Spontaneous-Breathing Trials with Pressure-Support Ventilation or a T-Piece.

BACKGROUND: Spontaneous-breathing trials can be performed with the use of either pressure-support ventilation (PSV) or a T-piece. Whether PSV trials may result in a shorter time to tracheal extubation than T-piece trials, without resulting in a higher risk of reintubation, among patients who have a high risk of extubation failure is unknown. METHODS: In this multicenter, open-label trial, we randomly assigned patients who had a high risk of extubation failure (i.e., were >65 years of age or had an underlying chronic cardiac or respiratory disease) to undergo spontaneous-breathing trials performed with the use of either PSV (with a pressure-support level of 8 cm of water and no positive end-expiratory pressure) or a T-piece. The primary outcome was the total time without exposure to invasive ventilation (reported as the number of ventilator-free days) at day 28 after the initial spontaneous-breathing trial. Secondary outcomes included extubation within 24 hours and extubation within 7 days after the initial spontaneous-breathing trial, as well as reintubation within 7 days after extubation. RESULTS: A total of 969 patients (484 in the PSV group and 485 in the T-piece group) were included in the analysis. At day 28, the median number of ventilator-free days was 27 (interquartile range, 24 to 27) in the PSV group and 27 (interquartile range, 23 to 27) in the T-piece group (difference, 0 days; 95% confidence interval [CI], -0.5 to 1; P = 0.31). Extubation was performed within 24 hours in 376 patients (77.7%) in the PSV group and in 350 patients (72.2%) in the T-piece group (difference, 5.5 percentage points; 95% CI, 0.01 to 10.9), and extubation was performed within 7 days in 473 patients (97.7%) and 458 patients (94.4%), respectively (difference, 3.3 percentage points; 95% CI, 0.8 to 5.9). Reintubation was performed in 72 of 481 patients (14.9%) in the PSV group and in 65 of 477 patients (13.6%) in the T-piece group (difference, 1.3 percentage points; 95% CI, -3.1 to 5.8). Cardiac or respiratory arrest was a reason for reintubation in 9 patients (3 in the PSV group and 6 in the T-piece group). CONCLUSIONS: Among patients who had a high risk of extubation failure, spontaneous-breathing trials performed with PSV did not result in significantly more ventilator-free days at day 28 than spontaneous-breathing trials performed with a T-piece. (Supported by the French Ministry of Health; TIP-EX ClinicalTrials.gov number, NCT04227639.).

Ventilator-associated pneumonia related to extended-spectrum beta-lactamase producing Enterobacterales during severe acute respiratory syndrome coronavirus 2 infection: risk factors and prognosis.

BACKGROUND: Patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-COV 2) and requiring mechanical ventilation suffer from a high incidence of ventilator associated pneumonia (VAP), mainly related to Enterobacterales. Data regarding extended-spectrum beta-lactamase producing Enterobacterales (ESBL-E) VAP are scarce. We aimed to investigate risk factors and outcomes of ESBL-E related VAP among critically ill coronavirus infectious disease-19 (COVID-19) patients who developed Enterobacterales related VAP. PATIENTS AND METHODS: We performed an ancillary analysis of a multicenter prospective international cohort study (COVID-ICU) that included 4929 COVID-19 critically ill patients. For the present analysis, only patients with complete data regarding resistance status of the first episode of Enterobacterales related VAP (ESBL-E and/or carbapenem-resistant Enterobacterales, CRE) and outcome were included. RESULTS: We included 591 patients with Enterobacterales related VAP. The main causative species were Enterobacter sp (n = 224), E. coli (n = 111) and K. pneumoniae (n = 104). One hundred and fifteen patients (19%), developed a first ESBL-E related VAP, mostly related to Enterobacter sp (n = 40), K. pneumoniae (n = 36), and E. coli (n = 31). Eight patients (1%) developed CRE related VAP. In a multivariable analysis, African origin (North Africa or Sub-Saharan Africa) (OR 1.7 [1.07-2.71], p = 0.02), time between intubation and VAP (OR 1.06 [1.02-1.09], p = 0.002), PaO2/FiO2 ratio on the day of VAP (OR 0.997 [0.994-0.999], p = 0.04) and trimethoprim-sulfamethoxazole exposure (OR 3.77 [1.15-12.4], p = 0.03) were associated with ESBL-E related VAP. Weaning from mechanical ventilation and mortality did not significantly differ between ESBL-E and non ESBL-E VAP. CONCLUSION: ESBL-related VAP in COVID-19 critically-ill patients was not infrequent. Several risk factors were identified, among which some are modifiable and deserve further investigation. There was no impact of resistance of the first Enterobacterales related episode of VAP on outcome.

Beneficial Effects of Noninvasive Ventilation after Extubation in Obese or Overweight Patients: A Post Hoc Analysis of a Randomized Clinical Trial.

