A differential therapeutic consideration for use of corticosteroids according to established COVID-19 clinical phenotypes in critically ill patients / Una consideración terapéutica diferencial para el uso de corticoesteroides en COVID-19 según los diferentes fenotipos clínicos establecidos en pacientes críticos

bjective 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 (AU)

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 (AU)

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 / Impacto del aislamiento de Aspergillus spp. en las primeras 24h de ingreso en pacientes críticos con neumonía grave por el virus influenza

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 (AU)

Objetivo Determinar la incidencia y el impacto sobre la mortalidad del aislamiento de Aspergillus spp. (AI) en paciente críticos con neumonía por influenza en las primeras 24h de ingreso. Diseño Análisis secundario de estudio de cohortes observacional y prospectivo. Ámbito Unidades de cuidados intensivos (UCI) participantes de forma voluntaria en el registro español de neumonía por influenza grave, desde junio de 2009 hasta junio de 2019. Pacientes Pacientes consecutivos con diagnóstico de neumonía grave por influenza, confirmado por prueba de reacción en cadena de la polimerasa. Intervenciones Ninguna. Variables principales Incidencia de AI. Variables demográficas, comorbilidades, necesidad de ventilación mecánica y presencia de shock al ingreso. APACHE II. Resultados Se analizaron 3.702 pacientes. La incidencia de AI fue del 1,13% (n=42). Las neoplasias hematológicas (OR: 4,39; IC 95%: 1,92-10,04); VIH (OR: 3,83; IC 95%: 1,08-13,63) y otras situaciones de inmunosupresión (OR: 4,87; IC 95%: 1,99-11,87) fueron variables que se asociaron de forma independiente con AI. El árbol de decisión de CHAID mostró que la variable neoplasias hematológicas era la más relacionada con la variable Aspergillus spp. con una incidencia del 3,3%. Neoplasias hematológicas (OR: 2,62; IC 95%: 1,95-3,51), inmunosupresión (OR: 2,05; IC 95%: 1,46-2,88) y AI (OR: 3,24; IC 95%: 1,60-6,53) se asociaron de forma independiente con mayor mortalidad en la UCI. Conclusiones El tratamiento antifúngico empírico en nuestra población estaría justificado en los pacientes con inmunosupresión. En los pacientes con riesgo moderado-grave, la búsqueda activa de Aspergillus spp. debería implementarse (AU)

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.

Severe infection due to the SARS-CoV-2 coronavirus: Experience of a tertiary hospital with COVID-19 patients during the 2020 pandemic. / Infección grave por coronavirus SARS-CoV-2: experiencia en un hospital de tercer nivel con pacientes afectados por COVID-19 durante la pandemia 2020.

OBJECTIVE: To describe the clinical and respiratory characteristics of a cohort of 43 patients with COVID-19 after an evolutive period of 28 days. DESIGN: A prospective, single-center observational study was carried out. SETTING: Intensive care. PATIENTS: Patients admitted due to COVID-19 and respiratory failure. INTERVENTIONS: None. VARIABLES: Automatic recording was made of demographic variables, severity parameters, laboratory data, assisted ventilation (HFO: high-flow oxygen therapy and IMV: invasive mechanical ventilation), oxygenation (PaO2, PaO2/FiO2) and complications. The patients were divided into three groups: survivors (G1), deceased (G2) and patients remaining under admission (G3). The chi-squared test or Fisher exact test (categorical variables) was used, along with the Mann-Whitney U-test or Wilcoxon test for analyzing the differences between medians. Statistical significance was considered for p<0.05. RESULTS: A total of 43 patients were included (G1=28 [65.1%]; G2=10 [23.3%] and G3=5 [11.6%]), with a mean age of 65 years (range: 52-72), 62% males, APACHE II 18 (15-24), SOFA 6 (4-7). Arterial hypertension (30.2%) and obesity (25.6%) were the most frequent comorbidities. High-flow oxygen therapy was used in 62.7% of the patients, with failure in 85%. In turn, 95% of the patients required IMV and 85% received ventilation in prone decubitus. In the general population, initial PaO2/FiO2 improved after 7 days (165 [125-210] vs.194 [153-285]; p=0.02), in the same way as in G1 (164 [125-197] vs. 207 [160-294]; p=0.07), but not in G2 (163 [95-197] vs. 135 [85-177]). No bacterial coinfection was observed. The incidence of IMV-associated pneumonia was high (13 episodes/1000 days of IMV). CONCLUSIONS: Patients with COVID-19 require early IMV, a high frequency of ventilation in prone decubitus, and have a high incidence of failed HFO. The lack of improvement of PaO2/FiO2 at 7 days could be a prognostic marker. .

