Hydrocortisone in Severe Community-Acquired Pneumonia.

BACKGROUND: Whether the antiinflammatory and immunomodulatory effects of glucocorticoids may decrease mortality among patients with severe community-acquired pneumonia is unclear. METHODS: In this phase 3, multicenter, double-blind, randomized, controlled trial, we assigned adults who had been admitted to the intensive care unit (ICU) for severe community-acquired pneumonia to receive intravenous hydrocortisone (200 mg daily for either 4 or 7 days as determined by clinical improvement, followed by tapering for a total of 8 or 14 days) or to receive placebo. All the patients received standard therapy, including antibiotics and supportive care. The primary outcome was death at 28 days. RESULTS: A total of 800 patients had undergone randomization when the trial was stopped after the second planned interim analysis. Data from 795 patients were analyzed. By day 28, death had occurred in 25 of 400 patients (6.2%; 95% confidence interval [CI], 3.9 to 8.6) in the hydrocortisone group and in 47 of 395 patients (11.9%; 95% CI, 8.7 to 15.1) in the placebo group (absolute difference, -5.6 percentage points; 95% CI, -9.6 to -1.7; P = 0.006). Among the patients who were not undergoing mechanical ventilation at baseline, endotracheal intubation was performed in 40 of 222 (18.0%) in the hydrocortisone group and in 65 of 220 (29.5%) in the placebo group (hazard ratio, 0.59; 95% CI, 0.40 to 0.86). Among the patients who were not receiving vasopressors at baseline, such therapy was initiated by day 28 in 55 of 359 (15.3%) of the hydrocortisone group and in 86 of 344 (25.0%) in the placebo group (hazard ratio, 0.59; 95% CI, 0.43 to 0.82). The frequencies of hospital-acquired infections and gastrointestinal bleeding were similar in the two groups; patients in the hydrocortisone group received higher daily doses of insulin during the first week of treatment. CONCLUSIONS: Among patients with severe community-acquired pneumonia being treated in the ICU, those who received hydrocortisone had a lower risk of death by day 28 than those who received placebo. (Funded by the French Ministry of Health; CAPE COD ClinicalTrials.gov number, NCT02517489.).

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.

Impact of Prone Position in COVID-19 Patients on Extracorporeal Membrane Oxygenation.

OBJECTIVES: Prone positioning and venovenous extracorporeal membrane oxygenation (ECMO) are both useful interventions in acute respiratory distress syndrome (ARDS). Combining the two therapies is feasible and safe, but the effectiveness is not known. Our objective was to evaluate the potential survival benefit of prone positioning in venovenous ECMO patients cannulated for COVID-19-related ARDS. DESIGN: Retrospective analysis of a multicenter cohort. PATIENTS: Patients on venovenous ECMO who tested positive for severe acute respiratory syndrome coronavirus 2 by reverse transcriptase polymerase chain reaction or with a diagnosis on chest CT were eligible. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All patients on venovenous ECMO for respiratory failure in whom prone position status while on ECMO and in-hospital mortality were known were included. Of 647 patients in 41 centers, 517 were included. Median age was 55 (47-61), 78% were male and 95% were proned before cannulation. After cannulation, 364 patients (70%) were proned and 153 (30%) remained in the supine position for the whole ECMO run. There were 194 (53%) and 92 (60%) deaths in the prone and the supine groups, respectively. Prone position on ECMO was independently associated with lower in-hospital mortality (odds ratio = 0.49 [0.29-0.84]; p = 0.010). In 153 propensity score-matched pairs, mortality rate was 49.7% in the prone position group versus 60.1% in the supine position group (p = 0.085). Considering only patients alive at decannulation, propensity-matched proned patients had a significantly lower mortality rate (22.4% vs 37.8%; p = 0.029) than nonproned patients. CONCLUSIONS: Prone position may be beneficial in patients supported by venovenous ECMO for COVID-19-related ARDS but more data are needed to draw definitive conclusions.

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.

Effects of a Chair Positioning Session on Awake Non-Intubated COVID-19 Pneumonia Patients: A Multicenter, Observational, and Pilot Study Using Lung Ultrasound.

