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

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

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.

Study Overview

• Status: Completed
• Conditions: Fluid Retention Tissue
• Intervention / Treatment: Other: liberal fluid management; Other: restrictive fluid management

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 Type: Interventional
• Enrollment (Actual): 37
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Turkey
  • Istanbul, Turkey, 34093
    • Istanbul University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: liberal fluid therapy; 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; 10 ml/ kg/ hr Ringer's lactate solution
ACTIVE_COMPARATOR: restrictive fluid therapy; 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; 2 ml/ kg/ hr Ringer's lactate solution with 2 mcg / kg / hr norepinephrine infusion

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Istanbul University
• Investigators: Principal Investigator: Meltem Savran KARADENİZ, Istanbul University

Publications and helpful links

Helpful Links

• Restrictive deferred hydration combined with preemptive norepinephrine infusion during radical cystectomy reduces postoperative complications and hospitalization time: a randomized clinical trial.
• Hypervolemia increases release of atrial natriuretic peptide and shedding of the endothelial glycocalyx.
• Revised Starling equation and the glycocalyx model of transvascular fluid exchange: an improved paradigm for prescribing intravenous fluid therapy

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 1, 2018
• Primary Completion (ACTUAL): March 15, 2021
• Study Completion (ACTUAL): April 1, 2021

Study Registration Dates

• First Submitted: February 6, 2020
• First Submitted That Met QC Criteria: March 2, 2021
• First Posted (ACTUAL): March 3, 2021

Study Record Updates

• Last Update Posted (ACTUAL): March 29, 2022
• Last Update Submitted That Met QC Criteria: March 28, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: endothelial glycocalyx; peroperative fluid management; restrictive fluid therapy; Liberal fluid therapy
• Other Study ID Numbers: 2018/374

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No