODS: We performed a systematic review and meta-analysis examining the prevalence of high-level burnout in physicians and nurses working in adult ICUs, including only studies that use the Maslach Burnout Inventory (MBI) as a tool to evaluate burnout and involving at least 3 different ICUs. RESULTS: Twenty-five studies with a combined population of 20,723 healthcare workers from adult ICUs satisfied the inclusion criteria. Combining 18 studies including 8187 ICU physicians, 3660 of them reported a high level of burnout (prevalence 0.41, range 0.15-0.71, 95% CI [0.33; 0.5], I2 97.6%, 95% CI [96.9%; 98.1%]). The heterogeneity can be at least in part explained by the definition of burnout used and the response rate as confirmed by the multivariable metaregression done. In contrast, there was no significant difference regarding other factors such as the study period (before or during the coronavirus disease 2019 (COVID-19) pandemic), the income of the countries, or the Healthcare Access and Quality (HAQ) index. Combining 20 studies including 12,536 ICU nurses, 6232 of nurses were reporting burnout (prevalence 0.44, range 0.14-0.74, [95% CI 0.34; 0.55], I2 98.6% 95% CI [98.4%; 98.9%]). The prevalence of high-level burnout in ICU nurses for studies performed during the COVID-19 pandemic was higher than that reported for studies performed before the COVID-19 pandemic (0.61 [95% CI, 0.46; 0.75] and 0.37 [95% CI, 0.26; 0.49] respectively, p = 0.003). As for physicians, the heterogeneity is at least in part explained by the definition used for burnout using the MBI but not by the number of participants. When compared, the prevalence of high-level burnout was not different between ICU physicians and ICU nurses. However, the proportion of ICU nurses with a high level of emotional exhaustion was higher than for ICU physicians (0.42 [95% CI, 0.37; 0.48] and 0.28 [0.2; 0.39], respectively, p = 0.022). CONCLUSION: According to this meta-analysis, the prevalence of high-level burnout is higher than 40% in all ICU professionals. However, there is a great heterogeneity in the results. To evaluate and to compare preventive and therapeutic strategies, there is the need to use a consensual definition of burnout when using the MBI instrument.

Awake prone position in COVID-19 acute respiratory failure: a randomised crossover study using electrical impedance tomography.

Background: The goal of this study was to determine whether an awake prone position (aPP) reduces the global inhomogeneity (GI) index of ventilation measured by electrical impedance tomography (EIT) in COVID-19 patients with acute respiratory failure (ARF). Methods: This prospective crossover study included COVID-19 patients with COVID-19 and ARF defined by arterial oxygen tension:inspiratory oxygen fraction (P aO2 :F IO2 ) of 100-300 mmHg. After baseline evaluation and 30-min EIT recording in the supine position (SP), patients were randomised into one of two sequences: SP-aPP or aPP-SP. At the end of each 2-h step, oxygenation, respiratory rate, Borg scale and 30-min EIT were recorded. Results: 10 patients were randomised in each group. The GI index did not change in the SP-aPP group (baseline 74±20%, end of SP 78±23% and end of aPP 72±20%, p=0.85) or in the aPP-SP group (baseline 59±14%, end of aPP 59±15% and end of SP 54±13%, p=0.67). In the whole cohort, P aO2 :F IO2 increased from 133±44 mmHg at baseline to 183±66 mmHg in aPP (p=0.003) and decreased to 129±49 mmHg in SP (p=0.03). Conclusion: In spontaneously breathing nonintubated COVID-19 patients with ARF, aPP was not associated with a decrease of lung ventilation inhomogeneity assessed by EIT, despite an improvement in oxygenation.

