Original Contribution
Neutrophil-to-lymphocyte ratio as a prognostic marker in critically-ill septic patients

https://doi.org/10.1016/j.ajem.2016.10.055Get rights and content

Abstract

Background

We evaluated the associations between the neutrophil-to-lymphocyte ratio (NLR) or changes in NLR and outcomes in septic patients.

Methods

Patients who met the criteria for severe sepsis or septic shock were categorized into five groups according to the quintile of initial NLR value. We defined two risk groups according to NLR value and changes in NLR during the first two days (defined as the persistently low NLR group and the persistently high NLR group). The primary outcome was 28-day mortality.

Results

A total of 1395 patients were included. The median initial NLR values from Quintile 1 to Quintile 5 were as follows: 0.2 (IQR [interquartile range], 0.1–0.7), 3.4 (IQR, 2.6–4.7), 8.6 (IQR, 7.1–9.9), 15.4 (IQR, 13.3–17.8), and 31.0 (IQR, 24.6–46.8), respectively. The 28-day mortality values for the same groups were as follows: 24.4%, 12.2%, 11.1%, 11.8%, and 16.1% (P < .01). Cox regression analysis showed that inclusion in Quintile 1 or Quintile 5 was a significant risk factor predicting 28-day mortality compared to Quintile 3 (adjusted hazard ratio [HR]: 1.79 (95% confidence interval [CI], 1.15–2.78) in Quintile 1; 1.67 (95% CI, 1.04–2.66) in Quintile 5). The analysis indicated that persistently low NLR (adjusted HR: 2.25, 95% CI, 1.63–3.11) and persistently high NLR (adjusted HR: 2.65, 95% CI, 1.64–4.29) were significant risk factors.

Conclusions

In summary, the initial NLR measured at ED admission was independently associated with 28-day mortality in patients with severe sepsis and septic shock. In addition, change in NLR may prove to be a valuable prognostic marker.

Introduction

Sepsis is a major cause of morbidity and mortality resulting from a devastating host response to infection, and it affects millions of people worldwide each year [1], [2]. Despite recent advances in knowledge about the disease and critical care modalities, the short-term mortality rate in patients with severe sepsis and septic shock remains high, accounting for approximately 30% of all cases [3], [4], [5].

Identifying patients that are at high risk of mortality and accurately anticipating outcomes in the early phase of sepsis is imperative for providing timely and adequate interventions for these patients [6]. However, the complexity and heterogeneity of the disease make this very challenging. In 2001, Zahorec et al. reported a correlation between neutrophilia/lymphocytopenia and the severity of clinical course in oncological intensive care unit (ICU) patients and suggested the neutrophil-to-lymphocyte ratio (NLR) as an indicator of disease severity [7]. Additionally, the NLR is advantageous in regard to simplicity, low cost, and availability compared to many other previously proposed biomarkers, which makes it promising for diagnostic clinicians. Several studies have reported that the NLR is useful in various clinical situations, including cardiovascular disease, malignancies, and infectious diseases [8], [9], [10], [11].

Although the association between the NLR and mortality in patients with sepsis has been investigated, the predictive value of the initial NLR and how it changes during the early resuscitation period are not well understood [12], [13]. In this study, we evaluated the association between the initial NLR and 28-day mortality in patients that presented to the emergency department (ED) with severe sepsis or septic shock. We also investigated the association between change in NLR after ED admission and 28-day mortality.

Section snippets

Study Design

This was a single-center, retrospective cohort study of patients with severe sepsis or septic shock who presented to the ED of Samsung Medical Center, a university-affiliated tertiary teaching hospital located in a metropolitan city. The Samsung Medical Center Institutional Review Board (IRB file number: 2016-01-101) approved this study, and informed consent was waived because the study was conducted retrospectively and no interventions were applied.

Study Population and Definitions

Patients who fulfilled the following

Baseline Characteristics

During the study period, a total of 1728 patients with severe sepsis or septic shock were registered in the sepsis registry. Of these, 333 patients were excluded due to terminal malignancy (n = 160), signed DNR orders, or refusal of invasive procedures (n = 173). A total of 1395 patients were included in the final analysis.

Baseline characteristics of patients across the quintiles are described in Table 1. The median age of the population was 65 years (IQR, 55–73) and 56.4% (n = 787) were male. The

Discussion

The results indicated that the initial NLR measured on ED admission was an independent risk factor for predicting 28-day mortality in patients with severe sepsis or septic shock. In addition, both the persistently low NLR group and the group that had a persistently high NLR during the first two days after ED admission were also associated with increased risk for 28-day mortality.

NLR has been used in critical care medicine and may prove to be a valuable prognostic tool based on the results of

Conclusion

The initial NLR measured at ED admission was independently associated with 28-day mortality in patients with severe sepsis or septic shock in the ED. Persistently low NLR or high NLR values were also significant predictors for 28-day mortality.

Conflict of Interest

The authors have no potential conflicts of interest or funding sources to declare.

References (36)

  • J.L. Vincent et al.

    Early management of sepsis

    Clin Exp Emerg Med

    (2014)
  • R. Zahorec

    Ratio of neutrophil to lymphocyte counts—rapid and simple parameter of systemic inflammation and stress in critically ill

    Bratisl Lek Listy

    (2001)
  • H. Yodying et al.

    Prognostic significance of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in oncologic outcomes of esophageal cancer: a systematic review and meta-analysis

    Ann Surg Oncol

    (2016)
  • C.P. de Jager et al.

    Lymphocytopenia and neutrophil-lymphocyte count ratio predict bacteremia better than conventional infection markers in an emergency care unit

    Crit Care

    (2010)
  • J.D. Salciccioli et al.

    The association between the neutrophil-to-lymphocyte ratio and mortality in critical illness: an observational cohort study

    Crit Care

    (2015)
  • F. Riche et al.

    Reversal of neutrophil-to-lymphocyte count ratio in early versus late death from septic shock

    Crit Care

    (2015)
  • M.M. Levy et al.

    2001 SCCM/ESICM/ACCP/ATS/SIS international sepsis definitions conference

    Crit Care Med

    (2003)
  • R.P. Dellinger et al.

    Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2008

    Crit Care Med

    (2008)
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