BACKGROUND: LUS is a validated tool for the management of COVID-19 pneumonia. Chair positioning (CP) may have beneficial effects on oxygenation and lung aeration, and may be an easier alternative to PP. This study assessed the effects of a CP session on oxygenation and lung aeration (LA) changes in non-intubated COVID-19 patients. METHODS: A retrospective multicenter study was conducted in an ICU. We analyzed data from LUS exams and SpO2:FiO2 performed before/after a CP session in non-intubated COVID-19 patients. Patients were divided into groups of responders or non-responders in terms of oxygenation or LA. RESULTS: Thirty-three patients were included in the study; fourteen (44%) were oxygenation non-responders and eighteen (56%) were oxygenation responders, while thirteen (40.6%) and nineteen (59.4%) patients were classified as LA non-responders and responders, respectively. Changes in oxygenation and LA before/after a CP session were not correlated (r = -0.19, p = 0.3, 95% CI: -0.5-0.17). The reaeration scores did not differ between oxygenation responders and non-responders (1 (-0.75-3.75) vs. 4 (-1-6), p = 0.41). The LUS score was significantly correlated with SpO2:FiO2 before a CP session (r = 0.37, p = 0.04, 95% CI: 0.03-0.64) but not after (r = 0.17, p = 0.35, 95% CI: -0.19-0.50). CONCLUSION: A CP session was associated with improved oxygenation and LA in more than half of the non-intubated COVID-19 patients.

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.

Management and outcomes of pregnant women admitted to intensive care unit for severe pneumonia related to SARS-CoV-2 infection: the multicenter and international COVIDPREG study.

PURPOSE: Management and outcomes of pregnant women with coronavirus disease 2019 (COVID-19) admitted to intensive care unit (ICU) remain to be investigated. METHODS: A retrospective multicenter study conducted in 32 ICUs in France, Belgium and Switzerland. Maternal management as well as maternal and neonatal outcomes were reported. RESULTS: Among the 187 pregnant women with COVID-19 (33 ± 6 years old and 28 ± 7 weeks' gestation), 76 (41%) were obese, 12 (6%) had diabetes mellitus and 66 (35%) had pregnancy-related complications. Standard oxygenation, high-flow nasal oxygen therapy (HFNO) and non-invasive ventilation (NIV) were used as the only oxygenation technique in 41 (22%), 55 (29%) and 18 (10%) patients, respectively, and 73 (39%) were intubated. Overall, 72 (39%) patients required several oxygenation techniques and 15 (8%) required venovenous extracorporeal membrane oxygenation. Corticosteroids and tocilizumab were administered in 157 (84%) and 25 (13%) patients, respectively. Awake prone positioning or prone positioning was performed in 49 (26%) patients. In multivariate analysis, risk factors for intubation were obesity (cause-specific hazard ratio (CSH) 2.00, 95% CI (1.05-3.80), p = 0.03), term of pregnancy (CSH 1.07, 95% CI (1.02-1.10), per + 1 week gestation, p = 0.01), extent of computed tomography (CT) scan abnormalities > 50% (CSH 2.69, 95% CI (1.30-5.60), p < 0.01) and NIV use (CSH 2.06, 95% CI (1.09-3.90), p = 0.03). Delivery was required during ICU stay in 70 (37%) patients, mainly due to maternal respiratory worsening, and improved the driving pressure and oxygenation. Maternal and fetal/neonatal mortality rates were 1% and 4%, respectively. The rate of maternal and/or neonatal complications increased with the invasiveness of maternal respiratory support. CONCLUSION: In ICU, corticosteroids, tocilizumab and prone positioning were used in few pregnant women with COVID-19. Over a third of patients were intubated and delivery improved the driving pressure.

Influence of socioeconomic status on functional recovery after ARDS caused by SARS-CoV-2: a multicentre, observational study.