Grado de adherencia al tratamiento antivírico recomendado durante la pandemia y periodo pospandémico de gripe A (H1N1) pdm09 en 148 unidades de cuidados intensivos españolas / Degree of adherence to recommended antiviral treatment during the pandemic and post-pandemic periods of influenza A (H1N1) pdm09 in 148 intensive care units in Spain

OBJETIVO: Evaluar el grado de adherencia a las recomendaciones sobre el tratamiento antivírico y su impacto en la mortalidad de pacientes críticos afectados por gripe A (H1N1) pdm09. DISEÑO: Análisis secundario de estudio prospectivo. ÁMBITO: Medicina intensiva (UCI). PACIENTES: Pacientes con gripe A (H1N1) pdm09 en el periodo pandémico 2009 y pospandémico 2010-11. Variables La adherencia a las recomendaciones se clasificó en: total (AT), parcial dosis (PD), parcial tiempo (PT) y no adherencia (NA). La neumonía vírica, obesidad y ventilación mecánica fueron considerados criterios de gravedad para el uso de dosificaciones elevadas de antivírico (CG). Análisis mediante «chi» cuadrado y t-test. Supervivencia mediante regresión de Cox. RESULTADOS: Se incluyeron 1.058 pacientes, 661(62,5%) en pandemia y 397 (37,5%) en pospandemia. La AT global del estudio fue del 41,6% (el 43,9% y el 38%, respectivamente; p = 0,07). Los pacientes con criterios de gravedad no fueron diferentes en ambos periodos (un 68,5% y un 62,8%; p = 0,06). En estos pacientes la AT fue del 54,7% durante el 2009 y del 36,4% en pospandemia (p < 0,01). La NA (19,7% vs. 11,3%; p < 0,05) y la PT (20,8% vs. 9,9%; p < 0,01) fueron más frecuentes durante la pospandemia. La mortalidad fue mayor en la pospandemia (30% vs. 21,8%; p < 0,001). El APACHE II(HR = 1,09) y la enfermedad hematológica (HR = 2,2) se asociaron a mortalidad y la adherencia (HR = 0,47) fue un factor protector. CONCLUSIONES: Se evidencia un bajo grado de adherencia al tratamiento en ambos periodos. La adherencia al tratamiento antivírico se asocia con menor mortalidad y debería ser recomendada en pacientes críticos afectados por gripe A (H1N1) pdm09

OBJECTIVE: To determine the degree of antiviral treatment recommendations adherence and its impact to critical ill patients affected by influenza A (H1N1) pdm09 mortality. DESIGN: Secondary analysis of prospective study. SETTING: Intensive care (UCI). PATIENTS: Patients with influenza A(H1N1)pdm09 in the 2009 pandemic and 2010-11 post-Pandemic periods. Variables Adherence to recommendations was classified as: Total (AT); partial in doses (PD); partial in time (PT), and non-adherence (NA). Viral pneumonia, obesity and mechanical ventilation were considered severity criteria for the administration of high antiviral dose. The analysis was performed using t-test or «chi» square. Survival analysis was performed and adjusted by Cox regression analysis. RESULTS: A total of 1,058 patients, 661 (62.5%) included in the pandemic and 397 (37.5%) in post-pandemic period respectively. Global adherence was achieved in 41.6% (43.9% and 38.0%; P = .07 respectively). Severity criteria were similar in both periods (68.5% vs. 62.8%; P = .06). The AT was 54.7% in pandemic and 36.4% in post-pandemic period respectively (P <.01). The NA (19.7% vs. 11.3%; P <.05) and PT (20.8% vs. 9.9%, P < .01) was more frequent in the post-pandemic period. The mortality rate was higher in the post-pandemic period (30% vs. 21.8%, P <.001). APACHE II (HR=1.09) and hematologic disease (HR = 2.2) were associated with a higher mortality and adherence (HR=0.47) was a protective factor. CONCLUSIONS: A low degree of adherence to the antiviral treatment was observed in both periods. Adherence to antiviral treatment recommendations was associated with lower mortality rates and should be recommended in critically ill patients with suspected influenza A(H1N1)pdm09

