A differential therapeutic consideration for use of corticosteroids according to established COVID-19 clinical phenotypes in critically ill patients.

Objective: To determine if the use of corticosteroids was associated with Intensive Care Unit (ICU) mortality among whole population and pre-specified clinical phenotypes. Design: A secondary analysis derived from multicenter, observational study. Setting: Critical Care Units. Patients: Adult critically ill patients with confirmed COVID-19 disease admitted to 63 ICUs in Spain. Interventions: Corticosteroids vs. no corticosteroids. Main variables of interest: Three phenotypes were derived by non-supervised clustering analysis from whole population and classified as (A: severe, B: critical and C: life-threatening). We performed a multivariate analysis after propensity optimal full matching (PS) for whole population and weighted Cox regression (HR) and Fine-Gray analysis (sHR) to assess the impact of corticosteroids on ICU mortality according to the whole population and distinctive patient clinical phenotypes. Results: A total of 2017 patients were analyzed, 1171 (58%) with corticosteroids. After PS, corticosteroids were shown not to be associated with ICU mortality (OR: 1.0; 95% CI: 0.98-1.15). Corticosteroids were administered in 298/537 (55.5%) patients of "A" phenotype and their use was not associated with ICU mortality (HR = 0.85 [0.55-1.33]). A total of 338/623 (54.2%) patients in "B" phenotype received corticosteroids. No effect of corticosteroids on ICU mortality was observed when HR was performed (0.72 [0.49-1.05]). Finally, 535/857 (62.4%) patients in "C" phenotype received corticosteroids. In this phenotype HR (0.75 [0.58-0.98]) and sHR (0.79 [0.63-0.98]) suggest a protective effect of corticosteroids on ICU mortality. Conclusion: Our finding warns against the widespread use of corticosteroids in all critically ill patients with COVID-19 at moderate dose. Only patients with the highest inflammatory levels could benefit from steroid treatment.

Objetivo: Evaluar si el uso de corticoesteroides (CC) se asocia con la mortalidad en la unidad de cuidados intensivos (UCI) en la población global y dentro de los fenotipos clínicos predeterminados. Diseño: Análisis secundario de estudio multicéntrico observacional. Ámbito: UCI. Pacientes: Pacientes adultos con COVID-19 confirmado ingresados en 63 UCI de España. Intervención: Corticoides vs. no corticoides. Variables de interés principales: A partir del análisis no supervisado de grupos, 3 fenotipos clínicos fueron derivados y clasificados como: A grave, B crítico y C potencialmente mortal. Se efectuó un análisis multivariado después de un propensity optimal full matching (PS) y una regresión ponderada de Cox (HR) y análisis de Fine-Gray (sHR) para evaluar el impacto del tratamiento con CC sobre la mortalidad en la población general y en cada fenotipo clínico. Resultados: Un total de 2.017 pacientes fueron analizados, 1.171 (58%) con CC. Después del PS, el uso de CC no se relacionó significativamente con la mortalidad en UCI (OR: 1,0; IC 95%: 0,98-1,15). Los CC fueron administrados en 298/537 (55,5%) pacientes del fenotipo A y no se observó asociación significativa con la mortalidad (HR = 0,85; 0,55-1,33). Un total de 338/623 (54,2%) pacientes del fenotipo B recibieron CC sin efecto significativo sobre la mortalidad (HR = 0,72; 0,49-1,05). Por último, 535/857 (62,4%) pacientes del fenotipo C recibieron CC. En este fenotipo, se evidenció un efecto protector de los CC sobre la mortalidad HR (0,75; 0,58-0,98). Conclusión: Nuestros hallazgos alertan sobre el uso indiscriminado de CC a dosis moderadas en todos los pacientes críticos con COVID-19. Solamente pacientes con elevado estado de inflamación podrían beneficiarse con el tratamiento con CC.

A differential therapeutic consideration for use of corticosteroids according to established COVID-19 clinical phenotypes in critically ill patients.

