Top

Published in:

01-12-2021 | Septicemia | Research article

Monocyte distribution width (MDW) as a new tool for the prediction of sepsis in critically ill patients: a preliminary investigation in an intensive care unit

Authors: Ennio Polilli, Antonella Frattari, Jessica Elisabetta Esposito, Andrea Stanziale, Giuliana Giurdanella, Giancarlo Di Iorio, Fabrizio Carinci, Giustino Parruti

Published in: BMC Emergency Medicine | Issue 1/2021

Abstract

Background

Monocyte Distribution Width (MDW), a simple proxy marker of innate monocyte activation, can be used for the early recognition of sepsis along with Procalcitonin. This study explored the added value of MDW as an early predictor of ensuing sepsis in patients hospitalised in an Intensive Care Unit.

Methods

We performed an observational prospective monocentric study to estimate the analytical performance of MDW in detecting ensuing sepsis in a sample of consecutive patients assisted in an Intensive Care Unit for > 48 h for any reason. Demographic and clinical characteristics, past medical history and other laboratory measurements were included as potential predictors of confirmed sepsis in multivariate logistic regression.

Results

A total of 211 patients were observed, 129 of whom were included in the final sample due to the suspect of ensuing sepsis; of these, 74 (57%) had a confirmed diagnosis of sepsis, which was best predicted with the combination of MDW > 23.0 and PCT > 0.5 ng/mL (Positive Predictive Value, PPV: 92.6, 95% CI: 82.1–97.9). The best MDW cut-off to rule out sepsis was ≤20.0 (Negative Predictive Value, NPV: 86.4, 95% CI: 65.1–97.1). Multivariate analyses using both MDW and PCT found a significant association for MDW > 23 only (OR:17.64, 95% CI: 5.53–67.91).

Conclusion

We found that values of MDW > 23 were associated with a high PPV for sepsis, whereas values of MDW ≤ 20 were associated with a high NPV. Our findings suggest that MDW may help clinicians to monitor ICU patients at risk of sepsis, with minimal additional efforts over standard of care.

Vincent J-L, Jones G, David S, Olariu E, Cadwell KK. Frequency and mortality of septic shock in Europe and North America: a systematic review and meta-analysis. Crit Care Lond Engl. 2019;23(1):196. https://doi.org/10.1186/s13054-019-2478-6.CrossRef

Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med. 2013;41(2):580–637. https://doi.org/10.1097/CCM.0b013e31827e83af.CrossRefPubMed

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(8):801–10. https://doi.org/10.1001/jama.2016.0287.CrossRefPubMedPubMedCentral

BalcI C, Sungurtekin H, Gürses E, Sungurtekin U, Kaptanoglu B. Usefulness of procalcitonin for diagnosis of sepsis in the intensive care unit. Crit Care Lond Engl. 2003;7(1):85–90. https://doi.org/10.1186/cc1843.CrossRef

Wang HE, Shapiro NI, Griffin R, Safford MM, Judd S, Howard G. Chronic medical conditions and risk of sepsis. PLoS ONE. 2012;7(10):e48307. https://doi.org/10.1371/journal.pone.0048307.CrossRefPubMedPubMedCentral

Wacker C, Prkno A, Brunkhorst FM, Schlattmann P. Procalcitonin as a diagnostic marker for sepsis: a systematic review and meta-analysis. Lancet Infect Dis. 2013;13(5):426–35. https://doi.org/10.1016/S1473-3099(12)70323-7.CrossRefPubMed

Wang A-Y, Ma H-P, Kao W-F, Tsai S-H, Chang C-K. Red blood cell distribution width is associated with mortality in elderly patients with sepsis. Am J Emerg Med. 2018;36(6):949–53. https://doi.org/10.1016/j.ajem.2017.10.056.CrossRefPubMed

Aydemir H, Piskin N, Akduman D, Kokturk F, Aktas E. Platelet and mean platelet volume kinetics in adult patients with sepsis. Platelets. 2015;26(4):331–5. https://doi.org/10.3109/09537104.2012.701027.CrossRefPubMed

Bartoletti M, Antonelli M, Bruno Blasi FA, Casagranda I, Chieregato A, Fumagalli R, et al. Procalcitonin-guided antibiotic therapy: an expert consensus. Clin Chem Lab Med. 2018;56(8):1223–9. https://doi.org/10.1515/cclm-2018-0259.CrossRefPubMed

10.

de Jong E, van Oers JA, Beishuizen A, Vos P, Vermeijden WJ, Haas LE, et al. Efficacy and safety of procalcitonin guidance in reducing the duration of antibiotic treatment in critically ill patients: a randomised, controlled, open-label trial. Lancet Infect Dis. 2016;16(7):819–27. https://doi.org/10.1016/S1473-3099(16)00053-0.CrossRefPubMed

11.

