Volume, Conductivity and Scatter Properties of Leukocytes (VCS Technology) in Detecting Sepsis in Critically Ill Adult Patients

Abstract

4729 Sepsis and its sequelae remain leading causes of death in critically ill patients. Early identification and subsequently prompt treatment of sepsis can have a major impact on the outcome of septic patients. White Blood Cell (WBC) count, neutrophils count or percentage and percentage of band and immature neutrophils have been included in the diagnostic criteria of sepsis d. Previous studies have shown that morphological changes of leukocytes during sepsis can be quantified using Volume, Conductivity and Scatter (VCS) technology by some hematology analyzers. DxH800 (Beckman Coulter, Fullerton, CA) has the potential to report, in addition to Volume and Conductivity, five extra-laser diffraction angles for each cellular event. The aim of the study was to evaluate the diagnostic accuracy of VCS parameters of leukocytes in detecting sepsis in critically ill adult patients. This prospective observational study involved all consecutive adult patients admitted to a 31-bed medico-surgical department of intensive care (ICU) for more than 4 hours in a 3.5-month period. Diagnosis of sepsis was based on standard definitions. Blood samples were run by DxH800. Complete blood count (CBC) and WBC differential, but not VCS parameters were reported to attending physicians. Of a total of 722 patients admitted during the observation period 422 had WBC differential (and thus VCS parameters) determined at admission, of whom 125 had sepsis Septic and non-septic patients had a median age (upper and lower quartile) of 60 (51-71) and 58 (45-72) years and APACHE II scores of 19 (14-25) and 11 (7-16). VCS parameters had higher Areas Under the Receiver Operating Characteristic Curve (AUC) than WBC or percentage of neutrophils for diagnosis of sepsis at admission (Table 1.).Table 1.DxH800 VCS parameters. Results as median values (upper and lower quartile)VCS parametersSepsis N=125No Sepsis N=317p valueAUC95%CI of AUCMean Volume of Neutrophils (MNVNE)153 (146–163)144 (140–148)<0.0010.780.72–0.83SD of Volume of Neutrophils (SDVNE)20 (18–23)17 (16–18)<0.0010.810.77–0.86Mean Axial Light loss of Neutrophils (MNAL2NE)155 (150–160)148 (144–151)<0.0010.780.73–0.84SD of Axial Light loss of Neutrophils (SDAL2NE)13 (12–16)11 (10–12)<0.0010.800.75–0.84Mean Volume of Monocytes (MNVMO)179 (169–189)163 (159–167)<0.0010.880.84–0.91SD of Volume of Monocytes (SDVMO)24 (21–28)18 (16–20)<0.0010.880.84–0.91SD of Axial Light loss of Monocytes (SDAL2MO)16 (15–20)13 (12–14)<0.0010.850.81–0.89WBC, 103/ml10.9 (7.3–15.3)10.5 (7.8–14.2)NS0.510.44–0.57Percent of Neutrophils, %85 (76–91)80 (68–88)<0.0010.610.55–0.67 On ICU admission, MNVMO had the highest discriminant values in detecting sepsis with sensitivity (Se) of 84%, specificity (Sp) 76%, positive predictive value (PPV)58%, negative predictive value (NPV) 92% and odds ratio (OR) 17 for a cutoff of 168. MNVMO<168 (59% of patients) gave reasonable evidence against sepsis (likelihood ratio (LR) of 0.21, pre- and post-test probability, 0.28 and 0.076,) and MNVMO≥175 (25% of patients) gave reasonable evidence for sepsis (LR of 6.85, pre- and post-test probability, 0.28 and 0.73, respectively). Only 16% of patients, in the intermediate range, had a rather uninformative test result (LR of 1.32). Combining monocyte or neutrophil VCS parameters with CRP slightly increases AUC to 0.91. During the ICU stay, VCS parameters were obtained in 316 initially non-septic patients, of whom 20 became septic. MNVMO < 174 excluded ICU-acquired infection with NPV of 99% and MNVMO > 174 predicted ICU-acquired infection 1.7 days earlier than clinical diagnosis (Se: 85%, Sp 68%, OR 12 and AUC=0.78, 95% CI: 66–90). CONCLUSIONS: This large prospective study in unselected critically ill adult patients demonstrates the diagnostic utility of VCS parameters, especially MNVMO, in detecting and, more importantly, excluding sepsis at admission and during ICU stay. VCS parameters are obtained automatically, routinely, within minutes, requiring neither additional sampling nor additional cost to that of complete blood count thus making their prospects very promising. Disclosures: Pradier: Beckman Coulter: Consultancy, Membership on an entity's Board of Directors or advisory committees.

Improved Early Detection of Sepsis in the ED With a Novel Monocyte Distribution Width Biomarker

“…To the extent that earlier detection of sepsis leads to earlier treatment, these findings have implications for reducing sepsis mortality. [5][6][7] Consistent with the results of recent human studies, [14][15][16][17][18][19][20][21] and the established function of neutrophils as first responders during the innate immune response to invading organisms, both MNV and NDW were reasonably sensitive and specific for the detection of sepsis (e-Table 5). Based on previous studies demonstrating that changes in neutrophil volume and cell activation markers (CD64) can detect sepsis in hospitalized pediatric patients, 14,17,18,32 we originally expected that neutrophil volume changes would be superior for the detection of sepsis in the ED population.…”

“…Volumetric increases are an early manifestation of immune cell responses to severe infections and as such have shown potential as sepsis biomarkers in humans. [14][15][16][17][18][19][20][21] We show that volumetric changes of circulating immune cells, particularly increased MDW, correspond with previously established criteria for sepsis 24 in a large patient population in the ED. MDW distinguished sepsis from SIRS, and the magnitude of MDW elevation correlated with infection severity and organ dysfunction, ranging from normal MDW in those with limited infections, and increasing incrementally with sepsis severity.…”

“…14 Recent studies suggest that immune cell volume increases may be useful for the detection of sepsis. [14][15][16][17][18][19][20][21] These recent studies, although encouraging, are limited by their small sample sizes and did not include patients in the ED. Therefore, we sought to determine the utility of measuring volumetric changes of circulating immune cells as predictors of sepsis in a large prospective study of adult patients in the ED.…”

The Leukocyte VCS Parameters Compared with Procalcitonin, Interleukin-6, and Soluble Hemoglobin Scavenger Receptor sCD163 for Prediction of Sepsis in Patients with Cirrhosis

“…In addition, lymphocytes are also an important cellular component of immune response. Volume increases are an early manifestation that these immune cells respond to severe infections and as such have been shown to serve as potential human biomarkers for latent sepsis [8][9][10][11][12]. Our results show changes in the volume of circulating immune cells, especially the increased mean neutrophil volume (MNV), mean monocyte volume (MMV), mean lymphocyte volume (MLV), and monocyte distribution width (MDW).…”

“…In addition to detecting routine blood cell parameters, it can also provide quantitative WBC volume, conductivity, and light scatter to reflect the morphological changes of them. Recent studies have shown that the increase in the volume of rudimentary immune cells reflected in the VCS parameter may help detect sepsis [8][9][10][11][12]. However, the application of VCS parameters in sepsis for patients with cirrhosis was less studied.…”