Rationale: Although noninvasive ventilation (NIV) may prevent reintubation in patients at high risk of extubation failure in ICUs, this oxygenation strategy has not been specifically assessed in obese patients. Objectives: We hypothesized that NIV may decrease the risk of reintubation in obese patients compared with high-flow nasal oxygen. Methods:Post hoc analysis of a multicenter randomized controlled trial (not prespecified) comparing NIV alternating with high-flow nasal oxygen versus high-flow nasal oxygen alone after extubation, with the aim of assessing NIV effects according to patient body mass index (BMI). Measurements and Main Results: Among 623 patients at high risk of extubation failure, 206 (33%) were obese (BMI ⩾ 30 kg/m2), 204 (33%) were overweight (25 kg/m2 ⩽ BMI < 30 kg/m2), and 213 (34%) were normal or underweight (BMI < 25 kg/m2). Significant heterogeneity of NIV effects on the rate of reintubation was found according to BMI (Pinteraction = 0.007). Reintubation rates at Day 7 were significantly lower with NIV alternating with high-flow nasal oxygen than with high-flow nasal oxygen alone in obese or overweight patients: 7% (15/204) versus 20% (41/206) (difference, -13% [95% confidence interval, -19 to -6]; P = 0.0002), whereas it did not significantly differ in normal or underweight patients. In-ICU mortality was significantly lower with NIV than with high-flow nasal oxygen alone in obese or overweight patients (2% vs. 9%; difference, -6% [95% confidence interval, -11 to -2]; P = 0.006). Conclusions: Prophylactic NIV alternating with high-flow nasal oxygen immediately after extubation significantly decreased the risk of reintubation and death compared with high-flow nasal oxygen alone in obese or overweight patients at high risk of extubation failure. By contrast, NIV was not effective in normal or underweight patients. Clinical trial registered with www.clinicaltrials.gov (NCT03121482).

COVID-19-associated pulmonary aspergillosis: an underdiagnosed or overtreated infection?

PURPOSE OF REVIEW: Coronavirus disease (COVID-19)-associated pulmonary aspergillosis (CAPA) may concern up to one third of intensive care unit (ICU) patients. The purpose of this review is to discuss the diagnostic criteria, the pathogenesis, the risk factors, the incidence, the impact on outcome, and the diagnostic and therapeutic management of CAPA in critically ill patients. RECENT FINDINGS: The incidence of CAPA ranges 3--28% of critically ill patients, depending on the definition used, study design, and systematic or triggered screening. COVID-19 is associated with direct damage of the respiratory epithelium, immune dysregulation, and common use of immunosuppressive drugs which might promote Aspergillus respiratory tract colonization and invasion. Positive Aspergillus tests among COVID-19 critically patients might reflect colonization rather than invasive disease. CAPA usually appears during the second week after starting invasive mechanical ventilation and is independently associated with ICU mortality. SUMMARY: Further studies are needed to validate CAPA case definitions, to determine the accurate incidence of CAPA in comparison to adequate controls, and its evolution during the pandemic. A pro-active diagnostic strategy, based on risk stratification, clinical assessment, and bronchoalveolar lavage could be recommended to provide early antifungal treatment in patients with high probability of CAPA and clinical deterioration.

Relationship between corticosteroid use and incidence of ventilator-associated pneumonia in COVID-19 patients: a retrospective multicenter study.

BACKGROUND: Ventilator-associated pneumonia (VAP) is common in patients with severe SARS-CoV-2 pneumonia. The aim of this ancillary analysis of the coVAPid multicenter observational retrospective study is to assess the relationship between adjuvant corticosteroid use and the incidence of VAP. METHODS: Planned ancillary analysis of a multicenter retrospective European cohort in 36 ICUs. Adult patients receiving invasive mechanical ventilation for more than 48 h for SARS-CoV-2 pneumonia were consecutively included between February and May 2020. VAP diagnosis required strict definition with clinical, radiological and quantitative microbiological confirmation. We assessed the association of VAP with corticosteroid treatment using univariate and multivariate cause-specific Cox's proportional hazard models with adjustment on pre-specified confounders. RESULTS: Among the 545 included patients, 191 (35%) received corticosteroids. The proportional hazard assumption for the effect of corticosteroids on the incidence of VAP could not be accepted, indicating that this effect varied during ICU stay. We found a non-significant lower risk of VAP for corticosteroid-treated patients during the first days in the ICU and an increased risk for longer ICU stay. By modeling the effect of corticosteroids with time-dependent coefficients, the association between corticosteroids and the incidence of VAP was not significant (overall effect p = 0.082), with time-dependent hazard ratios (95% confidence interval) of 0.47 (0.17-1.31) at day 2, 0.95 (0.63-1.42) at day 7, 1.48 (1.01-2.16) at day 14 and 1.94 (1.09-3.46) at day 21. CONCLUSIONS: No significant association was found between adjuvant corticosteroid treatment and the incidence of VAP, although a time-varying effect of corticosteroids was identified along the 28-day follow-up.

