Mortality comparison between the first and second/third waves among 3,795 critical COVID-19 patients with pneumonia admitted to the ICU : A multicentre retrospective cohort study

It is unclear whether the changes in critical care throughout the pandemic have improved the outcomes in coronavirus disease 2019 (COVID-19) patients admitted to the intensive care units (ICUs). We conducted a retrospective cohort study in adults with COVID-19 pneumonia admitted to 73 ICUs from Spain, Andorra and Ireland between February 2020 and March 2021. The first wave corresponded with the period from February 2020 to June 2020, whereas the second/third waves occurred from July 2020 to March 2021. The primary outcome was ICU mortality between study periods. Mortality predictors and differences in mortality between COVID-19 waves were identified using logistic regression. As of March 2021, the participating ICUs had included 3795 COVID-19 pneumonia patients, 2479 (65·3%) and 1316 (34·7%) belonging to the first and second/third waves, respectively. Illness severity scores predicting mortality were lower in the second/third waves compared with the first wave according with the Acute Physiology and Chronic Health Evaluation system (median APACHE II score 12 [IQR 9-16] vs 14 [IQR 10-19]) and the organ failure assessment score (median SOFA 4 [3-6] vs 5 [3-7], p <0·001). The need of invasive mechanical ventilation was high (76·1%) during the whole study period. However, a significant increase in the use of high flow nasal cannula (48·7% vs 18·2%, p <0·001) was found in the second/third waves compared with the first surge. Significant changes on treatments prescribed were also observed, highlighting the remarkable increase on the use of corticosteroids to up to 95.9% in the second/third waves. A significant reduction on the use of tocilizumab was found during the study (first wave 28·9% vs second/third waves 6·2%, p <0·001), and a negligible administration of lopinavir/ritonavir, hydroxychloroquine, and interferon during the second/third waves compared with the first wave. Overall ICU mortality was 30·7% (n = 1166), without significant differences between study periods (first wave 31·7% vs second/third waves 28·8%, p = 0·06). No significant differences were found in ICU mortality between waves according to age subsets except for the subgroup of 61-75 years of age, in whom a reduced unadjusted ICU mortality was observed in the second/third waves (first 38·7% vs second/third 34·0%, p = 0·048). Non-survivors were older, with higher severity of the disease, had more comorbidities, and developed more complications. After adjusting for confounding factors through a multivariable analysis, no significant association was found between the COVID-19 waves and mortality (OR 0·81, 95% CI 0·64-1·03; p = 0·09). Ventilator-associated pneumonia rate increased significantly during the second/third waves and it was independently associated with ICU mortality (OR 1·48, 95% CI 1·19-1·85, p <0·001). Nevertheless, a significant reduction both in the ICU and hospital length of stay in survivors was observed during the second/third waves. Despite substantial changes on supportive care and management, we did not find significant improvement on case-fatality rates among critical COVID-19 pneumonia patients. Ricardo Barri Casanovas Foundation (RBCF2020) and SEMICYU

Risk factors for developing ventilator-associated lower respiratory tract infection in patients with severe COVID-19:a multinational, multicentre study, prospective, observational study

Around one-third of patients diagnosed with COVID-19 develop a severe illness that requires admission to the Intensive Care Unit (ICU). In clinical practice, clinicians have learned that patients admitted to the ICU due to severe COVID-19 frequently develop ventilator-associated lower respiratory tract infections (VA-LRTI). This study aims to describe the clinical characteristics, the factors associated with VA-LRTI, and its impact on clinical outcomes in patients with severe COVID-19. This was a multicentre, observational cohort study conducted in ten countries in Latin America and Europe. We included patients with confirmed rtPCR for SARS-CoV-2 requiring ICU admission and endotracheal intubation. Only patients with a microbiological and clinical diagnosis of VA-LRTI were included. Multivariate Logistic regression analyses and Random Forest were conducted to determine the risk factors for VA-LRTI and its clinical impact in patients with severe COVID-19. In our study cohort of 3287 patients, VA-LRTI was diagnosed in 28.8% [948/3287]. The cumulative incidence of ventilator-associated pneumonia (VAP) was 18.6% [610/3287], followed by ventilator-associated tracheobronchitis (VAT) 10.3% [338/3287]. A total of 1252 bacteria species were isolated. The most frequently isolated pathogens were Pseudomonas aeruginosa (21.2% [266/1252]), followed by Klebsiella pneumoniae (19.1% [239/1252]) and Staphylococcus aureus (15.5% [194/1,252]). The factors independently associated with the development of VA-LRTI were prolonged stay under invasive mechanical ventilation, AKI during ICU stay, and the number of comorbidities. Regarding the clinical impact of VA-LRTI, patients with VAP had an increased risk of hospital mortality (OR [95% CI] of 1.81 [1.40-2.34]), while VAT was not associated with increased hospital mortality (OR [95% CI] of 1.34 [0.98-1.83]). VA-LRTI, often with difficult-to-treat bacteria, is frequent in patients admitted to the ICU due to severe COVID-19 and is associated with worse clinical outcomes, including higher mortality. Identifying risk factors for VA-LRTI might allow the early patient diagnosis to improve clinical outcomes. Trial registration: This is a prospective observational study; therefore, no health care interventions were applied to participants, and trial registration is not applicable

