Covid-19-associated pulmonary aspergillosis in mechanically ventilated patients: incidence and outcome in a French multicenter observational cohort (APICOVID).

BACKGROUND: Recent studies identified coronavirus disease 2019 (COVID-19) as a risk factor for invasive pulmonary aspergillosis (IPA) but produced conflicting data on IPA incidence and impact on patient outcomes. We aimed to determine the incidence and outcomes of COVID-19-associated pulmonary aspergillosis (CAPA) in mechanically ventilated patients. METHODS: We performed a multicenter retrospective observational cohort study in consecutive adults admitted to 15 French intensive care units (ICUs) in 2020 for COVID-19 requiring mechanical ventilation. CAPA was diagnosed and graded according to 2020 ECMM/ISHAM consensus criteria. The primary objective was to determine the incidence of proven/probable CAPA, and the secondary objectives were to identify risk factors for proven/probable CAPA and to assess associations between proven/probable CAPA and patient outcomes. RESULTS: The 708 included patients (522 [73.7%] men) had a mean age of 65.2 ± 10.8 years, a median mechanical ventilation duration of 15.0 [8.0-27.0] days, and a day-90 mortality rate of 28.5%. Underlying immunosuppression was present in 113 (16.0%) patients. Corticosteroids were used in 348 (63.1%) patients. Criteria for probable CAPA were met by 18 (2.5%) patients; no patient had histologically proven CAPA. Older age was the only factor significantly associated with probable CAPA (hazard ratio [HR], 1.04; 95% CI 1.00-1.09; P = 0.04). Probable CAPA was associated with significantly higher day-90 mortality (HR, 2.07; 95% CI 1.32-3.25; P = 0.001) but not with longer mechanical ventilation or ICU length of stay. CONCLUSION: Probable CAPA is a rare but serious complication of severe COVID-19 requiring mechanical ventilation and is associated with higher day-90 mortality.

Defining predictors for successful mechanical ventilation weaning, using a data-mining process and artificial intelligence.

Mechanical ventilation weaning within intensive care units (ICU) is a difficult process, while crucial when considering its impact on morbidity and mortality. Failed extubation and prolonged mechanical ventilation both carry a significant risk of adverse events. We aimed to determine predictive factors of extubation success using data-mining and artificial intelligence. A prospective physiological and biomedical signal data warehousing project. A 21-beds medical Intensive Care Unit of a University Hospital. Adult patients undergoing weaning from mechanical ventilation. Hemodynamic and respiratory parameters of mechanically ventilated patients were prospectively collected and combined with clinical outcome data. One hundred and eight patients were included, for 135 spontaneous breathing trials (SBT) allowing to identify physiological parameters either measured before or during the trial and considered as predictive for extubation success. The Early-Warning Score Oxygen (EWSO2) enables to discriminate patients deemed to succeed extubation, at 72-h and 7-days. Cut-off values for EWSO2 (AUC = 0.80; Se = 0.75; Sp = 0.76), mean arterial pressure and heart-rate variability parameters were determined. A predictive model for extubation success was established including body-mass index (BMI) on inclusion, occlusion pressure at 0,1 s. (P0.1) and heart-rate analysis parameters (LF/HF) both measured before SBT, and heart rate during SBT (global performance 62%; 83%). The data-mining process enabled to detect independent predictive factors for extubation success and to develop a dynamic predictive model using artificial intelligence. Such predictive tools may help clinicians to better discriminate patients deemed to succeed extubation and thus improve clinical performance.

Anticoagulation strategy and safety in critically ill COVID-19 patients: a French retrospective multicentre study.