INTRODUCTION: Prognosis of patients with COVID-19 depends on the severity of the pulmonary affection. The most severe cases may progress to acute respiratory distress syndrome (ARDS), which is associated with a risk of long-term repercussions on respiratory function and neuromuscular outcomes. The functional repercussions of severe forms of COVID-19 may have a major impact on quality of life, and impair the ability to return to work or exercise. Social inequalities in healthcare may influence prognosis, with socially vulnerable individuals more likely to develop severe forms of disease. We describe here the protocol for a prospective, multicentre study that aims to investigate the influence of social vulnerability on functional recovery in patients who were hospitalised in intensive care for ARDS caused by COVID-19. This study will also include an embedded qualitative study that aims to describe facilitators and barriers to compliance with rehabilitation, describe patients' health practices and identify social representations of health, disease and care. METHODS AND ANALYSIS: The "Functional Recovery From Acute Respiratory Distress Syndrome (ARDS) Due to COVID-19: Influence of Socio-Economic Status" (RECOVIDS) study is a mixed-methods, observational, multicentre cohort study performed during the routine follow-up of post-intensive care unit (ICU) functional recovery after ARDS. All patients admitted to a participating ICU for PCR-proven SARS-CoV-2 infection and who underwent chest CT scan at the initial phase AND who received respiratory support (mechanical or not) or high-flow nasal oxygen, AND had ARDS diagnosed by the Berlin criteria will be eligible. The primary outcome is the presence of lung sequelae at 6 months after ICU discharge, defined either by alterations on pulmonary function tests, oxygen desaturation during a standardised 6 min walk test or fibrosis-like pulmonary findings on chest CT. Patients will be considered to be socially disadvantaged if they have an "Evaluation de la Précarité et des Inégalités de santé dans les Centres d'Examen de Santé" (EPICES) score ≥30.17 at inclusion. ETHICS AND DISSEMINATION: The study protocol and the informed consent form were approved by an independent ethics committee (Comité de Protection des Personnes Sud Méditerranée II) on 10 July 2020 (2020-A02014-35). All patients will provide informed consent before participation. Findings will be published in peer-reviewed journals and presented at national and international congresses. TRIAL REGISTRATION NUMBER: NCT04556513.

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.

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.

Identifying Clinical Phenotypes in Moderate to Severe Acute Respiratory Distress Syndrome Related to COVID-19: The COVADIS Study.

Objectives: Different phenotypes have been identified in acute respiratory distress syndrome (ARDS). Existence of several phenotypes in coronavirus disease (COVID-19) related acute respiratory distress syndrome is unknown. We sought to identify different phenotypes of patients with moderate to severe ARDS related to COVID-19. Methods: We conducted an observational study of 416 COVID-19 patients with moderate to severe ARDS at 21 intensive care units in Belgium and France. The primary outcome was day-28 ventilatory free days. Secondary outcomes were mortality on day 28, acute kidney injury, acute cardiac injury, pulmonary embolism, and deep venous thrombosis. Multiple factor analysis and hierarchical classification on principal components were performed to distinguish different clinical phenotypes. Results: We identified three different phenotypes in 150, 176, and 90 patients, respectively. Phenotype 3 was characterized by short evolution, severe hypoxemia, and old comorbid patients. Phenotype 1 was mainly characterized by the absence of comorbidities, relatively high compliance, and long duration of symptoms, whereas phenotype 2 was characterized female sex, and the presence of mild comorbidities such as uncomplicated diabetes or chronic hypertension. The compliance in phenotype 2 was lower than that in phenotype 1, with higher plateau and driving pressure. Phenotype 3 was associated with higher mortality compared to phenotypes 1 and 2. Conclusions: In COVID-19 patients with moderate to severe ARDS, we identified three clinical phenotypes. One of these included older people with comorbidities who had a fulminant course of disease with poor prognosis. Requirement of different treatments and ventilatory strategies for each phenotype needs further investigation.

Static compliance of the respiratory system in COVID-19 related ARDS: an international multicenter study.

BACKGROUND: Controversies exist on the nature of COVID-19 related acute respiratory distress syndrome (ARDS) in particular on the static compliance of the respiratory system (Crs). We aimed to analyze the association of Crs with outcome in COVID-19-associated ARDS, to ascertain its determinants and to describe its evolution at day-14. METHODS: In this observational multicenter cohort of patients with moderate to severe Covid-19 ARDS, Crs was measured at day-1 and day-14. Association between Crs or Crs/ideal body weight (IBW) and breathing without assistance at day-28 was analyzed with multivariable logistic regression. Determinants were ascertained by multivariable linear regression. Day-14 Crs was compared to day-1 Crs with paired t-test in patients still under controlled mechanical ventilation. RESULTS: The mean Crs in 372 patients was 37.6 ± 13 mL/cmH2O, similar to as in ARDS of other causes. Multivariate linear regression identified chronic hypertension, low PaO2/FiO2 ratio, low PEEP, and low tidal volume as associated with lower Crs/IBW. After adjustment on confounders, nor Crs [OR 1.0 (CI 95% 0.98-1.02)] neither Crs/IBW [OR 0.63 (CI 95% 0.13-3.1)] were associated with the chance of breathing without assistance at day-28 whereas plateau pressure was [OR 0.93 (CI 95% 0.88-0.99)]. In a subset of 108 patients, day-14 Crs decreased compared to day-1 Crs (31.2 ± 14.4 mL/cmH2O vs 37.8 ± 11.4 mL/cmH2O, p < 0.001). The decrease in Crs was not associated with day-28 outcome. CONCLUSION: In a large multicenter cohort of moderate to severe COVID-19 ARDS, mean Crs was decreased below 40 mL/cmH2O and was not associated with day-28 outcome. Crs decreased between day-1 and day-14 but the decrease was not associated with day-28 outcome.