Regional oxygen saturation index (rSO2) in brachioradialis and deltoid muscle. Correlation and prognosis in patients with respiratory sepsis

Objective. To compare oxygen saturation index (rSO2) obtained simultaneously in two different brachial muscles. Design. Prospective and observational study. Setting. Intensive care unit. Patients. Critically ill patients with community-acquired pneumonia. Interventions. Two probes of NIRS device (INVOS 5100) were simultaneously placed on the brachioradialis (BR) and deltoid (D) muscles. Variables. rSO2 measurements were recorded at baseline (ICU admission) and at 24h. Demographic and clinical variables were registered. Pearson's correlation coefficient was used to assess the association between continuous variables. The consistency of the correlation was assessed using the intraclass correlation coefficient (ICC) and Bland–Altman plot. The predictive value of the rSO2 for mortality was calculated by ROC curve. Results. Nineteen patients were included with an ICU mortality of 21.1%. The rSO2 values at baseline and at 24h were significantly higher in D than in BR muscle. Values obtained simultaneously in both limbs showed a strong correlation and adequate consistency: BR (r=0.95; p<0.001; ICC=0.94; 95% CI: 0.90–0.96; p<0.001), D (r=0.88; p=0.01; ICC=0.88; 95% CI: 0.80–0.90; p>0.001) but a wide limit of agreement. Non-survivors had rSO2 values significantly lower than survivors at all times of the study. No patient with rSO2 >60% in BR died, and only 17.6% died with an rSO2 value >60% in D. Both muscles showed consistent discriminatory power for mortality. Conclusion. Both BR and D muscles were appropriate for measuring rSO2 (AU)

Objetivo. Comparar el índice de saturación tisular de oxígeno (rSO2) medido de forma simultánea en 2 diferentes músculos braquiales. Diseño. Estudio prospectivo, observacional. Ámbito. Servicio de Medicina Intensiva. Pacientes. Críticos con neumonía comunitaria. Intervenciones. Dos sensores con tecnología NIRS (INVOS™ 5100) fueron ubicados de forma simultánea en los músculos braquiorradial (BR) y deltoides (D). Variables. Las mediciones del rSO2 se efectuaron al ingreso (basal) y a las 24h. Se registraron los datos demográficos y clínicos. La correlación de Pearson se utilizó para estudiar la asociación entre variables continuas. La concordancia de la correlación fue valorada mediante el coeficiente de correlación intraclase (ICC) y el análisis de Bland-Altman. El valor predictivo de rSO2 para mortalidad fue calculado mediante curva ROC. Resultados. Se incluyeron 19 pacientes con una mortalidad de 21,1%. El valor basal y a las 24h de rSO2 fue significativamente mayor en D respecto del BR. Los valores obtenidos de forma simultánea en ambos miembros evidenciaron una buena correlación y una adecuada concordancia: BR (r=0,95; p<0,001. ICC=0,94; IC 95%: 0,90-0,96; p<0,001), D (r=0,88; p=0,01. ICC=0,88; IC 95%: 0,80-0,90; p<0,001), así como un amplio rango de concordancia. Los fallecidos presentaron valores de rSO2 significativamente menores que los supervivientes en todos los momentos del estudio. Ningún paciente con rSO2>60% en BR falleció, y solo el 17,6% fallecieron con un rSO2>60% en D. Ambos músculos evidenciaron un buen poder de discriminación para mortalidad. Conclusiones. Tanto el músculo BR como el D fueron apropiados para la medición del rSO2 (AU)

Regional oxygen saturation index (rSO2) in brachioradialis and deltoid muscle. Correlation and prognosis in patients with respiratory sepsis.

