Fluid Therapy and Glycocalyx Shedding During Moderate Surgery

• ClinicalTrials.gov Identifier: NCT05939518
• Recruitment Status: Recruiting
• First Posted: July 11, 2023
• Last Update Posted: September 13, 2023
• Sponsor: Hadassah Medical Organization
• Collaborator: Hebrew University of Jerusalem
• Information provided by (Responsible Party): Hadassah Medical Organization

Study Description

Brief Summary:

Goal-directed fluid therapy is one of the most accepted strategies in intraoperative fluid therapy, although potential fluid overload is a possible drawback. Fluid overload has recently been shown to cause damage to the glycocalyx and to increase extravasation of fluids into the interstitial space.

This study aims to determine whether liberal fluid administration during moderate surgery results in impairment to the endothelial glycocalyx and causes edema.

Participants will be randomized to receive either a liberal or restrictive fluid protocol with vasopressor support. The investigators will measure interstitial edema by clinical signs, pulmonary congestion by ultrasound, and extracellular water by bioimpedance. Impairment of glycocalyx will be estimated by measuring blood levels of shedding markers. In addition, wound healing and early postoperative outcome will be estimated by POMS.

Condition or disease	Intervention/treatment	Phase
Abdominoplasty	Other: Lactated Ringer's Fluid Bolus Response to Low Urinary Output; Other: Post-Anesthesia Care Unit Lactated Ringer's Fluid Management Protocol	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 45 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Basic Science
• Official Title: The Contribution of Liberal Fluid Therapy to Glycocalyx Shedding, Interstitial Edema and Fluid Accumulation During Moderate Surgery
• Actual Study Start Date: May 13, 2020
• Estimated Primary Completion Date: May 11, 2024
• Estimated Study Completion Date: June 1, 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: Liberal Lactated Ringer Fluid Protocol with Ephedrine and Phenylephrine Boluses; IV Infusion of 500 ml of lactated Ringer's (RL) solution during the induction of anesthesia followed by an infusion of RL at a rate of 8.0 ml/kg/h throughout the maintenance phase of anesthesia. The anesthesia care provider will be allowed free use of IV boluses of ephedrine or phenylephrine to target a mean arterial blood pressure of >60 mmHg.	Other: Lactated Ringer's Fluid Bolus Response to Low Urinary Output; During the surgical procedure and the subsequent stay in the Post-Anesthesia Care Unit: if the study participant's urine output (UO) remains <0.3 ml/kg/h for two consecutive hours, an IV bolus of 250 ml of lactated Ringer's solution will be administered over 15 min and repeated every 30 min until the UO reaches >0.3 ml/kg/h.; Other: Post-Anesthesia Care Unit Lactated Ringer's Fluid Management Protocol; During their stay in the Post-Anesthesia Care Unit, patients will receive a 1.5 ml/kg/h IV infusion of lactated Ringer's solution.; Other Name: Recovery Room Fluid Management Protocol
Active Comparator: Restrictive Lactated Ringer Fluid Protocol with Noradrenaline Infusion; IV Infusion of 200 ml of lactated Ringer's (RL) solution during the induction of anesthesia followed by an infusion of RL at a rate of 2.0 ml/kg/h + an infusion of noradrenaline throughout the maintenance phase of anesthesia, through a large peripheral vein. The noradrenaline infusion rate will be titrated after an initial bolus of 10 μg, from an initial rate of 2.0 μg/kg/h, which may be raised up to 8.0 μg/kg/h, to target a mean arterial blood pressure (MBP) of >60 mmHg. If the MBP target is still not achieved, the RL infusion rate may be increased up to 4.0 ml/kg/h.	Other: Lactated Ringer's Fluid Bolus Response to Low Urinary Output; During the surgical procedure and the subsequent stay in the Post-Anesthesia Care Unit: if the study participant's urine output (UO) remains <0.3 ml/kg/h for two consecutive hours, an IV bolus of 250 ml of lactated Ringer's solution will be administered over 15 min and repeated every 30 min until the UO reaches >0.3 ml/kg/h.; Other: Post-Anesthesia Care Unit Lactated Ringer's Fluid Management Protocol; During their stay in the Post-Anesthesia Care Unit, patients will receive a 1.5 ml/kg/h IV infusion of lactated Ringer's solution.; Other Name: Recovery Room Fluid Management Protocol

Outcome Measures

Primary Outcome Measures :