Wu CC, Lan HM, Han ST, Chaou CH, Yeh CF, Liu SH, et al. Comparison of diagnostic accuracy in sepsis between presepsin, procalcitonin, and C-reactive protein: a systematic review and meta-analysis. Ann Intensive Care. 2017;7(1):91. https://doi.org/10.1186/s13613-017-0316-z.CrossRefPubMedPubMedCentral

12.

Uzzan B, Cohen R, Nicolas P, Cucherat M, Perret G-Y. Procalcitonin as a diagnostic test for sepsis in critically ill adults and after surgery or trauma: a systematic review and meta-analysis. Crit Care Med. 2006;34(7):1996–2003. https://doi.org/10.1097/01.CCM.0000226413.54364.36.CrossRefPubMed

13.

Brodska H, Valenta J, Pelinkova K, Stach Z, Sachl R, Balik M, et al. Diagnostic and prognostic value of presepsin vs. established biomarkers in critically ill patients with sepsis or systemic inflammatory response syndrome. Clin Chem Lab Med. 2018;56(4):658–68. https://doi.org/10.1515/cclm-2017-0839.CrossRefPubMed

14.

Teggert A, Datta H, Ali Z. Biomarkers for point-of-care diagnosis of Sepsis. Micromachines. 2020;11(3). https://doi.org/10.3390/mi11030286.

15.

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(3):518–26. https://doi.org/10.1016/j.chest.2017.05.039.CrossRefPubMedPubMedCentral

16.

Zonneveld R, Molema G, Plötz FB. Analyzing neutrophil morphology, mechanics, and motility in Sepsis: options and challenges for novel bedside technologies. Crit Care Med. 2016;44(1):218–28. https://doi.org/10.1097/CCM.0000000000001266.CrossRefPubMed

17.

Baudesson de Chanville C, Chousterman BG, Hamon P, Laviron M, Guillou N, Loyher PL, et al. Sepsis Triggers a Late Expansion of Functionally Impaired Tissue-Vascular Inflammatory Monocytes During Clinical Recovery. Front Immunol. 2020;11:675.CrossRefPubMedPubMedCentral

18.

Fingerle G, Pforte A, Passlick B, Blumenstein M, Ströbel M, Ziegler-Heitbrock HW. The novel subset of CD14+/CD16+ blood monocytes is expanded in sepsis patients. Blood. 1993;82(10):3170–6. https://doi.org/10.1182/blood.V82.10.3170.3170.CrossRefPubMed

19.

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(5):464–74. https://doi.org/10.1159/000475665.CrossRefPubMedPubMedCentral

20.

Polilli E, Sozio F, Frattari A, Persichitti L, Sensi M, Posata R, et al. Comparison of monocyte distribution width (MDW) and Procalcitonin for early recognition of sepsis. PLoS ONE. 2020;15(1):e0227300. https://doi.org/10.1371/journal.pone.0227300.CrossRefPubMedPubMedCentral

21.

Centers for Disease Control and Prevention. Management of Multidrug-Resistant Organisms in Healthcare Settings, 2006. https://www.cdc.gov/infectioncontrol/guidelines/mdro/index.html. Last accessed August 10^th, 2021.

22.

Siegel JD. Rhinehart E, Jackson M, Chiarello L, healthcare infection control practices advisory committee. Management of multidrug-resistant organisms in health care settings, 2006. Am J Infect Control. 2007;35(10):S165–93. https://doi.org/10.1016/j.ajic.2007.10.006.CrossRefPubMed

23.

Agnello L, Lo Sasso B, Bivona G, Gambino CM, Giglio RV, Iacolino G, et al. Reference interval of monocyte distribution width (MDW) in healthy blood donors. Clin Chim Acta Int J Clin Chem. 2020;510:272–7. https://doi.org/10.1016/j.cca.2020.07.036.CrossRef

24.

