Fluid Therapy and Glycocalyx Shedding During Moderate Surgery

The Contribution of Liberal Fluid Therapy to Glycocalyx Shedding, Interstitial Edema and Fluid Accumulation During Moderate Surgery

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.

Study Overview

• Status: Completed
• Conditions: Abdominoplasty
• Intervention / Treatment: Other: Lactated Ringer's Fluid Bolus Response to Low Urinary Output; Other: Post-Anesthesia Care Unit Lactated Ringer's Fluid Management Protocol

• Study Type: Interventional
• Enrollment (Actual): 51
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Israel
  • Jerusalem, Israel, 9112001
    • Hadassah Ein-Carem Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

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

Exclusion Criteria:

• Pregnancy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / 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 Names: 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 Names: Recovery Room Fluid Management Protocol

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Hadassah Medical Organization
• Collaborators: Hebrew University of Jerusalem
• Investigators: Principal Investigator: Galel Yakobi, MD, Hadassah Medical Organization

Study record dates

Study Major Dates

• Study Start (Actual): May 13, 2020
• Primary Completion (Actual): August 3, 2023
• Study Completion (Actual): August 3, 2023

Study Registration Dates

• First Submitted: June 15, 2023
• First Submitted That Met QC Criteria: July 1, 2023
• First Posted (Actual): July 11, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 15, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Glycocalyx; IV Fluids
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics
• Other Study ID Numbers: 0388-19-HMO; 008932_2020-05-12_MOH (Registry Identifier: Israeli Ministry of Health)

Drug and device information, study documents

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