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

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ClinicalTrials.gov Identifier: NCT04780490
Recruitment Status : Recruiting
First Posted : March 3, 2021
Last Update Posted : March 3, 2021
Sponsor:
Information provided by (Responsible Party):
Meltem Savran Karadeniz, 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.


Condition or disease Intervention/treatment Phase
Fluid Retention Tissue Other: liberal fluid management Other: restrictive fluid management Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Estimated 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 : March 1, 2018
Estimated Primary Completion Date : March 2021
Estimated Study Completion Date : April 1, 2021

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




Primary Outcome Measures :
  1. Atrial Natriuretic Peptide (ANP)( pg/mL) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: From the beginning surgery to day 2 postoperatively ]
    Including red cell, fresh frozen plasma

  2. Total intensive care unit (ICU) stay (Hour, day) [ Time Frame: 30 days postoperative ]
    Including initial ICU admission and readmission times

  3. Hospital stay (Hour, day) [ Time Frame: 90 days postoperative ]
    From the beginning of surgery until actual hospital discharge

  4. Gastrointestinal complications [ Time Frame: 30 days postoperative ]
    Ileus, constipation, gastrointestinal bleeding, gastric ulcer, anastomotic intestinal leakage

  5. Infectious complications [ Time Frame: 30 days postoperative ]
    Urinary tract infection, pyelonephritis, urosepsis, pneumonia, wound infection

  6. Surgical site complications [ Time Frame: 30 days postoperative ]
    Wound dehiscence, evisceration

  7. Genitourinary complications [ Time Frame: 30 days postoperative ]
    Acute kidney injury, urethral anastamosis leak

  8. Cardiac complications [ Time Frame: 30 days postoperative ]
    Acute myocardial infarction, congestive heart failure, arrhythmia

  9. Thromboembolic complications [ Time Frame: 30 days postoperative ]
    pulmonary embolism

  10. Stroke Volume Variation (SVV)(%) [ Time Frame: 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), [ Time Frame: 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 ) [ Time Frame: 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



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04780490


Contacts
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Contact: Burcu Kulaksiz Mammadov, MD +905447361952 burcukulaksiz@istanbul.edu.tr
Contact: Meltem Savran Karadeniz, Assoc. Prof +902124142153 mskaradeniz@gmail.com

Locations
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Turkey
Istanbul University Recruiting
Istanbul, Turkey, 34093
Contact: Burcu Kulaksiz Mammadov, MD    +905447361952    burcukulaksiz@istanbul.edu.tr   
Contact: Meltem Savran Karadeniz, Assoc. Prof    +902124142153    mskaradeniz@gmail.com   
Sponsors and Collaborators
Istanbul University
Investigators
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Principal Investigator: Meltem Savran KARADENİZ Istanbul University
Additional Information:
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Responsible Party: Meltem Savran Karadeniz, Associate Professor, Istanbul University
ClinicalTrials.gov Identifier: NCT04780490    
Other Study ID Numbers: 2018/374
First Posted: March 3, 2021    Key Record Dates
Last Update Posted: March 3, 2021
Last Verified: March 2021

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