Awake prone position in COVID-19 acute respiratory failure: a randomized crossover study using electrical impedance tomography

Background The goal of this study was to determine whether an awake prone position (aPP) reduces the global inhomogeneity (GI) index of ventilation measured by electrical impedance tomography (EIT) in COVID-19 patients with acute respiratory failure (ARF). Methods This prospective crossover study included COVID-19 patients with COVID-19 and ARF defined by PaO2:FiO2 of 100–300 mmHg. After baseline evaluation and 30 min EIT recording in the supine position (SP), patients were randomized into one of two sequences: SP-aPP or aPP-SP. At the end of each 2 h step, oxygenation, respiratory rate, Borg scale, and 30 min EIT were recorded. Results Ten patients were randomized in each group. The GI index did not change in the SP-aPP group (baseline 74±20%, end of SP 78±23% and end of aPP 72±20%, p=0.85) or in the aPP-SP group (baseline 59±14%, end of aPP 59±15% and end of SP 54±13%, p=0.67). In the whole cohort, PaO2:FiO2 increased from 133±44 mmHg at baseline to 183±66 mmHg in aPP (p=0.003) and decreased to 129±49 mmHg in SP (p=0.03). Conclusion In spontaneously breathing non-intubated COVID-19 patients with acute respiratory failure, aPP was not associated with a decrease of lung ventilation inhomogeneity assessed by EIT, despite an improvement in oxygenation.

Management of lung transplantation in the COVID-19 era—An international survey

It is unknown if solid organ transplant recipients are at higher risk for severe COVID-19. The management of a lung transplantation (LTx) program and the therapeutic strategies to adapt the immunosuppressive regimen and antiviral measures is a major issue in the COVID-19 era, but little is known about worldwide practice. We sent out to 180 LTx centers worldwide in June 2020 a survey with 63 questions, both regarding the management of a LTx program in the COVID-19 era and the therapeutic strategies to treat COVID-19 LTx recipients. We received a total of 78 responses from 15 countries. Among participants, 81% declared a reduction of the activity and 47% restricted LTx for urgent cases only. Sixteen centers observed deaths on waiting listed patients and eight centers performed LTx for COVID-19 disease. In 62% of the centers, COVID-19 was diagnosed in LTx recipients, most of them not severe cases. The most common immunosuppressive management included a decreased dose or pausing of the cell cycle inhibitors. Remdesivir, hydroxychloroquine, and azithromycin were the most proposed antiviral strategies. Most of the centers have been affected by the COVID-19 pandemic and proposed an active therapeutic strategy to treat LTx recipients with COVID-19.

Eosinopenia as Predictor of Poor Outcome in Hospitalized COVID-19 Adult Patients from Waves 1 and 2 of 2020 Pandemic.

During SARS-CoV-2 infection, eosinopenia may reflect a hyperactive immune response. In this study of hospitalized COVID-19 patients, we aimed to better understand the prognostic value of severe eosinopenia (absolute eosinophil count = 0 G/L) and decipher its underlying mechanisms. We retrospectively analyzed the records of COVID-19 patients hospitalized from March to June 2020 in three university hospitals in Marseille, France. We assessed the association between severe eosinopenia and a composite poor outcome in these patients, including the need for oxygen supplementation at >6 L/min, ICU admission, and in-hospital death. Among the 551 COVID-19 patients included in this study, severe eosinopenia was found in 228 (51%) of them on admission to hospital and was associated with a composite poor outcome using multivariate analysis (OR = 2.58; CI95 [1.77−3.75]; p < 0.0001). We found a significant association between the presence of severe eosinopenia on admission and the elevation in C-reactive protein, ferritin, IP-10, and suPAR. The histological findings in a series of 37 autopsies from patients who died from severe COVID-19 and presented with severe eosinopenia showed no pulmonary eosinophil trapping. Severe eosinopenia can be a reliable biomarker associated with a composite poor outcome in hospitalized COVID-19 adult patients. It may reflect the magnitude of immune hyperactivation during severe-to-critical COVID-19.

Incidence, Outcomes and Risk Factors of Recurrent Ventilator Associated Pneumonia in COVID-19 Patients: A Retrospective Multicenter Study.

