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

• Sponsor: Istanbul University (Other)
• Overall Status: Completed
• CT.gov ID: NCT04780490
• Collaborator: (none)
• Enrollment: 37
• Location: 1
• Arms: 2
• Actual Duration (Months): 37
• Patients Per Site Per Month: 1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Fluid Retention Tissue	Other: liberal fluid management; Other: restrictive fluid management	N/A

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 Design

• Study Type: Interventional
• Actual Enrollment: 37 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Comparison of the Effects of Perioperative Liberal and Restrictive Fluid Management on the Endothelial Glycocalyx Layer in Radical Cystectomy and Urinary Diversion
• Actual Study Start Date: Mar 1, 2018
• Actual Primary Completion Date: Mar 15, 2021
• Actual Study Completion Date: Apr 1, 2021

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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

2. 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

3. 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

4. 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

Secondary Outcome Measures

1. Amount of blood transfusion (unit) [From the beginning surgery to day 2 postoperatively]

   Including red cell, fresh frozen plasma

2. Total intensive care unit (ICU) stay (Hour, day) [30 days postoperative]

   Including initial ICU admission and readmission times

3. Hospital stay (Hour, day) [90 days postoperative]

   From the beginning of surgery until actual hospital discharge

4. Gastrointestinal complications [30 days postoperative]

   Ileus, constipation, gastrointestinal bleeding, gastric ulcer, anastomotic intestinal leakage

5. Infectious complications [30 days postoperative]

   Urinary tract infection, pyelonephritis, urosepsis, pneumonia, wound infection

6. Surgical site complications [30 days postoperative]

   Wound dehiscence, evisceration

7. Genitourinary complications [30 days postoperative]

   Acute kidney injury, urethral anastamosis leak

8. Cardiac complications [30 days postoperative]

   Acute myocardial infarction, congestive heart failure, arrhythmia

9. Thromboembolic complications [30 days postoperative]

   pulmonary embolism

10. 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

11. 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

12. 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Istanbul University	Istanbul		Turkey	34093

Sponsors and Collaborators

• Istanbul University

Investigators

• Principal Investigator: Meltem Savran KARADENİZ, Istanbul University

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• 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

Publications

None provided.

• Responsible Party: Meltem Savran Karadeniz, Associate Professor, Istanbul University
• ClinicalTrials.gov Identifier: NCT04780490
• Other Study ID Numbers: 2018/374
• First Posted: Mar 3, 2021
• Last Update Posted: Mar 29, 2022
• Last Verified: Mar 1, 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Meltem Savran Karadeniz, Associate Professor, Istanbul University: peroperative fluid management; restrictive fluid therapy; endothelial glycocalyx; Liberal fluid therapy

Study Results

No Results Posted as of Mar 29, 2022