Invasive pulmonary aspergillosis among intubated patients with SARS-CoV-2 or influenza pneumonia: a European multicenter comparative cohort study.

BACKGROUND: Recent multicenter studies identified COVID-19 as a risk factor for invasive pulmonary aspergillosis (IPA). However, no large multicenter study has compared the incidence of IPA between COVID-19 and influenza patients. OBJECTIVES: To determine the incidence of putative IPA in critically ill SARS-CoV-2 patients, compared with influenza patients. METHODS: This study was a planned ancillary analysis of the coVAPid multicenter retrospective European cohort. Consecutive adult patients requiring invasive mechanical ventilation for > 48 h for SARS-CoV-2 pneumonia or influenza pneumonia were included. The 28-day cumulative incidence of putative IPA, based on Blot definition, was the primary outcome. IPA incidence was estimated using the Kalbfleisch and Prentice method, considering extubation (dead or alive) within 28 days as competing event. RESULTS: A total of 1047 patients were included (566 in the SARS-CoV-2 group and 481 in the influenza group). The incidence of putative IPA was lower in SARS-CoV-2 pneumonia group (14, 2.5%) than in influenza pneumonia group (29, 6%), adjusted cause-specific hazard ratio (cHR) 3.29 (95% CI 1.53-7.02, p = 0.0006). When putative IPA and Aspergillus respiratory tract colonization were combined, the incidence was also significantly lower in the SARS-CoV-2 group, as compared to influenza group (4.1% vs. 10.2%), adjusted cHR 3.21 (95% CI 1.88-5.46, p < 0.0001). In the whole study population, putative IPA was associated with significant increase in 28-day mortality rate, and length of ICU stay, compared with colonized patients, or those with no IPA or Aspergillus colonization. CONCLUSIONS: Overall, the incidence of putative IPA was low. Its incidence was significantly lower in patients with SARS-CoV-2 pneumonia than in those with influenza pneumonia. Clinical trial registration The study was registered at ClinicalTrials.gov, number NCT04359693 .

Hospital-Acquired Pneumonia/Ventilator-Associated Pneumonia and Ventilator-Associated Tracheobronchitis in COVID-19.

Although few studies evaluated the incidence of hospital-acquired pneumonia (HAP) or ventilator-associated tracheobronchitis in COVID-19 patients, several studies evaluated the incidence of ventilator-associated pneumonia (VAP) in these patients. Based on the results of a large multicenter European study, VAP incidence is higher in patients with SARS-CoV-2 pneumonia (36.1%), as compared with those with influenza pneumonia (22.2%), or no viral infection at intensive care unit (ICU) admission (16.5%). Potential explanation for the high incidence of VAP in COVID-19 patients includes long duration of invasive mechanical ventilation, high incidence of acute respiratory distress syndrome, and immune-suppressive treatment. Specific risk factors for VAP, including SARS-CoV-2-related pulmonary lesions, and bacteria-virus interaction in lung microbiota might also play a role in VAP pathogenesis. VAP is associated with increased mortality, duration of mechanical ventilation, and ICU length of stay in COVID-19 patients. Further studies should focus on the incidence of HAP especially in ICU non-ventilated patients, better determine the pathophysiology of these infections, and evaluate the accuracy of currently available treatment guidelines in COVID-19 patients.

Early Bacterial Identification among Intubated Patients with COVID-19 or Influenza Pneumonia: A European Multicenter Comparative Clinical Trial.

Rationale: Early empirical antimicrobial treatment is frequently prescribed to critically ill patients with coronavirus disease (COVID-19) based on Surviving Sepsis Campaign guidelines.Objectives: We aimed to determine the prevalence of early bacterial identification in intubated patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia, as compared with influenza pneumonia, and to characterize its microbiology and impact on outcomes.Methods: A multicenter retrospective European cohort was performed in 36 ICUs. All adult patients receiving invasive mechanical ventilation >48 hours were eligible if they had SARS-CoV-2 or influenza pneumonia at ICU admission. Bacterial identification was defined by a positive bacterial culture within 48 hours after intubation in endotracheal aspirates, BAL, blood cultures, or a positive pneumococcal or legionella urinary antigen test.Measurements and Main Results: A total of 1,050 patients were included (568 in SARS-CoV-2 and 482 in influenza groups). The prevalence of bacterial identification was significantly lower in patients with SARS-CoV-2 pneumonia compared with patients with influenza pneumonia (9.7 vs. 33.6%; unadjusted odds ratio, 0.21; 95% confidence interval [CI], 0.15-0.30; adjusted odds ratio, 0.23; 95% CI, 0.16-0.33; P < 0.0001). Gram-positive cocci were responsible for 58% and 72% of coinfection in patients with SARS-CoV-2 and influenza pneumonia, respectively. Bacterial identification was associated with increased adjusted hazard ratio for 28-day mortality in patients with SARS-CoV-2 pneumonia (1.57; 95% CI, 1.01-2.44; P = 0.043). However, no significant difference was found in the heterogeneity of outcomes related to bacterial identification between the two study groups, suggesting that the impact of coinfection on mortality was not different between patients with SARS-CoV-2 and influenza.Conclusions: Bacterial identification within 48 hours after intubation is significantly less frequent in patients with SARS-CoV-2 pneumonia than patients with influenza pneumonia.Clinical trial registered with www.clinicaltrials.gov (NCT04359693).

