AOrtic Surgery: Systemic Inflammatory Response Versus Sepsis

The goal of the prospective observational study is to evaluate the immunological background of inflammatory response often seen after open thoracic aortic surgery. Patients scheduled for this type of procedure will undergo a series of blood testing (preoperatively, and several times postoperatively). The blood samples will be used for a wide scale of immunological tests to better evaluate potential differential markers against infection. A control group will include patients with active infective endocarditis (preoperatively).

The main question is if there is a biomarker able to determine a difference between sterile systemic inflammation and infection after thoracic aortic surgery. The second question is if there is a difference in dynamics of evaluated biomarkers between sterile postoperative inflammation and active endocarditis.

It has been observed in daily clinical practice that patients after thoracic aortic replacement (of any extent, of any reason) often develop a set of specific symptoms. Those include fever, weakness and prolonged rise of standard laboratory parameters of inflammation (CRP and leucocyte level) in absence of infection. Those symptoms may, but do not have to, coincide with typical signs of postcardiotomy syndrome, rather characteristic by pericardial / pleural effusion and indifferent chest pain. They rather resemble a so called "postimplantation" syndrome, described after endovascular aortic repair. As a reaction to foreign vascular graft material, pro-inflammatory cytokines are being released, thus leading to flu-like symptoms in absence of true infection. Those occur in the short-term postoperatively, usually in the first 2 weeks after the surgery.

Patients after thoracic aortic surgery represent a high-risk patient cohort vulnerable to infections of any kind, mostly respiratory, urinary, wound infections, and, last but not least, early valve endocarditis / endoaortitis being the most feared of them. While clinicians (and patients) are often afraid of the abovementioned complications, the patients are forced to undergo complex diagnostic process including repeated echocardiography, collection of microbiology cultures and blood samples, chest computer tomography imaging with extensive radiation burden. The prolonged broad-spectrum empiric antibiotic treatment is often in place together with prolonged hospital stay and limited patient satisfaction. The question of starting the immunosuppressive treatment is often weighed against the potential aggravation of infection with eventual fatal consequences.

In absence of a specific biomarker to distinguish between the sterile systemic inflammation and infection, the clinicians must rely on complex evaluation of patient symptoms, clinical examination, imaging modalities, standard laboratory measures of inflammation and microbiology cultures (with some delay). However, in the era of molecular biology and extensive progress in immunology research, there has been a long row of potential biomarkers able to specify the etiology of inflammatory process significantly sooner.

The potential biomarkers of inflammation suitable for this issue are mentioned in detail further. Conventional biomarkers include CRP, leukocyte count, differential blood count, recently also procalcitonin (PCT), tumor necrosis factor-α (TNF- α) and interleukin-6 (IL-6). Hematology tests have reported novel early markers of sepsis, e.g. mean neutrophil volume or neutrophil-to-lymphocyte ratio. Novel serology markers (mostly assessed by ELISA) include soluble triggering receptor expressed on myeloid cell-1 (sTREM-1), presepsin, serum amyloid-A, pentraxin 3, hemoxygenase-1 (HO-1), soluble CD64 (sCD64), soluble CD163 (sCD163), high mobility group box-1 (HMGB-1), lipopolysaccharide-binding protein (LBP) and others. Newly, the molecules expressed on the surface of circulating blood cells may be examined using flow cytometry: CD64 on polymorphonuclears (PMN CD64 index) or monocytes, CD163, CD167, HLA-DR etc. Cell function assays which test ability of blood cells to respond to microbial stimuli (represented by LPS, flagellin, etc.) may reveal changes in soluble biomarkers, such as IL-18 or IFN-γ that reflect nature of inflammation in patients.

Recently, several scoring systems have emerged combining panels of various biomarkers. There is a promising evidence for a composite of serum and cell-expressed parameters, called "Bioscore", including procalcitonin, sTREM-1 and PMN CD64 index. A composite of 5 hematological parameters has proven to be a reliable marker of early sepsis, being called intensive care infection score (ICIS). Another scoring systems have been developed by group of Kofoed et al. Nevertheless, most of these scoring systems have been tested in the settings of unstable patients in the intensive care unit. The issue of inflammatory response described above is mostly a matter of stable patients in the standard ward who develop signs of undetermined inflammation. Eventual diagnostic modalities in these settings have been only scarcely evaluated before. The topic of inflammatory response after aortic surgery (IRAS) has not been studied in the literature yet.

Eligibility Criteria:
Inclusion Criteria (for study group):

* patient scheduled for elective replacement of thoracic aorta of any extent by artificial vascular graft, including Bentall procedure, Yacoub procedure, supracoronary aortic replacement, also Ross procedure with supracoronary aortic replacement, hemiarch and total aortic arch replacement
* signature of informed patient consent

Exclusion Criteria (for study group):

* active endocarditis or other infection
* unstable preoperative condition

Inclusion Criteria (for control group):

* patient with active infectious endocarditis
* signature of informed patient consent

Exclusion Criteria (for control group):

* more than 5 days since diagnosis