OBJECTIVE: To determine if the use of corticosteroids was associated with Intensive Care Unit (ICU) mortality among whole population and pre-specified clinical phenotypes. DESIGN: A secondary analysis derived from multicenter, observational study. SETTING: Critical Care Units. PATIENTS: Adult critically ill patients with confirmed COVID-19 disease admitted to 63 ICUs in Spain. INTERVENTIONS: Corticosteroids vs. no corticosteroids. MAIN VARIABLES OF INTEREST: Three phenotypes were derived by non-supervised clustering analysis from whole population and classified as (A: severe, B: critical and C: life-threatening). We performed a multivariate analysis after propensity optimal full matching (PS) for whole population and weighted Cox regression (HR) and Fine-Gray analysis (sHR) to assess the impact of corticosteroids on ICU mortality according to the whole population and distinctive patient clinical phenotypes. RESULTS: A total of 2017 patients were analyzed, 1171 (58%) with corticosteroids. After PS, corticosteroids were shown not to be associated with ICU mortality (OR: 1.0; 95% CI: 0.98-1.15). Corticosteroids were administered in 298/537 (55.5%) patients of "A" phenotype and their use was not associated with ICU mortality (HR=0.85 [0.55-1.33]). A total of 338/623 (54.2%) patients in "B" phenotype received corticosteroids. No effect of corticosteroids on ICU mortality was observed when HR was performed (0.72 [0.49-1.05]). Finally, 535/857 (62.4%) patients in "C" phenotype received corticosteroids. In this phenotype HR (0.75 [0.58-0.98]) and sHR (0.79 [0.63-0.98]) suggest a protective effect of corticosteroids on ICU mortality. CONCLUSION: Our finding warns against the widespread use of corticosteroids in all critically ill patients with COVID-19 at moderate dose. Only patients with the highest inflammatory levels could benefit from steroid treatment.

Impact of Aspergillus spp. isolation in the first 24 hours of admission in critically ill patients with severe influenza virus pneumonia.

OBJECTIVE: To determine the incidence and impact of Aspergillus spp. isolation (AI) on ICU mortality in critically ill patients with severe influenza pneumonia during the first 24h of admission. DESIGN: Secondary analysis of an observational and prospective cohort study. SETTING: ICUs voluntary participating in the Spanish severe Influenza pneumonia registry, between June 2009 and June 2019. PATIENTS: Consecutive patients admitted to the ICU with diagnosis of severe influenza pneumonia, confirmed by real-time polymerase chain reaction. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: Incidence of AI in respiratory samples. Demographic variables, comorbidities, need for mechanical ventilation and the presence of shock according at admission. Acute Physiology and Chronic Health Evaluation II (APACHE II) scale calculated on ICU admission. RESULTS: 3702 patients were analyzed in this study. AI incidence was 1.13% (n=42). Hematological malignancies (OR 4.39, 95% CI 1.92-10.04); HIV (OR 3.83, 95% CI 1.08-13.63), and other immunosuppression situations (OR 4.87, 95% CI 1.99-11.87) were factors independently associated with the presence of Aspergillus spp. The automatic CHAID decision tree showed that hematologic disease with an incidence of 3.3% was the most closely AI related variable. Hematological disease (OR 2.62 95% CI 1.95-3.51), immunosuppression (OR 2.05 95% CI 1.46-2.88) and AI (OR 3.24, 95% CI 1.60-6.53) were variables independently associated with ICU mortality. CONCLUSIONS: Empirical antifungal treatment in our population may only be justified in immunocompromised patients. In moderate-high risk cases, active search for Aspergillus spp. should be implemented.

Bacterial etiology of community-acquired pneumonia in immunocompetent hospitalized patients and appropriateness of empirical treatment recommendations: an international point-prevalence study.

