Abstract
Objectives
The diagnosis of sepsis in the Emergency Department (ED) is challenging and a reliable biomarker is needed. The current study aimed to evaluate the diagnostic accuracy of monocyte distribution width (MDW) for the early identification of sepsis in the ED.
Methods
We performed a large observational study including consecutive adult patients (≥18 years of age) presenting to the ED between September and November 2019, with an order for complete blood count (CBC) evaluation. A total of 2,215 patients were enrolled and classified based on Sepsis-2 criteria as the control group (1,855), infection group (172), Systemic Inflammatory Response Syndrome (SIRS) group (100), and sepsis group (88).
Results
MDW levels were higher in patients with sepsis than in all other groups (p<0.001). ROC curve analysis showed an optimal diagnostic accuracy of MDW for sepsis prediction at a cut-off point of 23.5, with an AUC of 0.964, sensitivity and specificity of 0.920 and 0.929, respectively.
Conclusions
Our findings encourage further investigation to validate the use of MDW as a screening tool for the early identification of patients at risk of sepsis in the ED.
Acknowledgments
Beckman Coulter provided the reagents for MDW measurement.
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Research funding: None declared.
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Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
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Competing interests: Authors state no conflict of interest.
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Ethical approval: The study protocol was approved by the Ethics Committee of the University Hospital of Palermo (nr 07/2019) and was performed in accordance with the current revision of the Helsinki Declaration.
References
1. Grande, E, Grippo, F, Frova, L, Pantosti, A, Pezzotti, P, Fedeli, U. The increase of sepsis-related mortality in Italy: a nationwide study, 2003-2015. Eur J Clin Microbiol Infect Dis 2019;38:1701–8. https://doi.org/10.1007/s10096-019-03601-3.10.1007/s10096-019-03601-3Search in Google Scholar PubMed
2. Rudd, KE, Johnson, SC, Agesa, KM, Shackelford, KA, Tsoi, D, Kievlan, DR, et al. Global, regional, and national sepsis incidence and mortality, 1990-2017: analysis for the Global Burden of Disease Study. Lancet 2020;395:200–11. https://doi.org/10.1016/S0140-6736(19)32989-7.10.1016/S0140-6736(19)32989-7Search in Google Scholar PubMed PubMed Central
3. McVeigh, SE. Sepsis management in the emergency department. Nurs Clin North Am 2020;55:71–9.10.1016/j.cnur.2019.10.009Search in Google Scholar PubMed
4. Liu, VX, Fielding-Singh, V, Greene, JD, Baker, JM, Iwashyna, TJ, Bhattacharya, J, et al. The timing of early antibiotics and hospital mortality in sepsis. Am J Respir Crit Care Med 2017;196:856–63. https://doi.org/10.1164/rccm.201609-1848OC.10.1164/rccm.201609-1848OCSearch in Google Scholar PubMed PubMed Central
5. Derlet, RW, Richards, JR. Overcrowding in the nation’s emergency departments: complex causes and disturbing effects. Ann Emerg Med 2000;35:63–8. https://doi.org/10.1016/s0196-0644(00)70105-3.10.1016/S0196-0644(00)70105-3Search in Google Scholar
6. Horwitz, LI, Green, J, Bradley, EH. US Emergency Department performance on wait time and length of visit. Ann Emerg Med 2010;55:133–41. https://doi.org/10.1016/j.annemergmed.2009.07.023.10.1016/j.annemergmed.2009.07.023Search in Google Scholar PubMed PubMed Central
7. Filbin, MR, Arias, SA, Camargo, CAJr, Barche, A, Pallin, DJ. Sepsis visits and antibiotic utilization in U.S. emergency departments*. Crit Care Med 2014;42:528–35. https://doi.org/10.1097/CCM.0000000000000037.10.1097/CCM.0000000000000037Search in Google Scholar PubMed
8. Singer, M, Deutschman, CS, Seymour, CW, Shankar-Hari, M, Annane, D, Bauer, M, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 2016;315:801–10. https://doi.org/10.1001/jama.2016.0287.10.1001/jama.2016.0287Search in Google Scholar PubMed PubMed Central