Timing of intubation and ICU mortality in COVID-19 patients: a retrospective analysis of 4198 critically ill patients during the first and second waves

Abstract Background The optimal time to intubate patients with SARS-CoV-2 pneumonia has not been adequately determined. While the use of non-invasive respiratory support before invasive mechanical ventilation might cause patient-self-induced lung injury and worsen the prognosis, non-invasive ventilation (NIV) is frequently used to avoid intubation of patients with acute respiratory failure (ARF). We hypothesized that delayed intubation is associated with a high risk of mortality in COVID-19 patients. Methods This is a secondary analysis of prospectively collected data from adult patients with ARF due to COVID-19 admitted to 73 intensive care units (ICUs) between February 2020 and March 2021. Intubation was classified according to the timing of intubation. To assess the relationship between early versus late intubation and mortality, we excluded patients with ICU length of stay (LOS) < 7 days to avoid the immortal time bias and we did a propensity score and a cox regression analysis. Results We included 4,198 patients [median age, 63 (54‒71) years; 71% male; median SOFA (Sequential Organ Failure Assessment) score, 4 (3‒7); median APACHE (Acute Physiology and Chronic Health Evaluation) score, 13 (10‒18)], and median PaO2/FiO2 (arterial oxygen pressure/ inspired oxygen fraction), 131 (100‒190)]; intubation was considered very early in 2024 (48%) patients, early in 928 (22%), and late in 441 (10%). ICU mortality was 30% and median ICU stay was 14 (7‒28) days. Mortality was higher in the “late group” than in the “early group” (37 vs. 32%, p < 0.05). The implementation of an early intubation approach was found to be an independent protective risk factor for mortality (HR 0.6; 95%CI 0.5‒0.7). Conclusions Early intubation within the first 24 h of ICU admission in patients with COVID-19 pneumonia was found to be an independent protective risk factor of mortality. Trial registration The study was registered at Clinical-Trials.gov (NCT04948242) (01/07/2021)

Dexamethasone as risk-factor for ICU-acquired respiratory tract infections in severe COVID-19.

Dexamethasone is the only drug that has consistently reduced mortality in patients with COVID-19, especially in patients needing oxygen or invasive mechanical ventilation. However, there is a growing concern about the relation of dexamethasone with the unprecedented rates of ICU-acquired respiratory tract infections (ICU-RTI) observed in patients with severe COVID-19. This was a multicenter, prospective cohort study; conducted in ten countries in Latin America and Europe. We included patients older than 18 with confirmed SARS-CoV-2 requiring ICU admission. A multivariate logistic regression and propensity score matching (PSM) analysis was conducted to determine the relation between dexamethasone treatment and ICU-RTI. A total of 3777 patients were included. 2065 (54.7%) were treated with dexamethasone within the first 24 h of admission. After performing the PSM, patients treated with dexamethasone showed significantly higher proportions of VAP (282/1652 [17.1%] Vs. 218/1652 [13.2%], p = 0.014). Also, dexamethasone treatment was identified as an adjusted risk factor of ICU-RTI in the multivariate logistic regression model (OR 1.64; 95%CI: 1.37-1.97; p Patients treated with dexamethasone for severe COVID-19 had a higher risk of developing ICU-acquired respiratory tract infections after adjusting for days of invasive mechanical ventilation and ICU length of stay, suggesting a cautious use of this treatment

World alliance against antibiotic resistance: The WAAAR declaration against antibiotic resistance

We must change how antibiotics are used and adopt proactive strategies, similar to those used to save endangered species. Preservation of the efficacy of antibiotics and to stabilization of antibiotic-susceptible bacterial ecosystems should be global goals