Non-invasive ventilation versus high-flow nasal oxygen for postextubation respiratory failure in ICU: a post-hoc analysis of a randomized clinical trial.

BACKGROUND: In intensive care units (ICUs), patients experiencing post-extubation respiratory failure have poor outcomes. The use of noninvasive ventilation (NIV) to treat post-extubation respiratory failure may increase the risk of death. This study aims at comparing mortality between patients treated with NIV alternating with high-flow nasal oxygen or high-flow nasal oxygen alone. METHODS: Post-hoc analysis of a multicenter, randomized, controlled trial focusing on patients who experienced post-extubation respiratory failure within the 7 days following extubation. Patients were classified in the NIV group or the high-flow nasal oxygen group according to oxygenation strategy used after the onset of post-extubation respiratory failure. Patients reintubated within the first hour after extubation and those promptly reintubated without prior treatment were excluded. The primary outcome was mortality at day 28 after the onset of post-extubation respiratory failure. RESULTS: Among 651 extubated patients, 158 (25%) experienced respiratory failure and 146 were included in the analysis. Mortality at day 28 was 18% (15/84) using NIV alternating with high-flow nasal oxygen and 29% (18/62) with high flow nasal oxygen alone (difference, - 11% [95% CI, - 25 to 2]; p = 0.12). Among the 46 patients with hypercapnia at the onset of respiratory failure, mortality at day 28 was 3% (1/33) with NIV and 31% (4/13) with high-flow nasal oxygen alone (difference, - 28% [95% CI, - 54 to - 6]; p = 0.006). The proportion of patients reintubated 48 h after the onset of post-extubation respiratory failure was 44% (37/84) with NIV and 52% (32/62) with high-flow nasal oxygen alone (p = 0.21). CONCLUSIONS: In patients with post-extubation respiratory failure, NIV alternating with high-flow nasal oxygen might not increase the risk of death. Trial registration number The trial was registered at http://www.clinicaltrials.gov with the registration number NCT03121482 the 20th April 2017.

Relationship between ventilator-associated pneumonia and mortality in COVID-19 patients: a planned ancillary analysis of the coVAPid cohort.

BACKGROUND: Patients with SARS-CoV-2 infection are at higher risk for ventilator-associated pneumonia (VAP). No study has evaluated the relationship between VAP and mortality in this population, or compared this relationship between SARS-CoV-2 patients and other populations. The main objective of our study was to determine the relationship between VAP and mortality in SARS-CoV-2 patients. METHODS: Planned ancillary analysis of a multicenter retrospective European cohort. VAP was diagnosed using clinical, radiological and quantitative microbiological criteria. Univariable and multivariable marginal Cox's regression models, with cause-specific hazard for duration of mechanical ventilation and ICU stay, were used to compare outcomes between study groups. Extubation, and ICU discharge alive were considered as events of interest, and mortality as competing event. FINDINGS: Of 1576 included patients, 568 were SARS-CoV-2 pneumonia, 482 influenza pneumonia, and 526 no evidence of viral infection at ICU admission. VAP was associated with significantly higher risk for 28-day mortality in SARS-CoV-2 (adjusted HR 1.70 (95% CI 1.16-2.47), p = 0.006), and influenza groups (1.75 (1.03-3.02), p = 0.045), but not in the no viral infection group (1.07 (0.64-1.78), p = 0.79). VAP was associated with significantly longer duration of mechanical ventilation in the SARS-CoV-2 group, but not in the influenza or no viral infection groups. VAP was associated with significantly longer duration of ICU stay in the 3 study groups. No significant difference was found in heterogeneity of outcomes related to VAP between the 3 groups, suggesting that the impact of VAP on mortality was not different between study groups. INTERPRETATION: VAP was associated with significantly increased 28-day mortality rate in SARS-CoV-2 patients. However, SARS-CoV-2 pneumonia, as compared to influenza pneumonia or no viral infection, did not significantly modify the relationship between VAP and 28-day mortality. CLINICAL TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov, number NCT04359693.