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This study was performed to evaluate the association of monocyte counts with mortality, the rate of bacteremia, and organ dysfunction and to evaluate whether the change in monocyte counts from the premorbid state to sepsis would differ between survivors and non-survivors in patients with severe sepsis including septic shock. A retrospective analysis of patients with severe sepsis including septic shock was performed. Monocyte counts were categorized into <250, 250–500, 500–750, and ≥750 cells/μL; in addition, 28-day mortality, the rate of bacteremia, and organ dysfunction were compared between the groups. Multivariate logistic regression analyses were performed to evaluate the independent association of initial blood cell counts with 28-day mortality. Subgroup analyses of patients who had premorbid data of blood cell counts were performed to evaluate the difference in the change in monocyte counts between survivors and non-survivors. During the study period, 2,012 patients were included. Neutrophil and monocyte counts were significantly different between survivors and non-survivors. However, only monocyte counts were independently associated with mortality in the multivariate logistic regression analyses. Patients with initial monocyte counts <250 cells/μL showed the highest mortality, rate of bacteremia, and organ dysfunction. In patients who had premorbid blood cell counts, the monocyte counts increased in survivors but decreased in non-survivors from the premorbid to sepsis. In conclusion, monocyte counts were associated with mortality, the rate of bacteremia, and organ dysfunction in patients with sepsis, possibly due to the relative lack of monocytopoiesis related to septic insults in non-survivors.