Lee CC, Kwa ALH, Apisarnthanarak A, Feng JY, Gluck EH, Ito A, et al. Procalcitonin (PCT)-guided antibiotic stewardship in Asia-Pacific countries: adaptation based on an expert consensus meeting. Clin Chem Lab Med. 2020;58(12):1983–91. https://doi.org/10.1515/cclm-2019-1122.CrossRefPubMed

25.

Furundarena JR, Uranga A, Sainz MR, González C, Uresandi N, Argoitia N, et al. Usefulness of the lymphocyte positional parameters in the Sysmex XN haematology analyser in lymphoproliferative disorders and mononucleosis syndrome. Int J Lab Hematol. 2018;40(1):41–8. https://doi.org/10.1111/ijlh.12726.CrossRefPubMed

26.

Urrechaga E. Reviewing the value of leukocytes cell population data (CPD) in the management of sepsis. Ann Transl Med. 2020;8(15):953. https://doi.org/10.21037/atm-19-3173.CrossRefPubMedPubMedCentral

27.

Chaves F, Tierno B, Xu D. Quantitative determination of neutrophil VCS parameters by the Coulter automated hematology analyzer: new and reliable indicators for acute bacterial infection. Am J Clin Pathol. 2005;124(3):440–4. https://doi.org/10.1309/LLF75W0FWQQ8TCC5.CrossRefPubMed

28.

Lee A-J, Kim S-G. Mean cell volumes of neutrophils and monocytes are promising markers of sepsis in elderly patients. Blood Res. 2013;48(3):193–7. https://doi.org/10.5045/br.2013.48.3.193.CrossRefPubMedPubMedCentral

29.

Rosner B. Fundamentals of biostatistics. Boston: Brooks/Cole, Cengage Learning; 2011.

30.

Obuchowski NA. ROC analysis. Am J Roentgenol. Am Roentgen Ray Soc. 2005;184(2):364–72. https://doi.org/10.2214/ajr.184.2.01840364.CrossRef

31.

Kleinbaum DG, Klein M. Logistic regression: a self-learning text. 3rd ed. New York: Springer; 2010. https://doi.org/10.1007/978-1-4419-1742-3.

32.

R Development Core Team. A language and environment for statistical computing. Vienna: R Foundation for Statistical Computing; 2005. http://www.R-project.org.

33.

Crouser ED, Parrillo JE, Martin GS, Huang DT, Hausfater P, Grigorov I, et al. Monocyte distribution width enhances early sepsis detection in the emergency department beyond SIRS and qSOFA. J Intensive Care. 2020;8(1):33. https://doi.org/10.1186/s40560-020-00446-3.CrossRefPubMedPubMedCentral

34.

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(8):1018–25. https://doi.org/10.1097/CCM.0000000000003799.CrossRefPubMedPubMedCentral

35.

Sharma K, Mogensen KM, Robinson MK. Pathophysiology of critical illness and role of nutrition. Nutr Clin Pract Off Publ Am Soc Parenter Enter Nutr. 2019;34(1):12–22. https://doi.org/10.1002/ncp.10232.CrossRef

36.

Buehler SS, Madison B, Snyder SR, Derzon JH, Cornish NE, Saubolle MA, et al. Effectiveness of practices to increase timeliness of providing targeted therapy for inpatients with bloodstream infections: a laboratory medicine best practices systematic review and Meta-analysis. Clin Microbiol Rev. 2016;29(1):59–103. https://doi.org/10.1128/CMR.00053-14.CrossRefPubMed

37.

Faix JD. Biomarkers of sepsis. Crit Rev Clin Lab Sci. 2013;50(1):23–36. https://doi.org/10.3109/10408363.2013.764490.CrossRefPubMedPubMedCentral

38.

Heilmann E, Gregoriano C, Schuetz P. Biomarkers of infection: are they useful in the ICU. Semin Respir Crit Care Med. 2019;40(4):465–75. https://doi.org/10.1055/s-0039-1696689.CrossRefPubMedPubMedCentral

39.

Meynaar IA, Droog W, Batstra M, Vreede R, Herbrink P. In critically ill patients, serum Procalcitonin is more useful in differentiating between Sepsis and SIRS than CRP, Il-6, or LBP. Crit Care Res Pract. 2011;2011:594645–6. https://doi.org/10.1155/2011/594645.CrossRefPubMedPubMedCentral

40.