BACKGROUND: Patients with critical illness due to COVID-19 exhibit increased coagulability associated with a high risk of venous thrombo-embolism (VTE). Data on prophylactic anticoagulation for these patients are limited and conflicting. The purpose of this study was to evaluate whether intermediate-dose prophylactic anticoagulation in patients with COVID-19 requiring ICU admission was associated with better outcomes compared to standard-dose prophylactic anticoagulation. METHODS: We retrospectively included adults admitted with severe COVID-19 to any of 15 ICUs, in 2020 or 2021. We compared the groups given intermediate-dose vs. standard-dose prophylactic anticoagulation. The primary outcome was all-cause day-90 mortality. Secondary outcomes were VTE (pulmonary embolism or deep vein thrombosis), ICU stay length, and adverse effects of anticoagulation. RESULTS: Of 1174 included patients (mean age, 63 years), 399 received standard-dose and 775 intermediate-dose prophylactic anticoagulation. Of the 211 patients who died within 90 days, 86 (21%) received intermediate and 125 (16%) standard doses. After adjustment on early corticosteroid therapy and critical illness severity, there were no significant between-group differences in day-90 mortality (hazard ratio [HR], 0.73; 95%CI, 0.52-1.04; p = 0.09) or ICU stay length (HR, 0.93; 95%CI, 0.79-1.10; p = 0.38). Intermediate-dose anticoagulation was significantly associated with fewer VTE events (HR, 0.55; 95%CI, 0.38-0.80; p < 0.001). Bleeding events occurred in similar proportions of patients in the two groups (odds ratio, 0.86; 95%CI, 0.50-1.47; p = 0.57). CONCLUSIONS: Mortality on day 90 did not differ between the groups given standard-dose and intermediate-dose prophylactic anticoagulation, despite a higher incidence of VTE in the standard-dose group.

Association of early dexamethasone therapy with mortality in critically Ill COVID-19 patients: a French multicenter study.

BACKGROUND: Dexamethasone is recommended for COVID-19 patients who require oxygen therapy. However, its effectiveness in reducing mortality and intubation, and its safety, remain debated. We aimed to investigate whether dexamethasone reduces day-28 mortality in unselected patients with critical COVID-19. METHODS: We performed an observational cohort study in consecutive COVID-19 patients admitted to any of 13 French intensive care units (ICUs) in 2020. The primary objective was to determine whether early dexamethasone therapy was associated with day-28 mortality and the secondary objectives were to assess whether early dexamethasone decreased intubation requirements and to collect adverse events. RESULTS: Of 1058 included patients, 611 (57.75%) received early dexamethasone (early dexamethasone group), 358 (33.83%) did not receive any steroids (no steroids group), and 89 (8.41%) received late dexamethasone or other steroids. Day-28 mortality was similar between the early dexamethasone and the no steroids groups (15.06% and 14.25%, respectively; P = 0.59). Factors associated with day-28 mortality were older age (adjusted hazard ratio [aHR], 1.06; 1.04-1.09; P < 0.001), worse SOFA score (aHR, 1.13; 1.06-1.20; P < 0.001), and immunocompromised status (aHR, 1.59; 1.01-2.50; P = 0.043). Early dexamethasone was associated with fewer intubations (48.55% vs. 61.49%, P < 0.001) and more ventilator-free days by day 28 (22 [2-28] vs. 17 [1-28] days, P = 0.003), compared to no steroids. Ventilator-associated pneumonia (VAP) was more common with early dexamethasone (HR, 1.29 [1.01-1.63], P = 0.04) than with no steroids, whereas no differences were noted for bloodstream infection, fungal infection, or gastrointestinal bleeding. CONCLUSIONS: Early dexamethasone in critically ill COVID-19 patients was not associated with lower day-28 mortality. However, early dexamethasone was associated with lower intubation needs and more ventilator-free days by day 28. In patients treated with invasive mechanical ventilation, early dexamethasone was associated with a higher risk of VAP.

Multiple-site decontamination regimen decreases acquired infection incidence in mechanically ventilated COVID-19 patients.