Background: High incidence of ventilator associated pneumonia (VAP) has been reported in critically ill patients with COVID-19. Among these patients, we aimed to assess the incidence, outcomes and risk factors of VAP recurrences. Methods: We conducted an observational retrospective study in three French intensive care units (ICUs). Patients admitted for a documented COVID-19 from March 2020 to May 2021 and requiring mechanical ventilation (MV) for ≥48 h were included. The study main outcome was the incidence of VAP recurrences. Secondary outcomes were the duration of MV, ICU and hospital length of stay and mortality according to VAP and recurrences. We also assessed the factors associated with VAP recurrences. Results: During the study period, 398 patients met the inclusion criteria. A total of 236 (59%) of them had at least one VAP episode during their ICU stay and 109 (46%) of these patients developed at least one recurrence. The incidence of VAP recurrence considering death and extubation as competing events was 29.6% (IC = [0.250−0.343]). Seventy-eight percent of recurrences were due to the same bacteria (relapses). Patients with a VAP recurrence had a longer duration of MV as compared with one VAP and no VAP patients (41 (25−56) vs. 16 (8−30) and 10 (5−18) days; p < 0.001) and a longer ICU length of stay (46 (29−66) vs. 22 (12−36) and 14 (9−25) days; p < 0.001). The 90-day mortality was higher in the recurrence group as compared with the no VAP group only (31.2 vs. 21.0% (p = 0.021)). In a multivariate analysis including bacterial co-infection at admission, the use of immunosuppressive therapies and the bacteria responsible for the first VAP episode, the duration of MV was the only factor independently associated with VAP recurrence. Conclusion: In COVID-19 associated respiratory failure, recurrences affected 46% of patients with a first episode of VAP. VAP recurrences were mainly relapses and were associated with a prolonged duration of MV and ICU length of stay but not with a higher mortality. MV duration was the only factor associated with recurrences.

Impact of Dexamethasone and Inhaled Nitric Oxide on Severe Acute Kidney Injury in Critically Ill Patients with COVID-19.

BACKGROUND: Acute kidney injury (AKI) is the second most frequent condition after acute respiratory distress syndrome (ARDS) in critically ill patients with severe COVID-19 and is strongly associated with mortality. The aim of this multicentric study was to assess the impact of the specific treatments of COVID-19 and ARDS on the risk of severe AKI in critically ill COVID-19 patients. METHODS: In this cohort study, data from consecutive patients older than 18 years admitted to 6 ICUs for COVID-19-related ARDS requiring invasive mechanical ventilation were included. The incidence and severity of AKI, defined according to the 2012 KDIGO definition, were monitored during the entire ICU stay until day 90. Patients older than 18 years admitted to the ICU for COVID-19-related ARDS requiring invasive mechanical ventilation were included. RESULTS: 164 patients were included in the final analysis; 97 (59.1%) displayed AKI, of which 39 (23.8%) had severe stage 3 AKI, and 21 (12.8%) required renal replacement therapy (RRT). In univariate analysis, severe AKI was associated with angiotensin-converting enzyme inhibitors (ACEI) exposure (p = 0.016), arterial hypertension (p = 0.029), APACHE-II score (p = 0.004) and mortality at D28 (p = 0.008), D60 (p < 0.001) and D90 (p < 0.001). In multivariate analysis, the factors associated with the onset of stage 3 AKI were: exposure to ACEI (OR: 4.238 (1.307-13.736), p = 0.016), APACHE II score (without age) (OR: 1.138 (1.044-1.241), p = 0.003) and iNO (OR: 5.694 (1.953-16.606), p = 0.001). Prone positioning (OR: 0.234 (0.057-0.967), p = 0.045) and dexamethasone (OR: 0.194 (0.053-0.713), p = 0.014) were associated with a decreased risk of severe AKI. CONCLUSIONS: Dexamethasone was associated with the prevention of the risk of severe AKI and RRT, and iNO was associated with severe AKI and RRT in critically ill patients with COVID-19. iNO should be used with caution in COVID-19-related ARDS.

