qS-Ne2Mo Score – A New Risk Stratication Tool For Early Detection of Septic Shock in The Field of Emergency Medicine

Sepsis is one of the most significant healthcare concerns of the 21 st century. In the United States 27 sepsis affect 1.7 million adults, with 270,000 fatal cases, according to the estimation of Centers 28 for Disease Control and Prevention. The management of sepsis relies on early recognition, 29 therefore the emergency departments have distinctive role in sepsis care, hence the need for 30 early reliable risk stratification tools. A retrospective, quantitative study was performed in Department of Emergency, University of 33 Szeged. Hungary. Patients with suspected infection were enrolled to four subgroups based on 34 the results of patient examination and laboratory results. In all cases (N=276), cell population 35 data markers were analyzed along with ordinary infection biomarkers, such as CRP, PCT and 36 WBC. Performance of cell population data parameters were investigated with ROC (Receiver 37 Operating Curve) analysis.

Organ Failure Assessment score (qSOFA score) is recommended as an initial screening tool for 74 sepsis. This is a simple bedside risk stratification method assessing the mental status, respiratory 75 rate, and systolic blood pressure. In cases having qSOFA score two or three points, sepsis or 76 septic shock is suspected, and the one-hour bundle is to be completed. If qSOFA score indicates 77 low risk, then the recommendation is to use clinical judgement. In cases with positive qSOFA 78 4 score or in cases where sepsis is suspected clinically, the Sequential Organ Failure Assessment 79 score (SOFA score) is to be calculated. SOFA is a 0-24-point scale, and sepsis-related organ 80 failure is confirmed by an increase of two or more points. Septic shock is confirmed if 81 vasopressor therapy is needed to maintain mean arterial pressure over 65 mmHg and the serum 82 lactate level is above 2 mmol/l [4]. Cases having SOFA less than two points, have significantly 83 lower chance for poor outcome, we considered them as infection without organ failure. (i.e., internal complexity, nucleic acid content and cell size). These descriptive data are known 103 as cell population data (CPD).

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Although CPD provides huge amount of data on white blood cells, clinical applicability in the 105 emergency setting is yet to be determined. Therefore, the aim of this retrospective study was to 106 analyze the performance of CPD parameters in the diagnosis of sepsis. We also tried to find 107 CPD parameters that could be combined with qSOFA for risk stratification benchmarked 108 against the calculated SOFA score, and the final Sepsis-3 category.

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This retrospective study was conducted at the Emergency Department (ED) of the University 111 of Szeged, Hungary. All data were collected from September 2019 until January 2020 from 112 patients who received emergency care in the ED because of a suspected infection.    Becton-Dickinson, Franklin Lakes, NJ, USA) and were analysed using automated haematology 129 analyser Sysmex XN20 (Sysmex Corporation, Kobe, Japan) within 2 hours of sample 130 collection. The measured parameters included total blood count and cell population data (CPD) 131 of neutrophils, lymphocytes and monocytes on white blood cell differential (WDF) channel.

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The precision of white blood cell (WBC) count determination was 3% or less according the 133 manufacturer, when the WBC count was 4.00 G/L or more. The precision of immature 134 granulocyte ratio (IGR) was 2% at the WBC count of 4.00 G/L or more.

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WDF channel of the Sysmex XN20 haematology analysers uses optical side scatter along X 136 axis to assess the granularity and internal structure (complexity) of the cells. Fluorescence  Table   152 1. The blood samples were collected in 5 ml vacutainer tubes (Plastic STT II Advance tubes;   hoc Bonferroni correction, based on the distribution of the data. Any difference was considered 179 significant above p=0.05 level, and confidence intervals were set to 95%.

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Performance of cell population data (CPD) parameters were investigated with ROC (Receiver

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Operating Curve) analysis. Cutoff values were set using Youden's method, based on AUC (area 182 under the curve) analysis. Data performance was considered good above 0.8, and excellent 183 above 0.9 AUC, respectively.

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From September 2019 to January 2020 overall 452 patients were enrolled to the study, who 186 arrived at the emergency department with a suspected infection. Data were collected from the 187 electronic patient records. After clearing the raw data, in 176 cases SOFA score was incomplete, 188 therefore these cases were excluded from the study.

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The baseline and descriptive characteristics of the whole cohort are summarized in Table 2   In 66 cases, microbiology results were not available at the time of the data collection, and the 197 confirmation of the initial diagnosis was based on imaging results. These cases were excluded 198 from the final sample, and data of the remaining 210 patients were analyzed separately (Table   199 3 and 4).

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Baseline and descriptive characteristics of the final sample can be seen in Table 4 and 5.     As a third step, ROC analyses aiming to validate the performance of all CPD parameters were 235 carried out in each subgroup. As seen in Figures 1-4 Sensitivity and specificity measurements showed acceptable performance. (Table 8   higher in patients admitted to ICU compared to healthy subjects [3].

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Our results suggested that although almost all CPD parameters showed significant changes in To complete qS-Ne2Mo score, simple vital signs and no additional blood samples are needed.

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With the fast turn-around-time of CPD, qS-Ne2Mo score can be completed within a short period 306 of time starting from triage and can identify septic shock patients way before the completion of 307 SOFA score or before the initial resuscitation attempts would have results.

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Possible fields of application of qS-Ne2Mo score 309 Final septic shock diagnosis can be made only after the initial treatment attempt, and only the septic shock related mortality compared to standard therapy, now this approach has been 323 challenged by many recent randomized controlled trials, that failed to reproduce those excellent 324 results in the Rivers study [1,9,12]. Maybe, this controversy lies in the fact that only the most 325 severe cases can profit from EGDT (i.e. septic shock), but on arrival no certain marker 326 distinguishes those patients and the initial indicators for early septic shock were insufficient.

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With qS-Ne2Mo score, septic shock can be identified early and reliably and maybe more 328 aggressive treatment strategy like EGDT can be justified by positive qS-Ne2Mo score. approximately 20 times more than a CBC and CPD measurement together. Therefore qS-

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Ne2Mo score might be used as an initial screening tool to select only those patients that need  366 Not applicable.

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Availability of data and materials 368 Research data is available upon reasonable request to the corresponding author.