An accurate knowledge of the epidemiology of community-acquired pneumonia (CAP) is key for selecting appropriate antimicrobial treatments. Very few etiological studies assessed the appropriateness of empiric guideline recommendations at a multinational level. This study aims at the following: (i) describing the bacterial etiologic distribution of CAP and (ii) assessing the appropriateness of the empirical treatment recommendations by clinical practice guidelines (CPGs) for CAP in light of the bacterial pathogens diagnosed as causative agents of CAP. Secondary analysis of the GLIMP, a point-prevalence international study which enrolled adults hospitalized with CAP in 2015. The analysis was limited to immunocompetent patients tested for bacterial CAP agents within 24 h of admission. The CAP CPGs evaluated included the following: the 2007 and 2019 American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA), the European Respiratory Society (ERS), and selected country-specific CPGs. Among 2564 patients enrolled, 35.3% had an identifiable pathogen. Streptococcus pneumoniae (8.2%) was the most frequently identified pathogen, followed by Pseudomonas aeruginosa (4.1%) and Klebsiella pneumoniae (3.4%). CPGs appropriately recommend covering more than 90% of all the potential pathogens causing CAP, with the exception of patients enrolled from Germany, Pakistan, and Croatia. The 2019 ATS/IDSA CPGs appropriately recommend covering 93.6% of the cases compared with 90.3% of the ERS CPGs (p < 0.01). S. pneumoniae remains the most common pathogen in patients hospitalized with CAP. Multinational CPG recommendations for patients with CAP seem to appropriately cover the most common pathogens and should be strongly encouraged for the management of CAP patients.

En respuesta a «Vacunación antigripal y protección del paciente crítico: responsabilidad de los profesionales sanitarios» / Reply to «Influenza vaccination and critical patient protection: responsibility of healthcare workers»

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Structural differences in the diaphragm of patients following controlled vs assisted and spontaneous mechanical ventilation.

PURPOSE: Ventilator-induced diaphragm dysfunction or damage (VIDD) is highly prevalent in patients under mechanical ventilation (MV), but its analysis is limited by the difficulty of obtaining histological samples. In this study we compared diaphragm histological characteristics in Maastricht III (MSIII) and brain-dead (BD) organ donors and in control subjects undergoing thoracic surgery (CTL) after a period of either controlled or spontaneous MV (CMV or SMV). METHODS: In this prospective study, biopsies were obtained from diaphragm and quadriceps. Demographic variables, comorbidities, severity on admission, treatment, and ventilatory variables were evaluated. Immunohistochemical analysis (fiber size and type percentages) and quantification of abnormal fibers (a surrogate of muscle damage) were performed. RESULTS: Muscle samples were obtained from 35 patients. MSIII (n = 16) had more hours on MV (either CMV or SMV) than BD (n = 14) and also spent more hours and a greater percentage of time with diaphragm stimuli (time in assisted and spontaneous modalities). Cross-sectional area (CSA) was significantly reduced in the diaphragm and quadriceps in both groups in comparison with CTL (n = 5). Quadriceps CSA was significantly decreased in MSIII compared to BD but there were no differences in the diaphragm CSA between the two groups. Those MSIII who spent 100 h or more without diaphragm stimuli presented reduced diaphragm CSA without changes in their quadriceps CSA. The proportion of internal nuclei in MSIII diaphragms tended to be higher than in BD diaphragms, and their proportion of lipofuscin deposits tended to be lower, though there were no differences in the quadriceps fiber evaluation. CONCLUSIONS: This study provides the first evidence in humans regarding the effects of different modes of MV (controlled, assisted, and spontaneous) on diaphragm myofiber damage, and shows that diaphragm inactivity during mechanical ventilation is associated with the development of VIDD.

Pacientes con gripe por el virus influenza A (H1N1)pdm09 ingresados en la UCI. Impacto de las recomendaciones de la SEMICYUC / Patients with influenza A (H1N1)pdm09 admitted to the ICU. Impact of the recommendations of the SEMICYUC