Prevalence of COVID-Associated Renal Injury in ICU and Prognosis of Proximal Tubular Dysfunction in Acute Respiratory Distress Syndrome

BACKGROUND AND AIMS During COVID-19, the renal impairment is the most frequent after lung impairment and is associated of poor prognosis particularly in the intensive care unit (ICU). In this work, we aim to assess the incidence of acute kidney injury (AKI) in COVID-19-related acute respiratory distress syndrome (ARDS) patients, the existence of an early renal dysfunction and its prognosis, and its specificity compared with patients with non-COVID ARDS. METHOD This a prospective and multicentric study led in four ICUs. Patients of 18 years and older in ICU with invasive mechanical ventilation for ARDS were enrolled. Precise evaluation of renal dysfunction markers, including urinary protein electrophoresis, was performed within 24 h after the onset of mechanical ventilation. RESULTS From March 2020 to September 2021, 131 patients in ICU for ARDS were enrolled, 98 COVID-19 ARDS and 33 ARDS from other causes. There was more tubular profile in COVID-19 patients (68% versus 24%;P = .001) and a more mixed, tubular and glomerular profile in non-COVID-19 patients (29% versus 14%;P = .001). COVID-19 patients displayed an important tubular proteinuria, tended to display more AKI (49% versus 31%;P = .07), and had a longer duration of mechanical ventilation (18 versus 10 days;P = .002) and longer ICU length of stay (23 versus 15 days;P = .013). In COVID-19 patients, tubular proteinuria was associated with poor renal prognosis with a significant association with the onset of KDIGO ≥ 2 AKI. CONCLUSION COVID-19 ARDS patients had a specific renal impairment with tubular dysfunction, which appeared to be of poor prognosis on kidney and disease evolution.

Sanitary safety of the 2021 French Intensive Care Society medical conference: a case/control study

BackgroundIn-person mass gathering events (MGE) are returning after a period of restrictions, yet few prospective scientific evaluations of their safety are available.MethodsProspective observational study, including both attendees of the French Intensive Care Society (FICS) annual meeting held in Paris between June the 9th and June the 11th, 2021 and matched controls (healthcare professionals who stayed in the ICU during the conference). SARS-CoV-2 lateral flow test was performed on day 7. Follow-up occurred until day 21.ResultsOut of the 1824 healthcare professionals attending the congress (all of which fulfilled legal requirements: 7 days or more following a second dose of vaccine or a negative PCR test performed within less than 72 h), 520 (28.5%) agreed to participate. Follow-up data were received for 216 (41.5%) out of the 520 included attendees, and for 191 matched controls. No positive SARS-CoV-2 lateral flow test was reported in the attendees or in the matched controls. The probability of SARS-CoV-2 infection during the MGE was less than 1.7% in the attendees (95% confidence interval [0;1.7%]), less than 2% in the controls (95%CI [0;2%]) and the difference in probabilities of infection was less than 1.9% (95% CI [0;1.9%]).ConclusionDuring a low incidence period, in this population of congress attendees screened for SARS-CoV-2 by a lateral flow test at day 7, no positive cases could be documented, no concomitant infection occurred in the matched controls;suggesting no extra risk of infection during the MGE.Trial Registration: ClinicalTrial.gov, #NCT04918160.

Effect of prone positioning on survival in adult patients receiving venovenous extracorporeal membrane oxygenation for acute respiratory distress syndrome: a systematic review and meta-analysis.

PURPOSE: Previous studies support the potential efficacy of venovenous extracorporeal membrane oxygenation (vvECMO) for improving survival in severe acute respiratory distress syndrome (ARDS) cases. Prone positioning (PP) has been shown to improve the outcomes of moderate-to-severe ARDS patients. Few studies and no randomized controlled trials have evaluated the effect of PP performed in ECMO patients. METHODS: We performed a systematic review and meta-analysis examining the effect of prone positioning for ARDS patients receiving vvECMO on survival. All authors were contacted to obtain complementary information not mentioned in the original articles. The main objective was to compare 28-day survival in vvECMO patients with PP to vvECMO patients without PP (controls). RESULTS: Thirteen studies with a combined population of 1836 patients satisfied the inclusion criteria. PP was associated with a significant improvement in 28-day survival (503 survivors among 681 patients in the PP group [74%; 95% CI 71-77] vs. 450 survivors among 770 patients in the control group [58%, 95% CI 55-62]; RR 1.31 [95% CI 1.21-1.41]; I2 22% [95% CI 0-62%]; P < 0.0001). Survival was also improved in terms of other endpoints (60-day survival, 90-day survival, ICU survival, and hospital survival). In contrast, the duration of mechanical ventilation was increased in vvECMO patients with PP (mean difference 11.4 days [95% CI 9.2-13.5]; 0.64 [95% CI 0.50-0.78]; I2 8%; P < 0.0001). CONCLUSION: According to this meta-analysis, survival was improved when prone positioning was used in ARDS patients receiving vvECMO. The impact of this combination on survival should be investigated in prospective randomized controlled trials.

