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

Abstract Purpose To determine the proportion of critically ill patients with and without sepsis who exhibit persistent lymphopenia and examine its relationship with hospital survival. Methods Database analysis of adult intensive care unit (ICU) patients at two hospitals in Queensland, Australia and the MIMIC III database from Boston, USA. Results We defined persistent lymphopenia at two thresholds (absolute lymphocyte count [ALC] <1.0 and <0.75 x 10 9 /L) based on two qualifying values recorded during the first four days in ICU. In the USA cohort 27,646/32,528 (85.0%) patients did not have two ALCs recorded with evidence that data were not missing at random; consequently, we report the analysis of the Australian cohort. In the Australian cohort 7605/8507 (89.4%) patients had two ALCs recorded, 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. 562/3030 (18.5%) patients with persistent lymphopenia (ALC<1.0) died in hospital compared with 439/4575 (9.6%) patients without persistent lymphopenia. Persistent lymphopenia was an independent risk factor for in hospital death in all patients. The hazard ratio for death at ALC<1.0 was 1.89 (95%CI 1.31 – 2.85) and 1.17 (1.02 – 1.36) in patients with and without sepsis respectively. Conclusions Persistent lymphopenia is common in critically ill patients and associated with increased risk of death. The association is stronger in patients with sepsis. Trials testing the hypothesis that reversing lymphopenia reduces mortality should initially target patients with sepsis.