Factors Associated With Pulmonary Embolism Among Coronavirus Disease 2019 Acute Respiratory Distress Syndrome: A Multicenter Study Among 375 Patients.

Risk factors associated with pulmonary embolism in coronavirus disease 2019 acute respiratory distress syndrome patients deserve to be better known. We therefore performed a post hoc analysis from the COronaVirus-Associated DIsease Study (COVADIS) project, a multicenter observational study gathering 21 ICUs from France (n = 12) and Belgium (n = 9). Three-hundred seventy-five consecutive patients with moderate-to-severe acute respiratory distress syndrome and positive coronavirus disease 2019 were included in the study. At day 28, 15% were diagnosed with pulmonary embolism. Known risk factors for pulmonary embolism including cancer, obesity, diabetes, hypertension, and coronary artery disease were not associated with pulmonary embolism. In the multivariate analysis, younger age (< 65 yr) (odds ratio, 2.14; 1.17-4.03), time between onset of symptoms and antiviral administration greater than or equal to 7 days (odds ratio, 2.39; 1.27-4.73), and use of neuromuscular blockers greater than or equal to 7 days (odds ratio, 1.89; 1.05-3.43) were independently associated with pulmonary embolism. These new findings reinforce the need for prospective studies that will determine the predictors of pulmonary embolism among patients with severe coronavirus disease 2019.

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.

Characteristics and outcomes of acute respiratory distress syndrome related to COVID-19 in Belgian and French intensive care units according to antiviral strategies: the COVADIS multicentre observational study.

BACKGROUND: Limited data are available regarding antiviral therapy efficacy in most severe patients under mechanical ventilation for Covid-19-related acute respiratory distress syndrome (ARDS). METHODS: Comparison of antiviral strategies (none, hydroxychloroquine (OHQ), lopinavir/ritonavir (L/R), others (combination or remdesivir) in an observational multicentre cohort of patients with moderate-to-severe Covid-19 ARDS. The primary endpoint was the number of day 28 ventilator-free days (VFD). Patients who died before d28 were considered as having 0 VFD. The variable was dichotomized into "patients still ventilated or dead at day 28" versus "patients weaned and alive at day 28". RESULTS: We analyzed 415 patients (85 treated with standard of care (SOC), 57 with L/R, 220 with OHQ, and 53 others). The median number of d28-VFD was 0 (IQR 0-13) and differed between groups (P = 0.03), SOC patients having the highest d28-VFD. After adjustment for age, sex, Charlson Comorbidity Index, PaO2/FiO2 ratio and plateau pressure and accounting for center effect with a generalized linear mixed model, none of the antiviral strategies increased the chance of being alive and weaned from MV at day 28 compared to the SOC strategy (OR 0.48 CI95% (0.18-1.25); OR 0.96 (0.47-2.02) and OR 1.43 (0.53-4.04) for L/R, OHQ and other treatments, respectively). Acute kidney injury during ICU stay was frequent (55%); its incidence was higher in patients receiving lopinavir (66 vs 53%, P = 0.03). After adjustment for age, sex, BMI, chronic hypertension and chronic renal disease, the use of L/R was associated with an increased risk of renal replacement therapy (RRT). (OR 2.52 CI95% 1.16-5.59). CONCLUSION: In this multicentre observational study of moderate-to-severe Covid-19 ARDS patients, we did not observe any benefit among patients treated with OHQ or L/R compared with SOC. The use of L/R treatment was associated with an increased need for RRT. Take home message Neither hydroxychloroquine nor lopinavir/ritonavir as COVID-19 antiviral treatment is associated with higher ventilator-free days at day 28 when compared with standard of care (no antiviral treatment) in ICU patients under invasive mechanical ventilation. Lopinavir/ritonavir is associated with an increased risk of renal replacement therapy requirement. Tweet COVID-19: Insights from ARDS cohort: no signal of efficacy of any antiviral drugs. Lopinavir/ritonavir may be associated with need for RRT.