Association of COVID-19 Acute Respiratory Distress Syndrome With Symptoms of Posttraumatic Stress Disorder in Family Members After ICU Discharge.

IMPORTANCE: Persistent physical and mental disorders are frequent in survivors of COVID-19-related acute respiratory distress syndrome (ARDS). However, data on these disorders among family members are scarce. OBJECTIVE: To determine the association between patient hospitalization for COVID-19 ARDS vs ARDS from other causes and the risk of posttraumatic stress disorder (PTSD)-related symptoms in family members. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study in 23 intensive care units (ICUs) in France (January 2020 to June 2020 with final follow-up ending in October 2020). ARDS survivors and family members (1 family member per patient) were enrolled. EXPOSURES: Family members of patients hospitalized for ARDS due to COVID-19 vs ARDS due to other causes. MAIN OUTCOMES AND MEASURES: The primary outcome was family member symptoms of PTSD at 90 days after ICU discharge, measured by the Impact of Events Scale-Revised (score range, 0 [best] to 88 [worst]; presence of PTSD symptoms defined by score >22). Secondary outcomes were family member symptoms of anxiety and depression at 90 days assessed by the Hospital Anxiety and Depression Scale (score range, 0 [best] to 42 [worst]; presence of anxiety or depression symptoms defined by subscale scores ≥7). Multivariable logistic regression models were used to determine the association between COVID-19 status and outcomes. RESULTS: Among 602 family members and 307 patients prospectively enrolled, 517 (86%) family members (median [IQR] age, 51 [40-63] years; 72% women; 48% spouses; 26% bereaved because of the study patient's death; 303 [50%] family members of COVID-19 patients) and 273 (89%) patients (median [IQR] age, 61 [50-69] years; 34% women; 181 [59%] with COVID-19) completed the day-90 assessment. Compared with non-COVID-19 ARDS, family members of patients with COVID-19 ARDS had a significantly higher prevalence of symptoms of PTSD (35% [103/293] vs 19% [40/211]; difference, 16% [95% CI, 8%-24%]; P < .001), symptoms of anxiety (41% [121/294] vs 34% [70/207]; difference, 8% [95% CI, 0%-16%]; P= .05), and symptoms of depression (31% [91/291] vs 18% [37/209]; difference, 13% [95% CI, 6%-21%]; P< .001). In multivariable models adjusting for age, sex, and level of social support, COVID-19 ARDS was significantly associated with increased risk of PTSD-related symptoms in family members (odds ratio, 2.05 [95% CI, 1.30 to 3.23]). CONCLUSIONS AND RELEVANCE: Among family members of patients hospitalized in the ICU with ARDS, COVID-19 disease, as compared with other causes of ARDS, was significantly associated with increased risk of symptoms of PTSD at 90 days after ICU discharge. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04341519.

Impact of obesity on survival in COVID-19 ARDS patients receiving ECMO: results from an ambispective observational cohort.

