U‐shaped correlation of lymphocyte count with all‐cause hospital mortality in sepsis and septic shock patients: a MIMIC‐IV and eICU‐CRD database study

U‐shaped correlation of lymphocyte count with all‐cause hospital mortality in sepsis and septic shock patients: a MIMIC‐IV and eICU‐CRD database study

Sepsis, Lymphocyte counts, Prediction, Restricted cubic spline, Intensive care unit

Abstract

Background In sepsis, the relationship between lymphocyte counts and patient outcomes is complex. Lymphocyto-
penia and lymphocytosis significantly influence survival, illustrating the dual functionality of lymphocytes in respond-
ing to infections. This study investigates this complex interaction, focusing on how variations in lymphocyte counts

correlate with all-cause hospital mortality among sepsis patients.

Methods This retrospective cohort study analyzed data from two extensive critical care databases: the Medical Infor-
mation Mart for Intensive Care IV 2.0 (MIMIC-IV 2.0) from Beth Israel Deaconess Medical Center, Boston, Massachusetts,

and the eICU Collaborative Research Database (eICU-CRD), which was Multi-center database from over 200 hospitals
across the United States conducted by Philips eICU Research Institute. We included adult patients aged 18 years
and older who met the Sepsis-3 criteria, characterized by documented or suspected infection and a Sequential

Organ Failure Assessment (SOFA) score of 2 or higher. Sepsis patients were categorized into quartiles based on lym-
phocyte counts. The primary outcome was all-cause mortality in the hospital, with 90 and 60-day all-cause mortality

as the secondary outcomes. Univariable and multivariable Cox proportional hazard regressions were utilized to assess
lymphocyte counts’ impact on hospital mortality. An adjusted restricted cubic spline (RCS) analysis was performed
to elucidate this relationship further. Subgroup analyses were also conducted to explore the association across various
comorbidity groups among sepsis and septic shock patients.
Results Our study included 37,054 patients, with an observed in-hospital mortality rate of 16.6%. Univariable

and multivariable Cox proportional hazard regression models showed that lymphocyte counts were indepen-
dently associated with in-hospital mortality (HR=1.04, P<0.01; HR=1.06, P<0.01). RCS regression analysis revealed

a U-shaped relationship between lymphocyte levels and hospital mortality risk in sepsis and septic shock patients
(P for overall<0.001, P for nonliner<0.01; P for overall=0.002, P for nonliner=0.014). Subgroup analyses revealed
that elevated lymphocyte counts correlated with increased hospital mortality among sepsis patients with liver disease

and requiring renal replacement therapy (P for overall=0.021, P for nonliner=0.158; P for overall=0.025, P for non-
liner=0.759). These findings suggest that lymphocytes may have enhanced prognostic value in specific subsets

of critically ill sepsis patients.

Guyu Zhang1

, Tao Wang1
, Le An1
, ChenChen Hang1

, XingSheng Wang1
, Fei Shao1
, Rui Shao1 and Ziren Tang1*

https://doi.org/10.1186/s12245-024-00682-6

2024

Peri Irawan

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