OBJECTIVE: To compare oxygen saturation index (rSO2) obtained simultaneously in two different brachial muscles. DESIGN: Prospective and observational study. SETTING: Intensive care unit. PATIENTS: Critically ill patients with community-acquired pneumonia. INTERVENTIONS: Two probes of NIRS device (INVOS 5100) were simultaneously placed on the brachioradialis (BR) and deltoid (D) muscles. VARIABLES: rSO2 measurements were recorded at baseline (ICU admission) and at 24h. Demographic and clinical variables were registered. Pearson's correlation coefficient was used to assess the association between continuous variables. The consistency of the correlation was assessed using the intraclass correlation coefficient (ICC) and Bland-Altman plot. The predictive value of the rSO2 for mortality was calculated by ROC curve. RESULTS: Nineteen patients were included with an ICU mortality of 21.1%. The rSO2 values at baseline and at 24h were significantly higher in D than in BR muscle. Values obtained simultaneously in both limbs showed a strong correlation and adequate consistency: BR (r=0.95; p<0.001; ICC=0.94; 95% CI: 0.90-0.96; p<0.001), D (r=0.88; p=0.01; ICC=0.88; 95% CI: 0.80-0.90; p>0.001) but a wide limit of agreement. Non-survivors had rSO2 values significantly lower than survivors at all times of the study. No patient with rSO2 >60% in BR died, and only 17.6% died with an rSO2 value >60% in D. Both muscles showed consistent discriminatory power for mortality. CONCLUSION: Both BR and D muscles were appropriate for measuring rSO2.

Degree of adherence to recommended antiviral treatment during the pandemic and post-pandemic periods of influenza A(H1N1)pdm09 in 148 intensive care units in Spain.

OBJECTIVE: To determine the degree of antiviral treatment recommendations adherence and its impact to critical ill patients affected by influenza A(H1N1)pdm09 mortality. DESIGN: Secondary analysis of prospective study. SETTING: Intensive care (UCI). PATIENTS: Patients with influenza A(H1N1)pdm09 in the 2009 pandemic and 2010-11 post-Pandemic periods. VARIABLES: Adherence to recommendations was classified as: Total (AT); partial in doses (PD); partial in time (PT), and non-adherence (NA). Viral pneumonia, obesity and mechanical ventilation were considered severity criteria for the administration of high antiviral dose. The analysis was performed using t-test or «chi¼ square. Survival analysis was performed and adjusted by Cox regression analysis. RESULTS: A total of 1,058 patients, 661 (62.5%) included in the pandemic and 397 (37.5%) in post-pandemic period respectively. Global adherence was achieved in 41.6% (43.9% and 38.0%; P=.07 respectively). Severity criteria were similar in both periods (68.5% vs. 62.8%; P=.06). The AT was 54.7% in pandemic and 36.4% in post-pandemic period respectively (P<.01). The NA (19.7% vs. 11.3%; P<.05) and PT (20.8% vs. 9.9%, P<.01) was more frequent in the post-pandemic period. The mortality rate was higher in the post-pandemic period (30% vs. 21.8%, P<.001). APACHE II (HR=1.09) and hematologic disease (HR=2.2) were associated with a higher mortality and adherence (HR=0.47) was a protective factor. CONCLUSIONS: A low degree of adherence to the antiviral treatment was observed in both periods. Adherence to antiviral treatment recommendations was associated with lower mortality rates and should be recommended in critically ill patients with suspected influenza A(H1N1)pdm09.

Oxidative stress in immunocompetent patients with severe community-acquired pneumonia. A pilot study

OBJECTIVE: A comparison was made of the oxidative stress (OS) levels of patients with either viral or bacterial severe community-acquired pneumonia (sCAP) and of patients without infection (healthy volunteers (HV) and patients with acute myocardial infarction (AMI)). DESIGN: A prospective observational study was made. PATIENTS: Critically ill patients with sCAP. VARIABLES: The TBARS level was measured as an index of oxidative injury. SOD, CAT and redox glutathione system (GSH, GSSG, GR, GPx) activities were measured as reflecting antioxidant capacity. Severity of illness was assessed by the APACHE II, SOFA and SIRS scores. RESULTS: Thirty-seven subjects were included: 15 patients with CAP (12 of bacterial origin [BCAP] and 3 due to 2009 A/H1N1 virus [VCAP]), 10 HV and 12 AMI patients. Intensive care CAP mortality was 26.7% (n = 4). Plasmatic TBARS levels were higher in CAP patients than in HV, but similar to those recorded in AMI patients. In contrast, VCAP was associated with lower TBARS levels, and some components of the glutathione redox system were higher in BCAP patients and HV. The OS levels did not differ between survivors and non-survivors. CONCLUSION: Our results suggest the occurrence of higher OS in sCAP patients compared with HV. In contrast, lower TBARS levels were observed in VCAP patients, suggesting an increase of antioxidant activity related to the redox glutathione system. However, further research involving a larger cohort is needed in order to confirm these findings