BACKGROUND: Since March 2020, health care systems were importantly affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak, with some patients presenting severe acute respiratory distress syndrome (ARDS), requiring extra-corporeal membrane oxygenation (ECMO). We designed an ambispective observational cohort study including all consecutive adult patients admitted to 5 different ICUs from a university hospital. The main objective was to identify the risk factors of severe COVID-19 ARDS patients supported by ECMO associated with 90-day survival. RESULTS: Between March 1st and November 30th 2020, 76 patients with severe COVID-19 ARDS were supported by ECMO. Median (interquartile range IQR) duration of mechanical ventilation (MV) prior to ECMO was of 6 (3-10) days. At ECMO initiation, patients had a median PaO2:FiO2 of 71 mmHg (IQR 62-81), median PaCO2 of 58 mmHg (IQR 51-66) and a median arterial pH of 7.33 (IQR 7.25-7.38). Forty-five patients (59%) were weaned from ECMO. Twenty-eight day, 60-day and 90-day survival rates were, respectively, 92, 62 and 51%. In multivariate logistic regression analysis, with 2 models, one with the RESP score and one with the PRESERVE score, we found that higher BMI was associated with higher 90-day survival [odds ratio (OR): 0.775 (0.644-0.934), p = 0.007) and 0.631 (0.462-0.862), respectively]. Younger age was also associated with 90-day survival in both models [OR: 1.1354 (1.004-1.285), p = 0.044 and 1.187 (1.035-1.362), p = 0.014 respectively]. Obese patients were ventilated with higher PEEP than non-obese patients and presented slightly higher respiratory system compliance. CONCLUSION: In this ambispective observational cohort of COVID-19 severe ARDS supported by ECMO, obesity was an independent factor associated with improved survival at 90-day.

Symptoms of Mental Health Disorders in Critical Care Physicians Facing the Second COVID-19 Wave: A Cross-Sectional Study.

BACKGROUND: Working in the ICU during the first COVID-19 wave was associated with high levels of mental health disorders. RESEARCH QUESTION: What are the mental health symptoms in health care providers (HCPs) facing the second wave? STUDY DESIGN AND METHODS: A cross-sectional study (October 30-December 1, 2020) was conducted in 16 ICUs during the second wave in France. HCPs completed the Hospital Anxiety and Depression Scale, the Impact of Event Scale-Revised (for post-traumatic stress disorder), and the Maslach Burnout Inventory. RESULTS: Of 1,203 HCPs, 845 responded (70%) (66% nursing staff, 32% medical staff, 2% other professionals); 487 (57.6%) had treated more than 10 new patients with COVID-19 in the previous week. Insomnia affected 320 (37.9%), and 7.7% were taking a psychotropic drug daily. Symptoms of anxiety, depression, post-traumatic stress disorder, and burnout were reported in 60.0% (95% CI, 56.6%-63.3%), 36.1% (95% CI, 32.9%-39.5%), 28.4% (95% CI, 25.4%-31.6%), and 45.1% (95% CI, 41.7%-48.5%) of respondents, respectively. Independent predictors of such symptoms included respondent characteristics (sex, profession, experience, personality traits), work organization (ability to rest and to care for family), and self-perceptions (fear of becoming infected or of infecting family and friends, feeling pressure related to the surge, intention to leave the ICU, lassitude, working conditions, feeling they had a high-risk profession, and "missing the clapping"). The number of patients with COVID-19 treated in the first wave or over the last week was not associated with symptoms of mental health disorders. INTERPRETATION: The prevalence of symptoms of mental health disorders is high in ICU HCPs managing the second COVID-19 surge. The highest tiers of hospital management urgently need to provide psychological support, peer-support groups, and a communication structure that ensure the well-being of HCPs.

Impact of dexamethasone on the incidence of ventilator-associated pneumonia and blood stream infections in COVID-19 patients requiring invasive mechanical ventilation: a multicenter retrospective study.

