Elevated circulating CD14++CD16+ intermediate monocytes are independently associated with extracardiac complications after cardiac surgery

Abstract

Elective cardiac surgery has low procedural complications. However, about 40% of patients develop extracardiac complications including delirium and acute kidney injury. We hypothesized that inflammatory processes and immune cell activation might be associated with these complications. We therefore prospectively included 104 patients undergoing cardiac surgery in our study. We assessed peripheral blood leukocyte populations by flow cytometry and circulating cytokines before operation, after surgery and at days one and four post-operatively. Patients undergoing cardiac surgery showed significantly elevated leukocytes and neutrophils after surgery. On the contrary, monocytes decreased after surgery and significantly increased at days 1 and 4, particularly classical (Mon1,CD14++CD16-) and intermediate (Mon2,CD14++CD16+) monocytes. While peripheral leukocyte subsets were unaltered in patients with infectious (n = 15) or cardiac complications (n = 31), post-operative leukocytes (p = 0.0016), neutrophils (p = 0.0061) and Mon2 (p = 0.0007) were clearly raised in patients developing extracardiac complications (n = 35). Using multiple logistic regression analyses, patient's age, ICU days, number of blood transfusions and elevated post-surgery Mon2 independently predicted extracardiac complications. Our findings demonstrate that elevated Mon2 after cardiac surgery are associated with an increased risk for extracardiac complications. These findings might improve the risk estimation after cardiac operations and the role of Mon2 for inflammation in cardiac surgery.

Figure 1

Characterization of immune cells in peripheral blood of patients undergoing cardiac surgery. (A) Immune cells (leukocytes, neutrophils, monocytes and lymphocytes) of patients undergoing cardiac surgery (n = 104) were analyzes before and immediately after cardiac surgery, at day 1 and 4 after cardiac surgery and compared to healthy controls (n = 23). (B) Representative gating of monocyte subpopulations into Mon1 (CD14++CD16− classical), Mon2 (CD14++CD16+ intermediate) and Mon3 (CD14−CD16+ non-classical) monocytes using flow cytometry. (C) Monocyte subpopulations in the peripheral blood of healthy controls and patients undergoing cardiac surgery at the different time-points (pre-operation, post-operation, day 1 and 4). *p < 0.05, ^**p < 0.01, ^***p < 0.001.

Figure 2

Characterization of immune cells in peripheral blood of patients developing cardiac or infectious complications after cardiac surgery. (A) Immune cell populations (leukocytes, neutrophils, monocytes) of patients undergoing cardiac surgery comparing patients developing cardiac complications (grey) to patients without cardiac complications (white), pre-operation, post-operation and at day 1 and 4 after surgery. (B) Immune cell populations of patients developing infectious complications (grey) compared to patients without infectious complications (white) during the first 4 days after surgery. *p < 0.05, ^**p < 0.01, ^***p < 0.001.

Figure 3

Characterization of immune cells and monocyte sub-populations of patients developing extracardiac complications. (A) Immune cells (leukocytes, neutrophils, monocytes) of patients undergoing cardiac surgery comparing patients developing extracardiac complications (grey) to patients without extracardiac complications (white), pre-operation, post-operation and at day 1 and 4 after operation. (B) Monocyte sub-populations of patients with (grey) or without (white) extracardiac complications at different time points before and after surgery. *p < 0.05, ^**p < 0.01, ^***p < 0.001. (C) Receiver operating characteristic (ROC) curve analyses for Mon2 (post-operation), SAPS and SOFA (both day 1) to predict extracardiac complications.