OBJETIVOS: Comparar el estrés oxidativo (EO) en pacientes con neumonía comunitaria grave (NCG) según su etiología y respecto de voluntarios sanos (VS) y pacientes con infarto agudo de miocardio (IAM). DISEÑO: Estudio prospectivo, observacional. PACIENTES: Pacientes con NCG ingresados en unidades de cuidados intensivos. Variables Los niveles de lipoperoxidación (TBARS) fueron considerados como índice de oxidación, mientras que SOD, CAT y la actividad del sistema redox- glutation (GSH, GSSG, GR, GPx) fueron considerados capacidad antioxidante. La gravedad de los pacientes fue valorada mediante las escalas APACHE II, SOFA y SIRS. RESULTADOS: Treinta y siete sujetos fueron incluidos, 15 pacientes con NCG (12 con etiología bacteriana [NB] y 3 viral 2009 A/H1N1 [NV]), 10 VS y 12 con IAM. La mortalidad global fue del 26,7% (n = 4). Los TBARS plasmáticos fueron superiores en NCG respecto de VS, pero similares al IAM. En contraste, la NV se asoció con menores niveles de TBARS e incremento de componentes del sistema redox-glutation respecto de NB y voluntarios sanos. No se observó asociación entre mortalidad y EO. CONCLUSIÓN: Nuestros resultados evidencian la presencia de EO en pacientes con NCG respecto de los controles. En contraste, la evidencia de un menor nivel de TBARS en la NV respecto de los VS sugiere un incremento de la actividad antioxidante relacionada con el sistema redox-glutation. Sin embargo, son necesarias nuevas investigaciones para confirmar estos hallazgos

Oxidative stress in immunocompetent patients with severe community-acquired pneumonia. A pilot study.

OBJECTIVE: A comparison was made of the oxidative stress (OS) levels of patients with either viral or bacterial severe community-acquired pneumonia (sCAP) and of patients without infection (healthy volunteers (HV) and patients with acute myocardial infarction (AMI)). DESIGN: A prospective observational study was made. PATIENTS: Critically ill patients with sCAP. VARIABLES: The TBARS level was measured as an index of oxidative injury. SOD, CAT and redox glutathione system (GSH, GSSG, GR, GPx) activities were measured as reflecting antioxidant capacity. Severity of illness was assessed by the APACHE II, SOFA and SIRS scores. RESULTS: Thirty-seven subjects were included: 15 patients with CAP (12 of bacterial origin [BCAP] and 3 due to 2009 A/H1N1 virus [VCAP]), 10 HV and 12 AMI patients. Intensive care CAP mortality was 26.7% (n=4). Plasmatic TBARS levels were higher in CAP patients than in HV, but similar to those recorded in AMI patients. In contrast, VCAP was associated with lower TBARS levels, and some components of the glutathione redox system were higher in BCAP patients and HV. The OS levels did not differ between survivors and non-survivors. CONCLUSION: Our results suggest the occurrence of higher OS in sCAP patients compared with HV. In contrast, lower TBARS levels were observed in VCAP patients, suggesting an increase of antioxidant activity related to the redox glutathione system. However, further research involving a larger cohort is needed in order to confirm these findings.

[Recommendations of the Infectious Diseases Work Group (GTEI) of the Spanish Society of Intensive and Critical Care Medicine and Coronary Units (SEMICYUC) and the Infections in Critically Ill Patients Study Group (GEIPC) of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) for the diagnosis and treatment of influenza A/H1N1 in seriously ill adults admitted to the Intensive Care Unit]. / Recomendaciones del Grupo de Trabajo Enfermedades Infecciosas (GTEI) de la Sociedad Española de Medicina Intensiva, Crítica y Unidades Coronarias (SEMICYUC) y el Grupo de Estudio de Infecciones en el Paciente Crítico (GEIPC) de la Sociedad Española de Enfermedades Infecciosas y Microbiología clínica (SEIMC) para el diagnóstico y tratamiento de la gripe A/H1N1 en pacientes adultos graves hospitalizados en las Unidades de Cuidados Intensivos.