Pandemic Influenza A in the ICU : Experience in Spain and Latin America GETGAG/SEMICYUC/(Spanish Work Group on Severe Pandemic Influenza A/SEMICYUC)

Introducción: La pandemia de gripe A(H1N1)v es la primera pandemia en la que las unidades de cuidados intensivos(UCI) desempeñan un papel fundamental. Su evolución ha sido muy rápida desde los primeros casos diagnosticados en México y la afectación posterior de países del cono sur hasta su llegada a Europa durante la época estival. Objetivo: Comparar las características clínicas y de evolución de los pacientes críticos ingresados hasta el 31 de julio de 2009 en España con algunas series de Latinoamérica. Material y método: Se consideraron 6 series de pacientes ingresados en la UCI. Se realizaron comparaciones de las características clínicas, complicaciones y evolución entre las series. Resultados: Los datos evidencian una población joven (35–45 años) con predominio de ingresos por neumonía viral con grave insuficiencia respiratoria y una elevada necesidad de ventilación mecánica (60–100%). Si bien algunas determinadas poblaciones, como los obesos, las embarazadas y los pacientes con enfermedad pulmonar crónica, parecen estar expuestas a un riesgo más elevado, la ausencia de comorbilidades alcanza un porcentaje considerable en casi todas las series (40–50%). La mortalidad superior en Latinoamérica osciló entre el 25 y el 50%, y demostró el particular potencial patogénico del nuevo virus. El uso del tratamiento antiviral es tardío (entre 3 y 6 días) y poco generalizado, con mayor retraso en Latinoamérica respecto de España. Conclusiones: Estos datos indican que una estrategia de tratamiento más intensivo con un acceso más precoz y fácil al antiviral podría reducir el número de pacientes que requieren UCI y su mortalidad.Abstract Introduction: Pandemic Influenza A (H1N1) v infection is the first pandemic in which intensive care units (ICU) play a fundamental role. It has spread very rapidly since the first cases were diagnosed in Mexico with the subsequent spread of the virus throughout the Southern Cone and Europe during the summer season. Objective: This study has aimed to compare the clinical presentation and outcome among the critical patients admitted to the ICU until July 31, 2009 in Spain with some series from Latin America. Material andmethod: Six series of critically ill patients admitted to the ICU were considered. Clinical characteristics, complications and outcome werecompared between series. Results: Young patients (35–45 years) with viral pneumonia as a predominant ICU admission cause with severe respiratory failure and a high need of mechanical ventilation (60–100%) were affected. Obesity, pregnancy and chronic lung disease were risk factors associated with a worse outcome, however there was a high number of patients without comorbidities (40–50%). Mortality rate was between 25–50% and higher in the Latin America series, demonstrating the specific potential pathogenesis of the new virus. The use of antiviral treatment was delayed (between 3 and 6 days) and not generalized, with greater delay in Latin America in regards to Spain. Conclusions: These data suggest that a more aggressive treatment strategy, with earlier and easier access to the antiviral treatment might reduce the number of ICU admissions and mortality

Pandemic Influenza A in the ICU : Experience in Spain and Latin America GETGAG/SEMICYUC/(Spanish Work Group on Severe Pandemic Influenza A/SEMICYUC)

