Clinical trial NCT06057207: Perioperative Adiponectin and Postoperative Inflammatory Response After Major Abdominal Surgery
Official title: Effects of Perioperative Serum Adiponectin on Postoperative Systemic Inflammatory Response in Patients Undergoing Major Abdominal Surgery
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Obesity, Abdominal
Surgery
Systemic Inflammatory Response Syndrome
Postoperative Complications
Keywords: adiponectin
IL-6
obesity
surgery
systemic infflamatory response syndrome
Lead sponsor: Osijek University Hospital
Sponsor class: OTHER
First posted: 2023-09-28
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients presenting for major (open) elective abdominal surgery of gastrointestinal system according to tumor.

Brief summary: 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.

Detailed description: 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.

Primary outcomes:
measure: Adiponectin
timeFrame: Preoperative, 24 hours after surgery, 72 hours after surgery
Secondary outcomes:
measure: IL-6
timeFrame: Preoperative, 24 hours after surgery, 72 hours after surgery
Other outcomes:
Locations:
city: Osijek
country: Croatia
facility: Osijek University Hospital
city: Osijek
country: Croatia
facility: Sonja Škiljić
Study officials:
affiliation: Department of Anaesthesiology, Resuscitation and ICU, Osijek University Hospital,
name: Slavica Kvolik
role: STUDY_DIRECTOR
References:
citation: Florescu A, Branisteanu D, Bilha S, Scripcariu D, Florescu I, Scripcariu V, Dimofte G, Grigoras I. Leptin and adiponectin dynamics at patients with rectal neoplasm - Gender differences. PLoS One. 2019 Aug 19;14(8):e0212471. doi: 10.1371/journal.pone.0212471. eCollection 2019.
citation: Boersema GSA, Wu Z, Menon AG, Kleinrensink GJ, Jeekel J, Lange JF. Systemic Inflammatory Cytokines Predict the Infectious Complications but Not Prolonged Postoperative Ileus after Colorectal Surgery. Mediators Inflamm. 2018 Mar 6;2018:7141342. doi: 10.1155/2018/7141342. eCollection 2018.
citation: Barbic J, Ivic D, Alkhamis T, Drenjancevic D, Ivic J, Harsanji-Drenjancevic I, Turina I, Vcev A. Kinetics of changes in serum concentrations of procalcitonin, interleukin-6, and C- reactive protein after elective abdominal surgery. Can it be used to detect postoperative complications? Coll Antropol. 2013 Mar;37(1):195-201.
citation: Neskovic N, Mandic D, Marczi S, Skiljic S, Kristek G, Vinkovic H, Mraovic B, Debeljak Z, Kvolik S. Different Pharmacokinetics of Tramadol, O-Demethyltramadol and N-Demethyltramadol in Postoperative Surgical Patients From Those Observed in Medical Patients. Front Pharmacol. 2021 Apr 15;12:656748. doi: 10.3389/fphar.2021.656748. eCollection 2021.
citation: Wei Y, Zhu F, Gong J, Yang J, Zhang T, Gu L, Zhu W, Guo Z, Li Y, Li N, Li J. High Visceral to Subcutaneous Fat Ratio Is Associated with Increased Postoperative Inflammatory Response after Colorectal Resection in Inflammatory Bowel Disease. Gastroenterol Res Pract. 2018 Apr 3;2018:6270514. doi: 10.1155/2018/6270514. eCollection 2018.