BACKGROUND: Dexamethasone decreases mortality in patients with severe coronavirus disease 2019 (COVID-19) and has become the standard of care during the second wave of pandemic. Dexamethasone is an immunosuppressive treatment potentially increasing the risk of secondary hospital acquired infections in critically ill patients. We conducted an observational retrospective study in three French intensive care units (ICUs) comparing the first and second waves of pandemic to investigate the role of dexamethasone in the occurrence of ventilator-associated pneumonia (VAP) and blood stream infections (BSI). Patients admitted from March to November 2020 with a documented COVID-19 and requiring mechanical ventilation (MV) for ≥ 48 h were included. The main study outcomes were the incidence of VAP and BSI according to the use of dexamethasone. Secondary outcomes were the ventilator-free days (VFD) at day-28 and day-60, ICU and hospital length of stay and mortality. RESULTS: Among the 151 patients included, 84 received dexamethasone, all but one during the second wave. VAP occurred in 63% of patients treated with dexamethasone (DEXA+) and 57% in those not receiving dexamethasone (DEXA-) (p = 0.43). The cumulative incidence of VAP, considering death, duration of MV and late immunosuppression as competing factors was not different between groups (p = 0.59). A multivariate analysis did not identify dexamethasone as an independent risk factor for VAP occurrence. The occurrence of BSI was not different between groups (29 vs. 30%; p = 0.86). DEXA+ patients had more VFD at day-28 (9 (0-21) vs. 0 (0-11) days; p = 0.009) and a reduced ICU length of stay (20 (11-44) vs. 32 (17-46) days; p = 0.01). Mortality did not differ between groups. CONCLUSIONS: In this cohort of COVID-19 patients requiring invasive MV, dexamethasone was not associated with an increased incidence of VAP or BSI. Dexamethasone might not explain the high rates of VAP and BSI observed in critically ill COVID-19 patients.

Awake prone positioning for hypoxaemic respiratory failure: past, COVID-19 and perspectives.

Prone positioning reduces mortality in the management of intubated patients with moderate-to-severe acute respiratory distress syndrome. It allows improvement in oxygenation by improving ventilation/perfusion ratio mismatching.Because of its positive physiological effects, prone positioning has also been tested in non-intubated, spontaneously breathing patients, or "awake" prone positioning. This review provides an update on awake prone positioning for hypoxaemic respiratory failure, in both coronavirus disease 2019 (COVID-19) and non-COVID-19 patients. In non-COVID-19 acute respiratory failure, studies are limited to a few small nonrandomised studies and involved patients with different diseases. However, results have been appealing with regard to oxygenation improvement, especially when combined with noninvasive ventilation or high-flow nasal cannula.The recent COVID-19 pandemic has led to a major increase in hospitalisations for acute respiratory failure. Awake prone positioning has been used with the aim to prevent intensive care unit admission and mechanical ventilation. Prone positioning in conscious, non-intubated COVID-19 patients is used in emergency departments, medical wards and intensive care units.Several trials reported an improvement in oxygenation and respiratory rate during prone positioning, but impacts on clinical outcomes, particularly on intubation rates and survival, remain unclear. Tolerance of prolonged prone positioning is an issue. Larger controlled, randomised studies are underway to provide results concerning clinical benefit and define optimised prone positioning regimens.

Dissemination of extreme levels of extracellular vesicles: tissue factor activity in patients with severe COVID-19.

Coronavirus disease 2019 (COVID-19) has become one of the biggest public health challenges of this century. Severe forms of the disease are associated with a thrombo-inflammatory state that can turn into thrombosis. Because tissue factor (TF) conveyed by extracellular vesicles (EVs) has been implicated in thrombosis, we quantified the EV-TF activity in a cohort of hospitalized patients with COVID-19 (n = 111) and evaluated its link with inflammation, disease severity, and thrombotic events. Patients with severe disease were compared with those who had moderate disease and with patients who had septic shock not related to COVID-19 (n = 218). The EV-TF activity was notably increased in patients with severe COVID-19 compared with that observed in patients with moderate COVID-19 (median, 231 [25th to 75th percentile, 39-761] vs median, 25 [25th to 75th percentile, 12-59] fM; P < .0001); EV-TF was correlated with leukocytes, D-dimer, and inflammation parameters. High EV-TF values were associated with an increased thrombotic risk in multivariable models. Compared with patients who had septic shock, those with COVID-19 were characterized by a distinct coagulopathy profile with significantly higher EV-TF and EV-fibrinolytic activities that were not counterbalanced by an increase in plasminogen activator inhibitor-1 (PAI-1). Thus, this article is the first to describe the dissemination of extreme levels of EV-TF in patients with severe COVID-19, which supports the international recommendations of systematic preventive anticoagulation in hospitalized patients and potential intensification of anticoagulation in patients with severe disease.