Comparison of Liberal and Restrictive Fluid Management on the Endothelial Glycocalyx in Radical Cystectomy

Study Overview
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Brief Summary
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The aim of this study is to compare the effect of the liberal and restrictive fluid treatments which are routinely performed in major urological surgeries in the perioperative period on ANP release and the endothelial glycocalyx layer. In the study, the investigators aimed to compare changes in the glycocalyx structure by measuring the blood levels of ANP and heparan sulfate, hyaluronan and syndecan 1, which form the glycocalyx structure on the patients who received the liberal and restrictive fluid treatments during major urological surgeries.

Detailed Description
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There is no strong evidence about the optimal fluid resuscitation for the patients undergoing major surgeries. Avoiding excess fluid resuscitation in the perioperative period is essential for reducing postoperative complications, morbidity and long-term mortality. In the perioperative period, ANP is released with increased wall stress in the cardiac atrium due to excess fluid loading. With the release of ANP, damage occurs in the glycocalyx layer, which is the structure primarily responsible for the permeability in the vascular endothelium. Thus, the amount of ANP released from atrium and heparan sulfate, syndecan 1, hyaluronan in the glycocalyx layer structure increases in the blood. The aim of this study is to compare changes in the glycocalyx structure by measuring the blood levels of ANP and heparan sulfate, hyaluronan and syndecan 1, which form the glycocalyx structure on the patients who received the liberal and restrictive fluid treatments during major urological surgeries. The blood samples will be taken at the beginning and at the end of the surgery. The primary outcome of this study is the increase in ANP levels and heparan sulfate , hyaluronic acid, syndecan 1 levels which are the glycocalyx damage products in blood. Secondary outcomes are intraoperative advanced hemodynamic cardiac measurement values, the amount of blood and blood products replaced to patients, duration of intensive care stay, duration of hospital stay, cardiac and respiratory complications, gastrointestinal complications, urinary complications, surgical complications such as anastomotic leaks, wound infection and fistula.

Official Title
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Comparison of the Effects of Perioperative Liberal and Restrictive Fluid Management on the Endothelial Glycocalyx Layer in Radical Cystectomy and Urinary Diversion

Conditions
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Fluid Retention Tissue

Intervention / Treatment
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* Other: liberal fluid management
* Other: restrictive fluid management


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ASA (The American Society of Anesthesiologists) status I-II-III patients Cases undergoing major urological surgery Cases for invasive artery monitoring and central venous catheterization Patients receiving general anesthesia Volunteering to participate in the study Exclusion Criteria: Coagulopathy Patients with severe heart, kidney and liver dysfunction (EF <35% and / or GFR <30, Cre:> 2.5 and / or impaired liver function tests)

Ages Eligible for Study
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Minimum Age: 18 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
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: liberal fluid therapy<br>Patients will be applied 2 mg midazolam for premedication. Before anesthesia induction, epidural catheter will be inserted to all patients and test dose will be made with 3 cc % 2 lidocaine (No medication from the epidural catheter will be administered during surgery). Standard anesthesia induction will be applied (fentanyl 2 mcg/kg; propofol 2 mg/kg; rocuronium 0.6 mg/kg ), and after intubation maintenance of anesthesia will be achieved with sevoflurane with a minimum alveolar concentration (MAC) of 0.8-1. Fluid resuscitation will be started with 10 ml / kg / hr Ringer's lactate solution. In patients with MAP <65 mmHg, 250 ml of Ringer's lactate solution will be given as a bolus. If the hypotension persists, the bolus 250 ml Ringer's lactate solution will be repeated up to 10 times. | Other: liberal fluid management<br>* 10 ml/ kg/ hr Ringer's lactate solution<br>|
| Active Comparator: restrictive fluid therapy<br>Patients will be applied 2 mg midazolam for premedication. Before anesthesia induction, epidural catheter will be inserted to all patients and test dose will be made with 3 cc % 2 lidocaine ( No medication from the epidural catheter will be administered during surgery. ) Standard anesthesia induction will be applied ( fentanyl 2 mcg/kg; propofol 2 mg/kg; rocuronium 0.6 mg/kg ) and after intubation maintenance of anesthesia will be achieved with sevoflurane with a minimum alveolar concentration (MAC) of 0.8-1. Fluid resuscitation will be started with 2 ml / kg / hr Ringer's lactate solution and norepinephrine infusion at a dose of 2 mcg / kg / hr. In patients with MAP<65 mmHg, norepinephrine dose will be increased up to 8 mcg / kg / hr. If the hypotension persists although the norepinephrine dose is 8 mcg / kg / hr, 250 ml bolus Ringer's lactate solution will be given. | Other: restrictive fluid management<br>* 2 ml/ kg/ hr Ringer's lactate solution with 2 mcg / kg / hr norepinephrine infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Atrial Natriuretic Peptide (ANP)( pg/mL) | Blood ANP concentration will be determined using an enzyme-linked immunosorbent assay kit | The blood sample will be taken at beginning and end of the surgery | 
| Heparan sulfate (ng/L) | Blood Heparan sulfate concentration will determine using an enzyme-linked immunosorbent assay kit | The blood sample will be taken at beginning and end of the surgery | 
| Syndecan 1 (pg/mL) | Blood Syndecan 1 concentration will be determined using an enzyme-linked immunosorbent | The blood sample will be taken at beginning and end of the surgery | 
| Hyaluronan (ng/L) | Blood Hyaluronan concentration will be determined using an enzyme-linked immunosorbent | The blood sample will be taken at beginning and end of the surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Amount of blood transfusion (unit) | Including red cell, fresh frozen plasma | From the beginning surgery to day 2 postoperatively | 
| Total intensive care unit (ICU) stay (Hour, day) | Including initial ICU admission and readmission times | 30 days postoperative | 
| Hospital stay (Hour, day) | From the beginning of surgery until actual hospital discharge | 90 days postoperative | 
| Gastrointestinal complications | Ileus, constipation, gastrointestinal bleeding, gastric ulcer, anastomotic intestinal leakage | 30 days postoperative | 
| Infectious complications | Urinary tract infection, pyelonephritis, urosepsis, pneumonia, wound infection | 30 days postoperative | 
| Surgical site complications | Wound dehiscence, evisceration | 30 days postoperative | 
| Genitourinary complications | Acute kidney injury, urethral anastamosis leak | 30 days postoperative | 
| Cardiac complications | Acute myocardial infarction, congestive heart failure, arrhythmia | 30 days postoperative | 
| Thromboembolic complications | pulmonary embolism | 30 days postoperative | 
| Stroke Volume Variation (SVV)(%) | SVV will be measured with Flo-Trac system (Edward Life Sciences). Normal range is about %10-15 | From onset of the surgery up to end of the surgery, every 30 minutes | 
| Cardiac Index(CI )(l min-1 m-2), | CI will be measured with Flo-Trac system (Edward Life Sciences). Normal value is 2,6-4,2 l min-1 m-2 | From onset of the surgery up to end of the surgery, every 30 minutes | 
| Systemic Vascular Resistance Index (SVRI )(dyn*s.cm-5 ) | SVRI will be measured with Flo-Trac system (Edward Life Sciences). Normal value is about 900-1300 dyn*s.cm-5 | From onset of the surgery up to end of the surgery, every 30 minutes | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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peroperative fluid management, restrictive fluid therapy, endothelial glycocalyx, Liberal fluid therapy