Abstract
BACKGROUND: Evidence on the changes in the absolute counts of monocyte subpopulations in sepsis is missing. METHODS: Firstly, absolute counts of circulating CD14(pos)/HLA-DR(pos)/CD45(pos) monocytes were measured by flow cytometry in 70 patients with Gram-negative sepsis and in 10 healthy volunteers. In the second phase, immunophenotyping was performed and the absolute count of circulating inflammatory monocytes and of circulating CD14(dim)/CD16(pos)/CD45(pos) patrolling monocytes were measured in another 55 patients and 10 healthy volunteers. Measurements were repeated on days 3, 7, and 10. Results were correlated with survival after 28 days. RESULTS: Greater numbers of CD14(pos)/HLA-DR(pos)/CD45(pos) monocytes were found on day 1 in survivors compared to nonsurvivors (p = 0.030). Receiver operating characteristic (ROC) analysis showed that a cutoff higher than 337 cells/mm(3) on day 1 could discriminate between survivors and nonsurvivors with a positive predictive value (PPV) of 91.1%. Logistic regression including Sequential Organ Failure Assessment (SOFA) score and Acute Physiology and Chronic Health Evaluation (APACHE) II score showed that an absolute count greater than 337 cells/mm(3) was independently associated with unfavorable outcome (odds ratio (OR) 0.19, p = 0.050). The absolute counts of inflammatory and of CD14(dim)/CD16(pos)/CD45(pos) monocytes were greater in patients than healthy controls during the entire 10 days of follow-up. The absolute counts on day 3 of CD14(dim)/CD16(pos)/CD45(pos) monocytes were greater in survivors than nonsurvivors (p = 0.027). ROC analysis revealed that the cutoff at 27 cells/mm(3) could discriminate between survivors and nonsurvivors with PPV of 94.1%. Logistic regression including age, SOFA score, and APACHE II score showed that an absolute count greater than 27 cells/mm(3) was independently associated with unfavorable outcome (OR 0.06, p = 0.033). Logistic regression analysis showed that intra-abdominal infection on day 1 was predictive of low CD14(dim)/ CD16(pos)/CD45(pos) count on day 3. CONCLUSION: Circulating counts of inflammatory and patrolling monocytes are greatly increased in Gram-negative sepsis. Absolute counts of CD14(pos)/HLA-DR(pos)/CD45(pos) monocytes on day 1 and CD14(dim)/CD16(pos)/CD45(pos) monocytes on day 3 are independently associated with final outcome. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01223690 . Registered retrospectively on 18 October 2010.