OBJETIVOS: Evaluar el impacto de las recomendaciones SEMICYUC 2012 en la gripe A grave. DISEÑO: Prospectivo multicéntrico observacional. Ámbito: UCI. PACIENTES: Pacientes con virus influenza A (H1N1) grave (registro GETGAG/SEMICYUC). INTERVENCIONES: Análisis de 2 grupos según el periodo epidémico del diagnóstico (2009-2011; 2013-2015). VARIABLES: Demográficas, temporales, comorbilidades, gravedad, tratamientos, mortalidad, diagnóstico tardío y lugar de adquisición. RESULTADOS: Se incluyeron 2.205 pacientes, 1.337 (60,6%) en el primer periodo y 868 (39,4%) en el segundo. La edad, la gravedad al ingreso y la coinfección bacteriana fueron significativamente mayores en el segundo periodo. Respecto al impacto de las recomendaciones, en el segundo periodo el diagnóstico fue más precoz (70,8 vs. 61,1%, p < 0,001), sin cambios en el inicio del tratamiento. Se administraron menos corticoides (39,7 vs. 44,9%, p < 0,05), se utilizó más VMNI (47,4 vs. 33,2%, p < 0,001) y se objetivó una mayor tasa de vacunación (11,1 vs. 1,7%, p < 0,001), sin cambios en la mortalidad (24,2 vs. 20,7%). También se evidenció una disminución de la infección adquirida en el hospital (9,8 vs. 16%, p < 0,001). Asimismo, los pacientes requirieron menos VM con más días de ventilación, más vasopresores y más decúbito prono. CONCLUSIONES: El manejo de los pacientes con gripe A (H1N1) grave se ha modificado con los años, sin cambios en la mortalidad. Las recomendaciones de la SEMICYUC del año 2012 han mejorado el diagnóstico precoz y el uso de corticoides. Queda por mejorar el retraso en el tratamiento, la tasa de vacunación y la utilización de la VMNI

OBJECTIVES: To evaluate the impact of the recommendations of the SEMICYUC (2012) on severe influenza A. DESIGN: A prospective multicenter observational study was carried out. SETTING: ICU. PATIENTS: Patients infected with severe influenza A (H1N1) from the GETGAG/SEMICYUC registry. INTERVENTIONS: Analysis of 2 groups according to the epidemic period of the diagnosis (2009-2011; 2013-2015). VARIABLES: Demographic, temporal, comorbidities, severity, treatments, mortality, late diagnosis and place of acquisition. RESULTS: A total of 2,205 patients were included, 1,337 (60.6%) in the first period and 868 (39.4%) in the second one. Age and severity on admission were significantly greater in the second period, as well as co-infection. With regard to the impact of the recommendations, in the second period the diagnosis was established earlier (70.8 vs. 61.1%, P<.001), without changes in the start of treatment. Patients received less corticosteroid treatment (39.7 vs. 44.9%, P<.05), more NIMV was used (47.4 vs. 33.2%, P<.001) and more vaccination was made (11.1 vs. 1.7%, P<.001), without changes in mortality (24.2 vs. 20.7%). A decrease in nosocomial infection was also noted (9.8 vs. 16%, P<.001). Patients needed less MV with more days of ventilation, more vasopressor drug use and more ventral decubitus. CONCLUSIONS: The management of patients with severe influenza A (H1N1) has changed over the years, though without changes in mortality. The recommendations of the SEMICYUC (2012) have allowed earlier diagnosis and improved corticosteroid use. Pending challenges are the delay in treatment, the vaccination rate and the use of NIMV

Patients with influenza A (H1N1)pdm09 admitted to the ICU. Impact of the recommendations of the SEMICYUC. / Pacientes con gripe por el virus influenza A (H1N1)pdm09 ingresados en la UCI. Impacto de las recomendaciones de la SEMICYUC.

OBJECTIVES: To evaluate the impact of the recommendations of the SEMICYUC (2012) on severe influenza A. DESIGN: A prospective multicenter observational study was carried out. SETTING: ICU. PATIENTS: Patients infected with severe influenza A (H1N1) from the GETGAG/SEMICYUC registry. INTERVENTIONS: Analysis of 2 groups according to the epidemic period of the diagnosis (2009-2011; 2013-2015). VARIABLES: Demographic, temporal, comorbidities, severity, treatments, mortality, late diagnosis and place of acquisition. RESULTS: A total of 2,205 patients were included, 1,337 (60.6%) in the first period and 868 (39.4%) in the second one. Age and severity on admission were significantly greater in the second period, as well as co-infection. With regard to the impact of the recommendations, in the second period the diagnosis was established earlier (70.8 vs. 61.1%, P<.001), without changes in the start of treatment. Patients received less corticosteroid treatment (39.7 vs. 44.9%, P<.05), more NIMV was used (47.4 vs. 33.2%, P<.001) and more vaccination was made (11.1 vs. 1.7%, P<.001), without changes in mortality (24.2 vs. 20.7%). A decrease in nosocomial infection was also noted (9.8 vs. 16%, P<.001). Patients needed less MV with more days of ventilation, more vasopressor drug use and more ventral decubitus. CONCLUSIONS: The management of patients with severe influenza A (H1N1) has changed over the years, though without changes in mortality. The recommendations of the SEMICYUC (2012) have allowed earlier diagnosis and improved corticosteroid use. Pending challenges are the delay in treatment, the vaccination rate and the use of NIMV.

