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.

Prognostic value of the biomarkers procalcitonin, interleukin-6 and C-reactive protein in severe sepsis.

AIM: To determine the prognostic value of the biomarkers procalcitonin, interlukin-6 and C-reactive protein in septic patients. DESIGN: A cohort of 81 septic patients. SETTING: Critical Care Unit. Dr. Peset Hospital. Valencia (Spain). PATIENTS: Divided according to sepsis classification (sepsis, severe sepsis and septic shock), source and two different groups (medical and postsurgical). VARIABLES ANALYZED: Quantitative (procalcitonin, interleukin-6, C-reactive protein, lactate, age, Apache II and SOFA scores upon admission and after 3 and 7 days). Qualitative (ICU mortality, multiorgan failure development and sex). STATISTICAL ANALYSIS: Mann-Whitney U-test for the comparison of quantitative variables, χ² test for qualitative variables. Multivariate analysis with mortality and multiorgan failure as dependent variables and the described quantitative parameters as independent variables. ROC curves of the variables found to be significant in the multivariate analysis. RESULTS: Septic shock patients showed greater mortality and more frequent multiorgan failure. Comparison of survivors versus deceased patients showed significant differences in Apache II score, interleukin-6 and lactate (p<0.001) upon admission and after 3 and 7 days. Similar findings applied to the comparison of patients with and without multiorgan failure, and on the same days. Procalcitonin only showed differences on days 3 and 7 (p=0.001). In the multivariate analysis with mortality as dependent variable, interleukin-6 proved significant on day 3 (OR 2.6). With multiorgan failure as dependent variable, only the SOFA score showed significance (OR 2.3). The Apache II and interleukin-6 ROC curves corresponding to day 3 showed areas of 0.80 and 0.86, respectively. CONCLUSIONS: 1) Interleukin-6 is an inflammatory biomarker with mortality prognostic value. 2) None of the biomarkers proved predictive of multiorgan failure.

Valor pronóstico de los biomarcadores procalcitonina, interleukina 6 y proteína C reactiva en la sepsis grave / Prognostic value of the biomarkers procalcitonin, interleukin-6 and C-reactive protein in severe sepsis

Objetivo: Comprobar el valor pronóstico de los biomarcadores procalcitonina, interleukina 6 y proteína C reactiva en pacientes sépticos graves Diseño: Cohorte de 81 pacientes críticos Ambito: Unidad de Críticos Hospital Dr. Peset. Valencia. Pacientes: Divididos según el grado de sepsis (sepsis, sepsis severa, shock séptico), foco de sepsis y grupo (pacientes médicos y posquirúrgicos de alto riesgo). Variables analizadas: Cuantitativas (procalcitonina, interleukina-6, proteína C reactiva, lactato, edad, Apache II y SOFA) al ingreso, 3.er y 7.o día de evolución. Cualitativas (mortalidad intra UCI, desarrollo Fallo Multiorgánico y sexo). Estadística: comparación variables cuantitativas con test U de Mann-Whitney; las cualitativas con test de χ2; análisis multivariante variables dependientes mortalidad y fallo multiorgánico e independientes las cuantitativas descritas; curvas ROC de las variables significativas en el multivariante Resultados: Pacientes con shock séptico fallecieron más y desarrollaron más fallo multiorgánico. Comparación entre vivos y fallecidos, mostró diferencias significativas Apache II, interleukina-6 y lactato (p <0,001) al ingreso, 3.er y 7.o día. Entre pacientes con fallo multiorgánico y sin él, también y los mismos días. La procalcitonina mostró diferencias solo en 3.er y 7.o día (p=0,001). Análisis multivariante con variable dependiente mortalidad la interleukina-6 mostró significación al 3.er día (O.R. 2,6). Con variable dependiente fallo multiorgánico solo SOFA tuvo significación (O.R. 2,3). Curva ROC Apache II e interleukina-6 3.er día mostró área 0,80 y 0,86 respectivamente. Conclusiones: 1) La interleukina-6 es un biomarcador inflamatorio con valor pronóstico de mortalidad; 2) Ningún biomarcador tuvo valor predictivo de fallo multiorgánico (AU)

Aim: To determine the prognostic value of the biomarkers procalcitonin, interlukin-6 and C-reactive protein in septic patients. Design: A cohort of 81 septic patients. Setting: Critical Care Unit. Dr. Peset Hospital. Valencia (Spain). Patients: Divided according to sepsis classification (sepsis, severe sepsis and septic shock), source and two different groups (medical and postsurgical). Variables analyzed: Quantitative (procalcitonin, interleukin-6, C-reactive protein, lactate, age, Apache II and SOFA scores upon admission and after 3 and 7 days). Qualitative (ICU mortality, multiorgan failure development and sex). Statistical analysis: Mann-Whitney U-test for the comparison of quantitative variables, X2 test for qualitative variables. Multivariate analysis with mortality and multiorgan failure as dependent variables and the described quantitative parameters as independent variables. ROC curves of the variables found to be significant in the multivariate analysis. Results: Septic shock patients showed greater mortality and more frequent multiorgan failure. Comparison of survivors versus deceased patients showed significant differences in Apache II score, interleukin-6 and lactate (p<0.001) upon admission and after 3 and 7 days. Similar findings applied to the comparison of patients with and without multiorgan failure, and on the same days. Procalcitonin only showed differences on days 3 and 7 (p=0.001). In the multivariate analysis with mortality as dependent variable, interleukin-6 proved significant on day 3 (OR 2.6). With multiorgan failure as dependent variable, only the SOFA score showed significance (OR 2.3). The Apache II and interleukin-6 ROC curves corresponding to day 3 showed areas of 0.80 and 0.86, respectively. Conclusions: 1) Interleukin-6 is an inflammatory biomarker with mortality prognostic value. 2) None of the biomarkers proved predictive of multiorgan failure (AU)

[Prevalence and prognosis significance of euthyroid sick syndrome in critical illness]. / Prevalencia y significación pronóstica del síndrome del enfermo eutiroideo en patología crítica.

The prevalence and prognosis of the sick euthyroid syndrome (SES) was studied in 91 patients admitted to the ICU by determining free thyroid hormones (FT3 and FT4), T3 reverse (rT3) and thyrotropin (TSH). The prevalence of SES was lower than expected, type I being higher that type II. The acute coronary syndrome had a lower prevalence of SES than other clinical conditions. Patients who developed type II SES had a higher mortality rate.

Prevalencia y significación pronóstica del síndrome del enfermo eutiroideo en patología crítica / Prevalence and prognostic meaning of euthyroid sick syndrome in critical diseases

Hemos estudiado la prevalencia y significación pronóstica del síndrome del enfermo eutiroideo (SEE) en 91 pacientes ingresados en la Unidad de Cuidados Intensivos (UCI) mediante la determinación de hormonas tiroideas libres (FT3 y FT4), T3 inversa (rT3) y hormona tiroestimulante (TSH). La prevalencia del SEE es menor de la esperada, siendo la del SEE tipo I mayor que la del tipo II. La cardiopatía isquémica aguda presenta menor prevalencia de SEE que el resto de patologías estudiadas. Los pacientes críticos que desarrollan el tipo II presentan mayor mortalidad (AU)