BACKGROUND: Among strategies that aimed to prevent acquired infections (AIs), selective decontamination regimens have been poorly studied in the COVID-19 setting. We assessed the impact of a multiple-site decontamination (MSD) regimen on the incidence of bloodstream infections (BSI) and ventilator-associated pneumonia (VAP) in COVID-19 patients receiving mechanical ventilation. METHODS: We performed an ancillary analysis of a multicenter retrospective observational study in 15 ICUs in western France. In addition to standard-care (SC), 3 ICUs used MSD, a variant of selective digestive decontamination, which consists of the administration of topical antibiotics four times daily in the oropharynx and the gastric tube, chlorhexidine body wash and a 5-day nasal mupirocin course. AIs were compared between the 3 ICUs using MSD (MSD group) and the 12 ICUs using SC. RESULTS: During study period, 614 of 1158 COVID-19 patients admitted in our ICU were intubated for at least 48 h. Due to missing data in 153 patients, 461 patients were finally included of whom 89 received MSD. There were 34 AIs in the MSD group (2117 patient-days), as compared with 274 AIs in the SC group (8957 patient-days) (p < 0.001). MSD was independently associated with a lower risk of AI (IRR = 0.56 [0.38-0.83]; p = 0.004) (Table 2). When the same model was used for each site of infection, MSD remained independently associated with a lower risk of VAP (IRR = 0.52 [0.33-0.89]; p = 0.005) but not of BSI (IRR = 0.58, [0.25-1.34], p = 0.21). Hospital mortality was lower in the MSD group (16.9% vs 30.1%, p = 0.017). CONCLUSIONS: In ventilated COVID-19 patients, MSD was independently associated with lower AI incidence.

Early steroids and ventilator-associated pneumonia in COVID-19-related ARDS.

RATIONALE: Early corticosteroid treatment is used to treat COVID-19-related acute respiratory distress syndrome (ARDS). Infection is a well-documented adverse effect of corticosteroid therapy. OBJECTIVES: To determine whether early corticosteroid therapy to treat COVID-19 ARDS was associated with ventilator-associated pneumonia (VAP). METHODS: We retrospectively included adults with COVID-19-ARDS requiring invasive mechanical ventilation (MV) for ≥ 48 h at any of 15 intensive care units in 2020. We divided the patients into two groups based on whether they did or did not receive corticosteroids within 24 h. The primary outcome was VAP incidence, with death and extubation as competing events. Secondary outcomes were day 90-mortality, MV duration, other organ dysfunctions, and VAP characteristics. MEASUREMENTS AND MAIN RESULTS: Of 670 patients (mean age, 65 years), 369 did and 301 did not receive early corticosteroids. The cumulative VAP incidence was higher with early corticosteroids (adjusted hazard ratio [aHR] 1.29; 95% confidence interval [95% CI] 1.05-1.58; P = 0.016). Antibiotic resistance of VAP bacteria was not different between the two groups (odds ratio 0.94, 95% CI 0.58-1.53; P = 0.81). 90-day mortality was 30.9% with and 24.3% without early corticosteroids, a nonsignificant difference after adjustment on age, SOFA score, and VAP occurrence (aHR 1.15; 95% CI 0.83-1.60; P = 0.411). VAP was associated with higher 90-day mortality (aHR 1.86; 95% CI 1.33-2.61; P = 0.0003). CONCLUSIONS: Early corticosteroid treatment was associated with VAP in patients with COVID-19-ARDS. Although VAP was associated with higher 90-day mortality, early corticosteroid treatment was not. Longitudinal randomized controlled trials of early corticosteroids in COVID-19-ARDS requiring MV are warranted.

Risk of recurrent venous thromboembolism and bleeding in patients with interstitial lung disease: a cohort study.

