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

Not Applicable

Completed

• Conditions: Fluid Retention Tissue
• Interventions: Other: liberal fluid management; Other: restrictive fluid management

• Registration Number: NCT04780490
• Lead Sponsor: Istanbul University

Brief Summary

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

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.

Study Timeline

• Study Start: 2018-03-01
• Study First Submitted: 2020-02-06
• Study First Submitted QC: 2021-03-02
• Study First Posted: 2021-03-03
• Primary Completion: 2021-03-15
• Study Completion: 2021-04-01
• Status Verified: 2022-03
• Last Update Submitted: 2022-03-28
• Last Update Posted: 2022-03-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 37

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
liberal fluid therapy	liberal fluid management	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.
restrictive fluid therapy	restrictive fluid management	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.

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Istanbul University; 🇹🇷 Istanbul, Turkey