9. Askim, Å, Moser, F, Gustad, LT, Stene, H, Gundersen, M, Åsvold, BO, et al. Poor performance of quick-SOFA (qSOFA) score in predicting severe sepsis and mortality - a prospective study of patients admitted with infection to the emergency department. Scand J Trauma Resusc Emerg Med 2017;25:56. https://doi.org/10.1186/s13049-017-0399-4.10.1186/s13049-017-0399-4Search in Google Scholar PubMed PubMed Central
10. Jouffroy, R, Saade, A, Carpentier, A, Ellouze, S, Philippe, P, Idialisoa, R, et al. Triage of septic patients using qSOFA criteria at the SAMU regulation: a retrospective analysis. Prehosp Emerg Care 2018;22:84–90. https://doi.org/10.1080/10903127.2017.1347733.10.1080/10903127.2017.1347733Search in Google Scholar PubMed
11. Churpek, MM, Snyder, A, Han, X, Sokol, S, Pettit, N, Howell, MD, et al. Quick sepsis-related organ failure assessment, systemic inflammatory response syndrome, and early warning scores for detecting clinical deterioration in infected patients outside the Intensive Care Unit. Am J Respir Crit Care Med 2017;195:906–11. https://doi.org/10.1164/rccm.201604-0854OC.10.1164/rccm.201604-0854OCSearch in Google Scholar PubMed PubMed Central
12. Williams, JM, Greenslade, JH, McKenzie, JV, Chu, K, Brown, AFT, Lipman, J. Systemic inflammatory response syndrome, quick sequential organ function assessment, and organ dysfunction: insights from a prospective database of ED patients with infection. Chest 2017;151:586–96. https://doi.org/10.1016/j.chest.2016.10.057.10.1016/j.chest.2016.10.057Search in Google Scholar PubMed
13. Lippi, G, Panteghini, M, Bernardini, S, Bonfanti, L, Carraro, P, Casagranda, I, et al. Laboratory testing in the emergency department: an Italian Society of Clinical Biochemistry and Clinical Molecular Biology (SIBioC) and Academy of Emergency Medicine and Care (AcEMC) consensus report. Clin Chem Lab Med 2018;56:1655–9. https://doi.org/10.1515/cclm-2017-0077.10.1515/cclm-2017-0077Search in Google Scholar PubMed
14. Bellia, C, Agnello, L, Lo Sasso, B, Bivona, G, Raineri, MS, Giarratano, A, et al. Mid-regional pro-adrenomedullin predicts poor outcome in non-selected patients admitted to an intensive care unit. Clin Chem Lab Med 2019;57:549–55. https://doi.org/10.1515/cclm-2018-0645.10.1515/cclm-2018-0645Search in Google Scholar PubMed
15. Kim, MJ, Cheng, G, Agrawal, DK. Cl- channels are expressed in human normal monocytes: a functional role in migration, adhesion and volume change. Clin Exp Immunol 2004;138:453–9. https://doi.org/10.1111/j.1365-2249.2004.02635.x.10.1111/j.1365-2249.2004.02635.xSearch in Google Scholar PubMed PubMed Central
16. Goasguen, JE, Bennett, JM, Bain, BJ, Vallespi, T, Brunning, R, Mufti, GJ; International Working Group on Morphology of Myelodysplastic Syndrome. Morphological evaluation of monocytes and their precursors. Haematologica 2009;94:994–7. https://doi.org/10.3324/haematol.2008.005421.10.3324/haematol.2008.005421Search in Google Scholar PubMed PubMed Central
17. Bomans, K, Schenz, J, Sztwiertnia, I, Schaack, D, Weigand, MA, Uhle, F. Sepsis induces a long-lasting state of trained immunity in bone marrow monocytes. Front Immunol 2018;9:2685. https://doi.org/10.3389/fimmu.2018.02685.10.3389/fimmu.2018.02685Search in Google Scholar PubMed PubMed Central
18. Tak, T, van Groenendael, R, Pickkers, P, Koenderman, L. Monocyte subsets are differentially lost from the circulation during acute inflammation induced by human experimental endotoxemia. J Innate Immun 2017;9:464–74. https://doi.org/10.1159/000475665.10.1159/000475665Search in Google Scholar PubMed PubMed Central
19. Crouser, ED, Parrillo, JE, Seymour, C, Angus, DC, Bicking, K, Tejidor, L, et al. Improved early detection of sepsis in the ED with a novel monocyte distribution width biomarker. Chest 2017;152:518–26. https://doi.org/10.1016/j.chest.2017.05.039.10.1016/j.chest.2017.05.039Search in Google Scholar PubMed PubMed Central
