The neutrophil-to-lymphocyte ratio levels over time correlate to all-cause hospital mortality in sepsis

Objective: This research aims to investigate the prognosis value using the time-weighted average neutrophil-to-lymphocyte ratio (TWA-NLR) for predicting all-cause hospital mortality among sepsis patients. Data were analyzed through the use of the eICU Collaborative Research Database (eICU-CRD 2.0) as well as Medical Information Mart for Intensive Care IV 2.2 (MIMIC-IV 2.2). Methods: Septic patients from both eICU-CRD 2.0 as well as MIMIC-IV 2.2 databases were included. The neutrophil-to-lymphocyte ratios (NLR) were available for analysis, utilizing complete blood counts obtained on days one, four, and seven following ICU admission. The TWA-NLR was computed at the end of the seven days, and patients were then stratified based on TWA-NLR thresholds. 90-day all-cause mortality during hospitalization was the primary objective, with 60day all-cause hospital mortality as a secondary objective. The correlation between TWA-NLR and sepsis patients' primary outcome was analyzed using univariable and multivariable Cox proportional hazard regressions. A restricted cubic spline (RCS) analysis was conducted in an attempt to confirm this association further, and subgroup analyses were employed to evaluate the correlation across various comorbidity groups. Results: 3921 patients were included from the eICU-CRD 2.0, and the hospital mortality rate was 20.8 %. Both multivariable as well as univariable Cox proportional hazard regression analyses revealed that TWA-NLR was independently correlated with 90-day all-cause hospital mortality, yielding a hazard ratio (HR) of 1.02 (95 % CI 1.01-1.02, P-value<0.01) as well as 1.12 (95 % CI 1.01-1.15, P-value<0.01), respectively. The RCS analysis demonstrated a significant nonlinear relationship between TWA-NLR and 90-day all-cause hospital mortality risk. The study subjects were divided into higher (>10.5) and lower (<= 10.5) TWA-NLR cohorts. A significantly decreased incidence of 90-day all-cause hospital mortality (HR = 0.56, 95 % CI 0.48-0.64, P-value<0.01) and longer median survival time (40 days vs 24 days, P-value<0.05) were observed in the lower TWA-NLR cohort. However, septic patients with chronic pulmonary (interaction of P-value = 0.009) or renal disease (interaction of P-value = 0.008) exhibited significant interactive associations between TWA-NLR and 90-day all-cause hospital mortality, suggesting the predictive power of TWA-NLR may be limited in these subgroups. The MIMIC-IV 2.2 was utilized as a validation cohort and exhibited a similar pattern. Conclusion: Our findings suggest that TWA-NLR is a powerful and independent prognostic indicator for 90-day all-cause hospital mortality among septic patients, and the TWA-NLR cutoff value may prove a useful method for identifying high-risk septic patients.