Prognostic value of neutrophil-to-lymphocyte ratio in sepsis: A meta-analysis

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Abstract

Background

Neutrophil-to-lymphocyte ratio (NLR) has been used to predict the prognosis of patients with sepsis with inconsistent results. This meta-analysis aimed to clarify the prognostic value of NLR in patients with sepsis.

Methods

A comprehensive literature search for relevant studies, published prior to March 2019, was conducted using PubMed, Web of Science, and the China National Knowledge.

Infrastructure database. Standard mean differences (SMDs) with 95% confidence intervals (CI) were used to evaluate the NLR of patients with sepsis retrospectively. Hazard ratios (HRs) with 95% CIs were used to evaluate the prognostic value of NLR in patients with sepsis.

Results

Patients from 14 studies (n = 11,564) were selected for evaluation. Nine studies (1371 patients) analyzed the NLR in these patients. The pooled results showed significantly higher NLR in non-survivors than in survivors (random-effects model: SMD = 1.18, 95% CI; 0.42–1.94). Nine studies (10,685 patients) evaluated the prognostic value of NLR for sepsis; the pooled results showed that higher NLR was associated with poor prognosis in patients with sepsis (fixed-effects model: HR = 1.75, 95% CI; 1.56–1.97). Subgroup analysis revealed that study design, cut-off NLR, or primary outcome did not affect the prognostic value of NLR in patients with sepsis.

Conclusion

This meta-analysis indicates that NLR may be a helpful prognostic biomarker of patients with sepsis and that higher NLR values may indicate unfavorable prognoses in these patients.

Introduction

To date, sepsis remains a major cause of morbidity and mortality in both developed and developing countries. Despite advances in sepsis treatment and critical care modalities in the past decades, the mortality rate in patients with sepsis, especially septic shock patients, remains high at approximately 30%.[1], [2] This high mortality rate can attributed in part to low awareness, late identification, and improper management of the disease.[3] Early and accurate identification of patients with sepsis with high mortality risk is critical for appropriate management of these patients.[4] Although many clinical biomarkers have been investigated,[5], [6], [7] few are currently applied in clinical practice because of the complexity and heterogeneity of sepsis. Therefore, the identification of useful biomarkers is imperative to provide timely and adequate interventions to patients with sepsis.

The neutrophil-to-lymphocyte ratio (NLR) is an indicator of systemic inflammation based on complete blood count values. In general, blood neutrophil count increases with the progress of inflammatory disease; however, in certain conditions like cachexia, the neutrophil count does not increase, resulting in “false negative” condition when evaluating disease progression. Lymphocyte count reflects the immune status of a patient, and generally decreases as inflammatory disease progresses; however, this decrease is relatively delayed and may not reflect disease progression well.[8], [9] Recently, studies have reported that the NLR is more reliable when predicting patient survival than either neutrophil count or lymphocyte count alone.[10], [11] The NLR increases with disease progression, especially in inflammatory disease, and this increase is consistent with the development of some diseases.[12] Furthermore, NLR is simple, inexpensive, and easily obtained. According to Forget et al., the mean NLR in Belgian adults who were non‑geriatric and in good health was 1.65.[13] Similarly, data from a healthy South Korean population (n = 12,160) showed that the mean NLR across all ages was 1.65, and the mean NLR of men and women were 1.63 and 1.66, respectively.[14] These results demonstrate that the NLR may be similar among different ethnicities, and an NLR of 1.65 might be proposed as a reference value for healthy patients.

Numerous studies have shown that a high NLR can be an independent predictor of prognosis in various clinical situations, including malignancies, cardiovascular disease, acute respiratory distress syndrome, and fibrotic liver diseases.[15], [16], [17], [18], [19] Although the association between NLR and mortality has been investigated in patients with sepsis, the association between NLR and clinical prognosis remains controversial.[20], [21] Generally, the discrepancies in study results are attributed to different sample sizes or other confounding parameters that may affect the association.

Meta-analysis is a quantitative statistical analysis of several separate but similar studies that is used to systematically assess the pooled data for statistical significance. Conclusions from a meta-analysis may more precisely estimate the effect of treatment or risk of disease than any individual study contributing to the pooled analysis[22]. This approach is widely used for assessing prognostic indicators in critically ill patients. In general, the NLR increases with both the occurrence of systemic inflammatory disease and the degree of inflammation. However, the exact prognostic value of NLR in sepsis remains to be clarified. Therefore, this study aimed to evaluate the association between NLR and the prognoses of patients with sepsis by meta-analysis.

Section snippets

Search strategy and selection criteria

The meta-analysis was conducted in accordance with the guidelines of the Preferred Reporting Items for Systematic Review and Meta-analyses statement.[23] PubMed, Web of Science, the Chinese National Knowledge Infrastructure database (CNKI), and the Chinese Biomedical Database (SinoMed) were systematically searched to identify suitable articles published before March 2019. The search terms included: “sepsis” or “septic,” “neutrophil-to-lymphocyte ratio” or “NLR,” and “prognosis.” We searched for

Identification of relevant studies

The initial literature search retrieved 68 potentially eligible studies based on the predefined selection criteria. We excluded 30 studies after screening the titles and abstracts. After a detailed evaluation of the full texts, 24 studies were excluded, including 10 with insufficient data, eight that were case series, four that were reviews, and two that were irrelevant to the present analysis. Thus, 14 studies [20], [21], [29], [30], [31], [32], [33], [34], [35], [36], [37], [38], [39], [40]

Discussion

The present meta-analysis of 14 studies, including 11,564 patients with sepsis, showed that the NLR was significantly higher in non-survivors than in survivors and that higher NLR was associated with prognosis in patients with sepsis. Furthermore, analysis of the combined data of nine studies, after adjusting for potential confounders, showed that patients with sepsis and increased NLR had poor prognoses, suggesting that the NLR can serve as an independent predictive indicator in patients with

Conclusions

This meta-analysis demonstrates that initial NLR may be a helpful prognostic biomarker for sepsis and that high NLR may indicate unfavorable prognoses in patients with sepsis. However, these findings should be interpreted with caution due to the aforementioned limitations.

Contributors

FZY and HKG conceived and designed the study; HZW and HWJ performed the research; HZW, FZY and HKG performed the statistical analysis; HZW and HKG wrote the manuscript; all authors read and approved the final manuscript.

Funding

This work was supported by grants from the Scientific and Technology Development Project of Qinzhou (201614505; 201616814). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Patient consent

Not required.

Consent for publication

Not required.

Data sharing statement

No additional data are available.

Declaration of Competing Interest

The authors do not have any conflicts of interest in relation to this manuscript.

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