Interstitial lung disease (ILD) encompasses various parenchymal lung disorders, which has the potential to increase the risk of venous thromboembolism (VTE). To evaluate, in patients with ILD and VTE, the risk of recurrent VTE during follow-up after stopping anticoagulation. This was a cohort of patients with a first VTE recruited between 1997 and 2015. The primary outcome was adjudicated fatal or nonfatal recurrent VTE after stopping anticoagulation. Main secondary outcomes were major or clinically relevant non-major bleeding under anticoagulation. Among 4314 patients with VTE, 50 had ILD diagnosed before VTE. Of these, anticoagulation was stopped in 30 patients after a median duration of 180 days and continued indefinitely in 20 patients. During a median follow-up of 27.8 months after anticoagulation discontinuation, recurrent VTE occurred in 15 on 30 patients (annual incidence of 19.2 events per 100-person-years [95%CI 12.0-29.3], case-fatality rate of 6.7% [95%CI 1.21-29.8]). The risk of recurrence was threefold higher when VTE was unprovoked and case-fatality rate of recurrence was increased by 3 when VTE index was PE. During the anticoagulant period, (median duration of 8.6 months), 6 patients had a major or clinically relevant bleeding (annual incidence of 7.3 events per 100-person-years [95%CI 3.4-15.1], case-fatality rate of 16.7% [95%CI 3.0-56.4]). In patients with ILD, the risk of recurrent VTE after stopping anticoagulation and the risk of bleeding under anticoagulation were very high. Our results suggest that anticoagulation should not be prolonged beyond 3-6 months of anticoagulation in most of cases.

Transfusion-related respiratory complications in intensive care: A diagnosis challenge.

Transfusion-related respiratory complications can be challenging to diagnose especially in mechanically-ventilated patients in the intensive care unit (ICU) due to the concurrent respiratory symptoms associated with the patients' primary diagnoses. In this narrative review, transfusion-related respiratory complications, including transfusion-associated dyspnea (TAD), transfusion-related acute lung injury (TRALI), transfusion-associated circulatory overload (TACO), and transfusion-related allergic reaction (TRAR), are briefly presented in light of the recent consensus or experts' definitions; and the diagnosis issues for ICU patients are discussed. Acute respiratory failure occurring during, or within 6 to 24hours, of transfusion might be a transfusion-related respiratory complication. The recent updated definitions for TRALI and TACO should assist clinicians to differentiate between possible diagnoses. The issues for ICU clinicians are first to recognize the acute respiratory deterioration and the possible causality between the deterioration and blood transfusion and secondly to make the proper diagnosis. This remains challenging for mechanically-ventilated patients. Clinical assessment to identify ICU patients at particular risk of transfusion-related respiratory complications and non-invasive investigation tools could be beneficial and may help to remind clinicians to be alert to the link between transfusion and worsening of respiratory symptoms in these vulnerable critically ill patients.

Screening for COPD in primary care, involving dentists, pharmacists, physiotherapists, nurses and general practitioners (the UNANIME pilot study).

BACKGROUND: COPD is underdiagnosed and is projected to be the third cause of death in 2030. However, recent reviews do not recommend screening for COPD in the general population. METHODS: We conducted a prospective study to assess the feasibility of implementing COPD screening in a high-risk COPD population, with the help of various healthcare professionals (General practitioners, pharmacists, dentists, physiotherapists, and nurses). Participants filled out a questionnaire, performed a spirometry (COPD6™) and counselling was performed, including smoking cessation and chest physician referral. Participants were contacted at two months to evaluate the effect of the intervention. RESULTS: Between April 7th, 2017 and July 30th, 2018, 157 participants filled out the questionnaires, performed spirometry and were contacted at two months. Thirty-five out of 157 (22% [95% CI, 15.8-28.8]) participants were detected with an airflow obstruction (FEV1/FEV6 < 0.7), using COPD6™ device. At the two-month-contact, 68 participants (43%, [95%CI 35.5-51.1]) were engaged in a smoking cessation program and 22 (14% [95 % CI, 8.6-19.4]) reported having quit smoking. CONCLUSION: This pilot study suggested that a predefined screening of COPD by different healthcare professionals could be implemented in primary care and might be part of counselling for smoking cessation (NCT03104348 on ClinicalTrials.gov).