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.Despite advances in surgical and anesthetic techniques as well as enhanced postoperative care, cardiac surgery is still associated with a high risk of postoperative complications 1 . Besides typical cardiac (e.g., arrhythmia, myocardial infarction) and infectious complications (e.g., wound infection, pneumonia and sepsis), extracardiac non-infectious complications like acute kidney injury (AKI, 30%) and delirium (up to 26-52%) are frequent in patients after cardiac surgery 2,3 . It has been speculated that a large part of these complications could be explained by excessive inflammation caused by extracorporeal cardio-pulmonary bypass (CPB), hypothermia, myocardial ischemia and reperfusion and tissue damage due to the surgical procedure 4,5 . The influence of distinct immune cells and their subpopulations on the occurrence of post-operative complications is still ambiguous and needs further investigations. Particularly monocytes seems to play in important role within this context 6,7 .Circulating monocyte subsets represent a continuum of differentiation stages 8,9 . Using the surface markers CD14 (LPS receptor) and CD16 (FcγRIII), blood monocytes can be subdivided into three subpopulations, CD14++CD16− "classical" monocytes (Mon1), CD14++CD16+ "intermediate" (Mon2) and CD14-16+

The Innate Immune Response Characterizes Posterior Reversible Encephalopathy Syndrome

“…The importance of intermediate monocytes as a potential driver of vascular disorders in general and PRES in particular is further highlighted by the association with the length of hospital stay providing a potential use for these cells in risk stratification, as already proposed for other vascular events, such as cardiac surgery [15]. Here, similar to the present study, levels of intermediate monocytes correlated with the length of hospital stay as surrogate marker for disease severity [15].…”

“…The importance of intermediate monocytes as a potential driver of vascular disorders in general and PRES in particular is further highlighted by the association with the length of hospital stay providing a potential use for these cells in risk stratification, as already proposed for other vascular events, such as cardiac surgery [15]. Here, similar to the present study, levels of intermediate monocytes correlated with the length of hospital stay as surrogate marker for disease severity [15]. Lastly, identification of intermediate monocytes might hold clinical value as this subpopulation differentiates PRES from PML patients as neuroinflammatory disorder presenting with similar radiographic features through readily accessible blood testing, thus, potentially improving diagnostic approaches and consequently management of PRES.…”

“…However, the pathophysiological mechanism by which monocytes might mediate vascular disease remains elusive and requires further studies. Interestingly, intermediate monocytes are associated with systemic complications following cardiac surgery and are increased in advancedstage peripheral artery occlusive disease [15], pointing towards a common mechanism of action. We hypothesize that monocyte alterations might either mediate or are evidence of "downstream" vascular dysfunction in response to a systemic challenge, such as infections, surgery, or immunosuppressant therapies.…”

“…Next, we aimed to investigate whether CD14 ++ /CD16 + cell numbers correlate with disease severity. As there are no established clinical measurements for assessing disease severity in PRES, we used the length of hospital stay as surrogate marker (median = 10 days (IQR 8)), particularly as this parameter has been previously used in association with intermediate monocytes [15]. As hospital stay is likely influenced by clinical parameters such as the number of comorbidities, we used a multiple regression model (Fig.…”

Monocyte subsets predict mortality after cardiac arrest

“…24,25 Several clinical observations have described elevated IM as biomarkers for outcome and disease severity in critical conditions. 13,15,26 In addition, largescale studies evaluated monocyte subsets as predictors of adverse cardiac outcomes in stable cohorts suggesting such a role for both the classical and intermediate subset. 11,12,27 In our analysis, the proportion of CM at admission was inversely correlated with CRP levels, an unspecific marker of inflammatory activity as well as with PCT, a novel biomarker with potential to differentiate between inflammation and infection.…”