Suprin E, Camus C, Gacouin A, Le Tulzo Y, Lavoue S, Feuillu A, et al. Procalcitonin: a valuable indicator of infection in a medical ICU. Intensive Care Med. 2000;26(9):1232–8. https://doi.org/10.1007/s001340000580.CrossRefPubMed

41.

Xu Y, Chen R, Qin W, Wang P, Li P, Hu W, et al. Early diagnostic value of serum procalcitonin levels for catheter-related blood stream infection in first-ever acute ischemic stroke patients. BMC Neurol. 2020;20(1):6. https://doi.org/10.1186/s12883-019-1557-2.CrossRefPubMedPubMedCentral

42.

Bell K, Wattie M, Byth K, Silvestrini R, Clark P, Stachowski E, et al. Procalcitonin: a marker of bacteraemia in SIRS. Anaesth Intensive Care. 2003;31(6):629–36. https://doi.org/10.1177/0310057X0303100603.CrossRefPubMed

43.

Castelli GP, Pognani C, Meisner M, Stuani A, Bellomi D, Sgarbi L. Procalcitonin and C-reactive protein during systemic inflammatory response syndrome, sepsis and organ dysfunction. Crit Care Lond Engl. 2004;8(4):R234–42. https://doi.org/10.1186/cc2877.CrossRef

44.

Riedel S, Melendez JH, An AT, Rosenbaum JE, Zenilman JM. Procalcitonin as a marker for the detection of bacteremia and sepsis in the emergency department. Am J Clin Pathol. 2011;135(2):182–9. https://doi.org/10.1309/AJCP1MFYINQLECV2.CrossRefPubMed

45.

Hoeboer SH, van der Geest PJ, Nieboer D, Groeneveld ABJ. The diagnostic accuracy of procalcitonin for bacteraemia: a systematic review and meta-analysis. Clin Microbiol Infect Off Publ Eur Soc Clin Microbiol Infect Dis. 2015;21(5):474–81. https://doi.org/10.1016/j.cmi.2014.12.026.CrossRef

46.

Agnello L, Sasso BL, Giglio RV, Bivona G, Gambino CM, Cortegiani A, et al. Monocyte distribution width as a biomarker of sepsis in the intensive care unit: a pilot study. Ann Clin Biochem. 2021;58(1):70–3. https://doi.org/10.1177/0004563220970447.CrossRefPubMed

47.

Global report on the epidemiology and burden of sepsis: current evidence, identifying gaps and future directions. Geneva: World Health Organization; 2020. Https://www.who.int/publications/i/item/9789240010789. Last accessed August 4th, 2021

48.

Piva E, Zuin J, Pelloso M, Tosato F, Fogar P, Plebani M. Monocyte distribution width (MDW) parameter as a sepsis indicator in intensive care units. Clin Chem Lab Med. 2021;59(7):1307–14. https://doi.org/10.1515/cclm-2021-0192.CrossRefPubMed

49.

Vincent J-L, Sakr Y, Sprung CL, Ranieri VM, Reinhart K, Gerlach H, et al. Sepsis in European intensive care units: results of the SOAP study. Crit Care Med. 2006;34:344–53.CrossRefPubMed

Title: Monocyte distribution width (MDW) as a new tool for the prediction of sepsis in critically ill patients: a preliminary investigation in an intensive care unit
Authors: Ennio Polilli
Antonella Frattari
Jessica Elisabetta Esposito
Andrea Stanziale
Giuliana Giurdanella
Giancarlo Di Iorio
Fabrizio Carinci
Giustino Parruti
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Septicemia
Septicemia
Published in: BMC Emergency Medicine / Issue 1/2021
Electronic ISSN: 1471-227X
DOI: https://doi.org/10.1186/s12873-021-00521-4

At a glance: The STEP trials

Springer Medicine

Monocyte distribution width (MDW) as a new tool for the prediction of sepsis in critically ill patients: a preliminary investigation in an intensive care unit

Abstract

Background

Methods

Results

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 1/2021

Starting ambulance care professionals and critical incidents: a qualitative study on experiences, consequences and coping strategies

Clinical factors associated with bloodstream infection at the emergency department

Differences in radiation dose for computed tomography of the brain among pediatric patients at the emergency departments: an observational study

Determinants of time-to-disposition in patients who underwent CT for pulmonary embolism: a retrospective study

Characteristics of helicopter emergency medical services (HEMS) dispatch cancellations during a six-year period in a Dutch HEMS region

Predicting factors for abnormal brain computed tomography in children with minor head trauma