Early persistent lymphopenia and risk of death in critically ill patients with and without sepsis

Abstract

ABSTRACT Purpose To examine the relationship of early persistent lymphopenia with hospital survival in critically ill patients with and without sepsis to assess whether it can be considered a treatable trait. Methods Retrospective database analysis of patients with non-elective admission to ICUs during January 2015 to December 2018. Patients were classified as having sepsis if the Acute Physiology and Chronic Health Evaluation (APACHE) III admission diagnostic code included sepsis or coded for an infection combined with a Sequential Organ Failure Assessment (SOFA) score of ≥2. We defined early persistent lymphopenia at two thresholds (absolute lymphocyte count [ALC] <1.0 and < 0.75x109/L) based on two qualifying values recorded during the first four days in ICU. The main outcome measure was time to in-hospital death. Results Of 8507 eligible patients, 7605 (89.4%) had two ALCs recorded during their first four days in ICU, of these 1482 (19.5%) had sepsis. Persistent lymphopenia (ALC < 1.0) was present in 728/1482 (49.1%) and 2302/6123 (37.6%) of patients with and without sepsis, respectively. For ALC <0.75 the results were 487/1482 (32.9%) and 1125/6123 (18.4%), respectively. Of 3030 patients with persistent lymphopenia (ALC < 1.0) 562 (18.5%) died compared with 439/4575 (9.6%) without persistent lymphopenia. Persistent lymphopenia was an independent risk factor for in-hospital death in all patients. The hazard ratios for death at ALC < 1.0 were 1.89 (95%CI 1.32–2.71, p = 0.0005) and 1.17 (1.02–1.35, p = 0.0246) in patients with and without sepsis respectively. Conclusions Early persistent lymphopenia is common in critically ill patients and associated with increased risk of death in patients with and without sepsis. Although the association is stronger in patients with sepsis, lymphopenia is a candidate to be considered a treatable trait; drugs that reverse lymphopenia should be trialled in critically ill patients.