The diagnosis of influenza A/H1N1 is mainly clinical, particularly during peak or seasonal flu outbreaks. A diagnostic test should be performed in all patients with fever and flu symptoms that require hospitalization. The respiratory sample (nasal or pharyngeal exudate or deeper sample in intubated patients) should be obtained as soon as possible, with the immediate start of empirical antiviral treatment. Molecular methods based on nucleic acid amplification techniques (RT-PCR) are the gold standard for the diagnosis of influenza A/H1N1. Immunochromatographic methods have low sensitivity; a negative result therefore does not rule out active infection. Classical culture is slow and has low sensitivity. Direct immunofluorescence offers a sensitivity of 90%, but requires a sample of high quality. Indirect methods for detecting antibodies are only of epidemiological interest. Patients with A/H1N1 flu may have relative leukopenia and elevated serum levels of LDH, CPK and CRP, but none of these variables are independently associated to the prognosis. However, plasma LDH> 1500 IU/L, and the presence of thrombocytopenia <150 x 10(9)/L, could define a patient population at risk of suffering serious complications. Antiviral administration (oseltamivir) should start early (<48 h from the onset of symptoms), with a dose of 75 mg every 12h, and with a duration of at least 7 days or until clinical improvement is observed. Early antiviral administration is associated to improved survival in critically ill patients. New antiviral drugs, especially those formulated for intravenous administration, may be the best choice in future epidemics. Patients with a high suspicion of influenza A/H1N1 infection must continue with antiviral treatment, regardless of the negative results of initial tests, unless an alternative diagnosis can be established or clinical criteria suggest a low probability of influenza. In patients with influenza A/H1N1 pneumonia, empirical antibiotic therapy should be provided due to the possibility of bacterial coinfection. A beta-lactam plus a macrolide should be administered as soon as possible. The microbiological findings and clinical or laboratory test variables may decide withdrawal or not of antibiotic treatment. Pneumococcal vaccination is recommended as a preventive measure in the population at risk of suffering severe complications. Although the use of moderate- or low-dose corticosteroids has been proposed for the treatment of influenza A/H1N1 pneumonia, the existing scientific evidence is not sufficient to recommend the use of corticosteroids in these patients. The treatment of acute respiratory distress syndrome in patients with influenza A/H1N1 must be based on the use of a protective ventilatory strategy (tidal volume <10 ml / kg and plateau pressure <35 mmHg) and positive end-expiratory pressure set to high patient lung mechanics, combined with the use of prone ventilation, muscle relaxation and recruitment maneuvers. Noninvasive mechanical ventilation cannot be considered a technique of choice in patients with acute respiratory distress syndrome, though it may be useful in experienced centers and in cases of respiratory failure associated with chronic obstructive pulmonary disease exacerbation or heart failure. Extracorporeal membrane oxygenation is a rescue technique in refractory acute respiratory distress syndrome due to influenza A/H1N1 infection. The scientific evidence is weak, however, and extracorporeal membrane oxygenation is not the technique of choice. Extracorporeal membrane oxygenation will be advisable if all other options have failed to improve oxygenation. The centralization of extracorporeal membrane oxygenation in referral hospitals is recommended. Clinical findings show 50-60% survival rates in patients treated with this technique. Cardiovascular complications of influenza A/H1N1 are common. Such problems may appear due to the deterioration of pre-existing cardiomyopathy, myocarditis, ischemic heart disease and right ventricular dysfunction. Early diagnosis and adequate monitoring allow the start of effective treatment, and in severe cases help decide the use of circulatory support systems. Influenza vaccination is recommended for all patients at risk. This indication in turn could be extended to all subjects over 6 months of age, unless contraindicated. Children should receive two doses (one per month). Immunocompromised patients and the population at risk should receive one dose and another dose annually. The frequency of adverse effects of the vaccine against A/H1N1 flu is similar to that of seasonal flu. Chemoprophylaxis must always be considered a supplement to vaccination, and is indicated in people at high risk of complications, as well in healthcare personnel who have been exposed.