Endothelial dysfunction is an early indicator of sepsis and neutrophil degranulation of septic shock in surgical patients

Background Stratification of the severity of infection is currently based on the Sequential Organ Failure Assessment (SOFA) score, which is difficult to calculate outside the ICU. Biomarkers could help to stratify the severity of infection in surgical patients. Methods Levels of ten biomarkers indic...

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Published in:	BJS open Vol. 4; no. 3; pp. 524 - 534
Main Authors:	Martin‐Fernandez, M., Vaquero‐Roncero, L. M., Almansa, R., Gómez‐Sánchez, E., Martín, S., Tamayo, E., Esteban‐Velasco, M. C., Ruiz‐Granado, P., Aragón, M., Calvo, D., Rico‐Feijoo, J., Ortega, A., Gómez‐Pesquera, E., Lorenzo‐López, M., López, J., Doncel, C., González‐Sanchez, C., Álvarez, D., Zarca, E., Ríos‐Llorente, A., Diaz‐Alvarez, A., Sanchez‐Barrado, E., Andaluz‐Ojeda, D., Calvo‐Vecino, J. M., Muñoz‐Bellvís, L., Gomez‐Herreras, J. I., Abad‐Molina, C., Bermejo‐Martin, J. F., Aldecoa, C., Heredia‐Rodríguez, M.
Format:	Journal Article
Language:	English
Published:	Chichester, UK John Wiley & Sons, Ltd 01-06-2020 Oxford University Press
Subjects:	Abdomen Biomarkers Blood & organ donations Emergency medical care Infections Lower GI Mortality Neutrophils Original Patients Sepsis Statistical analysis Surgery Vascular United States > US
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Summary:	Background Stratification of the severity of infection is currently based on the Sequential Organ Failure Assessment (SOFA) score, which is difficult to calculate outside the ICU. Biomarkers could help to stratify the severity of infection in surgical patients. Methods Levels of ten biomarkers indicating endothelial dysfunction, 22 indicating emergency granulopoiesis, and six denoting neutrophil degranulation were compared in three groups of patients in the first 12 h after diagnosis at three Spanish hospitals. Results There were 100 patients with infection, 95 with sepsis and 57 with septic shock. Seven biomarkers indicating endothelial dysfunction (mid‐regional proadrenomedullin (MR‐ProADM), syndecan 1, thrombomodulin, angiopoietin 2, endothelial cell‐specific molecule 1, vascular cell adhesion molecule 1 and E‐selectin) had stronger associations with sepsis than infection alone. MR‐ProADM had the highest odds ratio (OR) in multivariable analysis (OR 11·53, 95 per cent c.i. 4·15 to 32·08; P = 0·006) and the best area under the curve (AUC) for detecting sepsis (0·86, 95 per cent c.i. 0·80 to 0·91; P < 0·001). In a comparison of sepsis with septic shock, two biomarkers of neutrophil degranulation, proteinase 3 (OR 8·09, 1·34 to 48·91; P = 0·028) and lipocalin 2 (OR 6·62, 2·47 to 17·77; P = 0·002), had the strongest association with septic shock, but lipocalin 2 exhibited the highest AUC (0·81, 0·73 to 0·90; P < 0·001). Conclusion MR‐ProADM and lipocalin 2 could be alternatives to the SOFA score in the detection of sepsis and septic shock respectively in surgical patients with infection. Antecedentes La estratificación de la gravedad de una infección se basa actualmente en la puntuación SOFA (Sequential Organ Failure Assessment), que es difícil de calcular fuera de la unidad de cuidados intensivos. Los biomarcadores podrían ayudar a estratificar la gravedad de la infección en pacientes quirúrgicos. Métodos Se compararon las concentraciones de 10 biomarcadores que denotan disfunción endotelial, 22 que indican granulopoyesis de emergencia y 6 que expresan la degranulación de neutrófilos en tres grupos de pacientes de tres hospitales españoles (100 con infección, 95 con sepsis y 57 con shock séptico) en las primeras doce horas después del diagnóstico. Resultados Siete biomarcadores que expresan disfunción endotelial (proadrenomedulina, sindecan‐1, trombomodulina, angiopoyetina‐2, endocan‐1, molécula de adhesión endotelial 1 y E‐selectina) mostraron una fuerte asociación con la sepsis en comparación con la infección aislada. La proadrenomedulina presentó el valor más alto de la razón de oportunidades (odds ratio, OR) en el análisis multivariable (OR 11,53, i.c. del 95% 4,15‐32,08, P = 0,006) y la mejor área bajo la curva para detectar sepsis (AUC 0,86, i.c. del 95% 0,80‐0,91, P < 0,001). En la comparación entre sepsis y shock séptico, los biomarcadores que mostraron la asociación más estrecha con el shock séptico fueron dos biomarcadores de degranulación de neutrófilos (proteinasa‐3 y lipocalina‐2) (OR 8,09, i.c. del 9% 1,34‐48,91, P = 0,028; OR 6.62, i.c. del 95% 2,47‐17,77, P = 0,002), pero la lipocalina‐2 presentó la mejor AUC (0,81, i.c. del 95% 0,73‐0,90, P < 0,001). Conclusión la proadrenomedulina y la lipocalina‐2 podrían representar alternativas a la puntuación SOFA para detectar sepsis y shock séptico en pacientes quirúrgicos con infección. In surgical patients, endothelial dysfunction is an early indicator differentiating sepsis from simple infection, whereas neutrophil degranulation is an early indicator differentiating septic shock from sepsis. Mid‐regional proadrenomedullin and lipocalin 2 are the most representative biomarkers of sepsis and septic shock respectively. Useful biomarkers that merit validation elsewhere.
Bibliography:	Funding information Instituto de Salud Carlos III, PI15/01959, PI15/01451, PI16/01156 Consejería de Educación de Castilla y León/Fondo social Europeo European Union (Fondo Europeo de Desarrollo Regional, Una manera de hacer Europa) ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2474-9842 2474-9842
DOI:	10.1002/bjs5.50265