Glycocalyx Levels in Patients Undergoing Pancreatectomy

Study Overview
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Brief Summary
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Background: On the surface of every healthy cellular membrane resides a layer known as the glycocalyx. This structure consists of extracellular domains of receptor, adhesion and transmembrane molecules such as syndecan-1 covalently bound to highly negatively charged glycosaminoglycans, heparan sulfates. It has a principal role to maintain wall integrity, avoid inflammation and tissue oedema in vessels but in contrast, glycocalyx is robust and elevated on cancer cells. This study examines whether the endothelial glycocalyx layer is preserved in patients undergoing pancreatectomy with human albumin 5% vs. gelofusine in a restrictive goal directed fluid regime perioperatively for the first 24hours. Degradation of glycocalyx will be investigated by analyzing basic levels of the core protein syndecan-1 and heparan sulfates with post-operative samples.

Detailed Description
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This is a prospective study that will be conducted in the Main Operating theatres of UMMC on patients with pancreatic cancer undergoing elective pancreatectomy (includes all forms of pancreatectomy such as Whipple's procedure, total or distal pancreatectomy). This study aim to determine the association of glycocalyx degradation by measuring levels of syndecan-1 and heparan sulfate with type of colloidal fluid given, human albumin 5% versus gelofusine in a restrictive goal directed fluid therapy in pancreatectomy. Institutional ethics approval and registration in Clinical Trial Registry will be obtained before recruiting the first case. Recruited patients will be randomly allocated to either the group receiving human albumin 5% or gelofusine. Sample size: There is no previously published literature related exactly to the pathology and methods of this proposed study. Therefore, a preliminary sample size calculation will be based on the closest study on fluids with a two-sided confidence interval of 0.95 and a desired power of 0.80 to yield a result that investigators need nine patients in each group. After adjusting for drop out rate of 10%, investigators will recruit ten in each group for human albumin 5% and gelofusine respectively within the study period of 2 years. Data collection: Intraoperative phase All preoperative preparation including fasting will be done in accordance to UMMC protocol. Intraoperative monitoring includes standard routine monitoring as per American Society of Anaesthesiologist Guidelines, invasive haemodynamic monitoring with arterial blood pressure incorporating FloTrac, BIS and neuromuscular monitoring. All patients will be under general anesthesia. Fluid management for both groups are in accordance to goal directed therapy and guided by stroke volume variation of approximately 12-15%. If SVV is > 15%, 250ml of fluid replacement according to patient group will be given over 30 min within 24 hours intra and post operatively in the Intensive Care Unit (ICU). In both groups, all clinical parameters and fluids including blood that will be given will be recorded. Post-operative phase: The allocated colloid fluid will be continued. Patients will be assessed for pancreatic fistula leak. The grading of pancreatic fistula will be defined according to the guideline of Revised 2016 International Study Group on Pancreatic Fistula (ISGPF). Reviews will be done on post op days 1, 3, 5 and 30. Amylase levels from drain tube post-op Day 3, 5 and 7 will be measured. The total duration of stay in intensive care, hospital and rate of mortality/ morbidity (re-laparotomy/ re-admission to ICU/ sepsis) within 30 days after surgery will be assessed and recorded. Laboratory phase Blood samples are collected at 5 time points, a) preoperative, b) immediate postoperative and c) 24 hours postoperative d) Day 3 and e) Day 7 postoperative from both groups. The serum fraction will be frozen and stored at -80°C until assayed. Syndecan 1 concentrations and heparan sulfate concentrations are quantified using special enzyme-linked immunosorbent assay kit as previously reported. Inflammatory markers Interleukin-1 and CRP and any blood investigations as per hospital sepsis protocol will be determined as well.

Official Title
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Glycocalyx Levels in Patients Undergoing Pancreatectomy With Human Albumin 5% vs. Gelofusine

Conditions
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Pancreatectomy, Endothelial Degeneration, Pancreatic Cancer, Postoperative Pancreatic Fistula

Intervention / Treatment
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* Other: human albumin 5%
* Other: gelofusine.


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ASA 1-3 patients aged between 18-75 years old with written informed consent Exclusion Criteria: Patients who refuse to participate, Have severe congestive heart failure (NYHA class III/IV) or severe respiratory disease (PaO2/FiO2 < 200), Suffer significant renal or hepatic dysfunction (creatinine raised >50 % or liver enzymes >50 % of normal values), Pregnant Allergic to gelofusine and human albumin

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized control trial with Albumin 5% given as the intervention and Gelofusine as active control.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: human albumin 5%<br>10 patients with pancreatic cancer will receive human albumin 5% in a restrictive goal directed fluid regime preoperatively for the first 24 hours. | Other: human albumin 5%<br>* Human Albumin 5% will be given as fluid management for this group in accordance to goal directed therapy and guided by stroke volume variation of approximately 12-15%. This percentage of SVV has been validated as a threshold above which fluid administration increases stroke volume with an area under the receiver operating characteristics curve reported at 0.87. If the SVV remains more than 15% for more than 2 minutes, 250ml of fluid replacement according to patient group will be given. These boluses are given in aliquots over 30 min to avoid effects of rapid volume expansion. and the same fluid and technique will be carried out within 24 hours intra and post operatively in the Intensive Care Unit (ICU). All clinical parameters and fluids including blood that will be given will be recorded.<br>* Other names: Fluid management;|
| Active Comparator: gelofusine<br>10 patients with pancreatic cancer will receive gelofusine in a restrictive goal directed fluid regime preoperatively for the first 24 hours. | Other: gelofusine.<br>* Gelofusine will be given as fluid management for this group in accordance to goal directed therapy and guided by stroke volume variation of approximately 12-15%. This percentage of SVV has been validated as a threshold above which fluid administration increases stroke volume with an area under the receiver operating characteristics curve reported at 0.87. If the SVV remains more than 15% for more than 2 minutes, 250ml of fluid replacement according to patient group will be given. These boluses are given in aliquots over 30 min to avoid effects of rapid volume expansion. and the same fluid and technique will be carried out within 24 hours intra and post operatively in the Intensive Care Unit (ICU). All clinical parameters and fluids including blood that will be given will be recorded.<br>* Other names: Fluid management;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurence of pancreatic fistula leak | Review will be done according to guideline of Revised 2016 International Study Group on Pancreatic Fistula (ISGPF) | Within post-op 30 days | 
| Changes in serum syndecan 1 concentrations | Blood samples are collected to check for syndecan 1 concentrations in serum | Within post-op 7 days | 
| Changes in serum heparan sulfate concentrations | Blood samples are collected to check for heparan sulfate concentrations in serum | Within post-op 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in levels of Inflammatory markers Interleukin-1 and CRP | Blood samples are collected to check level of the Inflammatory markers Interleukin-1 and CRP | Within post-op 7 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Glycocalyx levels, pancreatectomy, human albumin 5%, gelofusine, pancreatic fistula