Characteristics of patients with hospital-acquired influenza A (H1N1)pdm09 virus admitted to the intensive care unit.

BACKGROUND: Influenza A (H1N1)pdm09 virus infection acquired in the hospital and in critically ill patients admitted to the intensive care unit (ICU) has been poorly characterized. AIM: To assess the clinical impact of hospital-acquired infection with influenza A (H1N1)pdm09 virus in critically ill patients. METHODS: Analysis of a prospective database of the Spanish registry (2009-2015) of patients with severe influenza A admitted to the ICU. Infection was defined as hospital-acquired when diagnosis and starting of treatment occurred from the seventh day of hospital stay with no suspicion on hospital admission, and community-acquired when diagnosis was established within the first 48 h of admission. FINDINGS: Of 2421 patients with influenza A (H1N1)pdm09 infection, 224 (9.3%) were classified as hospital-acquired and 1103 (45.6%) as community-acquired (remaining cases unclassified). Intra-ICU mortality was higher in the hospital-acquired group (32.9% vs 18.8%, P < 0.001). Independent factors associated with mortality were hospital-acquired influenza A (H1N1)pdm09 infection (odds ratio: 1.63; 95% confidence interval: 1.37-1.99), APACHE II score on ICU admission (1.09; 1.06-1.11), underlying haematological disease (3.19; 1.78-5.73), and need of extrarenal depuration techniques (4.20; 2.61-6.77) and mechanical ventilation (4.34; 2.62-7.21). CONCLUSION: Influenza A (H1N1)pdm09 infection acquired in the hospital is an independent factor for death in critically ill patients admitted to the ICU.

Prognostic value of brachioradialis muscle oxygen saturation index and vascular occlusion test in septic shock patients / Valor pronóstico del índice de saturación de oxígeno y el test de oclusión vascular en el músculo braquiorradial de pacientes con shock séptico

OBJECTIVES: To compare rSO2 (muscle oxygen saturation index) static and dynamic variables obtained by NIRS (Near Infrared Spectroscopy) in brachioradialis muscle of septic shock patients and its prognostic implications. DESIGN: Prospective and observational study. SETTING: Intensive care unit. SUBJECTS: Septic shock patients and healthy volunteers. Interventions: The probe of a NIRS device (INVOS 5100) was placed on the brachioradialis muscle during a vascular occlusion test (VOT). VARIABLES: Baseline, minimum and maximum rSO2 values, deoxygenation rate (DeOx), reoxygenation slope (ReOx) and delta value. RESULTS: Septic shock patients (n = 35) had lower baseline rSO2 (63.8 ± 12.2 vs. 69.3 ± 3.3%, p < 0.05), slower DeOx (-(-0.54 ± 0.31 vs. -0.91 ± 0.35%/s, p = 0.001), slower ReOx (2.67 ± 2.17 vs. 9.46 ± 3.5%/s, p<0.001) and lower delta (3.25 ± 5.71 vs. 15.1 ± 3.9%, p < 0.001) when compared to healthy subjects (n=20). Among septic shock patients, non-survivors showed lower baseline rSO2 (57.0 ± 9.6 vs. 69.8 ± 11.3%, p = 0.001), lower minimum rSO2 (36.0 ± 12.8 vs. 51.3±14.8%, p < 0.01) and lower maximum rSO2 values (60.6 ± 10.6 vs. 73.3 ± 11.2%, p < 0.01). Baseline rSO2 was a good mortality predictor (AUC 0.79; 95% CI: 0.63-0.94, p < 0.01). Dynamic parameters obtained with VOT did not improve the results. CONCLUSION: Septic shock patients present an important alteration of microcirculation that can be evaluated by NIRS with prognostic implications. Monitoring microvascular reactivity in the brachioradialis muscle using VOT with our device does not seem to improve the prognostic value of baseline rSO2

