Monocyte distribution width enhances early sepsis detection in the emergency department beyond SIRS and qSOFA

Abstract

Background: The initial presentation of sepsis in the emergency department (ED) is difficult to distinguish from other acute illnesses based upon similar clinical presentations. A new blood parameter, a measurement of increased monocyte volume distribution width (MDW), may be used in combination with other clinical parameters to improve early sepsis detection. We sought to determine if MDW, when combined with other available clinical parameters at the time of ED presentation, improves the early detection of sepsis.

Methods: A retrospective analysis of prospectively collected clinical data available during the initial ED encounter of 2158 adult patients who were enrolled from emergency departments of three major academic centers, of which 385 fulfilled Sepsis-2 criteria, and 243 fulfilled Sepsis-3 criteria within 12 h of admission. Sepsis probabilities were determined based on MDW values, alone or in combination with components of systemic inflammatory response syndrome (SIRS) or quick sepsis-related organ failure assessment (qSOFA) score obtained during the initial patient presentation (i.e., within 2 h of ED admission).

Results: Abnormal MDW (> 20.0) consistently increased sepsis probability, and normal MDW consistently reduced sepsis probability when used in combination with SIRS criteria (tachycardia, tachypnea, abnormal white blood count, or body temperature) or qSOFA criteria (tachypnea, altered mental status, but not hypotension). Overall, and regardless of other SIRS or qSOFA variables, MDW > 20.0 (vs. MDW ≤ 20.0) at the time of the initial ED encounter was associated with an approximately 6-fold increase in the odds of Sepsis-2, and an approximately 4-fold increase in the odds of Sepsis-3.

Conclusions: MDW improves the early detection of sepsis during the initial ED encounter and is complementary to SIRS and qSOFA parameters that are currently used for this purpose. This study supports the incorporation of MDW with other readily available clinical parameters during the initial ED encounter for the early detection of sepsis.

Trial registration: ClinicalTrials.gov, NCT03145428. First posted May 9, 2017. The first subjects were enrolled June 19, 2017, and the study completion date was January 26, 2018.

Keywords: Biomarker; Blood; ED; Infection; Sepsis-2; Sepsis-3; Severe sepsis.

Conflict of interest statement

Competing interestsAuthors EDC and JEP were supported by a grant from Beckman Coulter, Inc. to perform the clinical trial. Authors DTH, PH, and TO have consulting agreements with Beckman Coulter, Inc. IG, DC, MH, and LT are employees of Beckman Coulter, Inc., the sponsor of the project.

© The Author(s) 2020.

Figures

Fig. 1

Flow diagram describing patient screening and enrollment. The study was conducted between April 2017 and January 2018. 2.5% of subjects screened were excluded for various reasons, as noted above, such that 97.5% of subjects screened were enrolled in the study

Fig 2

MDW improves early sepsis detection when combined with each SIRS vital sign criterion. The probability of sepsis in patients presenting initially to the ED with abnormal vital signs of tachycardia (a), tachypnea (b), both tachycardia and tachypnea (c), or abnormal temperature (d) is consistently lower if the MDW is normal (solid blue line) compared to abnormal MDW (dashed red line). The probability of sepsis is also higher when a vital sign abnormality is combined with abnormal WBC (dashed purple line). When a vital sign is abnormal along with abnormal WBC, abnormal MDW indicates higher sepsis probability (dashed black line) and normal MDW indicates lower sepsis probability (dashed green line)

Fig. 3

MDW improves early sepsis detection in combination with altered mental status and hypotension. The probability of sepsis in patients presenting initially to the ED with altered mental status (AMS) (a) is lower if the MDW is normal (solid blue line) compared to abnormal MDW (dashed red line). The probability of sepsis is also higher when AMS is combined with abnormal WBC (dashed purple line). When AMS is associated with abnormal WBC, abnormal MDW further predicts higher sepsis probability (dashed black line) and normal MDW predicts lower sepsis probability (dashed green line). In the setting of hypotension (b) with elevated WBC (purple dashed line), normal MDW is associated with lower sepsis risk (green dashed line)

Fig. 4

MDW improves detection of sepsis in ED patients regardless of WBC value at presentation. An elevated MDW value predicts higher sepsis probability in ED patients presenting with abnormal WBC ( 12,000, orange shading) and within the range of normal WBC values (4000–12,000, no shading). In contrast, a normal MDW at presentation to the ED reduces sepsis probability regardless of normal or abnormal WBC value. When all patients with normal CBC are combined, the risk of sepsis is 6-fold higher if MDW is elevated compared to those with a normal MDW value. Notably, 31% of all sepsis cases presented to the ED with a WBC in the normal range. Associated table summarizes sepsis probabilities for combinations of MDW and WBC determined in trial (P0 = 18%) and modeled at P0 = 8%. The chart numbers reflect sepsis probabilities at P0 = 8%. Abnormal WBC cohort combines patients with WBC < 4000 and WBC > 12,000