Use of a Weighted, Automated Analysis of the Differential Blood Count to Differentiate Sepsis from Non-Infectious Systemic Inflammation: The Intensive Care Infection Score (ICIS)

Axel      Nierhaus; Jo      Linssen; Dominic      Wichmann; Stephan      Braune; Stefan      Kluge

Abstract

Introduction: Rapid and accurate diagnosis and immediate treatment of sepsis are of crucial importance. However, differentiating sepsis from Systemic Inflammatory Response Syndrome (SIRS) is a difficult challenge. Many diagnostic approaches based on clinical chemistry surrogate markers have not improved the situation. Material and Methods: The ICIS score was established in a cohort of 70 consecutive patients with SIRS. The score includes five parameters involved in the early innate immune response: mature neutrophils count, immature neutrophils count, antibody-secreting cells count, detection of neutrophils and monocytes/macrophages activation. The score can be provided in real-time without sample preparation and is independent from inter-observer variability. Results: Each ICIS score parameter itself is highly correlated with the occurrence of infection. A mean ICIS value of < 5 (lower cut-off level) indicated the absence of infection whereas the score did not fall below a value of 6 in infected patients throughout the observation time. The area under curve to detect infection for ICIS was found to be highest compared to CRP, LBP, EPO, IL-6 and TNF-α (AUC=0.851, P < 0.0001). Conclusion: Cut-off values for ICIS as a marker of infection were defined by this pilot study. The superior discriminative power of ICIS compared to CRP, LBP, EPO, IL-6 and TNF-α is underlined by its high positive and negative predictive value, particularly within the first 48 hours (PPV=79.7%, NPV=74.5%). The ICIS score provides promising potential for reliably and swiftly discriminating sepsis from SIRS in the first critical hours.

Keywords: Differential blood count, hematological immune-response based infection score, routine flowcytometry, Systemic Inflammatory Response Syndrome (SIRS), Intensive Care Infection Score, Infection, Cellular Parameters, ICIS parameters, inflammation, sepsis