OBJETIVO: Comparar las variables microcirculatorias estáticas y dinámicas obtenidas mediante espectroscopia cercana al infrarojo en el músculo braquiorradial de pacientes con shock séptico y sus implicaciones pronósticas. DISEÑO: Estudio prospectivo y observacional. ÁMBITO: Unidad de Cuidados Intensivos. PACIENTES: Pacientes con shock séptico y voluntarios sanos. Intervenciones: En el músculo braquioradial de todos los sujetos se realizaron mediciones NIRS (del inglés Near Infrared Spectroscopy) durante un test de oclusión vascular. Variables: Valores rSO2 basal, mínimo y máximo, pendiente de desoxigenación, pendiente de reoxigenación y valor delta. Resultados: Los pacientes con shock séptico (n = 35) presentaron unos valores basales de rSO2 más bajos (63,8 ± 12,2 frente a 69,3 ± 3,3%; p< 0,05), una pendiente de desoxigenación y reoxigenación más lenta (-0,54 ± 0,31 frente a -0,91 ± 0,35 %/s, p = 0,001; 2,67 ± 2,17 frente a 9,46 ± 3,5%/s, p < 0,001) y un delta menor (3,25±5,71 frente a 15,1 ± 3,9%; p < 0,001) en comparación con los sujetos sanos (n = 20). De los pacientes con shock séptico, los no supervivientes presentaron unos valores basales de rSO2 más bajos (57,0 ± 9,6 frente a 69,8 ± 11,3%; p = 0,001), de rSO2 mínimo y máximo igualmente inferiores (36,0 ± 12,8 frente a 51,3 ± 14,8%; p < 0,01; 60,6 ± 10,6 frente a 73,3 ± 11,2%; p < 0,01). El rSO2 basal fue un buen factor predictivo de mortalidad (AUC 0,79; IC del 95%: 0,63-0,94; p < 0,01). Los parámetros dinámicos obtenidos mediante la prueba de oclusión vascular no mejoraron los resultados. Conclusión: Los pacientes con shock séptico presentan una alteración importante de la microcirculación que se puede evaluar mediante la espectroscopia cercana al infrarrojo con implicaciones pronósticas. La monitorización de la reactividad microvascular en el músculo braquiorradial mediante el test de oclusión vascular con nuestro dispositivo no parece mejorar el valor pronóstico de la rSO2 basal

Prognostic value of brachioradialis muscle oxygen saturation index and vascular occlusion test in septic shock patients.

OBJECTIVES: To compare rSO2 (muscle oxygen saturation index) static and dynamic variables obtained by NIRS (Near Infrared Spectroscopy) in brachioradialis muscle of septic shock patients and its prognostic implications. DESIGN: Prospective and observational study. SETTING: Intensive care unit. SUBJECTS: Septic shock patients and healthy volunteers. INTERVENTIONS: The probe of a NIRS device (INVOS 5100) was placed on the brachioradialis muscle during a vascular occlusion test (VOT). VARIABLES: Baseline, minimum and maximum rSO2 values, deoxygenation rate (DeOx), reoxygenation slope (ReOx) and delta value. RESULTS: Septic shock patients (n=35) had lower baseline rSO2 (63.8±12.2 vs. 69.3±3.3%, p<0.05), slower DeOx (-0.54±0.31 vs. -0.91±0.35%/s, p=0.001), slower ReOx (2.67±2.17 vs. 9.46±3.5%/s, p<0.001) and lower delta (3.25±5.71 vs. 15.1±3.9%, p<0.001) when compared to healthy subjects (n=20). Among septic shock patients, non-survivors showed lower baseline rSO2 (57.0±9.6 vs. 69.8±11.3%, p=0.001), lower minimum rSO2 (36.0±12.8 vs. 51.3±14.8%, p<0.01) and lower maximum rSO2 values (60.6±10.6 vs. 73.3±11.2%, p<0.01). Baseline rSO2 was a good mortality predictor (AUC 0.79; 95%CI: 0.63-0.94, p<0.01). Dynamic parameters obtained with VOT did not improve the results. CONCLUSION: Septic shock patients present an important alteration of microcirculation that can be evaluated by NIRS with prognostic implications. Monitoring microvascular reactivity in the brachioradialis muscle using VOT with our device does not seem to improve the prognostic value of baseline rSO2.