Perioperative Adiponectin and Postoperative Inflammatory Response After Major Abdominal Surgery

Surgical stress after major abdominal surgery in perioperative period causes neuroendocrine, metabolic and imunologic changes in organism with production of proinfflamatory citokines and results with appearance of systemic infflammmatory response syndrome (SIRS). Dysregulated and overrated SIRS in early postoperative period can lead to complications with additional comorbidities, longer hospital stay and poorer outcome. A low grade chronic infflammatory state in obesity and hypoadiponectinemia can enable the cytokine storm and exaggerated /dysregulated SIRS in obese patients after surgery. Obesity according to this knowledge presents independent risk factor for developing more severe systemic infflamatory response syndrome in early postoperative period after major abdominal surgery.

Hypothesis: Lower blood adiponectin levels are associated with higher systemic infflamatory response in patients after major abdominal surgery. Major aim of this study is to investigate correlation between perioperative blood levels of adiponectin and markers of systemic infflamation in patients after major abdominal surgery.

Gastrointestinal tumors are commonly presented for surgical resections. According to Global Cancer Statistics 2020: GLOBOCAN estimates colorectal carcinoma ranks third in terms of incidence, but second in terms of mortality for overall carcinomas worldwide. At the same time, obesity is a fast growing disease with of pandemic proportions with a current global prevalence of 39% according to the World Health Organisation (WHO). Many patients presented for major abdominal resections of gastrointestinal tumors are obese. Obesity is chronic disease with complex pathophisiology. Adipose tissue besides being a storage site is responsible for secretion of various adipokines with imunometabolic role. Adipokines (also called adipocytokines) are cell-signaling molecules (cytokines) produced by the adipose tissue that play many functional roles in energy/metabolic status of the body, and inflammation. Among adipokines, adiponectin is predominantly antiinfflamatory adipokine which inhibits production of infflammatory citokines (IL-6) and is decreased in obesity. Adipocyte dysfunction in obesity with altered adipokines release results in chronic low-grade inflammatory state.

Surgical stress after major abdominal surgery in perioperative period causes neuroendocrine, metabolic and imunologic changes in organism with production of proinfflamatory citokines and results with appearance of systemic infflammmatory response syndrome (SIRS). Dysregulated and overrated SIRS in early postoperative period can lead to complications with additional comorbidities, longer hospital stay and poorer outcome. A low grade chronic infflammatory state in obesity and hypoadiponectinemia can enable the cytokine storm and exaggerated /dysregulated SIRS in obese patients after surgery. Obesity according to this knowledge presents independent risk factor for developing more severe systemic infflamatory response syndrome in early postoperative period after major abdominal surgery.

Hypothesis: Lower blood adiponectin levels are associated with higher systemic infflamatory response in patients after major abdominal surgery.

Aim of this study is to:

1. Investigate correlation between perioperative blood levels of adiponectin and markers of systemic infflamation in patients after major abdominal surgery.
2. Investigate correlation between perioperative blood levels of adiponectin and appearance of systemic infflamatory response in patients after major abdominal surgery.
3. Investigate correlation between body mass index (BMI), waist circumference (WC), ultrasound measurments of abdominal fat thickness and perioperative adiponectin levels in patients presenting for major abdominal surgery.
4. Investigate correlation between perioperative blood levels of adiponectin, body mass index (BMI), waist circumference (WC), ultrasound measurments of abdominal fat thickness and appearance of postoperative complications, intensive care unit (ICU) length of stay, overall hospital length of stay and final outcome after discharge in patients after major abdominal surgery.

Research plan: After ethical approval and written informed consent, demographic, antropometric and comorbidities data will be taken from all patients included in study. BMI, waist circumference and ultrasound measurments of abdominal fat thickness ( superficial and visceral abdominal fat thickness) will be taken preoperatively. Patients will bi divivded in two groups according to BMI: obese/overweight and non obese.

Blood collections for determining adiponectin levels, IL-6, Complete Blood Count with Differential Blood Count, lactats in arterial blood, C-reactive protein(CRP), procalcitonin(PCT), plasma cholinesterase(PCE), albumins (ALB), neutrophil/lymphocite ratio (NLR), platelet/lymphocyte ratio (PLR), CRP/ALB ratio will be taken before surgery (1), 24 hours after surgery (2) and 72 hours after surgery (3). All patients will bi given the same technique of balanced general endotracheal anesthesia with the same drugs and the same postoperative multimodal analgesia regimen. Appearance of SIRS in first 72 hours postoperative period will be detected and documented according to standardized major clinical SIRS criteria. Complications in early postoperative period during hospitalisation will be including: surgical operation site related according to standardized Clavien-Dindo classification: anastomotic dehiscence, wound/local infection, postoperative bleeding, reoperation and systemic complications: sepsis, pneumonia, uroinfection, noncardiac respiratory failure, (need for noninvasive oxygen therapy), prolonged mechanical ventilation \>24 hours postoperative, reintubation, repeated mechanical ventilation, cardiovascular complivations: atrial fibrillation, congestive heart failure, myocardial infarction, acute kidney injury/failure.

Length of ICU and overall hospital stay with final outcome after discharge from hospital will be documented.

Significance/Expected scientific contribution: Understanding of the underlying mechanisms which contributes to the appearance and severity of SIRS in early postoperative period is important for developing more predictive diagnostics and possible treatment options for postoperative complications. The adipocytokines have important role in many aspects of inflammation and immunity. This study can help in better understanding the role od adiponectin in pathophysiology of SIRS after major surgery.

Eligibility Criteria:
Inclusion Criteria:

Age \>18 years Patient presenting for major elective abdominal surgery of gastrointestinal system according to tumor.

Exclusion Criteria:

Age\<18 years BMI\<18.5kg/m2 Acute surgical conditions Established acute systemic/local infection Chronic/actual corticosteroid therapy Active immunomodulation therapy Allergie to used anestehetics/analgetics in study.