Introducción: La pandemia de gripe A(H1N1)v es la primera pandemia en la que las unidades de cuidados intensivos(UCI) desempeñan un papel fundamental. Su evolución ha sido muy rápida desde los primeros casos diagnosticados en México y la afectación posterior de países del cono sur hasta su llegada a Europa durante la época estival. Objetivo: Comparar las características clínicas y de evolución de los pacientes críticos ingresados hasta el 31 de julio de 2009 en España con algunas series de Latinoamérica. Material y método: Se consideraron 6 series de pacientes ingresados en la UCI. Se realizaron comparaciones de las características clínicas, complicaciones y evolución entre las series. Resultados: Los datos evidencian una población joven (35–45 años) con predominio de ingresos por neumonía viral con grave insuficiencia respiratoria y una elevada necesidad de ventilación mecánica (60–100%). Si bien algunas determinadas poblaciones, como los obesos, las embarazadas y los pacientes con enfermedad pulmonar crónica, parecen estar expuestas a un riesgo más elevado, la ausencia de comorbilidades alcanza un porcentaje considerable en casi todas las series (40–50%). La mortalidad superior en Latinoamérica osciló entre el 25 y el 50%, y demostró el particular potencial patogénico del nuevo virus. El uso del tratamiento antiviral es tardío (entre 3 y 6 días) y poco generalizado, con mayor retraso en Latinoamérica respecto de España. Conclusiones: Estos datos indican que una estrategia de tratamiento más intensivo con un acceso más precoz y fácil al antiviral podría reducir el número de pacientes que requieren UCI y su mortalidad.Abstract Introduction: Pandemic Influenza A (H1N1) v infection is the first pandemic in which intensive care units (ICU) play a fundamental role. It has spread very rapidly since the first cases were diagnosed in Mexico with the subsequent spread of the virus throughout the Southern Cone and Europe during the summer season. Objective: This study has aimed to compare the clinical presentation and outcome among the critical patients admitted to the ICU until July 31, 2009 in Spain with some series from Latin America. Material andmethod: Six series of critically ill patients admitted to the ICU were considered. Clinical characteristics, complications and outcome werecompared between series. Results: Young patients (35–45 years) with viral pneumonia as a predominant ICU admission cause with severe respiratory failure and a high need of mechanical ventilation (60–100%) were affected. Obesity, pregnancy and chronic lung disease were risk factors associated with a worse outcome, however there was a high number of patients without comorbidities (40–50%). Mortality rate was between 25–50% and higher in the Latin America series, demonstrating the specific potential pathogenesis of the new virus. The use of antiviral treatment was delayed (between 3 and 6 days) and not generalized, with greater delay in Latin America in regards to Spain. Conclusions: These data suggest that a more aggressive treatment strategy, with earlier and easier access to the antiviral treatment might reduce the number of ICU admissions and mortality

Negative predictive value of procalcitonin to rule out bacterial respiratory co-infection in critical covid-19 patients.

Procalcitonin (PCT) and C-Reactive Protein (CRP) are useful biomarkers to differentiate bacterial from viral or fungal infections, although the association between them and co-infection or mortality in COVID-19 remains unclear. The study represents a retrospective cohort study of patients admitted for COVID-19 pneumonia to 84 ICUs from ten countries between (March 2020-January 2021). Primary outcome was to determine whether PCT or CRP at admission could predict community-acquired bacterial respiratory co-infection (BC) and its added clinical value by determining the best discriminating cut-off values. Secondary outcome was to investigate its association with mortality. To evaluate the main outcome, a binary logistic regression was performed. The area under the curve evaluated diagnostic performance for BC prediction. 4635 patients were included, 7.6% fulfilled BC diagnosis. PCT (0.25[IQR 0.1-0.7] versus 0.20[IQR 0.1-0.5]ng/mL, p These biomarkers at ICU admission led to a poor ability to predict BC among patients with COVID-19 pneumonia. Baseline values of PC

Deploying unsupervised clustering analysis to derive clinical phenotypes and risk factors associated with mortality risk in 2022 critically ill patients with COVID-19 in Spain.

The identification of factors associated with Intensive Care Unit (ICU) mortality and derived clinical phenotypes in COVID-19 patients could help for a more tailored approach to clinical decision-making that improves prognostic outcomes. Prospective, multicenter, observational study of critically ill patients with confirmed COVID-19 disease and acute respiratory failure admitted from 63 ICUs in Spain. The objective was to utilize an unsupervised clustering analysis to derive clinical COVID-19 phenotypes and to analyze patient's factors associated with mortality risk. Patient features including demographics and clinical data at ICU admission were analyzed. Generalized linear models were used to determine ICU morality risk factors. The prognostic models were validated and their performance was measured using accuracy test, sensitivity, specificity and ROC curves. The database included a total of 2022 patients (mean age 64 [IQR 5-71] years, 1423 (70.4%) male, median APACHE II score (13 [IQR 10-17]) and SOFA score (5 [IQR 3-7]) points. The ICU mortality rate was 32.6%. Of the 3 derived phenotypes, the A (mild) phenotype (537; 26.7%) included older age ( 65 years), high severity of illness and a higher likelihood of development shock. Crude ICU mortality was 20.3%, 25% and 45.4% for A, B and C phenotype respectively. The ICU mortality risk factors and model performance differed between whole population and phenotype classifications. The presented machine learning model identified three clinical phenotypes that significantly correlated with host-response patterns and ICU mortality. Different risk factors across the whole population and clinical phenotypes were observed which may limit the application of a "one-size-fits-all" model in practice