20. Dilmoula, A, Kassengera, Z, Turkan, H, Dalcomune, D, Sukhachev, D, Vincent, JL, et al. Volume, conductivity and scatter properties of leukocytes (VCS Technology) in detecting sepsis in critically Ill adult patients. Blood 2011;118:4729.10.1182/blood.V118.21.4729.4729Search in Google Scholar
21. Crouser, ED, Parrillo, JE, Seymour, CW, Angus, DC, Bicking, K, Esguerra, VG, et al. Monocyte distribution width: a novel indicator of Sepsis-2 and Sepsis-3 in high-risk emergency department patients. Crit Care Med 2019;47:1018–25. https://doi.org/10.1097/CCM.0000000000003799.10.1097/CCM.0000000000003799Search in Google Scholar PubMed PubMed Central
22. Lee, AJ, Kim, SG. Mean cell volumes of neutrophils and monocytes are promising markers of sepsis in elderly patients. Blood Res 2013;48:193–7. https://doi.org/10.5045/br.2013.48.3.193.10.5045/br.2013.48.3.193Search in Google Scholar PubMed PubMed Central
23. Mardi, D, Fwity, B, Lobmann, R, Ambrosch, A. Mean cell volume of neutrophils and monocytes compared with C-reactive protein, interleukin-6 and white blood cell count for prediction of sepsis and nonsystemic bacterial infections. Int J Lab Hematol 2010;32:410–8. https://doi.org/10.1111/j.1751-553X.2009.01202.x.10.1111/j.1751-553X.2009.01202.xSearch in Google Scholar PubMed
24. Polilli, E, Sozio, F, Frattari, A, Persichitti, L, Sensi, M, Posata, R. Comparison of Monocyte Distribution Width (MDW) and Procalcitonin for early recognition of sepsis. PLoS One 2020;15:e0227300.10.1371/journal.pone.0227300Search in Google Scholar PubMed PubMed Central
25. Levy, MM, Fink, MP, Marshall, JC, Abraham, E, Angus, D, Cook, D, et al. 2001 SCCM/ESICM/ACCP/ATS/SIS international sepsis definitions conference. Intensive Care Med 2003;29:530–8.10.1007/s00134-003-1662-xSearch in Google Scholar PubMed
26. Celik, IH, Demirel, G, Aksoy, HT, Erdeve, O, Tuncer, E, Biyikli, Z, et al. Automated determination of neutrophil VCS parameters in diagnosis and treatment efficacy of neonatal sepsis. Pediatr Res 2012;71:121–5. https://doi.org/10.1038/pr.2011.16.10.1038/pr.2011.16Search in Google Scholar PubMed
27. Umberger, RA, Hatfield, LA, Speck, PM. Understanding negative predictive value of diagnostic tests used in clinical practice. Dimens Crit Care Nurs 2017;36:22–9. https://doi.org/10.1097/DCC.0000000000000219.10.1097/DCC.0000000000000219Search in Google Scholar PubMed
28. Giulia, B, Luisa, A, Concetta, S, Bruna, LS, Chiara, B, Marcello, C. Procalcitonin and community-acquired pneumonia (CAP) in children. Clin Chim Acta 2015;451:215–8. https://doi.org/10.1016/j.cca.2015.09.031.10.1016/j.cca.2015.09.031Search in Google Scholar PubMed
29. Agnello, L, Bellia, C, Di Gangi, M, Lo Sasso, B, Calvaruso, L, Bivona, G, et al. Utility of serum procalcitonin and C-reactive protein in severity assessment of community-acquired pneumonia in children. Clin Biochem 2016;49:47–50. https://doi.org/10.1016/j.clinbiochem.2015.09.008.10.1016/j.clinbiochem.2015.09.008Search in Google Scholar PubMed
30. Gregoriano, C, Heilmann, E, Molitor, A, Schuetz, P. Role of procalcitonin use in the management of sepsis. J Thorac Dis 2020;12:S5–15. https://doi.org/10.21037/jtd.2019.11.63.10.21037/jtd.2019.11.63Search in Google Scholar PubMed PubMed Central
31. Guo, F, Feng, YC, Zhao, G, Wu, HL, Xu, L, Zhao, J, et al. The leukocyte VCS parameters compared with procalcitonin, Interleukin-6, and soluble hemoglobin scavenger receptor sCD163 for prediction of sepsis in patients with cirrhosis. Dis Markers 2019:2019:1369798.10.1155/2019/1369798Search in Google Scholar PubMed PubMed Central
Supplementary Material
The online version of this article offers supplementary material https://doi.org/10.1515/cclm-2020-0417.
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