1. Change from preoperative serum concentration of Heparan Sulfate. [ Time Frame: Two hours after completion of surgery. ]
   Measured using blood samples drawn from a peripheral vein of the study participant and analyzed in a laboratory.
2. Change from preoperative serum concentration of Syndecan-1. [ Time Frame: Two hours after completion of surgery. ]
   Measured using blood samples drawn from a peripheral vein of the study participant and analyzed in a laboratory.
3. Change from preoperative serum concentration of Hyaluronic Acid. [ Time Frame: Two hours after completion of surgery. ]
   Measured using blood samples drawn from a peripheral vein of the study participant and analyzed in a laboratory.
4. Change from preoperative serum concentration of Sphingosine-1-Phosphate. [ Time Frame: Two hours after completion of surgery. ]
   Measured using blood samples drawn from a peripheral vein of the study participant and analyzed in a laboratory.
5. Appearance of B-lines on lung ultrasonography. [ Time Frame: Two hours after completion of surgery. ]
   Bilateral ultrasonography of the study participant's lungs, performed by a physician using two views: posterior and lateral.
6. Early appearance of peripheral pitting edema. [ Time Frame: Two hours after completion of surgery. ]
   Bilateral physical examination of the study participant's wrists and ankles, performed by a physician.
7. Late appearance of peripheral pitting edema. [ Time Frame: During the first postoperative day. ]
   Bilateral physical examination of the study participant's wrists and ankles, performed by a physician.
8. Postoperative Morbidity Survey (POMS) Score. [ Time Frame: During the first postoperative day. ]
   Clinically evaluated by a physician for each study participant.
9. Early change in the percentage of Total Body Water and Extracellular Water. [ Time Frame: Immediately after completion of surgery. ]
   Measured by bioimpedance using a commercially available device connected to the study participant.
10. Late change in the percentage of Total Body Water and Extracellular Water. [ Time Frame: Two hours after completion of surgery. ]
    Measured by bioimpedance using a commercially available device connected to the study participant.

Secondary Outcome Measures :

1. Change from preoperative body weight. [ Time Frame: During the first postoperative day. ]
   Recorded while the study participant stands on an electronic scale.
2. Volume of urine produced during the procedure. [ Time Frame: Immediately after completion of surgery. ]
   Measured using a volumetric graduated urine collection container connected to a Foley catheter placed in the urinary bladder of the study participant.
3. Change from preoperative Heart Rate. [ Time Frame: Immediately after completion of surgery. ]
   Measured using a continuous electrocardiography monitor connected to the study participant.
4. Change from preoperative Mean Arterial Blood Pressure. [ Time Frame: Immediately after completion of surgery. ]
   Measured using an automated oscillometric blood pressure monitoring device with its cuff placed on one of the arms of the study participant.
5. Early change from preoperative Cardiac Output. [ Time Frame: Immediately after completion of surgery. ]
   Measured non-invasively using a commercially available device connected to the study participant.
6. Late change from preoperative Cardiac Output. [ Time Frame: Two hours after completion of surgery. ]
   Measured non-invasively using a commercially available device connected to the study participant.
7. Early change from preoperative serum concentration of C-Reactive Protein. [ Time Frame: Immediately after completion of surgery. ]
   Measured using blood samples drawn from a peripheral vein of the study participant and analyzed in a laboratory.
8. Late change from preoperative serum concentration of C-Reactive Protein. [ Time Frame: Two hours after completion of surgery. ]
   Measured using blood samples drawn from a peripheral vein of the study participant and analyzed in a laboratory.
9. Early change from preoperative serum concentration of Lactate. [ Time Frame: Immediately after completion of surgery. ]
   Measured using blood samples drawn from a peripheral vein of the study participant and analyzed in a laboratory.
10. Late change from preoperative serum concentration of Lactate. [ Time Frame: Two hours after completion of surgery. ]
    Measured using blood samples drawn from a peripheral vein of the study participant and analyzed in a laboratory.
11. Change from preoperative serum concentration of Creatinine. [ Time Frame: Immediately after completion of surgery. ]
    Measured using blood samples drawn from a peripheral vein of the study participant and analyzed in a laboratory.
12. Change from preoperative serum concentration of Hemoglobin. [ Time Frame: Immediately after completion of surgery. ]
    Measured using blood samples drawn from a peripheral vein of the study participant and analyzed in a laboratory.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Patients scheduled for abdominoplasty.
• American Society of Anesthesiologists Classification 1 or 2.

Exclusion Criteria:

• Pregnancy.

Contacts and Locations

Contacts

Contact: Peter Davydov, MD; +972-50-721-2550; petka88@gmail.com

Contact: Yevgeni Plotkin, MD; +972507765781; yevgenip@gmail.com

Locations

Israel

Hadassah Ein-Carem Medical Center; Recruiting

Jerusalem, Israel, 9112001

Contact: Peter Davydov, MD +972-50-721-2550 petka88@gmail.com

Sponsors and Collaborators

Hadassah Medical Organization

Hebrew University of Jerusalem

Investigators

• Principal Investigator: Galel Yakobi, MD; Hadassah Medical Organization

More Information

• Responsible Party: Hadassah Medical Organization
• ClinicalTrials.gov Identifier: NCT05939518
• Other Study ID Numbers: 0388-19-HMO; 008932_2020-05-12_MOH ( Registry Identifier: Israeli Ministry of Health )
• First Posted: July 11, 2023
• Last Update Posted: September 13, 2023
• Last Verified: May 2023

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Hadassah Medical Organization:

Glycocalyx; IV Fluids

Additional relevant MeSH terms:

Anesthetics; Central Nervous System Depressants; Physiological Effects of Drugs